SARS-CoV-2 Update 2/10/23

02/12/2023 davidcwrightmd

In 2022, multiple new Omicron variants BA.1, BA.2, BA.4, and BA.5 assaulted the world’s population of humans and other animals. By the time multiple companies made and tested Omicron BA.1 vaccines, BA.1 was no longer the dominant variant; in fact, it was no longer present. On August 31, 2022, the FDA allowed rapid introduction of an Omicron BA.5 bivalent vaccine. In 2023 our problems are being caused by XBB recombinant variants and BA.5 sub-variants BQ.1 and BQ.1.1. The Omicron BA.5 bivalent vaccine has had no effect on the immune evading BQ variants or XBB recombinant variants. In December the first highly infectious recombinant variant, XBB, began spreading around the world. The XBB variant XBB.1.5, has rapidly spread across the country and the world. Another new variant, CH.1.1 (BA.2.75.3.4.1.1.1.1) caused 5.9% of infections in the world from December 25 to January 14, 2023 and, from December 26 to January 1, 19.5% of infections in the United Kingdom.

On January 13, the World Health Organization (WHO) updated its recommendations on mask wearing to specify that, given the global spread of COVID-19, masks should be worn “irrespective of the local epidemiological situation,” meaning that masks are now recommended for everyone, not just people in areas with high levels of transmission.

Here are our 14-day moving average determinations for SARS-CoV-2 for the United States. We use the WORLDOMETERS aggregators data set to make any projections since it includes data from the Department of Veterans Affairs, the U.S. Military, federal prisons and the Navajo Nation.

XBB.1.5 Variant Continues to Dominate in the United States

During the week ending in 2/11/23, the CDC estimates that based on genomic surveillance, XBB.1.5 accounted for 74.7% of infections, followed by BQ.1.1 at 16.3%, BQ.1 at 5.1%, XBB at 1.9%, CH.1.1 at 1.3%, BN.1 at 0.8%, BA.5 at 0.3%, and BF.7 at 0.3%.

BQ.1.1 has five spike mutations that are different from BA.5. Four of these mutations allow escape from immunity from monoclonal antibodies, any prior infection (including Omicron BA.5), or any vaccine to include the bivalent Omicron BA.5 vaccine. Infections are still occurring in our clinic in patients that received the Omicron BA.5 bivalent vaccine. The XBB recombinant isolate XBB.1.5 has rapidly become the dominant infection in the USA. It took 28 days to become the cause of 40% of infections in the USA. As of 1/14/23, XBB.1.5 now causes over 80% of infections in Regions 1 and 2.

The “Omicron family feud” is a phrase coined by Dr. Raj Rajnarayanan to describe what’s going on between the Omicron BQ variants, BQ.1, BQ,1.1 (and other BQ variants) and XBB.1.5 (and other XBB variants). In the USA in regions 1 and 2, XBB.1.5 has won the feud. A new variant of BA2.75, CH.1.1, is now 4.9% of SARS-CoV-2 isolates in the world. It has the Delta mutation, P681R, which should raise a red flag. According to Saito et al, the P681R mutation, “facilitates cleavage of the spike protein and enhances viral fusogenicity [the ability of the virus to fuse to human cell membranes]….and pathogenicity [lethality].”

XBB.1.5 Proportion of Sequenced Isolates in the USA

12/3/22	12/10/22	12/17/22	12/24/22	12/31/22	1/7/23	1/14/23	1/21/23	1/28/23	2/04/23	2/11/23
2.3%	4.4%	7.4%	11.8%	20.1%	30.4%	43.0%	49.1%	61.3%	65.9%	74.7%

BQ. 1 and BQ.1.1 Totaled Proportion of Sequenced Isolates in the USA

12/3/22	12/10/22	12/17/22	12/24/22	12/31/22	1/7/23	1/14/23	1/21/23	1/28/23	2/04/23	2/11/23
53.5%	57.4%	58.6%	60.3%	59.2%	53.2%	44.7%	40.2%	31.1%	27.4%	21.4%

Percent of isolates identified as XBB.1.5 by Region

	Region
Week ending in	1	2	3	4	5	6	7	8	9	10
12/31/22	75.3%	72.2%	32.7%	19.0%	6.0%	21.5%	8.1%	2.1%	9.2%	2.5%
1/14/23	81.7%	82.7%	49.0%	31.1%	14%	24.9%	8.8%	15%	15.8%	8.1%
1/28/23	89.3%	91.1%	72.5%	52.1%	36.5%	42.8%	24.4%	32.5%	35.1%	20.3%
2/11/23	93.8%	95.2%	85.8%	72.4%	60.4%	63.4%	53.1%	60.9%	56.9%	37.4%

SARS-CoV-2 infections per day in the United States have increased for the second time in 6 weeks. There is still widespread underreporting by states, a failure to capture all positive home tests, and a decreased PCR screening program in most states. Deaths per day in the United States have increased by 147 deaths per day. Many states are not reporting deaths or infections in a timely manner. The number of infections per day is expected to increase in the next four weeks due to a lack of mask use in schools, businesses, and airports; a failure of adequate building ventilation; lack of social distancing; and low rates of bivalent booster uptake. XBB, an Omicron recombinant variant first identified in India, caused a major outbreak in Singapore. XBB is the first recombinant variant combining spike protein sequences from two other Omicron BA.2 variants, that has spread aggressively around the world. New mutations of XBB, specifically XBB.1.5 have rapidly crowded out other variants in the USA. Current vaccines, monoclonal antibodies and prior infections will not protect you from getting an XBB.1.5 infection. A more detailed description of XBB variant mutations and epidemiology can be found on page 17 of the UK Health Security Agency Technical Briefing from November 25.

Troubling Variant News from the UK

The latest UK Health Security Agency Technical Briefing, published February 10, reports that variants XBB.1.5 and CH.1.1, along with their sublineages, have a growth advantage over previously dominant variants, are likely responsible for the current increase in cases in the UK, and “will continue to increase overall transmission as they become more prevalent.” In addition, they state that, based on their data, vaccine effectiveness against CH.1.1 and XBB.1.5 may be reduced compared to BQ.1. From this, we can conclude, as we have previously, that vaccination alone is not enough to protect people from being infected with these newer SARS-CoV-2 variants.

Another new variant, XBF, which is a recombinant of BA.5 and CJ.1 (which is a descendant of BA.2.75) has also shown up in low proportions in the UKHSA’s signal monitoring. More troubling is that, per GISAID, XBF currently accounts for more than 15% of sequences in Australia. We’ll be watching carefully to see which isolate will eventually supplant XBB.1.5. At this stage, it’s unclear whether it will be a mutation of XBB.1.5, another recombinant like XBF, or something else.

Yet another piece of bad news from UKHSA concerns molnupiravir, one of two oral antiviral medications approved in the U.S. for the treatment of COVID-19. This drug works by causing a large number of random mutations in the virus, which hinder its replication. That also means that molnupiravir leaves a particular “signature” of mutations that can be observed through viral sequencing. The Technical Briefing references a new preprint out of the London-based Francis Crick Institute which contains analysis of more than 13 million SARS-CoV-2 sequences in global databases. The researchers observed “a set of long phylogenetic branches that exhibit a high number of transition mutations.” In other words, on the SARS-CoV-2 family tree, there are some variants that are very different from their parents. They also observed that the number of these long branches (with more mutations between variant and sub-variant) increased in 2022, after the introduction of molnupiravir, and that the variants on those branches were more common in countries where molnupiravir was in use. In addition, they noted that the patterns of mutations among these variants were “highly similar to that in patients known to be treated with molnupiravir.” They conclude that there have been some cases in which “viruses with a large number of molnupiravir-induced substitutions have been transmitted to other individuals.” This analysis was compelling enough that the UKHSA’s Variant Technical Group is recommending further investigation into the impact of molnupiravir treatment on the evolution of the virus, especially in the case of chronic infections and infections in immunocompromised people.

In our clinic, we only treat patients with Paxlovid because of our concerns about the potential of developing new resistant variants on molnupiravir therapy, particularly in our immunocompromised patients. If additional information develops about the mutation problem with molnupiravir, then the drug may need to be pulled off the market.

For a more detailed picture of COVID variant evolution in the United States, we recommend checking out the dashboard put together by Raj Rajnarayanan, Assistant Dean of Research and Associate Professor at NYITCOM at Arkansas State University.

To understand the true impact of these variants, it’s helpful to examine their evolution. Two virologists collaborated on Twitter to create the figure below, which Professor Johnson titled “Convergent Evolution on Steroids.” It shows the key mutations present in many of the currently-circulating Omicron subvariants and demonstrates that mutation at site 346 is becoming more and more common.

From Daniele Focosi, M.D., Ph.D. @dfocosi on Twitter, February 3, 2023

Past infections with a BA.1, BA.2 or BA.5 variants will not prevent infections with any of the newer variants. Monoclonal antibodies are no longer effective against newer BQ variants, XBB variants and other spike protein mutated variants. The last remaining monoclonal antibody, bebtelovimab, was removed from use by the FDA on 12/2/22. Paxlovid was only 89% effective in the original clinical trials against SARS-CoV-2. If resistance develops this winter to oral Paxlovid, we will have more Paxlovid failures and increased hospitalizations and deaths.

A Deeper Dive into U.S. COVID Data

On 1/27/23, the United States had 12,107 documented new infections. There were also 159 deaths. Thirty-nine states did not report their infections, and 38 states and the District of Columbia didn’t report their deaths. In the United States on 2/09/23 the number of hospitalized patients (29,299) has decreased (-13.83% compared to the previous 14 days) and was 34,015 on January 27. On 1/27/23 there were 3,608 patients who were seriously or critically ill (a 17.03% decrease); that number was 4,349 two weeks ago. The number of critically ill patients has decreased by 741 in the last 14 days, while at least 7,743 new deaths occurred. Patients are still dying each day (average 553/day).

As of 2/10/23, we have had 1,139,979 deaths and 104,760,445 SARS-CoV-2 infections in the United States. We have had 653,533 new infections in the last 14 days. We are adding an average of 326,767 new infections every seven days. For the pandemic in the United States we are averaging one death for every 91.89 infections or over 10,882 deaths for each one million infections. As of 2//23, thirty-nine states have had greater than 500,000 total infections, and 38 states and Puerto Rico have had greater than 5,000 total deaths. Forty-six states have had greater than 2,000 deaths. Only Vermont has had less than a thousand deaths (901 deaths). Now 11 states have over 4,000 deaths per million population: Mississippi (4,444), Arizona (4,525), Alabama (4,261), West Virginia (4,410), New Mexico (4,293), Tennessee (4,234), Arkansas (4,281), Michigan (4,186), New Jersey (4,038), Kentucky (4,015) and Louisiana (4,006). Eighteen states (Alabama, Virginia, Missouri, North Carolina, Indiana, Tennessee, Massachusetts, Ohio, Michigan, Georgia, Illinois, New Jersey, Pennsylvania, Florida, Texas, New York, Arizona and California) have had greater than 20,000 deaths. Nine states have had greater than 40,000 deaths: Florida (85,710 deaths), Texas (93,364 deaths), New York (76,800 deaths), Pennsylvania (49,921 deaths), Georgia (42,161 deaths), Ohio (41,535 deaths), Illinois (41,263 deaths), Michigan (41,809), and California (100,345 deaths, 20th most deaths in the world).

On 11/20/20, there were 260,331 (cumulative) deaths in the US from SARS-CoV-2. Since 11/20/20 (27 months), there were 872,878 new deaths from SARS-CoV-2. For twenty-three of those months, vaccines have been available to all adults. During these twenty-three months, 567,780 people have died of SARS-CoV-2 infections. Clearly, a vaccine-only approach is not working anywhere, especially not in the United States. In addition to getting more people vaccinated, most of the hospitalizations and deaths could have been prevented by proper masking (N95 or better), social distancing, and treatment with oral antiviral agents like Paxlovid. We recommend all of these precautions and treatments to every patient in our clinic, and we have only lost one patient to COVID in 3 years.

As of 2/10/23, California was ranked 31st in the USA in infection percentage at 30.39%. In California, 26.42% of the people were infected in the last 22 months. As of 2/10/23, 33 states have had greater than 30% of their population infected. Fifty states, the District of Columbia and Puerto Rico have greater than 20% of their population infected.

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FDA-Approved Oral Drug Treatments for SARS-CoV-2

Pfizer has developed PAXLOVID™, an oral reversible inhibitor of C3-like protease of SARS-CoV-2. The drug inhibits this key enzyme that is crucial for virus production. The compound, also called Compound 6 (PF-07321332), is part of the drug combination PAXLOVID™ (PF-07321332; ritonavir), which successfully completed a Phase 2-3 trial in humans in multiple countries. The preliminary results were announced on 11/5/21 by Pfizer. The results showed that 89% of the hospitalizations and deaths were prevented in the drug treatment arm. The drug was administered twice a day for five days. No deaths occurred in the treatment group, and ten deaths occurred in the placebo group. The study was stopped by an independent data safety monitoring board, and the FDA concurred with this decision. Pfizer applied for an Emergency Use Authorization for this drug on 11/15/21. This drug was approved on 12/23/21. PAXLOVID™ one year later is widely available at major pharmaceutical chains and smaller independent drug stores throughout the USA. We have been able to obtain PAXLOVID™ for any patient desiring treatment. We have only had one drug failure and death from SARS-CoV-2 during 2022. That death occurred in an octogenarian male in the fourth quarter of 2022.

Watching World Data

Over the next few months, we’ll be paying close attention to correlations between the SARS-CoV-2 data, the number of isolates identified in various countries and states, and the non-pharmaceutical interventions (like mask mandates and lockdowns) put in place by state and national governments. Data on infections, deaths, and percent of population infected was compiled from Worldometers. Data for this table for SARS-CoV-2 Isolates Currently Known in Location was compiled from GISAID and the CDC. It’s worth noting that GISAID provided more data than the CDC.

Location	Total Infections as of 2/10/23	New Infections on 2/10/23	Total Deaths	New Deaths on 2/10/23	% of Pop.Infected	SARS-CoV-2 Isolates Currently Known in Location	National/ State Mask Mandate	Currently in Lockdown
World	677,294,111(2,779,648 new infections in the last 14 days with an average of 198,546 infections per day).	135,509	6,780755(52,474 new deaths in the last 14 days with an average of 3,748 deaths per day.)	888	8.68%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines) Mu/B.1.621 (Colombia)C.1.2 (South Africa 2% of isolates in July 2021)R1 (Japan)Omicron/B.1.1.529 + BA.1 + BA.2 + BA.3 (South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)Four new recombinants 12/31 to 3/22)BA.2.12.1 (USA)BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)BF.7BJ.1XBB (new recombinant India)BQ.1BQ.1.1BS.1BN.1XBB.1XBB.1.5CH.1.1*	No	No
USA	104,760,445(ranked #1) 653,533 new infections in the last 14 days with an average of 46,681 infections/day	12,107(ranked #7) 39 states failed to report infections on 2/10/23.	1,139,979(ranked #1) 7,743 new deaths reported in the last 14 days or an average of 553 deaths/ day.	159 38 states failed to report deaths on 2/10/23.	31.29%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan) Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)Recombinant Delta AY.119.2- Omicron BA.1.1 (Tennessee, USA 12/31/21)\BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)BA.4.6 (USA 7/22)BF.7BJ.1XBB (new recombinant India)BQ.1BQ.1.1BN.1XBB.1XBB.1.5CH.1.1*	No	No
Brazil	36,930,339(ranked #5) 124,372 new infections in the last 14 days.	12,716 (ranked#5)	697,662(ranked #2; 1,777 new deaths in the last 14 days)	42	17.14%		No	No
India	44,682,530(ranked #2).	–	530,739(ranked #3)	–	3.17% Unchanged in 8 weeks		No	No
United Kingdom	24,293,752(ranked #9) 34,506 new infections in the last 2 weeks.	–	204,898 (ranked #7) 1,669 new deaths in the last 2 weeks	–	35.46%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)C.1.2 (South Africa)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)XD (AY.4/BA.1) recombinantXF (Delta/BA.1) recombinantXE (BA.1/BA.2) recombinantBA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)*	No	No
California, USA	12,011,521(ranked #12 in the world; 50,447 new infections in the last 14 days).	1,459	100,345 (ranked #20 in world; 452 new deaths in the last 14 days	22	30.39%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)BQ.1BQ.1.1BN.1XBBXBB.1XBB.1.5CH.1.1*	No	No
Mexico	7,400,848(ranked #19) 47,218 new infections in 14 days).	–	332,850(ranked #5) 834 new deaths in the last 14 days)	–	5.62%		No	No
South Africa	4,057,211(ranked #38; 1,927 new infections in the last 14 days).	–	102,595 (ranked #18) no new deaths in the last 14 days).	–	6.67%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India) C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)	No	No
Canada	4,560,962(ranked #34) 21,733 new infections in 14 days).	–	50,629(ranked #24) 494 new deaths in the last 14 days.	–	11.88%		No	No
Russia	22,047,525 (ranked #10), 77,539 new infections in 14 days).	12,392 (ranked #6)	395,484(ranked #4)582 new deaths in 14 days	37	15.12%		No	No
Peru	4,483,236(ranked #35, 2,408 new infections in 14 days).	200	219,229(ranked #6) 500 new deaths in the last 14 days.	1	13.31%		No	No
Spain	13,748,918(ranked #12; 37,667 new infections in 14 days).	1,119 (ranked #13)	118,876 (ranked #16) 542 new deaths in 14 days.	36	29.42%		No	No
France	39,,559,127 (ranked #3)	3,336 (ranked #9)	164,537 (ranked #10) 457 new deaths in 14 days.	44	60.31% a 0.07% increase in 14 days.		No	No
Germany	37,739,472(ranked #4; 167,840 new infections in 14 days.)	13,420 (ranked #4)	166,763 (ranked #9)1,322 new deaths in 14 days.	103	45.19%0.20% increase in 14 days		No	No
South Korea	30,325,483 (ranked #7; 218,129 new infections in 14 days).	13,504(ranked #3)	33,697 (ranked #34) 365 new deaths in 14 days.	17	59.07%0.42% increase in 14 days		No	No
Netherlands	8,586,372 (ranked #17; 4,951 new infections in 14 days).	396	22,992 (ranked #41)	–	49.88%		No	No
Taiwan	9,773,627(ranked #16); 345,147 new infections in 14 days	16,964 (ranked #2)	16,964 (ranked #56; 760 new deaths in the last 14 days)	70	40.91% 1.45% of population has been infected in the last 14 days		No	No
Japan	32,908,240(ranked #6)543,390 new infections in the last 14 days	28,615(ranked #1)	70,377(ranked #20) 3,327 new deaths in the last 14 days for an average of 238 deaths per day.	192	26.20% 0.43-% of the population infected in the last 14 days.		No	No
Australia	11,330,342(ranked #14) 34,876 new infections in 14 days.	2,491 (ranked #10)	19,070(ranked #49) 455 new deaths in 14 days.	35	43.46% 0.14-% of the population infected in last 14 days.		No	No
Hong Kong	2,880,518(ranked# 41) 62,811 new infections in the last 14 days.	250	13,412 (ranked#60)132 new deaths in the last 14 days.	5	37.88% 0.15% of the population infected in the last 14 days.		No	No
China	503,302	–	–	–	–	–	–	–

What Our Team Is Reading This Week

SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 50, 10 February 2023 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1135877/variant-technical-briefing-50-10-february-2023.pdf
Identification of a molnupiravir-associated mutational signature in SARS-CoV-2 sequencing databases (Preprint) https://doi.org/10.1101/2023.01.26.23284998
COVID drug drives viral mutations — and now some want to halt its use https://www.nature.com/articles/d41586-023-00347-z#ref-CR1
SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 49, 11 January 2023 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1128554/variant-technical-briefing-49-11-january-2023.pdf
Long COVID: major findings, mechanisms and recommendations (Nature) https://www.nature.com/articles/s41579-022-00846-2
Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation (Nature) https://doi.org/10.1038/s41586-021-04266-9
Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants (Preprint) https://doi.org/10.1101/2022.12.27.521986
SARS-CoV-2 infection and persistence in the human body and brain at autopsy (Nature) https://doi.org/10.1038/s41586-022-05542-y
Lifting Universal Masking in Schools — Covid-19 Incidence among Students and Staff (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2211029
FDA Announces Bebtelovimab is Not Currently Authorized in Any US Region (FDA) https://www.fda.gov/drugs/drug-safety-and-availability/fda-announces-bebtelovimab-not-currently-authorized-any-us-region
SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 48, 25 November 2022 (UK Health Security Agency) https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1120304/technical-briefing-48-25-november-2022-final.pdf
Omicron sublineage BQ.1.1 resistance to monoclonal antibodies (The Lancet) https://doi.org/10.1016/S1473-3099(22)00733-2
SARS-CoV-2 Infection and Increased Risk for Pediatric Stroke (Pediatric Neurology) https://www.pedneur.com/article/S0887-8994(22)00210-7/fulltext
Single-cell multiomics revealed the dynamics of antigen presentation, immune response and T cell activation in the COVID-19 positive and recovered individuals https://doi.org/10.3389/fimmu.2022.1034159
Novel treatment combining antiviral and neutralizing antibody-based therapies with monitoring of spike-specific antibody and viral load for immunocompromised patients with persistent COVID-19 infection (Experimental Hematology & Oncology) https://ehoonline.biomedcentral.com/articles/10.1186/s40164-022-00307-9
Covid-19 is a leading cause of death in children and young people ages 0-19 years in the United States (Preprint) https://doi.org/10.1101/2022.05.23.22275458
Post-COVID-19-associated morbidity in children, adolescents, and adults: A matched cohort study including more than 157,000 individuals with COVID-19 in Germany (PLOS Medicine) https://journals.plos.org/plosmedicine/article?id=10.1371%2Fjournal.pmed.1004122
Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies (Acta Pharmacologica Sinica) https://doi.org/10.1038/s41401-022-00998-0
Cognitive Deficits in Long Covid-19 (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMcibr2210069
Brain 18F-FDG PET imaging in outpatients with post-COVID-19 conditions: findings and associations with clinical characteristics (European Journal of Nuclear Medicine and Molecular Imaging) https://doi.org/10.1007/s00259-022-06013-2
Acute and postacute sequelae associated with SARS-CoV-2 reinfection (Nature) https://doi.org/10.1038/s41591-022-02051-3
Associations between indoor relative humidity and global COVID-19 outcomes (Journal of the Royal Society) https://doi.org/10.1098/rsif.2021.0865
Successful treatment of prolonged, severe COVID-19 lower respiratory tract disease in a B-cell ALL patient with an extended course of remdesivir and nirmatrelvir/ritonavir (Clinical Infectious Diseases) https://doi.org/10.1093/cid/ciac868
Impact of SARS-CoV-2 ORF6 and its variant polymorphisms on host responses and viral pathogenesis (Preprint) https://doi.org/10.1101/2022.10.18.512708
Anti-PF4 antibodies associated with disease severity in COVID-19 (PNAS) https://www.pnas.org/doi/10.1073/pnas.2213361119
A multinational Delphi consensus to end the COVID-19 public health threat (Nature) https://doi.org/10.1038/s41586-022-05398-2
Pfizer and BioNTech Announce Updated Clinical Data for Omicron BA.4/BA.5-Adapted Bivalent Booster Demonstrating Substantially Higher Immune Response in Adults Compared to the Original COVID-19 Vaccine https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-updated-clinical-data-omicron
Paxlovid and Long Covid (Ground Truths, Eric Topol) https://erictopol.substack.com/p/paxlovid-and-long-covid?utm_source=substack&utm_medium=email
Risk of Infection and Hospitalization Among Children and Adolescents in New York After Emergence of the SARS-CoV-2 Omicron Variant – Comment and Response (JAMA) https://jamanetwork.com/journals/jama/article-abstract/2797231
Myocarditis (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMra2114478
SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 47 (UK Health Security Agency) https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1115077/Technical-Briefing-47.pdf
Effectiveness of Monovalent mRNA Vaccines Against COVID-19–Associated Hospitalization Among Immunocompetent Adults During BA.1/BA.2 and BA.4/BA.5 Predominant Periods of SARS-CoV-2 Omicron Variant in the United States — IVY Network, 18 States, December 26, 2021–August 31, 2022 (MMWR) https://www.cdc.gov/mmwr/volumes/71/wr/mm7142a3.htm
- “Three-dose monovalent mRNA VE estimates against COVID-19–associated hospitalization decreased with time since vaccination. Three-dose VE during the BA.1/BA.2 and BA.4/BA.5 periods was 79% and 60%, respectively, during the initial 120 days after the third dose and decreased to 41% and 29%, respectively, after 120 days from vaccination.”
Saliva antibody-fingerprint of reactivated latent viruses after mild/asymptomatic COVID-19 is unique in patients with myalgic-encephalomyelitis/chronic fatigue syndrome (Frontiers in Immunology) https://doi.org/10.3389/fimmu.2022.949787
SARS-CoV-2 Nsp6 causes cardiac defects through MGA/MAX complex-mediated increased glycolysis (Preprint) https://doi.org/10.21203/rs.3.rs-1677754/v1

COVID-19

Pandemic Year 3 in Review

01/01/2023 davidcwrightmd

When my daughter, Emily, and I started writing this blog in the spring of 2020, we did not anticipate that almost three years later, there would still be no end in sight for this pandemic. As we begin a new year, we wish we had better news, but the data continues to tell a grim story, and, as our long-time readers know, we always ground our outlook in the numbers.

In the United States, from March 2020 to December 31, 2021, we had 55,696,500 SARS CoV-2 infections and 846,905 deaths (66 infections per death). In the last 12 months we have had an additional 46,813,072 new infections and an additional 271,051 deaths (173 infections per death). That’s an average of 742 deaths per day. The majority of these deaths were in people over the age of 65, and all of them were preventable. In November 2022, KFF reported that COVID-19 was still the number 3 cause of death in the United States. It’s also worth noting that the number one cause of death, cardiovascular disease, is a known complication of COVID.

In late December 2021 the FDA approved both oral Paxlovid and oral Molnupiravir for outpatient treatment of SARS-CoV-2 with distribution beginning in January 2022. Unfortunately, all of the mask mandates were removed by individual states in 2022, and despite President Biden’s vow to institute a federal mask mandate during his 2020 campaign, the President and his administration adopted a decidedly anti-mask policy this year. CDC Director Rochelle Walensky even went so far as to describe masks as “the scarlet letter of this pandemic.” This irresponsible public health messaging has led to thousands of infections and deaths that could have been otherwise prevented by responsible mask wearing. We continue to urge our patients to protect themselves and others by wearing an N95 (or better) mask in public.

This year, multiple new Omicron variants BA.1, BA.2, BA.4, and BA.5 assaulted the world’s population of humans and other animals. By the time multiple companies made and tested Omicron BA.1 vaccines, BA.1 was no longer the dominant variant; in fact, it was no longer present. On August 31, 2022, the FDA allowed rapid introduction of an Omicron BA.5 bivalent vaccine. However, this has had no effect on new immune evading BQ variants. In December the first highly infectious recombinant variant, XBB, began spreading around the world. An additional variant, XBB.1.5, is now rapidly spreading across the country and the world causing increased numbers of hospitalizations and critically ill patients in the USA.

At the same time, we have had outbreaks and deaths from Influenza A H3N2 and RSV. Travel and lack of masking and social distancing have exacerbated the spread of these viruses. In addition, Mpox virus outbreaks occurred nationwide, a measles outbreak began in Ohio in unvaccinated children, and several cases of polio in New York were reported.

Part of why the United States’ vaccine-only approach to COVID-19 is so dangerous is that SARS-CoV-2 mutates, evading immune protection, and spreads more quickly than anyone can make, get approved, and distribute new vaccines. The Omicron BQ.1.1 variant is now being rapidly replaced by XBB.1.5. As an example, at D4 Labs, we designed, manufactured and packaged a new vaccine for Omicron BQ.1.1 in 6 weeks. Minimal animal testing, IRB approval, human testing, and expedited FDA approval under an EUA would probably require at least another 6 months. Even if we skipped or delayed animal testing, obtained IRB approval, and internally did a standard two-dose immunogenicity study in 20 humans using IgG antibody to the RBD of SARS-CoV-2 as the surrogate marker for protection, it would still take three months in our in-house human testing and assay facility to complete the study. This approach would probably not be acceptable to the FDA for even EUA approval but might be attempted in individual states. The timely production and distribution of any new vaccine against any new SARS-CoV-2 mutant will be difficult to accomplish by any company using the current regulatory framework for approval of vaccines in the United States. Using XBB.1.5 as an example, it is responsible for over 40% of the infections in the United States in the last 28 days. Vaccines would have to be designed, manufactured, and distributed in less than four weeks to stop an outbreak of a virulent, highly-infectious respiratory pathogen. Considerable thought needs to be entertained on how to accomplish this task rapidly.

Sadly, we do not see things improving in 2023 for respiratory virus control in the United States unless people wear high quality masks (N95 or better) and practice social distancing again. Continued infection and death increases are expected in the next eight weeks with 113 million people expected to travel during the holiday season, schools reopening on January 2, and people returning to work in poorly ventilated spaces.

After Delays, CDC Discloses XBB.1.5 Variant Data

On 12/31/22 the CDC estimates that BA.5 accounted for 3.7% of infections (a 49.6% point drop from its peak), BQ.1 accounted for 18.3% (a 12.4% point drop decrease from its peak on 12/17/22), BQ.1.1 accounted for 26.9% (a 11.5% point drop from its peak on 12/17/22), BA.4.6 accounted for 0.3%, BF.7 accounted for 2.1% of infections, BN.1 accounted for 2.4% of isolates, and BA.2.75.2 accounted for 0.1%. XBB is 3.6% of isolates, XBB.1.5 is 40.5% of isolates, BA.5.2.6 is 0.6% of isolates, and BF.11 0.3% of isolates. In the week ending December 31, 2022, BQ isolates accounted for 45.2% of isolates (a 23.9% point decrease in infections caused by these BQ variants since 12/17/22).

BQ.1.1 has five spike mutations that are different from BA.5. Four of these mutations allow escape from immunity from monoclonal antibodies, any prior infection (including Omicron BA.5), or any vaccine to include the bivalent Omicron BA.5 vaccine. Infections are still occurring in our clinic in patients that received the Omicron BA.5 bivalent vaccine. The XBB recombinant isolate XBB.1.5 has rapidly become the dominant infection in the USA. It took 28 days to become the cause of 40% of infections in the USA and it now causes over 70% of infections in Regions 1 and 2.

XBB.1.5 Proportion of Sequenced Isolates in the USA

12/03/22	12/10/22	12/17/22	12/24/22	12/31/22
1.3%	3.7%	9.9%	21.7%	40.5%

XBB.1.5 by Region on 12/31/22

Region	1	2	3	4	5	6	7	8	9	10
Percent of isolates identified as XBB.1.5	75.3%	72.2%	32.7%	19.0%	6.0%	21.5%	8.1%	2.1%	9.2%	18.2%

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COVID-19

SARS-CoV-2 Update

11/06/202211/06/2022 davidcwrightmd

It’s time for our next 14-day moving average determinations for SARS-CoV-2 for the United States and my thoughts on vaccines, SARS-CoV-2 therapeutic agents and mutant viruses. We use the WORLDOMETERS aggregators data set to make any projections since it includes data from the Department of Veterans Affairs, the U.S. Military, federal prisons and the Navajo Nation.

SARS-CoV-2 infections per day in the United States have increased for the first time in 14 weeks. There is still widespread underreporting by states, a failure to capture positive home tests, and a decreased PCR screening program in most states. Deaths per day in the United States have increased by 34 deaths per day. Many states are not reporting deaths or infections in a timely manner. The number of infections per day has increased by 1,683. The CDC estimates that BA.5 accounted for 39.2% (a 23% drop from 10/21/22), BQ.1 accounted for 16.5% (a 7.1% increase since 10/21/22), BQ.1.1 accounted for 18.8% (a 11.6% increase since 10/21/22), BA.4.6 accounted for 9.5%, BF.7 accounted for 9%, BA.2.75.2 accounted for 1.3%, and BA.4 accounted for 0.2%. In the week ending November 5, 2022 BQ isolates accounted for 35.3% of infections. BQ.1.1 has five spike mutations that are different from BA.5. Four of these mutations allow escape from immunity from monoclonal antibodies, any prior infection (including BA.5), or any vaccine to include a BA.5 vaccine.

The total percentage of BQ variant infections in the region that includes New York and New Jersey was 28.4% two weeks ago and is now 52.3%. BA.5.2.6 isolates now account for 3.1% of cases. The BA.2.75 lineages account for 4.2%.

The total percentage of BQ variant infections in the region that includes Pennsylvania, Delaware, Maryland, West Virginia, and Virginia was 17.8% two weeks ago and is now 36.6%. BA.5.2.6 isolates now account for 3.4% of cases. The BA.2.75 lineages account for 3% of cases.

The total percentage of BQ variant infections in the region that includes California, Nevada, Arizona, and Hawaii was 13.6% two weeks ago and is now 36.9%. BA.5.2.6 isolates now account for 2.4% of cases. The BA.2.75 lineages account for 4.2%.

Data on the rapid spread of a dangerous variant category, the BQ variants, was withheld by the CDC in their weekly reports until three weeks ago. The data on BQ.1 and BQ.1.1, the last being a variant with five significant spike protein mutations leading to escape from immunity from prior infections or vaccination. In addition, our monoclonal antibody therapies do not work for these isolates. Infections and hospitalizations in New York are rapidly increasing, secondary to BQ variants. BQ variants have been found in all 10 regions in the United States. Since New York has been a harbinger of things to come throughout the pandemic, we expect the pattern of increased infections, hospitalizations and deaths to continue in many states. These emerging BQ variants are descendants of BA.5. It’s troubling that, despite the availability of a BA.5 bivalent SARS-CoV-2 vaccine, few people are getting vaccinated. As of November 2, 2022, the CDC reports that only 26,378,963 people have received the bivalent vaccine. The Pfizer Omicron BA.5 mRNA booster was administered to 16,748,737 people and the Moderna Omicron BA.5 mRNA booster was administered to 9,630,226 people. In total, 26.3 million people (5 years and up) have received the bivalent vaccine. That’s only 11.6% of people who received the primary series and 7.9% of the overall population.

Children under the age of 5 have not been approved to receive either Omicron BA.5 mRNA boosters. Sadly, in children between 0 and 5 years of age only 1.47 million have received at least one dose of any SARS-CoV-2 mRNA vaccine. In the United States, at least 1,332 children have died of COVID-19, and another 74 have died of multisystem inflammatory syndrome (MIS-C). Worldwide, according to UNICEF, over 16,100 children and young adults aged 0-20 have died of COVID-19.

The October 28 UK Health Security Agency Technical Briefing identifies lineages BQ.1, BQ.1.1, XBB, and BF.7 as isolates of concern. Although BA.5 remains the dominant lineage in the UK, the authors explain, “In the most recent week, logistic growth of variants with 1, 2 or 3 convergent and antigenically significant RBD mutations was respectively 23%, 47%, and 66% per week. The category with 3 RBD mutations consisted largely of BQ.1.1 (59%) with the remainder consisting primarily of a mixture of BA.2.75 sub-lineages (29%).”

Variant	Sublineage of	Spike Mutations	Global Sequences	UK Sequences
BF.7	BA.5.2.1	R346T	11,922	2,644
BQ.1	BA.5	L452RN460KK444T	2,490	3,207
BQ.1.1	BA.5	N460KK444TR346T	2,304(35 countries)	1,272
BS.1	BA.2.3.2	R346TL452RN460KG476S	79	2

Data from UK Health Security Agency

In Monterey County, as of 11/5/22, 2.6% of 0-4 year-olds and 40.1% of 5-11 year-olds have received the first two doses of vaccine, while 73.4% of 12-17 year-olds have received two doses. Only 54.5% of Monterey County residents have received a third dose of the vaccine. The Monterey County Health Department does not publish data on how many residents have received the new BA.5 bivalent booster vaccine. On June 17, The FDA authorized both the Pfizer and Moderna vaccines for use in children ages 6 months to four years. We believe children under 5 should be vaccinated as soon as possible. All Monterey County residents should get up to date on COVID-19 vaccinations, including the bivalent BA.5 booster, as soon as possible.

On 11/04/22, the United States had 21,312 documented new infections. There were also 148 deaths. Thirty-five states did not report their infections, and 37 states didn’t report their deaths. In the United States the number of hospitalized patients has increased slightly (+2% compared to the previous 14 days) in many areas and was 27,395 on November 5. On 11/05/22 there were 3,146 patients who were seriously or critically ill; that number was 2,707 two weeks ago. The number of critically ill patients has increased by 439 in the last 14 days, while at least 5,432 new deaths occurred. The number of critically ill patients has decreased for the sixth time in thirty 14-day periods. Patients are still dying each day (average 388/day). Two new Omicron variants BQ.1 and BQ.1.1 are causing increased numbers of infections and hospitalizations in New York. BA.4, BA.4.6, BA.5, and BF.7 variants are still causing infections. In Singapore a different Omicron BA.2 variant, XBB, has caused rapidly increasing infections and now has been named a designated variant along with BQ.1 in the October 28 UK Health Security Agency Technical Briefing. Past infections with a BA.1, BA.2 or BA.5 variants will not prevent infections with any of the newer variants.

As of 11/04/22, we have had 1,098,038 deaths and 99,602,478 SARS-CoV-2 infections in the United States. We have had 546,941 new infections in the last 14 days. We are adding an average of 273,348 new infections every seven days. For the pandemic in the United States we are averaging one death for every 90.71 infections or over 11,024 deaths for each one million infections. As of 11/04/22, thirty-eight states have had greater than 500,000 total infections, and 38 states have had greater than 5,000 total deaths. Forty-six states have had greater than 2,000 deaths, and 43 states have greater than 2,000 deaths per million population. Seven states have over 4,000 deaths per million population: Mississippi (4,365), Arizona (4,338), Alabama (4,193), West Virginia (4,202), New Mexico (4,132), Tennessee (4,118), and Arkansas (4,148). . Eighteen states (Alabama, Virginia, Missouri, North Carolina, Indiana, Tennessee, Massachusetts, Ohio, Michigan, Georgia, Illinois, New Jersey, Pennsylvania, Florida, Texas, New York, Arizona and California) have had greater than 20,000 deaths. Eight states have had greater than 40,000 deaths: Florida (82,357 deaths), Texas (91,737 deaths), New York (73,549 deaths), Pennsylvania (47,840 deaths), Georgia (40,696 deaths), Ohio (40,249 deaths) , Illinois (40,058 deaths), and California (96,984 deaths, 20th most deaths in the world).

On 11/20/20, there were 260,331 (cumulative) deaths in the US from SARS-CoV-2. Since 11/20/20 (23 months), there were 830,937 new deaths from SARS-CoV-2. For nineteen of those months, vaccines have been available to all adults. During these nineteen months, 525,939 people have died of SARS-CoV-2 infections. Clearly, a vaccine-only approach is not working anywhere, especially not in the United States. In addition to getting more people vaccinated, most of the hospitalizations and deaths could have been prevented by proper masking (N95 or better), social distancing, and treatment with oral antiviral agents like Paxlovid. We recommend all of these precautions and treatments to every patient in our clinic, and we have only lost one patient to COVID in 2.5 years.

As of 11/04/22, California was ranked 33rd in the USA in infection percentage at 28.73%. In California, 24.76% of the people were infected in the last 20 months. As of 11/06/22, 24 states have had greater than 30% of their population infected. Fifty states have greater than 20% of their population infected.

Worldwide, average deaths per day are 1,637 for the last 14 days, which is a 68 deaths-per-day increase over the previous 14 days. The United States accounts for 23.70% (388 per day) of all deaths per day in the world over the last two weeks. Worldwide infections per day were 346,369. The United States accounts for 11.28% of those infections (or 39,067 infections per day).

FDA-Approved Oral Drug Treatments for SARS-CoV-2

Pfizer has developed PAXLOVID™, an oral reversible inhibitor of C3-like protease of SARS-CoV-2. The drug inhibits this key enzyme that is crucial for virus production. The compound, also called Compound 6 (PF-07321332), is part of the drug combination PAXLOVID™ (PF-07321332; ritonavir), which just successfully completed a Phase 2-3 trial in humans in multiple countries. The preliminary results were announced on 11/5/21 by Pfizer. The results show that 89% of the hospitalizations and deaths were prevented in the drug treatment arm. The drug was administered twice a day for five days. No deaths occurred in the treatment group, and ten deaths occurred in the placebo group. The study was stopped by an independent data safety monitoring board, and the FDA concurred with this decision. Pfizer applied for an Emergency Use Authorization for this drug on 11/15/21. This drug was approved on 12/23/21. We have only been able to obtain PAXLOVID™ for two patients who we successfully treated with this drug obtained from CVS in Salinas (East Alisal Street; phone number 831-424-0026). They were expecting another shipment on 1/28/22. In my opinion, this agent, if more widely available, could markedly alter the course of every coronavirus infection throughout the world.

Merck has developed the oral drug Molnupiravir, which induces RNA mutagenesis by viral RNA-dependent RNA polymerase of SARS-CoV-2 and other viruses. According to Kabinger et al, “Viral RNA-dependent RNA polymerase uses the active form of Molnupiravir, β-D-N4-hydroxycytidine triphosphate, as a substrate instead of cytidine triphosphate or uridine triphosphate. When the RNA-dependent RNA polymerase uses the resulting RNA as a template, β-D-N4-hydroxycytidine triphosphate directs incorporation of either guanine or adenine, leading to mutated (viral) RNA products. Analysis of RNA-dependent RNA polymerase–RNA complexes that contain mutagenesis products has demonstrated that β-D-N4-hydroxycytidine (the active form of Molnupiravir) can form stable base pairs with either guanine or adenine in RNA-dependent RNA polymerase explaining how the polymerase escapes proofreading and synthesizes mutated RNA” (quotation modified for clarity). The results of the phase 3 trial of Molnupiravir were published in the NEJM article “Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients” by Angélica Jayk Bernal, M.D. et al. (December 16, 2021 DOI: 10.1056/NEJMoa2116044). In this phase 3 study in the Molnupiravir group, 28 patients were hospitalized and one death occurred. In the placebo group, 53 patients were hospitalized and 9 died. Overall, 47% of hospitalizations and deaths were prevented by Molnupiravir. If you do a post hoc analysis and just look at deaths, Molnupiravir would prevent 89% of deaths. An Emergency Use Authorization by the FDA for Molnupiravir was approved on 12/24/21.The dose of Molnupiravir approved is four 200 mg capsules orally twice a day for five days. Diarrhea is reportedly a side effect in two percent of patients. I treated my first patient with Molnupiravir on 1/28/22. Currently more Molnupiravir is available weekly in the United States than PAXLOVID™ (see chart below; data from PHE.gov). Locally Molnupiravir is still available at CVS in Monterey (Fremont Blvd.; phone number: 831-375-5135) and CVS in Salinas (East Alisal Street; phone number 831-424-0026).

28, p740–746 (2021)with four 200 mg capsules orally twice a day for five dayfour 200 mg capsules orally twice a day for five daysIntravenous Drug Treatment for non-hospitalized SARS-CoV-2 Infected Patient

FDA-Approved Intravenous Monoclonal Antibody Treatment for Non-Hospitalized SARS-CoV-2 Patients

Bebtelovimab is a monoclonal antibody treatment for mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options approved or authorized by FDA are not accessible or clinically appropriate. The authorized dose of bebtelovimab is 175 mg, given as an intravenous injection over at least 30 seconds. The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for this drug on 2/11/22. Bebtelovimab is a human antibody that demonstrates neutralization against the Omicron variants and is available in every state and many hospitals and some clinics. If you are planning on using a monoclonal antibody to treat a SARS-CoV-2 infection, currently only bebtelovimab has activity against all Omicron variants, including BA.4.6. Researchers at Columbia University recently reported that “The loss of activity of tixagevimab and cilgavimab [components of Evusheld] against BA.4.6 leaves us with bebtelovimab as the only therapeutic mAb that has retained potent activity against all circulating forms of SARS-CoV-2.” For this reason, we no longer recommend Evusheld for immunocompromised patients with Omicron infections.

An examination of the three variants that Wang et al identified as capable of immune escape in patients who receive the two monoclonal antibodies that are contained in Evusheld reveals that all three variants have a mutation in the spike protein at position 346. The changes substitute an uncharged amino acid— threonine (T), serine (S), or isoleucine (I)—for a positively-charged amino acid, arginine. This just goes to show that a single point mutation in the spike protein can render a monoclonal antibody treatment ineffective. Policy makers should keep in mind that the only way to prevent new drug-resistant variants like BA.4.6 from emerging is to prevent transmission of SARS-CoV-2 in the first place, using non-pharmaceutical interventions. The lack of use of N95 masks, with impending winter and influenza outbreaks, on top of COVID-19, is not wise public health and infectious disease policy. If we don’t make effective use of the non-pharmaceutical interventions available to us (masks, ventilation, social distancing), then the pharmaceutical interventions we have will all eventually be useless.

Two virologists collaborated on Twitter to create the figure below, which Professor Johnson titled “Convergent Evolution on Steroids.” It shows the key mutations present in many of the currently-circulating Omicron subvariants and demonstrates that mutation at site 346 is becoming more and more common. This means that even if prevalence of BA.4.6 wanes, we are still likely to have drug resistance issues with other newer variants.

From Daniele Focosi, M.D., Ph.D. @dfocosi on Twitter

Watching World Data

Location	Total Infections as of 11/04/22	New Infections on 11/04/22	Total Deaths	New Deaths on 11/04/22	% of Pop.Infected	SARS-CoV-2 Isolates Currently Known in Location	National/ State Mask Mandate	Currently in Lockdown
World	637,281,842(4,849,164 new infections in 14 days).	273,333	6,604,448(22,918 new deaths in last 14 days)	1,091	8.17%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines) Mu/B.1.621 (Colombia)C.1.2 (South Africa 2% of isolates in July 2021)R1 (Japan)Omicron/B.1.1.529 + BA.1 + BA.2 + BA.3 (South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)Four new recombinants 12/31 to 3/22)BA.2.12.1 (USA)BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)BF.7BJ.1XBBBQ.1BQ.1.1BS.1*	No	No
USA	99,602,478(ranked #1) 546,941 new infections in the last 14 days or 39,067/day.	19,652(ranked #6) 35 states and D,C. failed to report infections on 11/04/22.	1,098,038(ranked #1) 5,432 new deaths reported in the last 14 days or 388/day.	148 37 states and D.C. failed to report deaths on 11/04/22.	29.74%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan) Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)Recombinant Delta AY.119.2- Omicron BA.1.1 (Tennessee, USA 12/31/21)\BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)*	No	No
Brazil	34,890,243(ranked #5) 62,069 new infections in the last 14 days.	2,738	688,384(ranked #2; 803 new deaths in 14 days)	68	16.20%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)	No	No
India	44,659,447(ranked #2); 18,699 new infections in 2 weeks.	1,082	530,486(ranked #3) 1,529 new deaths in 2 weeks.	7	3.17%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)Eta/B.1.525 (Nigeria/UK)APTK India VOI 32421Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Iota/B.1.526 (USA-NYC) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India)*	No	No
United Kingdom	23,930,041(ranked #7) 74,519 new infections in 2 weeks.	–	194,704 (ranked #7) 2,022 new deaths in 2 weeks	–	34.93%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)C.1.2 (South Africa)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)XD (AY.4/BA.1) recombinantXF (Delta/BA.1) recombinantXE (BA.1/BA.2) recombinantBA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)*	No	No
California, USA	11,353,896(ranked #13 in the world; 21,351 new infections in the last 14 days).	1,434	96,984 (ranked #20 in world) 303 new deaths in the last 14 days	7	28.73%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)*	No	No
Mexico	7,113,132(ranked #19) 7,114 new infections in 14 days).	628	330,415(ranked #5)94 new deaths in 14 days)	5	5.40%		No	No
South Africa	4,029,737(ranked #37; 4,362 new infections in 14 days).	241	102,363 (ranked #18) 106 new deaths in 14 days)	52	6.63%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India) C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)	No	No
Canada	4,336,860(ranked #33) 22,142 new infections in 14 days).	–	46,389(ranked #25 ) 364 new deaths in the last 14 days	–	11.29%		No	No
Poland	6,333,591 (ranked #21; 9,506 new infections in 14 days).	693	118,157 (ranked #15)142 new deaths in the last 14 days	14	16.80%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3	No	No
Russia	21,453667(ranked #10), 98,753 new infections in 14 days).	6,149 (ranked #9)	390,459(ranked #4)1,100 new deaths in 14 days	71	14.71%		No	No
Peru	4,159,132(ranked #36, 7,113new infections in 14 days).	598	216,972(ranked #6) 95 new deaths in the last 14 days	5	12.34%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Iran	7,558,002(ranked #17; 2,308 new infections in last 14 days)	40	144,587(ranked #12) 47 new deaths in the last 14 days	4	8.78%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Spain	13,529,643(ranked #12; 41,628 new infections in 14 days).	2,551	115,239 (ranked #16)381 new deaths in 14 days	23	28.95%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)	No	No
France	36,920,064 (ranked #3; 395,459 new infections in the last 14 days).	29,438 (ranked #4)	157,277 (ranked #10)940 new deaths in 14 days.	78	56.29% a 0.60% increase in 14 days.	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinant	No	No
Germany	35,823,771(ranked #4; 651,078 new infections in 14 days.)	38,859 (ranked #2)	154,535 (ranked #11)2,053 new deaths in 14 days	207	42.70% 0.77% increase in 14 days	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinant	No	No
South Korea	25,760,701 (ranked #6 516,446 new infections in 14 days).	43,424(ranked #1)	29,315 (ranked #36) 363 new deaths in 14 days	35	49.18%1.00% increase in 14 days	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No
Vietnam	11,505,249 (ranked #13; 8,895 new infections in 14 days).	339	43,165(ranked #26)	–	11.62%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No
Netherlands	8,521,729 (ranked #16; 27,024 new infections in 14 days).	1,225	22,845 (ranked #41)	3	49.51%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinant	No	No
Denmark	3,138,750 (ranked #40) 7,601 new infections in 14 days.	355	7,387 (ranked #78 139 new deaths in the last 14 days)	12	53.79%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinant	No	No
Taiwan	7,837,658(ranked #17)458,453 new infections in 14 days	27,594 (ranked #5)	13,084 (ranked #59 878 new deaths in the last 14 days)	74	32.80% 1.91% of population has been infected in the last 14 days	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No
Japan	22,534,377(ranked #9)608,146 new infections in the last 14 days	34,064(ranked #5)	46,898(ranked #24) 757 new deaths in the last 14 days	59	17.94%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)BA.2BA.5	No	No
Argentina	9,718,875 (ranked #15)	–	129,991(ranked #14)	–	21.12%		No	No
Italy	23,642,011 (ranked #8)	–	179,436(ranked #8)		39,23%		No	No
Chile	4,777,208(ranked #28)	7,570	61,737(ranked #22)	12	24.81%		No	No
Colombia	6,310,332(ranked #14)	–	141,850(ranked #13)	–	12.25%		No	No
Australia	9,718,875(ranked #14)	15,618 (ranked #7)	15,776(ranked #55)	59	39.95%		No	No
Turkey	16,919,638(ranked #11)	–	101,203(ranked #19)	–	19.77%		No	No
Indonesia	6,512,913 (ranked #20)	5,303 (ranked #11)	158,768 (ranked #9)	31	23,23%		No	No
Malaysia	4,918,917 (ranked #29)	4,360 (ranked #13)	36,481 (ranked #29)	1	14.75%		No	No

What Our Team Is Reading This Week

Successful treatment of prolonged, severe COVID-19 lower respiratory tract disease in a B-cell ALL patient with an extended course of remdesivir and nirmatrelvir/ritonavir (Clinical Infectious Diseases) https://doi.org/10.1093/cid/ciac868
Impact of SARS-CoV-2 ORF6 and its variant polymorphisms on host responses and viral pathogenesis (Preprint) https://doi.org/10.1101/2022.10.18.512708
Anti-PF4 antibodies associated with disease severity in COVID-19 (PNAS) https://www.pnas.org/doi/10.1073/pnas.2213361119
A multinational Delphi consensus to end the COVID-19 public health threat (Nature) https://doi.org/10.1038/s41586-022-05398-2
Pfizer and BioNTech Announce Updated Clinical Data for Omicron BA.4/BA.5-Adapted Bivalent Booster Demonstrating Substantially Higher Immune Response in Adults Compared to the Original COVID-19 Vaccine https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-updated-clinical-data-omicron
Paxlovid and Long Covid (Ground Truths, Eric Topol) https://erictopol.substack.com/p/paxlovid-and-long-covid?utm_source=substack&utm_medium=email
Risk of Infection and Hospitalization Among Children and Adolescents in New York After Emergence of the SARS-CoV-2 Omicron Variant – Comment and Response (JAMA) https://jamanetwork.com/journals/jama/article-abstract/2797231
Myocarditis (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMra2114478
SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 47 (UK Health Security Agency) https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1115077/Technical-Briefing-47.pdf
Effectiveness of Monovalent mRNA Vaccines Against COVID-19–Associated Hospitalization Among Immunocompetent Adults During BA.1/BA.2 and BA.4/BA.5 Predominant Periods of SARS-CoV-2 Omicron Variant in the United States — IVY Network, 18 States, December 26, 2021–August 31, 2022 (MMWR) https://www.cdc.gov/mmwr/volumes/71/wr/mm7142a3.htm
- “Three-dose monovalent mRNA VE estimates against COVID-19–associated hospitalization decreased with time since vaccination. Three-dose VE during the BA.1/BA.2 and BA.4/BA.5 periods was 79% and 60%, respectively, during the initial 120 days after the third dose and decreased to 41% and 29%, respectively, after 120 days from vaccination.”
Saliva antibody-fingerprint of reactivated latent viruses after mild/asymptomatic COVID-19 is unique in patients with myalgic-encephalomyelitis/chronic fatigue syndrome (Frontiers in Immunology) https://doi.org/10.3389/fimmu.2022.949787
SARS-CoV-2 Nsp6 causes cardiac defects through MGA/MAX complex-mediated increased glycolysis (Preprint) https://doi.org/10.21203/rs.3.rs-1677754/v1
WHO’s Therapeutics and COVID-19 Living Guideline on mAbs needs to be reassessed (The Lancet) https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)01938-9/fulltext
SARS-CoV-2 disrupts host epigenetic regulation via histone mimicry (Nature) https://doi.org/10.1038/s41586-022-05282-z
Real-world effectiveness of molnupiravir and nirmatrelvir plus ritonavir against mortality, hospitalisation, and in-hospital outcomes among community-dwelling, ambulatory patients with confirmed SARS-CoV-2 infection during the omicron wave in Hong Kong: an observational study (The Lancet) https://doi.org/10.1016/S0140-6736(22)01586-0
An ACE2-dependent Sarbecovirus in Russian bats is resistant to SARS-CoV-2 vaccines (PLOS Pathogens) https://doi.org/10.1371/journal.ppat.1010828
Plasma cytokine levels reveal deficiencies in IL-8 and gamma interferon in Long-COVID (Preprint) https://doi.org/10.1101/2022.10.03.22280661
Lingering cardiac involvement in previously well people after mild COVID-19 (Nature Medicine) https://www.nature.com/articles/s41591-022-02002-y
SARS-CoV-2 variants of concern and variants under investigation in England: technical briefing 46 (UK Health Security Agency) https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1109820/Technical-Briefing-46.pdf
Rapid initiation of nasal saline irrigation to reduce severity in high-risk COVID+ outpatients (Ear, Nose, and Throat Journal) https://doi.org/10.1177/01455613221123737
SARS-CoV-2 Omicron boosting induces de novo B cell response in humans (Preprint) https://doi.org/10.1101/2022.09.22.509040
Imprinted SARS-CoV-2 humoral immunity induces converging Omicron RBD evolution (Preprint) https://www.biorxiv.org/content/10.1101/2022.09.15.507787v2
- Note: This is a frightening paper and if the conclusions are accurate humans in general are in trouble. From other papers the facts that HERV-M and EBV are activated by SARS-CoV-2 infection does not bode well for humans moving forward.
SARS-CoV-2 Omicron boosting induces de novo B cell response in humans (Preprint) https://www.biorxiv.org/content/10.1101/2022.09.22.509040v1
Evolution of antibody immunity following Omicron BA.1 breakthrough infection (Preprint) https://www.biorxiv.org/content/10.1101/2022.09.21.508922v1
SARS-CoV-2 Spike protein promotes vWF secretion and thrombosis via endothelial cytoskeleton-associated protein 4 (CKAP4) (Signal Transduction and Targeted Therapy) https://www.nature.com/articles/s41392-022-01183-9
Long-term neurologic outcomes of COVID-19 (Nature Medicine) https://www.nature.com/articles/s41591-022-02001-z
Pulmonary Dysfunction after Pediatric COVID-19 (Radiology) https://pubs.rsna.org/doi/10.1148/radiol.221250
Severe Respiratory Illnesses Associated with Rhinoviruses and/or Enteroviruses Including EV-D68 – Multistate, 2022 (CDC) https://emergency.cdc.gov/han/2022/han00474.asp
VACCINE INFORMATION FACT SHEET FOR RECIPIENTS AND CAREGIVERS ABOUT COMIRNATY (COVID-19 VACCINE, mRNA), THE PFIZER-BIONTECH COVID-19 VACCINE, AND THE PFIZER-BIONTECH COVID-19 VACCINE BIVALENT (ORIGINAL AND OMICRON BA.4/BA.5) TO PREVENT CORONAVIRUS DISEASE 2019 (COVID-19) FOR USE IN INDIVIDUALS 12 YEARS OF AGE AND OLDER https://labeling.pfizer.com/ShowLabeling.aspx?id=14472
Pfizer/BioNTech COVID-19 Omicron-Modified Bivalent Vaccine https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-09-01/07-covid-swanson-508.pdf
Coronavirus (COVID-19) Update: FDA Authorizes Moderna, Pfizer-BioNTech Bivalent COVID-19 Vaccines for Use as a Booster Dose (FDA) https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-moderna-pfizer-biontech-bivalent-covid-19-vaccines-use
Resistance of SARS-CoV-2 Omicron Subvariant BA.4.6 to Antibody Neutralization (Preprint) https://www.biorxiv.org/content/10.1101/2022.09.05.506628v1.full
SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 45, 9 September 2022 (UK Health Security Agency) https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1103869/Technical-Briefing-45-9September2022.pdf
SARS CoV-2 detected in neonatal stool remote from maternal COVID-19 during pregnancy (Pediatric Research) https://doi.org/10.1038/s41390-022-02266-7
SARS-CoV-2 variants of concern: spike protein mutational analysis and epitope for broad neutralization (Nature Communications) https://doi.org/10.1038/s41467-022-32262-8
Is SARS-CoV-2 an oncogenic virus? (Journal of Infection) https://doi.org/10.1016/j.jinf.2022.08.005
Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope (Cell) https://doi.org/10.1016/j.cell.2022.07.002
Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: an analysis of 2-year retrospective cohort studies including 1 284 437 patients (The Lancet Psychiatry) https://doi.org/10.1016/S2215-0366(22)00260-7
An Antibody from Single Human VH-rearranging Mouse Neutralizes All SARS-CoV-2 Variants Through BA.5 by Inhibiting Membrane Fusion (Science Immunology) https://doi.org/10.1126/sciimmunol.add5446
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is common in post-acute sequelae of SARS-CoV-2 infection (PASC): Results from a post-COVID-19 multidisciplinary clinic (Preprint) https://doi.org/10.1101/2022.08.03.22278363
Evaluation of publication bias for 12 clinical trials of molnupiravir to treat SARS-CoV-2 infection in 13,694 patients (Preprint) https://www.researchsquare.com/article/rs-1913200/v1
Anti-neuronal antibodies against brainstem antigens are associated with COVID-19 (eBioMedicine) https://doi.org/10.1016/j.ebiom.2022.104211
Risk of SARS-CoV-2 Acquisition in Health Care Workers According to Cumulative Patient Exposure and Preferred Mask Type (JAMA Infectious Diseases) http://jamanetwork.com/article.aspx?doi=10.1001/jamanetworkopen.2022.26816
Coronavirus spike protein activated natural immune response, damaged heart muscle cells (AHA Basic Cardiovascular Sciences Meeting) https://newsroom.heart.org/news/coronavirus-spike-protein-activated-natural-immune-response-damaged-heart-muscle-cells
Distinguishing features of Long COVID identified through immune profiling (Preprint) https://doi.org/10.1101/2022.08.09.22278592
Virological characteristics of the SARS-CoV-2 Omicron BA.2.75 (Preprint) https://doi.org/10.1101/2022.08.07.503115
Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir (Preprint) https://doi.org/10.1101/2022.08.07.499047
Transmissible SARS-CoV-2 variants with resistance to clinical protease inhibitors (Preprint) https://doi.org/10.1101/2022.08.07.503099
Comparative pathogenicity of SARS-CoV-2 Omicron subvariants including BA.1, BA.2, and BA.5 (Preprint) https://doi.org/10.1101/2022.08.05.502758
Neuropathology and virus in brain of SARS-CoV-2 infected non-human primates (Nature Communications) https://doi.org/10.1038/s41467-022-29440-z
SARS-CoV-2 Brain Regional Detection, Histopathology, Gene Expression, and Immunomodulatory Changes in Decedents with COVID-19 (Journal of Neuropathology and Experimental Neurology) https://doi.org/10.1093/jnen/nlac056
Examination of SARS-CoV-2 In-Class Transmission at a Large Urban University With Public Health Mandates Using Epidemiological and Genomic Methodology (JAMA) http://jamanetwork.com/article.aspx?doi=10.1001/jamanetworkopen.2022.25430
Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection (Nature) https://doi.org/10.1038/nature04295
Impact of Pre-Existing Chronic Viral Infection and Reactivation on the Development of Long COVID (Preprint) https://doi.org/10.1101/2022.06.21.22276660
Notes from the Field: Increase in Pediatric Intracranial Infections During the COVID-19 Pandemic — Eight Pediatric Hospitals, United States, March 2020–March 2022 (MMWR) http://dx.doi.org/10.15585/mmwr.mm7131a4
Broadly neutralizing antibodies target the coronavirus fusion peptide (Science) https://doi.org/10.1126/science.abq3773
Efficacy and Safety of a Recombinant Plant-Based Adjuvanted Covid-19 Vaccine (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2201300
Efficacy and Safety of the RBD-Dimer–Based Covid-19 Vaccine ZF2001 in Adults (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2202261

COVID-19

SARS-CoV-2 Update

08/14/2022 davidcwrightmd

SARS-CoV-2 infections per day in the United States have decreased for the first time in two weeks; however, there is still widespread underreporting by states, a failure to capture positive home tests, and a decreased PCR screening program in most states. Deaths per day had been decelerating at a rapid rate in the United States but are now increased by 57 more deaths per day. The number of infections have increased as the Omicron BA.2.12.1, BA.2, BA.4, and BA.5 variants of SARS CoV-2 have spread across the nation. The CDC estimates that BA.2.12.1 accounted for 0.8% of isolates, BA.2 accounted for 0%, BA.5 accounted for 88.8%, BA.4 accounted for 5.3%, BA.4.6 accounted for 5.1%, and B.1.1.529 accounted for 0% in the week ending August 13.

We frequently hear messaging from health officials and politicians that Omicron is “mild,” especially compared to the Delta variant, and as a result, many of our patients believe that they no longer need to wear their masks. This is a dangerous misconception. SARS-CoV-2 still remains a highly transmissible, airborne virus. The following graph, based on CDC data from April 2, 2022, shows that Omicron deaths in people over 65 are much higher than Delta deaths in the same age group. In fact, the peak of Omicron deaths in people over 65 years of age is 163% higher than the Delta peak. The death rate from Omicron is only lower than Delta in the populations between 12 and 64 years of age. Until we have more data on these newer mutants of SARS-CoV-2, we will not know the lethality of each variant. It may take months to measure objective differences in the death rates of new circulating variants. We recommend that all of our patients and family members continue to wear N95 masks in all enclosed spaces.

In patients treated with Paxlovid for five days who have persistent symptoms and continued positivity, we feel that clinicians should consider giving a second course of Paxlovid for five days. Boucau et al have demonstrated that in a study of seven patients with recurrent symptoms, “High viral loads (median 6.1 log10 copies/mL) were detected after rebound for a median of 17 days after initial diagnosis. Three had culturable virus for up to 16 days after initial diagnosis.” This was not due to resistance-associated mutations of the virus, suggesting that the course of therapy may be inadequate in this group of persistently infected patients.

The Omicron variant has continued to mutate just like Delta. There are now 230 Omicron sub-variants (an unexplained decrease of 9 in the last two weeks) that have been assigned Pango lineages, including 116 sub-lineages of BA.2 (no increase in two weeks), one sub-lineage of BA.3, 14 sub-lineages of BA.4 (no increase in two weeks), and 24 sub-lineages of BA.5 (no increase in two weeks). The BF lineage (new eight weeks ago) now has 11 sublineages, no increase in two weeks. The BE lineage (also new eight weeks ago), with BE.1 first detected in South Africa, Austria and England, still has 4 sublineages. There are also new lineages from eight weeks ago: BC.1 (Japan), BC.2 (Peru),BD.1 (UK), BG.1 (Peru), BG.2 (US, Denmark, Canada), BG.3 (Peru), BG.4 (Israel).

Omicron variants have mutations which decrease the effectiveness of current vaccines and monoclonal antibodies. The effectiveness of the new Pfizer drug, PAXLOVID^TM, should not be compromised by any of the current mutations in Omicron or Delta variants. Pfizer completed their filing with the FDA on 11/15/21. The FDA approved PAXLOVID^TM on December 22 , 2021.The FDA approved Merck’s drug Molnupiravir on December 23, 2021. On 12/23/21 CVS announced by fax it was selected by the Government to distribute oral PAXLOVID^TM and Molnupiravir. On 12/27/21, another fax from CVS listed which CVS pharmacies in California would have these drugs. Monterey County covers 3,771 square miles with a population of 434,061. Three CVS pharmacies in Monterey, Salinas, and Soledad are the only listed pharmacies in our county. I have now been able to obtain PAXLOVID^TM for infected patients from the CVS in Salinas (phone 831-424-0026), the CVS on Fremont Street in Monterey (phone 831-375-5135) and the CVS in Soledad in south Monterey County (phone 831-678-5110). All require electronic prescriptions written as Paxlovid three tablets twice daily orally for five days (thirty total tablets). Physicians or their staff probably should call to check on drug availability that day.

In the absence of obtaining intravenous Sotrovimab or Bebtelovimab, only oral PAXLOVID^TM and Molnupiravir are available to treat SARS-CoV-2 as an outpatient. Our first Paxlovid failure in an immunocompromised patient was treated the week of 4/5/22 at the Community Hospital of the Monterey Peninsula (Montage) ER as an outpatient with a single one-minute intravenous injection of Bebtelovimab.

In Monterey County, as of 8/14/22, 0.3% of 0-4 year-olds and 38.9% of 5-11 year-olds have received the first two doses of vaccine, while 72.8% of 12-17 year-olds have received two doses. Only 53.3% of Monterey County residents have received a third dose of the vaccine. On June 17, The FDA authorized both the Pfizer and Moderna vaccines for use in children ages 6 months to four years. We believe children under 5 should be vaccinated as soon as possible. We would anticipate, with the start of school on August 5 and the low vaccination rates in our county, that we’ll have a marked increase in the number of infected patients. All Monterey County residents should get up to date on COVID-19 vaccinations as soon as possible.

FDA Approved Intramuscular Prophylaxis of SARS-CoV-2 Immunocompromised Patients

Evusheld (from AstraZeneca) contains two human monoclonal antibodies, Tixagevimab (150 mg in 1.5 mL) and Cilgavimab (150 mg in 1.5 mL), in separate vials. According to the manufacturer, “Tixagevimab and Cilgavimab are two recombinant human IgG1κ monoclonal antibodies with amino acid substitutions to extend antibody half-life (YTE), reduce antibody effector function, and minimize the potential risk of antibody-dependent enhancement of disease (TM). Tixagevimab and Cilgavimab can simultaneously bind to non-overlapping regions of the receptor binding domain (RBD) of SARS-CoV-2 spike protein. Tixagevimab, Cilgavimab, and their combination bind to spike protein with equilibrium dissociation constants of KD = 2.76 pM, 13.0 pM and 13.7 pM, respectively, blocking its interaction with human ACE2, the SARS-CoV-2 receptor, which is required for virus attachment. Tixagevimab, Cilgavimab, and their combination blocked RBD binding to human ACE2 with IC50 values of 0.32 nM (48 ng/mL), 0.53 nM (80 ng/mL), and 0.43 nM (65 ng/mL), respectively.” Each monoclonal antibody is administered intramuscularly to immunocompromised patients in two separate injections every six months. Evusheld availability in California is limited and has been rationed/distributed by our local Public Health Department only to hospitals. Physicians in Monterey County who want to receive a distribution (or redistribution) of Evusheld need to be added to the list of eligible facilities by the State Therapeutics group. The first step is for the Monterey County EMS Agency (phone: 831-755-5713) to make a request to the State Therapeutics group to have the facility added to the system for further verification. Due to extremely limited availability, evidently the State Therapeutics group is currently only considering additions on a case by case basis. Physicians who wish to submit their facility for consideration will need to provide the following information to the Monterey County EMS Agency:

Facility/Provider Name for Registration
Provider Type (Hospital, Pharmacy, Etc)
Shipping Address
Contact Name(s)
Contact Email(s)
Contact Phone Number(s)

As for my immunocompromised patients: We provided this information by email to the Monterey County EMS Agency on 1/26/22 and will update you when or if we become an eligible provider and receive our first doses of Evusheld.

Watching World Data

Location	Total Infections as of 8/12/22	New Infections on 8/12/22	Total Deaths	New Deaths on 8/12/22	% of Pop.Infected	SARS-CoV-2 Isolates Currently Known in Location	National/ State Mask Mandate	Currently in Lockdown
World	593,948,648(13,178,472 new infections in 14 days).	792,572	6,451,858(34,360 new deaths in last 14 days)	2,241	7.61%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines) Mu/B.1.621 (Colombia)C.1.2 (South Africa 2% of isolates in July 2021)R1 (Japan)Omicron/B.1.1.529 + BA.1 + BA.2 + BA.3 (South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)Four new recombinants 12/31 to 3/22)BA.2.12.1 (USA)BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)*	No	No
USA	94,643,632(ranked #1) 1,589,448 new infections in the last 14 days.	85,116(ranked #3) 22 states failed to report infections on 8/12/22.	1,062,151(ranked #1) 7,131 new deaths reported in the last 14 days.	335 28 states failed to report deaths on 8/12/22..	26.72%* *Not updated for 6 weeks by Worldometer.	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan) Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)Recombinant Delta AY.119.2- Omicron BA.1.1 (Tennessee, USA 12/31/21)\BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)*	No	No
Brazil	34,148,131(ranked #3) 352,939 new infections in the last 14 days.	23,552 (ranked #7)	681,317(ranked #2; 2,942 new deaths in 14 days)	292	15.82%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)	No	No
India	44,239.372(ranked #2); 239,234 new infections in 2 weeks.	15,815 (ranked#11)	526,966(ranked #3) 654 new deaths in 2 weeks.	68	3.14%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)Eta/B.1.525 (Nigeria/UK)APTK India VOI 32421Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Iota/B.1.526 (USA-NYC) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India)*	No	No
United Kingdom* *No reported data for 8/12/22	23,420,826(ranked #6) 116,347 new infections in 2 weeks.	–	186,087 (ranked #7) 2,134 new deaths in 2 weeks	–	34.12%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)C.1.2 (South Africa)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)XD (AY.4/BA.1) recombinantXF (Delta/BA.1) recombinantXE (BA.1/BA.2) recombinantBA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)*	No	No
California, USA	10,896,796(ranked #14 in the world; 198618 new infections in the last 14 days).	13,306	94,319 (ranked #20 in world) 615 new deaths in the last 14 days	50	27.57%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)*	No	No
Mexico	6,903,862(ranked #18) 192,015 new infections in 14 days).	13,313(ranked #12)	328,596(ranked #5)1,071 new deaths in 214 days)	71	5.23%	B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)*	No	No
South Africa	4,007,925(ranked #33; 3,370 new infections in 14 days).	313	101,982 (ranked #18) Not updated in last 2 weeks.	–	6.58%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India) C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)	No	No
Canada	4,109,931(ranked #33) 87,572 new infections in 14 days).	3,603	43,583(ranked #24)	37	10.69%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)*	No	No
Poland	6,113,840 (ranked #21; 48,508 new infections in 14 days).	4,223	116,751 (ranked #15)	14	16.19%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3	No	No
Russia	18,824,282(ranked #9), 247,309 new infections in 14 days).	27,810	383,011(ranked #4 in world)	57	12.88%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)R1 (Japan) B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Peru	4,013,831(ranked #34, 118,345 new infections in 14 days).	10,882	214,890(ranked #6)	72	11.82%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Iran	7,465,579(ranked #17; 88,785 new infections in last 14 days)	6,404	142,806(ranked #12)	54	8.65%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Spain	13,294,139(ranked #12; 67,560 new infections in 14 days).	4,528(ranked #22)	111,667 (ranked #16)	110	28.41%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)	No	No
France	34,191,919 (ranked #3; 405,153 new infections in the last 14 days).	22,638 (ranked #9)	153,064 (ranked #10) 1,101 new deaths in 14 days	74	52.13%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinant	No	No
Germany	31,535,343(ranked #5; 682,031 new infections in 14 days.).	45,859 (ranked #4)	145,698 (ranked #11) 1,726 new deaths in 14 days	137	37.38%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinant	No	No
South Korea	21,111,840 (ranked #8 1,491,323 new infections in 14 days).	128,671(ranked #2)	25,499 (ranked #37)	58	41.10%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No
Vietnam	11,362,540 (ranked #13; 586,056 new infections in 14 days).	2,192	43,096 (ranked #25)	1	11.45%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No
Netherlands	8,362,564 (ranked #16; 31,241 new infections in 14 days).	1,882	22,542 (ranked #41)	4	48.57%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinant	No	No
Denmark	3,076,642 (ranked #40) 16,658 new infections in 14 days	1,323	6,792 (ranked #80)	12	52.72%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinant	No	No
Taiwan	4,846,477(ranked #24) 300,841 new infections in 14 days	21,965 (ranked #10)	9,373 (ranked #67)	31	20.27%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No
Japan	15,086,304(ranked #11) 2,908,192 new infections in the last 14 days	224,929(ranked #1)	34,537(ranked #30) 2,251 new deaths in the last 14 days	214	12.00%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)BA.2BA.5	No	No

What Our Team Is Reading This Week

Distinguishing features of Long COVID identified through immune profiling (Preprint) https://doi.org/10.1101/2022.08.09.22278592
Virological characteristics of the SARS-CoV-2 Omicron BA.2.75 (Preprint) https://doi.org/10.1101/2022.08.07.503115
Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir (Preprint) https://doi.org/10.1101/2022.08.07.499047
Transmissible SARS-CoV-2 variants with resistance to clinical protease inhibitors (Preprint) https://doi.org/10.1101/2022.08.07.503099
Comparative pathogenicity of SARS-CoV-2 Omicron subvariants including BA.1, BA.2, and BA.5 (Preprint) https://doi.org/10.1101/2022.08.05.502758
Neuropathology and virus in brain of SARS-CoV-2 infected non-human primates (Nature Communications) https://doi.org/10.1038/s41467-022-29440-z
SARS-CoV-2 Brain Regional Detection, Histopathology, Gene Expression, and Immunomodulatory Changes in Decedents with COVID-19 (Journal of Neuropathology and Experimental Neurology) https://doi.org/10.1093/jnen/nlac056
Examination of SARS-CoV-2 In-Class Transmission at a Large Urban University With Public Health Mandates Using Epidemiological and Genomic Methodology (JAMA) http://jamanetwork.com/article.aspx?doi=10.1001/jamanetworkopen.2022.25430
Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection (Nature) https://doi.org/10.1038/nature04295
Impact of Pre-Existing Chronic Viral Infection and Reactivation on the Development of Long COVID (Preprint) https://doi.org/10.1101/2022.06.21.22276660
Notes from the Field: Increase in Pediatric Intracranial Infections During the COVID-19 Pandemic — Eight Pediatric Hospitals, United States, March 2020–March 2022 (MMWR) http://dx.doi.org/10.15585/mmwr.mm7131a4
Broadly neutralizing antibodies target the coronavirus fusion peptide (Science) https://doi.org/10.1126/science.abq3773
Efficacy and Safety of a Recombinant Plant-Based Adjuvanted Covid-19 Vaccine (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2201300
Efficacy and Safety of the RBD-Dimer–Based Covid-19 Vaccine ZF2001 in Adults (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2202261
Risk of Reinfection, Vaccine Protection, and Severity of Infection with the BA.5 Omicron Subvariant: A Danish Nation-Wide Population-Based Study (Preprint) https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4165630
SARS-CoV-2 Omicron BA.5: Evolving tropism and evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern. (Preprint) https://doi.org/10.1101/2022.07.07.22277128
Brain imaging and neuropsychological assessment of individuals recovered from mild to moderate SARS-CoV-2 infection (Preprint) https://doi.org/10.1101/2022.07.08.22277420
Increased Risk of Herpes Zoster in Adults ≥50 Years Old Diagnosed With COVID-19 in the United States (Open Forum Infectious Diseases) https://doi.org/10.1093/ofid/ofac118
Neutralization sensitivity of Omicron BA.2.75 to therapeutic monoclonal antibodies (Preprint) https://doi.org/10.1101/2022.07.14.500041
Neutralizing antibody activity against 21 SARS-CoV-2 variants in older adults vaccinated with BNT162b2 (Nature Microbiology) https://doi.org/10.1038/s41564-022-01163-3
How COVID-19 affects microvessels in the brain (Brain) https://doi.org/10.1093/brain/awac211
Fine Analysis of Lymphocyte Subpopulations in SARS-CoV-2 Infected Patients: Differential Profiling of Patients With Severe Outcome (Frontiers in Immunology) https://doi.org/10.3389/fimmu.2022.889813
SARS-CoV-2 accelerated clearance using a novel nitric oxide nasal spray (NONS) treatment: A randomized trial (The Lancet Regional Health – Southeast Asia) https://doi.org/10.1016/j.lansea.2022.100036
Effectiveness of 2, 3, and 4 COVID-19 mRNA Vaccine Doses Among Immunocompetent Adults During Periods when SARS-CoV-2 Omicron BA.1 and BA.2/BA.2.12.1 Sublineages Predominated — VISION Network, 10 States, December 2021–June 2022 (MMWR) http://dx.doi.org/10.15585/mmwr.mm7129e1
Characterization of virologic rebound following nirmatrelvir-ritonavir treatment for COVID-19 (Clinical Infectious Diseases) https://doi.org/10.1093/cid/ciac512
Potential Autoimmunity Resulting from Molecular Mimicry between SARS-CoV-2 Spike and Human Proteins (Preprint) https://doi.org/10.1101/2021.08.10.455737
COVID-19 positive patients at higher risk of developing neurodegenerative disorders, new study shows (Medical Express) https://medicalxpress.com/news/2022-06-covid-positive-patients-higher-neurodegenerative.html
Evidence of previous SARS-CoV-2 infection in seronegative patients with long COVID (eBioMedicine) https://doi.org/10.1016/j.ebiom.2022.104129
SARS-CoV-2 infection induces inflammatory bone loss in golden Syrian hamsters (Nature Communications) https://doi.org/10.1038/s41467-022-30195-w
Persistent 129Xe MRI Pulmonary and CT Vascular Abnormalities in Symptomatic Individuals with Post-Acute COVID-19 Syndrome (Radiology) https://doi.org/10.1148/radiol.220492
ACE2-independent infection of T lymphocytes by SARS-CoV-2 (Signal Transduction and Targeted Therapy) https://doi.org/10.1038/s41392-022-00919-x
Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae (Preprint) https://doi.org/10.1101/2022.06.14.22276401
SARS-CoV-2 is detected in the gastrointestinal tract of asymptomatic endoscopy patients but is unlikely to pose a significant risk to healthcare personnel (Gastro Hep Adv) https://doi.org/10.1016/j.gastha.2022.06.002
Long COVID symptoms in SARS-CoV-2-positive children aged 0–14 years and matched controls in Denmark (LongCOVIDKidsDK): a national, cross-sectional study (Child & Adolescent Health) https://doi.org/10.1016/S2352-4642(22)00154-7
Age and sex-specific risks of myocarditis and pericarditis following Covid-19 messenger RNA vaccines (Nature Communications) https://doi.org/10.1038/s41467-022-31401-5
COVID-19 positive patients at higher risk of developing neurodegenerative disorders, new study shows https://medicalxpress.com/news/2022-06-covid-positive-patients-higher-neurodegenerative.html
Posttranslational modifications optimize the ability of SARS-CoV-2 spike for effective interaction with host cell receptors (Biophysics and Computational Biology) https://doi.org/10.1073/pnas.2119761119
Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2 (The Lancet) https://doi.org/10.1016/S0140-6736(22)00941-2
Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum (Cell) https://doi.org/10.1016/j.cell.2022.06.005
Immunomodulatory treatment in postural tachycardia syndrome: A case series (European Journal of Neurology) https://doi.org/10.1111/ene.14711

COVID-19

SARS-CoV-2 Update

07/31/2022 davidcwrightmd

SARS-CoV-2 infections per day have been increasing in the United States for 16 consecutive weeks despite underreporting by states and the failure to capture positive home tests and a decreased screening program in most states. Deaths per day had been decelerating at a rapid rate in the United States but are now increased by 65 more deaths per day. The number of infections have increased as the Omicron BA.2.12.1, BA.2, BA.4, and BA.5 variants of SARS CoV-2 have spread across the nation. The CDC estimates that BA.2.12.1 accounted for 5.0% of isolates, BA.2 accounted for 0.3%, BA.5 accounted for 89.1%, BA.4 accounted for 12.9%, and B.1.1.529 accounted for 0% in the week ending July 23.

The Omicron variant has continued to mutate just like Delta. There are now 239 Omicron sub-variants (an increase of 28 in the last two weeks) that have been assigned Pango lineages, including 116 sub-lineages of BA.2 (an increase of 4 in two weeks), one sub-lineage of BA.3, 14 sub-lineages of BA.4 (an increase of 3 in two weeks), and 24 sub-lineages of BA.5 (an increase of 7 in two weeks). The BF lineage (new six weeks ago) now has 11 sublineages, an increase of 5 in two weeks. The BE lineage (also new six weeks ago), with BE.1 first detected in South Africa, Austria and England, still has 4 sublineages. There are also new lineages from six weeks ago: BC.1 (Japan), BC.2 (Peru), BD.1 (UK), BG.1 (Peru), BG.2 (US, Denmark, Canada), BG.3 (Peru), BG.4 (Israel).

In Monterey County, as of 7/31/22, 0.1% of 0-4 year-olds and 38.6% of 5-11 year-olds have received the first two doses of vaccine, while 72.6% of 12-17 year-olds have received two doses. Only 53.2% of Monterey County residents have received a third dose of the vaccine. On June 17, The FDA authorized both the Pfizer and Moderna vaccines for use in children ages 6 months to four years. We believe children under 5 should be vaccinated as soon as possible. We would anticipate, with the start of school on August 5 and the low vaccination rates in our county, that we’ll have a marked increase in the number of infected patients. All Monterey County residents should get up to date on COVID-19 vaccinations as soon as possible.

On 7/29/22, the United States had 99,061 documented new infections. There were also 286 deaths. Twenty-two states did not report their infections, and 28 states didn’t report their deaths. In the United States the number of hospitalized patients has been increasing in many areas and was 44,207 on July 29, an increase of 9% compared to the previous 14 days. Now there are 4,723 patients who are seriously or critically ill; that number was 4,180 two weeks ago. The number of critically ill patients has increased by 543 in the last 14 days, while at least 6,327 new deaths occurred (an increase of 65 deaths per day from the previous 14 days). The number of critically ill patients has increased for the seventh time in twenty-four 14-day periods. Patients are still dying each day (average 387/day). Omicron BA.2, BA.2.12.1, BA.4, and BA.5 variants causing infections should continue to increase and critically ill patients may continue to increase. Deaths, which usually lag two to four weeks behind exponential increase in infections, are increasing now. Past infections with a BA.1 or BA.2 variant will not prevent infections with BA.2.12.1, BA.4, or BA.5.

As of 7/29/22, we have had 1,055,020 deaths and 93,054,184 SARS-CoV-2 infections in the United States. We have had 1,883,613 new infections in the last 14 days. We are adding an average of 941,807 infections every seven days. For the pandemic in the United States we are averaging one death for every 88.20 infections or over 11,338 deaths for each one million infections. As of 7/29/22, thirty-eight states have had greater than 500,000 total infections, and 37 states have had greater than 5,000 total deaths. Seventeen states (Virginia, Missouri, North Carolina, Indiana, Tennessee, Massachusetts, Ohio, Michigan, Georgia, Illinois, New Jersey, Pennsylvania, Florida, Texas, New York, Arizona and California) have had greater than 20,000 deaths. Four states (Florida, Texas, New York, and California) have had greater than 70,000 deaths. California and Texas have each had greater than 89,000 deaths with California having 93,704 deaths (20th most deaths in the world).

As of 7/1/22, in the United States, 26.72% of the population has had a documented SARS-CoV-2 infection. In the 18 months preceding 7/1/22, 23.97% of our country became infected with SARS-CoV-2. On 11/20/20, there were 260,331 (cumulative) deaths in the US from SARS-CoV-2.

In the last 18 months, there were 794,889 new deaths from SARS-CoV-2. For fifteen of those months, vaccines have been available to all adults. During these fifteen months, 483,923 people have died of SARS-CoV-2 infections. Most of the hospitalizations and deaths could have been prevented by vaccination, proper masking, and social distancing.

As of 7/29/22, California was ranked 32th in the USA in infection percentage at 27.07%. In California, 23.1% of people were infected in the last 18 months. As of 7/29/22, 38 states have had greater than 25% of their population infected.

Worldwide, average deaths per day are 2,263 for the last 14 days, which is a 417 deaths-per-day increase over the previous 14 days. The United States accounts for 19.97% (452 per day) of all deaths per day in the world over the last two weeks. Worldwide infections per day were 1,030,492. The United States accounts for 13.06% of those infections (or 134,544 infections per day).

FDA-Approved Oral Drug Treatments for SARS-CoV-2

Pfizer has developed PAXLOVID™, an oral reversible inhibitor of C3-like protease of SARS-CoV-2. The drug inhibits this key enzyme that is crucial for virus production. The compound, also called Compound 6 (PF-07321332), is part of the drug combination PAXLOVID™ (PF-07321332; ritonavir), which just successfully completed a Phase 2-3 trial in humans in multiple countries. The preliminary results were announced on 11/5/21 by Pfizer. The results show that 89% of the hospitalizations and deaths were prevented in the drug treatment arm. The drug was administered twice a day for five days. No deaths occurred in the treatment group, and ten deaths occurred in the placebo group. The study was stopped by an independent data safety monitoring board, and the FDA concurred with this decision. Pfizer applied for an Emergency Use Authorization for this drug on 11/15/21. This drug was approved on 12/23/21. We have only been able to obtain PAXLOVID™ for two patients who we successfully treated with this drug obtained from CVS in Salinas (East Alisal Street; phone number 831-424-0026). They were expecting another shipment on 1/28/22. In my opinion, this agent, if more widely available, could markedly alter the course of every coronavirus infection throughout the world.

FDA Approved Intramuscular Prophylaxis of SARS-CoV-2 Immunocompromised Patients

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On 2/24/22, the FDA revised its dosing guidance for Evusheld, doubling the dosage of its two components, Tixagevimab and Cilgavimab, from 150 mg each to 300 mg each. They explain, “Based on the most recent information and data available, Evusheld may be less active against certain Omicron subvariants. The dosing regimen was revised because available data indicate that a higher dose of Evusheld may be more likely to prevent infection by the COVID-19 Omicron subvariants BA.1 and BA.1.1 than the originally authorized Evusheld dose.” Patients who have already received their first administration of Evusheld intramuscularly will need to contact their healthcare provider to get a second 150 mg injection of Tixagevimab and Cilgavimab. If you have not received Evusheld yet, the correct dose is 3 mL/300 mg of each monoclonal antibody injected intramuscularly. This large volume necessitates administration of the antibodies in the gluteus, with two separate injections.

Watching World Data

Location	Total Infections as of 7/29/22	New Infections on 7/29/22	Total Deaths	New Deaths on 7/29/22	% of Pop.Infected	SARS-CoV-2 Isolates Currently Known in Location	National/ State Mask Mandate	Currently in Lockdown
World	580,770,176(14,426,888 new infections in 14 days).	905,405	6,417,498(31,678 new deaths in last 14 days)	2,808	7.45%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines) Mu/B.1.621 (Colombia)C.1.2 (South Africa 2% of isolates in July 2021)R1 (Japan)Omicron/B.1.1.529 + BA.1 + BA.2 + BA.3 (South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)Four new recombinants 12/31 to 3/22)BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)*	No	No
USA	93,054,184(ranked #1) 1,883,613 new infections in the last 14 days.	99,081(ranked #4) 22 states failed to report infections.	1,055,020(ranked #1) 6,327 new deaths in the last 14 days.	28628 states failed to report deaths.	26.72%* *Not updated for four weeks by Worldometers	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan) Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)Recombinant Delta AY.119.2- Omicron BA.1.1 (Tennessee, USA 12/31/21)\BA.2BA.2.12.1 (United States)BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India)*	No	No
Brazil	33,795,192(ranked #3) 545,075 new infections in the last 14 days.	42,816 (ranked #8)	678,375(ranked #2; 3,230 new deaths in 14 days)	228	15.66%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
India	44,000,138(ranked #2); 270,067 new infections in 2 weeks.	20,408	526,312(ranked #3)	54	3.12%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)Eta/B.1.525 (Nigeria/UK)APTK India VOI 32421Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Iota/B.1.526 (USA-NYC) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2.75 (India)*	No	No
United Kingdom* *No reported data for 7/29/22	23,304,479(ranked #6) 229,119 new infections in 2 weeks.	–	183,953 (ranked #7) 2,373 new deaths in 2 weeks	–	33.95%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)C.1.2 (South Africa)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)XD (AY.4/BA.1) recombinantXF (Delta/BA.1) recombinantXE (BA.1/BA.2) recombinantBA.2BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India)*	No	No
California, USA	10,698,178(ranked #14 in the world; 317,309 new infections in the last 14 days).	18,715	93,704 (ranked #20 in world) 687 new deaths in the last 14 days	51	27.07%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa)BA.5 (South Africa)*	No	No
Mexico	6,711,847(ranked #18) 337,971 new infections in 14 days).	24,893(ranked #9)	327,525(ranked #5)	113	5.09%	B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)*	No	No
South Africa	4,004,555(ranked #33; 4,704 new infections in 14 days).	354	101,982 (ranked #18)	5	6.58%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India) C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)	No	No
Canada	4,012,359(ranked #32) 4,896 new infections in 14 days).	–	43,583(ranked #24)	–	10.44% .	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)*	No	No
Poland	6,065,332 (ranked #21; 35,385 new infections in 14 days).	3,391	116,556 (ranked #15)	9	16.06%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3	No	No
Russia	18,576,973(ranked #9), 96,039 new infections in 14 days).	11,422	382,352(ranked #4 in world)	39	12.71%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)R1 (Japan) B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Peru	3,895,486(ranked #37, 181,125 new infections in 14 days).	6,467	214,195(ranked #6)	41	11.48%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Iran	7,376,794(ranked 17th; 106,771 new infections in last 14 days)	7,849	141,891(ranked #12)	54	8.55%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Spain	13,226,579(ranked 11th; 136,103 new infections in 14 days).	7,783(ranked #18)	110,719 (ranked #16)	109	28.26%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)	No	No
France	33,786,766 (ranked #4; 967,865 new infections in the last 14 days).	45,515 (ranked #6)	151,983 (ranked #10) 1,407 new deaths in 14 days	89	51.52%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinant	No	No
Germany	30,853,312(ranked #5; 1,170,323 new infections in 14 days.).	66,003 (ranked #4)	143,972 (ranked #11) 1,437 new deaths in 14 days	117	36.58%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinant	No	No
South Korea	19,620,517 (ranked #9 940,375 new infections in 14 days).	85,275(ranked #3)	24,999 (ranked #38)	35	38.20%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No
Vietnam	10,776,484 (ranked #13; 17,339 new infections in 14 days).	1,803	43,093 (ranked #25)	1	10.86%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No
Netherlands	8,331,315 (ranked #18; 57,081 new infections in 14 days).	3,238	22,492 (ranked #41)	4	48.40%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinant	No	No
Denmark	3,059,984 (ranked #39) 20,125 new infections in 14 days	1,037	6,639 (ranked #81)	11	52.44%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinant	No	No
Taiwan	4,545,636(ranked #29) 330,436 new infections in 14 days	23,289 (ranked #10)	8,833 (ranked #69) 916 new deaths in 14 days	57	19.01%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No
Japan	12,118,112(ranked #12) 2,117,392 new infections in the last 14 days	230,055(ranked #1)	32,286(ranked #30)	116	9.64%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No

What Our Team Is Reading This Week

Broadly neutralizing antibodies target the coronavirus fusion peptide (Science) https://doi.org/10.1126/science.abq3773
Efficacy and Safety of a Recombinant Plant-Based Adjuvanted Covid-19 Vaccine (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2201300
Efficacy and Safety of the RBD-Dimer–Based Covid-19 Vaccine ZF2001 in Adults (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2202261
Risk of Reinfection, Vaccine Protection, and Severity of Infection with the BA.5 Omicron Subvariant: A Danish Nation-Wide Population-Based Study (Preprint) https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4165630
SARS-CoV-2 Omicron BA.5: Evolving tropism and evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern. (Preprint) https://doi.org/10.1101/2022.07.07.22277128
Brain imaging and neuropsychological assessment of individuals recovered from mild to moderate SARS-CoV-2 infection (Preprint) https://doi.org/10.1101/2022.07.08.22277420
Increased Risk of Herpes Zoster in Adults ≥50 Years Old Diagnosed With COVID-19 in the United States (Open Forum Infectious Diseases) https://doi.org/10.1093/ofid/ofac118
Neutralization sensitivity of Omicron BA.2.75 to therapeutic monoclonal antibodies (Preprint) https://doi.org/10.1101/2022.07.14.500041
Neutralizing antibody activity against 21 SARS-CoV-2 variants in older adults vaccinated with BNT162b2 (Nature Microbiology) https://doi.org/10.1038/s41564-022-01163-3
How COVID-19 affects microvessels in the brain (Brain) https://doi.org/10.1093/brain/awac211
Fine Analysis of Lymphocyte Subpopulations in SARS-CoV-2 Infected Patients: Differential Profiling of Patients With Severe Outcome (Frontiers in Immunology) https://doi.org/10.3389/fimmu.2022.889813
SARS-CoV-2 accelerated clearance using a novel nitric oxide nasal spray (NONS) treatment: A randomized trial (The Lancet Regional Health – Southeast Asia) https://doi.org/10.1016/j.lansea.2022.100036
Effectiveness of 2, 3, and 4 COVID-19 mRNA Vaccine Doses Among Immunocompetent Adults During Periods when SARS-CoV-2 Omicron BA.1 and BA.2/BA.2.12.1 Sublineages Predominated — VISION Network, 10 States, December 2021–June 2022 (MMWR) http://dx.doi.org/10.15585/mmwr.mm7129e1
Characterization of virologic rebound following nirmatrelvir-ritonavir treatment for COVID-19 (Clinical Infectious Diseases) https://doi.org/10.1093/cid/ciac512
Potential Autoimmunity Resulting from Molecular Mimicry between SARS-CoV-2 Spike and Human Proteins (Preprint) https://doi.org/10.1101/2021.08.10.455737
COVID-19 positive patients at higher risk of developing neurodegenerative disorders, new study shows (Medical Express) https://medicalxpress.com/news/2022-06-covid-positive-patients-higher-neurodegenerative.html
Evidence of previous SARS-CoV-2 infection in seronegative patients with long COVID (eBioMedicine) https://doi.org/10.1016/j.ebiom.2022.104129
SARS-CoV-2 infection induces inflammatory bone loss in golden Syrian hamsters (Nature Communications) https://doi.org/10.1038/s41467-022-30195-w
Persistent 129Xe MRI Pulmonary and CT Vascular Abnormalities in Symptomatic Individuals with Post-Acute COVID-19 Syndrome (Radiology) https://doi.org/10.1148/radiol.220492
ACE2-independent infection of T lymphocytes by SARS-CoV-2 (Signal Transduction and Targeted Therapy) https://doi.org/10.1038/s41392-022-00919-x
Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae (Preprint) https://doi.org/10.1101/2022.06.14.22276401
SARS-CoV-2 is detected in the gastrointestinal tract of asymptomatic endoscopy patients but is unlikely to pose a significant risk to healthcare personnel (Gastro Hep Adv) https://doi.org/10.1016/j.gastha.2022.06.002
Long COVID symptoms in SARS-CoV-2-positive children aged 0–14 years and matched controls in Denmark (LongCOVIDKidsDK): a national, cross-sectional study (Child & Adolescent Health) https://doi.org/10.1016/S2352-4642(22)00154-7
Age and sex-specific risks of myocarditis and pericarditis following Covid-19 messenger RNA vaccines (Nature Communications) https://doi.org/10.1038/s41467-022-31401-5
COVID-19 positive patients at higher risk of developing neurodegenerative disorders, new study shows https://medicalxpress.com/news/2022-06-covid-positive-patients-higher-neurodegenerative.html
Posttranslational modifications optimize the ability of SARS-CoV-2 spike for effective interaction with host cell receptors (Biophysics and Computational Biology) https://doi.org/10.1073/pnas.2119761119
Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2 (The Lancet) https://doi.org/10.1016/S0140-6736(22)00941-2
Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum (Cell) https://doi.org/10.1016/j.cell.2022.06.005
Immunomodulatory treatment in postural tachycardia syndrome: A case series (European Journal of Neurology) https://doi.org/10.1111/ene.14711
Long COVID-19 Liver Manifestation in Children (JPGN) https://journals.lww.com/jpgn/abstract/9900/long_covid_19_liver_manifestation_in_children.84.aspx
Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C (Nature Communications) https://doi.org/10.1038/s41467-022-30649-1
C.D.C. Dismisses Airborne Transmission of Monkeypox. Some Experts Disagree. (NY Times) https://www.nytimes.com/2022/06/10/health/monkeypox-airborne.html
Omicron BA.1 breakthrough infection drives cross-variant neutralization and memory B cell formation against conserved epitopes (Science Immunology) https://doi.org/10.1126/sciimmunol.abq2427
SARS-CoV-2 Infection and Persistence Throughout the Human Body and Brain (National Institutes of Health) https://videocast.nih.gov/watch=45296?jwsource=twi
Long COVID is associated with extensive in-vivo neuroinflammation on [18F]DPA-714 PET (Preprint) https://doi.org/10.1101/2022.06.02.22275916
Unexpected worsening of progressive multifocal leucoencephalopathy following COVID-19 pneumonia (Journal of Neurovirology) https://doi.org/10.1007%2Fs13365-021-00980-2
Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5 (Preprint) https://doi.org/10.1101/2022.05.26.493539
During the Omicron Wave, Death Rates Soared for Older People (NY Times with CDC data) https://www.nytimes.com/2022/05/31/health/omicron-deaths-age-65-elderly.html
PD-1 blockade counteracts post–COVID-19 immune abnormalities and stimulates the anti–SARS-CoV-2 immune response (JCI Insight) https://insight.jci.org/articles/view/146701
Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance (Nature Reviews Clinical Oncology) https://doi.org/10.1038/s41571-019-0218-0
Herpesvirus infections and post-COVID-19 manifestations: a pilot observational study (Observational Research) https://doi.org/10.1007/s00296-022-05146-9
An early warning system for emerging SARS-CoV-2 variants (Nature Medicine) https://doi.org/10.1038/s41591-022-01836-w
SARS-CoV-2 Omicron Variant is as Deadly as Previous Waves After Adjusting for Vaccinations, Demographics, and Comorbidities (Preprint) https://doi.org/10.21203/rs.3.rs-1601788/v1
Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1 (Preprint) https://www.medrxiv.org/content/10.1101/2022.04.25.22274187v1
COVID-19 Associated Hepatitis in Children (CAH-C) during the second wave of SARS-CoV-2 infections in Central India: Is it a complication or transient phenomenon. (Preprint) https://doi.org/10.1101/2021.07.23.21260716
Liver and Gastrointestinal Involvement in Patients With COVID-19: A Retrospective Study https://www.cureus.com/articles/90062-liver-and-gastrointestinal-involvement-in-patients-with-covid-19-a-retrospective-study
Cortical Grey Matter Volume Loss links to Neurological Sequelae in post COVID-19 “Long Haulers” (Preprint) https://doi.org/10.21203/rs.3.rs-1582065/v1
Virological characteristics of the SARS-CoV-2 Omicron BA.2 spike (Cell) https://doi.org/10.1016/j.cell.2022.04.035
Continued Emergence and Evolution of Omicron in South Africa: New BA.4 and BA.5 lineages https://www.krisp.org.za/manuscripts/MEDRXIV-2022-274406v1-deOliveira.pdf
Molecular consequences of SARS-CoV-2 liver tropism (Nature Metabolism) https://doi.org/10.1038/s42255-022-00552-6
China CDC shares latest COVID-19 data (GISAID) https://www.gisaid.org/resources/gisaid-in-the-news/china-shares-latest-11-apr-2022/#c920
Persistent COVID-19 symptoms in a community study of 606,434 people in England (Nature) https://www.nature.com/articles/s41467-022-29521-z
Brain Inflammation and Intracellular α-Synuclein Aggregates in Macaques after SARS-CoV-2 Infection (Viruses) https://www.mdpi.com/1999-4915/14/4/776
Antibody Resistance of SARS-CoV-2 Omicron BA.1, BA.1.1, BA.2 and BA.3 Sub-lineages (Preprint) https://www.biorxiv.org/content/10.1101/2022.04.07.487489v1
Infectious viral load in unvaccinated and vaccinated individuals infected with ancestral, Delta or Omicron SARS-CoV-2 (Nature Medicine) https://www.nature.com/articles/s41591-022-01816-0
Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain (Preprint) https://www.biorxiv.org/content/10.1101/2022.01.07.475453v1
Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study (BMJ) https://www.bmj.com/content/377/bmj-2021-069590
SARS-CoV-2 Infection Induces Ferroptosis of Sinoatrial Node Pacemaker Cells (Circulation Research) https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.121.320518
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First evidence that an emerging mammalian alphacoronavirus is able to infect an avian species (Transboundary and Emerging Diseases) https://doi.org/10.1111/tbed.14535
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COVID-19

SARS-CoV-2 Update

07/19/2022 davidcwrightmd

SARS-CoV-2 infections per day have been increasing in the United States for 14 consecutive weeks despite underreporting by states and the failure to capture positive home tests and a decreased screening program in most states. Deaths per day had been decelerating at a rapid rate in the United States but are now increased by 29 more deaths per day. The number of infections have increased as the Omicron BA.2.12.1, BA.2, BA.4, and BA.5 variants of SARS CoV-2 have spread across the nation. The CDC estimates that BA.2.12.1 accounted for 17.3% of isolates, BA.2 accounted for 1.4%, BA.5 accounted for 65.0%, BA.4 accounted for 16.3%, and B.1.1.529 accounted for 0% in the week ending June 25.

We frequently hear messaging from health officials and politicians that Omicron is “mild,” especially compared to the Delta variant, and as a result, many of our patients believe that they no longer need to wear their masks. This is a dangerous misconception. SARS-CoV-2 still remains a highly transmissible, airborne virus. The following graph, based on CDC data from April 2, 2022, shows that Omicron deaths in people over 65 are much higher than Delta deaths in the same age group. In fact, the peak of Omicron deaths in people over 65 years of age is 163% higher than the Delta peak. The death rate from Omicron is only lower than Delta in the populations between 12 and 64 years of age. Until we have more data on these newer mutants of SARS-CoV-2, we will not know the lethality of each variant. It may take months to measure objective differences in the death rates of new circulating variants. We recommend that all of our patients and family members continue to wear N95 masks in all enclosed spaces.

The Omicron variant has continued to mutate just like Delta. There are now 211 Omicron sub-variants (an increase of 12 in the last two weeks) that have been assigned Pango lineages, including 112 sub-lineages of BA.2 (an increase of 8 in two weeks), one sub-lineage of BA.3, 11 sub-lineages of BA.4 (an increase of 2 in two weeks), and 17 sub-lineages of BA.5 (an increase of 2 in two weeks). The BF lineage (new four weeks ago), with BF.1 first detected in England, Denmark, Spain and Scotland still has 6 sublineages. The BE lineage (also new four weeks ago), with BE.1 first detected in South Africa, Austria and England, now has 4 sublineages (one new in the past two weeks). There are also new lineages from four weeks ago: BC.1 (Japan), BC.2 (Peru),BD.1 (UK), BG.1 (Peru), BG.2 (US, Denmark, Canada), BG.3 (Peru), BG.4 (Israel).

In Monterey County, as of 7/17/22, 0.0% of 0-4 year-olds and 38.3% of 5-11 year-olds have received the first two doses of vaccine, while 72.4% of 12-17 year-olds have received two doses. Only 53% of Monterey County residents have received a third dose of the vaccine. On June 17, The FDA authorized both the Pfizer and Moderna vaccines for use in children ages 6 months to four years. We believe children under 5 should be vaccinated as soon as possible. We would anticipate, with the start of school on August 5 and the low vaccination rates in our county, that we’ll have a marked increase in the number of infected patients. All Monterey County residents should get up to date on COVID-19 vaccinations as soon as possible.

On 7/15/22, the United States had 94,037 documented new infections. There were also 207 deaths. Twenty-one states did not report their infections, and 28 states didn’t report their deaths. In the United States the number of hospitalized patients has been increasing in many areas and was 40,650 on July 15, an increase of 20% compared to the previous 14 days. Now there are 4,180 patients who are seriously or critically ill; that number was 3,400 two weeks ago. The number of critically ill patients has increased by 780 in the last 14 days, while at least 5,412 new deaths occurred (an increase of 29 deaths per day from the previous 14 days). The number of critically ill patients has increased for the sixth time in twenty-three 14-day periods. Patients are still dying each day (average 387/day). Omicron BA.2, BA.2.12.1, BA.4, and BA.5 variants causing infections should continue to increase and critically ill patients may continue to increase. Deaths, which usually lag two to four weeks behind exponential increase in infections, are increasing now. Past infections with a BA.1 or BA.2 variant will not prevent infections with BA.2.12.1, BA.4, or BA.5.

As of 7/15/22, we have had 1,048,693 deaths and 91,170,571 SARS-CoV-2 infections in the United States. We have had 1,663,488 new infections in the last 14 days. We are adding an average of 831,744 infections every seven days. For the pandemic in the United States we are averaging one death for every 86.94 infections or over 11,503 deaths for each one million infections. As of 7/15/22, thirty-eight states have had greater than 500,000 total infections, and 37 states have had greater than 5,000 total deaths. Seventeen states (Virginia, Missouri, North Carolina, Indiana, Tennessee, Massachusetts, Ohio, Michigan, Georgia, Illinois, New Jersey, Pennsylvania, Florida, Texas, New York, Arizona and California) have had greater than 20,000 deaths. Four states (Florida, Texas, New York, and California) have had greater than 70,000 deaths. California and Texas have each had greater than 89,000 deaths with California having 93,017 deaths (20th most deaths in the world).

As of 7/1/22, in the United States, 26.72% of the population has had a documented SARS-CoV-2 infection. In the last 18 months, 23.97% of our country became infected with SARS-CoV-2. On 11/20/20, there were 260,331 (cumulative) deaths in the US from SARS-CoV-2. In the last 18 months, there were 788,562 new deaths from SARS-CoV-2. For fifteen of those months, vaccines have been available to all adults. During these fifteen months, 477,596 people have died of SARS-CoV-2 infections. Most of the hospitalizations and deaths could have been prevented by vaccination, proper masking, and social distancing.

As of 7/15/22, California was ranked 32th in the USA in infection percentage at 26.27%. In California, 22.3% of people were infected in the last 18 months. As of 7/15/22, 38 states have had greater than 25% of their population infected.

Worldwide, average deaths per day are 1,846 for the last 14 days. The United States has 20.96% (387 per day) of all deaths per day in the world over the last two weeks. Worldwide infections per day were 910,374. The United States accounts for 13.05% of those infections (or 118,821 infections per day).

Watching World Data

Location	Total Infections as of 7/15/22	New Infections on 7/15/22	Total Deaths	New Deaths on 7/15/22	% of Pop.Infected	SARS-CoV-2 Isolates Currently Known in Location	National/ State Mask Mandate	Currently in Lockdown
World	566,343,288(12,745,232 new infections in 14 days).	903,272	6,385,820(25,848 new deaths in last 14 days)	1,737	7.26%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines) Mu/B.1.621 (Colombia)C.1.2 (South Africa 2% of isolates in July 2021)R1 (Japan)Omicron/B.1.1.529 + BA.1 + BA.2 + BA.3 (South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)Four new recombinants 12/31 to 3/22)BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)*	No	No
USA	91,170,571(ranked #1) 1,663,488 new infections in the last 14 days.	94,037(ranked #4) 21 states failed to report infections.	1,048,693(ranked #1) 5,412 new deaths in the last 14 days.	207 27 states failed to report deaths.	26.72%* *Not updated	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan) Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)Recombinant Delta AY.119.2- Omicron BA.1.1 (Tennessee, USA 12/31/21)\BA.2BA.2.12.1 (United States)BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India)*	No	No
Brazil	33,250,117(ranked #3) 816,054 new infections in the last 14 days.	107,959 (ranked #4)	675,145(ranked #2; 3,145 new deaths in 14 days)	299	15.42%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
India	43,730,071(ranked #2); 241,552 new infections in 2 weeks.	20,044	525,660(ranked #3)	56	3.10%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)Eta/B.1.525 (Nigeria/UK)APTK India VOI 32421Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Iota/B.1.526 (USA-NYC) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2.75 (India)*	No	No
United Kingdom* *No reported data for 7/14/22- 7/16/22	23,075,360(ranked #6) 334,295 new infections in 2 weeks.	–	181,580 (ranked #7)	–	33.63%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)C.1.2 (South Africa)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)XD (AY.4/BA.1) recombinantXF (Delta/BA.1) recombinantXE (BA.1/BA.2) recombinantBA.2BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India)*	No	No
California, USA	10,380,889(ranked #12 in the world; 226,544 new infections in the last 14 days).	8,694	93,017 (ranked #20 in world) 397 new deaths in the last 14 days	16	26.27%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa)BA.5 (South Africa)*	No	No
Mexico	6,373,876(ranked #18) 339,174 new infections in 14 days).	34,885(ranked #9)	326,335(ranked #5)	74	4.84%	B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)*	No	No
South Africa	3,999,751(ranked #33; 5,528 new infections in 14 days).	406	101,918 (ranked #18)	3	6.57%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India) C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)	No	No
Canada	4,007,463(ranked #32) 61,376 new infections in 14 days).	1,881	43,555(ranked #24)	51	10.43% .	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)*	No	No
Poland	6,029,947 (ranked #21; 14,313 new infections in 14 days).	1,974	116,470 (ranked #15)	2	15.96%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3	No	No
Russia	18,480,934(ranked #9), 47,540 new infections in 14 days).	4,457	381,794(ranked #4 in world)	40	12.65%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)R1 (Japan) B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Argentina	9,426,171(ranked #14; 58,999 new infections in 14 days).	———–	140,365 (ranked #14)	——–	20.47%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gama/P.1 (Brazil)Delta/B.1.617.2 (India)Lambda/C.37 (Peru)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)*	No	No
Colombia	6,223,497(ranked #19, 48,316 new infections in 14 days).	3,523	140,365 (ranked #13)	26	11.97%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Epsilon/B.1.427 + B.1.429 (USA)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)*	No	No
Peru	3,714,361(ranked #38, 84,565 new infections in 14 days).	10,610	235,526(ranked #6)	15	10.95%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Iran	7,270,023(ranked 17th; 31,434 new infections in last 14 days)	4,772	141,477(ranked #11)	13	8.43%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Spain	13,090,476(ranked 11th; 272,292 new infections in 14 days).	19,211(ranked #12)	109,348 (ranked #17)	134	27.97%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)	No	No
France	32,818,901 (ranked #4; 1,609,976 new infections in the last 14 days).	119,684 (ranked #1)	150,576 (ranked #10)	108	50.05%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinant	No	No
Germany	29,692,989(ranked #5; 1,300,360 new infections in 14 days.).	123,046 (ranked #2)	142,535 (ranked #11)	134	35.21%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinant	No	No
South Korea	18,680,142 (ranked #9 310,285 new infections in 14 days).	38,864(ranked #8)	24,712 (ranked #38)	16	36.37%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No
Vietnam	10,759,145 (ranked #12; 11,748 new infections in 14 days).	956	43,090 (ranked #26)	–	10.85%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No
Netherlands	8,274,234 (ranked #16; 83,979 new infections in 14 days).	6,527	22,422 (ranked #41)	5	48.07%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinant	No	No
Denmark	3,039,859 (ranked #39) 23,810 new infections in 14 days	1,567	6,551 (ranked #81)	8	52.10%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinant	No	No
North Korea (DPRK)	4,770,400 (ranked #24; 25,670 new infections in 14 days)	500	74	–	18.34%	Omicron/B.1.1.529 South Africa November 2021)	No	No
Taiwan	4,215,200(ranked #30) 412,171 new infections in 14 days	25,310 (ranked #10)	7,917 (ranked #73)	114	17.63%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No
Japan	10,000,720(ranked #13) 671,200 new infections in the last 14 days	97,339(ranked #5)	31,528(ranked #34)	34	7.95%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No

What Our Team Is Reading This Week

SARS-CoV-2 Omicron BA.5: Evolving tropism and evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern. (Preprint) https://doi.org/10.1101/2022.07.07.22277128
Brain imaging and neuropsychological assessment of individuals recovered from mild to moderate SARS-CoV-2 infection (Preprint) https://doi.org/10.1101/2022.07.08.22277420
Increased Risk of Herpes Zoster in Adults ≥50 Years Old Diagnosed With COVID-19 in the United States (Open Forum Infectious Diseases) https://doi.org/10.1093/ofid/ofac118
Neutralization sensitivity of Omicron BA.2.75 to therapeutic monoclonal antibodies (Preprint) https://doi.org/10.1101/2022.07.14.500041
Neutralizing antibody activity against 21 SARS-CoV-2 variants in older adults vaccinated with BNT162b2 (Nature Microbiology) https://doi.org/10.1038/s41564-022-01163-3
How COVID-19 affects microvessels in the brain (Brain) https://doi.org/10.1093/brain/awac211
Fine Analysis of Lymphocyte Subpopulations in SARS-CoV-2 Infected Patients: Differential Profiling of Patients With Severe Outcome (Frontiers in Immunology) https://doi.org/10.3389/fimmu.2022.889813
SARS-CoV-2 accelerated clearance using a novel nitric oxide nasal spray (NONS) treatment: A randomized trial (The Lancet Regional Health – Southeast Asia) https://doi.org/10.1016/j.lansea.2022.100036
Effectiveness of 2, 3, and 4 COVID-19 mRNA Vaccine Doses Among Immunocompetent Adults During Periods when SARS-CoV-2 Omicron BA.1 and BA.2/BA.2.12.1 Sublineages Predominated — VISION Network, 10 States, December 2021–June 2022 (MMWR) http://dx.doi.org/10.15585/mmwr.mm7129e1
Characterization of virologic rebound following nirmatrelvir-ritonavir treatment for COVID-19 (Clinical Infectious Diseases) https://doi.org/10.1093/cid/ciac512
Potential Autoimmunity Resulting from Molecular Mimicry between SARS-CoV-2 Spike and Human Proteins (Preprint) https://doi.org/10.1101/2021.08.10.455737
COVID-19 positive patients at higher risk of developing neurodegenerative disorders, new study shows (Medical Express) https://medicalxpress.com/news/2022-06-covid-positive-patients-higher-neurodegenerative.html
Evidence of previous SARS-CoV-2 infection in seronegative patients with long COVID (eBioMedicine) https://doi.org/10.1016/j.ebiom.2022.104129
SARS-CoV-2 infection induces inflammatory bone loss in golden Syrian hamsters (Nature Communications) https://doi.org/10.1038/s41467-022-30195-w
Persistent 129Xe MRI Pulmonary and CT Vascular Abnormalities in Symptomatic Individuals with Post-Acute COVID-19 Syndrome (Radiology) https://doi.org/10.1148/radiol.220492
ACE2-independent infection of T lymphocytes by SARS-CoV-2 (Signal Transduction and Targeted Therapy) https://doi.org/10.1038/s41392-022-00919-x
Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae (Preprint) https://doi.org/10.1101/2022.06.14.22276401
SARS-CoV-2 is detected in the gastrointestinal tract of asymptomatic endoscopy patients but is unlikely to pose a significant risk to healthcare personnel (Gastro Hep Adv) https://doi.org/10.1016/j.gastha.2022.06.002
Long COVID symptoms in SARS-CoV-2-positive children aged 0–14 years and matched controls in Denmark (LongCOVIDKidsDK): a national, cross-sectional study (Child & Adolescent Health) https://doi.org/10.1016/S2352-4642(22)00154-7
Age and sex-specific risks of myocarditis and pericarditis following Covid-19 messenger RNA vaccines (Nature Communications) https://doi.org/10.1038/s41467-022-31401-5
COVID-19 positive patients at higher risk of developing neurodegenerative disorders, new study shows https://medicalxpress.com/news/2022-06-covid-positive-patients-higher-neurodegenerative.html
Posttranslational modifications optimize the ability of SARS-CoV-2 spike for effective interaction with host cell receptors (Biophysics and Computational Biology) https://doi.org/10.1073/pnas.2119761119
Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2 (The Lancet) https://doi.org/10.1016/S0140-6736(22)00941-2
Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum (Cell) https://doi.org/10.1016/j.cell.2022.06.005
Immunomodulatory treatment in postural tachycardia syndrome: A case series (European Journal of Neurology) https://doi.org/10.1111/ene.14711
Long COVID-19 Liver Manifestation in Children (JPGN) https://journals.lww.com/jpgn/abstract/9900/long_covid_19_liver_manifestation_in_children.84.aspx
Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C (Nature Communications) https://doi.org/10.1038/s41467-022-30649-1
C.D.C. Dismisses Airborne Transmission of Monkeypox. Some Experts Disagree. (NY Times) https://www.nytimes.com/2022/06/10/health/monkeypox-airborne.html
Omicron BA.1 breakthrough infection drives cross-variant neutralization and memory B cell formation against conserved epitopes (Science Immunology) https://doi.org/10.1126/sciimmunol.abq2427
SARS-CoV-2 Infection and Persistence Throughout the Human Body and Brain (National Institutes of Health) https://videocast.nih.gov/watch=45296?jwsource=twi
Long COVID is associated with extensive in-vivo neuroinflammation on [18F]DPA-714 PET (Preprint) https://doi.org/10.1101/2022.06.02.22275916
Unexpected worsening of progressive multifocal leucoencephalopathy following COVID-19 pneumonia (Journal of Neurovirology) https://doi.org/10.1007%2Fs13365-021-00980-2
Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5 (Preprint) https://doi.org/10.1101/2022.05.26.493539
During the Omicron Wave, Death Rates Soared for Older People (NY Times with CDC data) https://www.nytimes.com/2022/05/31/health/omicron-deaths-age-65-elderly.html
PD-1 blockade counteracts post–COVID-19 immune abnormalities and stimulates the anti–SARS-CoV-2 immune response (JCI Insight) https://insight.jci.org/articles/view/146701
Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance (Nature Reviews Clinical Oncology) https://doi.org/10.1038/s41571-019-0218-0
Herpesvirus infections and post-COVID-19 manifestations: a pilot observational study (Observational Research) https://doi.org/10.1007/s00296-022-05146-9
An early warning system for emerging SARS-CoV-2 variants (Nature Medicine) https://doi.org/10.1038/s41591-022-01836-w
SARS-CoV-2 Omicron Variant is as Deadly as Previous Waves After Adjusting for Vaccinations, Demographics, and Comorbidities (Preprint) https://doi.org/10.21203/rs.3.rs-1601788/v1
Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1 (Preprint) https://www.medrxiv.org/content/10.1101/2022.04.25.22274187v1
COVID-19 Associated Hepatitis in Children (CAH-C) during the second wave of SARS-CoV-2 infections in Central India: Is it a complication or transient phenomenon. (Preprint) https://doi.org/10.1101/2021.07.23.21260716
Liver and Gastrointestinal Involvement in Patients With COVID-19: A Retrospective Study https://www.cureus.com/articles/90062-liver-and-gastrointestinal-involvement-in-patients-with-covid-19-a-retrospective-study
Cortical Grey Matter Volume Loss links to Neurological Sequelae in post COVID-19 “Long Haulers” (Preprint) https://doi.org/10.21203/rs.3.rs-1582065/v1
Virological characteristics of the SARS-CoV-2 Omicron BA.2 spike (Cell) https://doi.org/10.1016/j.cell.2022.04.035
Continued Emergence and Evolution of Omicron in South Africa: New BA.4 and BA.5 lineages https://www.krisp.org.za/manuscripts/MEDRXIV-2022-274406v1-deOliveira.pdf
Molecular consequences of SARS-CoV-2 liver tropism (Nature Metabolism) https://doi.org/10.1038/s42255-022-00552-6
China CDC shares latest COVID-19 data (GISAID) https://www.gisaid.org/resources/gisaid-in-the-news/china-shares-latest-11-apr-2022/#c920
Persistent COVID-19 symptoms in a community study of 606,434 people in England (Nature) https://www.nature.com/articles/s41467-022-29521-z
Brain Inflammation and Intracellular α-Synuclein Aggregates in Macaques after SARS-CoV-2 Infection (Viruses) https://www.mdpi.com/1999-4915/14/4/776
Antibody Resistance of SARS-CoV-2 Omicron BA.1, BA.1.1, BA.2 and BA.3 Sub-lineages (Preprint) https://www.biorxiv.org/content/10.1101/2022.04.07.487489v1
Infectious viral load in unvaccinated and vaccinated individuals infected with ancestral, Delta or Omicron SARS-CoV-2 (Nature Medicine) https://www.nature.com/articles/s41591-022-01816-0
Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain (Preprint) https://www.biorxiv.org/content/10.1101/2022.01.07.475453v1
Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study (BMJ) https://www.bmj.com/content/377/bmj-2021-069590
SARS-CoV-2 Infection Induces Ferroptosis of Sinoatrial Node Pacemaker Cells (Circulation Research) https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.121.320518
SARS-CoV-2 variants of concern and variants under investigation in England (UK Health Security Agency) https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1063424/Tech-Briefing-39-25March2022_FINAL.pdf
Neutralization of Omicron BA.1, BA.2, and BA.3 SARS-CoV-2 by 3 doses of BNT162b2 vaccine (Preprint) https://doi.org/10.1101/2022.03.24.485633
COVID-19-Associated Encephalitis: Two Case Reports https://www.cureus.com/articles/86903-covid-19-associated-encephalitis-two-case-reports
First evidence that an emerging mammalian alphacoronavirus is able to infect an avian species (Transboundary and Emerging Diseases) https://doi.org/10.1111/tbed.14535
SARS-CoV-2 co-infection with influenza viruses, respiratory syncytial virus, or adenoviruses (The Lancet) https://doi.org/10.1016/S0140-6736(22)00383-X
Evidence for SARS-CoV-2 Delta and Omicron co-infections and recombination (Preprint) https://www.medrxiv.org/content/10.1101/2022.03.09.22272113v1
Culture and identification of a “Deltamicron” SARS-CoV-2 in a three cases cluster in southern France (Preprint) https://www.medrxiv.org/content/10.1101/2022.03.03.22271812v1.full
Mandatory masking in schools reduced COVID-19 cases during Delta surge (NIH press release) https://www.nih.gov/news-events/news-releases/mandatory-masking-schools-reduced-covid-19-cases-during-delta-surge
School Masking Policies and Secondary SARS-CoV-2 Transmission (Pediatrics) https://publications.aap.org/pediatrics/article/doi/10.1542/peds.2022-056687/185379/School-Masking-Policies-and-Secondary-SARS-CoV-2
Transmission of SARS-CoV-2 delta variant (AY.127) from pet hamsters to humans, leading to onward human-to-human transmission: a case study (The Lancet) https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00326-9/fulltext
COVID-19 Variant Dashboard – USA by Raj Rajnarayanan https://public.tableau.com/app/profile/raj.rajnarayanan/viz/USAVariantDB/VariantDashboard
SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 38 (UK Health Security Agency) https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1060337/Technical-Briefing-38-11March2022.pdf
SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 37 (UK Health Security Agency) https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1057359/Technical-Briefing-37-25February2022.pdf
Engineered extracellular vesicles antagonize SARS-CoV-2 infection by inhibiting mTOR signaling (Biomaterials and Biosystems) https://www.sciencedirect.com/science/article/pii/S2666534422000046?via%3Dihub
Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study (Preprint) https://doi.org/10.21203/rs.3.rs-1385593/v1
Dynamics of the Delta and Omicron variants of SARS-CoV-2 in the United States: the battle of supremacy in the presence of vaccination, mask usage and antiviral treatment (Preprint) https://doi.org/10.21203/rs.3.rs-1420446/v1
Virological characteristics of SARS-CoV-2 BA.2 variant (Preprint) https://www.biorxiv.org/content/10.1101/2022.02.14.480335v1
Transmission of SARS-CoV-2 Omicron VOC subvariants BA.1 and BA.2: Evidence from Danish Households (Preprint) https://www.medrxiv.org/content/10.1101/2022.01.28.22270044v1
Waning 2-Dose and 3-Dose Effectiveness of mRNA Vaccines Against COVID-19–Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominance — VISION Network, 10 States, August 2021–January 2022 (MMWR) https://www.cdc.gov/mmwr/volumes/71/wr/mm7107e2.htm?s_cid=mm7107e2_e&ACSTrackingID=USCDC_921-DM75599&ACSTrackingLabel=MMWR%20Early%20Release%20-%20Vol.%2071%2C%20February%2011%2C%202022&deliveryName=USCDC_921-DM75599
SARS-CoV-2 B.1.1.529 (Omicron) Variant Transmission Within Households — Four U.S. Jurisdictions, November 2021–February 2022 (MMWR) https://www.cdc.gov/mmwr/volumes/71/wr/mm7109e1.htm?s_cid=mm7109e1_w
Pediatric Emergency Department Visits Before and During the COVID-19 Pandemic — United States, January 2019–January 2022 (MMWR) https://www.cdc.gov/mmwr/volumes/71/wr/mm7108e1.htm?s_cid=mm7108e1_w#F2_down
Birth Of The Omicron Family: BA.1, BA.2, BA.3. Each As Different As Alpha Is From Delta. (Forbes) https://www.forbes.com/sites/williamhaseltine/2022/01/26/birth-of-the-omicron-family-ba1-ba2-ba3-each-as-different-as-alpha-is-from-delta/?sh=403de4ee3da9
Take a look at SARS-CoV-2’s family tree. It’s full of surprises (NPR) https://www.npr.org/sections/goatsandsoda/2022/02/09/1047616658/take-a-look-at-sars-cov-2s-family-tree-its-full-of-surprises
SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 35 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1050999/Technical-Briefing-35-28January2022.pdf
Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants (Nature) https://www.nature.com/articles/s41586-022-04466-x_reference.pdf
Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time (Preprint) https://www.medrxiv.org/content/10.1101/2022.01.14.22269235v1
Syncytin, envelope protein of human endogenous retrovirus (HERV): no longer ‘fossil’ in human genome (Animal Cells and Systems) https://doi.org/10.1080/19768354.2021.2019109
Host Chitinase 3-like-1 is a Universal Therapeutic Target for the Delta, Omicron and Other SARS-CoV-2 Viral Variants in COVID 19 (Preprint) https://www.biorxiv.org/content/10.1101/2022.01.21.477274v1
COVID-19 reinfections among naturally infected and vaccinated individuals (Nature) https://www.nature.com/articles/s41598-022-05325-5
Duration of Protection against Mild and Severe Disease by Covid-19 Vaccines (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2115481
Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants (Preprint) https://www.medrxiv.org/content/10.1101/2022.01.25.22269794v1
COVID-19 and the Common Cold—Preexisting Coronavirus Antibodies May Hinder SARS-CoV-2 Immunity (JAMA) https://jamanetwork.com/journals/jama/fullarticle/2788621?guestAccessKey=0bbad800-e651-496b-8046-d124bbc63a5a&term=01262022&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jama&utm_content=olf&utm_term=012622
Viral dynamics and duration of PCR positivity of the SARS-CoV-2 Omicron variant https://dash.harvard.edu/handle/1/37370587

COVID-19

SARS-CoV-2 Update

07/04/2022 davidcwrightmd

SARS-CoV-2 infections per day have been increasing in the United States for 14 consecutive weeks despite underreporting by states and the failure to capture positive home tests and a decreased screening program in most states. Deaths per day had been decelerating at a rapid rate in the United States but are now increased by 8 more deaths per day. The number of infections have increased as the Omicron BA.2.12.1, BA.2, BA.4, and BA.5 variants of SARS CoV-2 have spread across the nation. The CDC estimates that BA.2.12.1 accounted for 42% of isolates, BA.2 accounted for 5.7%, BA.5 accounted for 36.6%, BA.4 accounted for 15.7%, and B.1.1.529 accounted for 0% in the week ending June 25.

We frequently hear messaging from health officials and politicians that Omicron is “mild,” especially compared to the Delta variant, and as a result, many of our patients believe that they no longer need to wear their masks. This is a dangerous misconception. SARS-CoV-2 still remains a highly transmissible, airborne virus. The following graph, based on CDC data from April 2, 2022, shows that Omicron deaths in people over 65 are much higher than Delta deaths in the same age group. In fact, the peak of Omicron deaths in people over 65 years of age is 163% higher than the Delta peak. The death rate from Omicron is only lower than Delta in the populations between 12 and 64 years of age. Until we have more data on these newer mutants of SARS-CoV-2, we will not know the lethality of each variant. It may take months to measure objective differences in the death rates of new circulating variants. We recommend that all of our patients and family members continue to wear N95 masks in all enclosed spaces.

In patients treated with Paxlovid for five days who have persistent symptoms and continued positivity, we feel that clinicians should consider giving a second course of Paxlovid for five days. Boucau et al have demonstrated that in a study of seven patients with recurrent symptoms, “High viral loads (median 6.1 log10 copies/mL) were detected after rebound for a median of 17 days after initial diagnosis. Three had culturable virus for up to 16 days after initial diagnosis.” This was not due to resistance-associated mutations of the virus, suggesting that the course of therapy may be inadequate in this group of persistently infected patients.

According to the UK Health Security Agency, “BA.4 shares all mutations/deletions with the BA.2 lineage except the following: S: 69/70 deletion, R408 (WT, wild type)*, L452R, F486V, Q493 (WT); ORF 7b: L11F; N: P151S; synonymous SNP G12160A” and “BA.5 shares all mutations/deletions with the BA.2 lineage except the following: S: 69/70 deletion, R408 (WT), L452R, F486V, Q493 (WT); ORF6: D61 (WT); M: D3N; synonymous SNPs: G12160A, A27038G, and C27889T.” On May 12, the European CDC designated both BA.4 and BA.5 as variants of concern.

The Omicron variant has continued to mutate just like Delta. There are now 199 Omicron sub-variants (an increase of 42 in the last two weeks) that have been assigned Pango lineages, including 104 sub-lineages of BA.2 (an increase of 12 in two weeks), one sub-lineage of BA.3, nine sub-lineages of BA.4 (an increase of 6 in two weeks), and 15 sub-lineages of BA.5 (an increase of 10 in two weeks). The BF lineage (new two weeks ago), with BF.1 first detected in England, Denmark, Spain and Scotland now has 6 sublineages. The BE lineage (also new two weeks ago), with BE.1 first detected in South Africa, Austria and England, now has 3 new sublineages. There are also new lineages: BC.1 (Japan), BC.2 (Peru),BD.1 (UK), BG.1 (Peru), BG.2 (US, Denmark, Canada), BG.3 (Peru), BG.4 (Israel).

An additional problem may be the development of recombinant SARS-CoV-2 isolates. A recombinant isolate occurs when two isolates infect the same cell and, in the process of viral reproduction, exchange nucleic acids, creating a new isolate that is a recombination of parts from the genomes of both isolates. A recombinant isolate of Delta AY.4.2.2 and Omicron BA.1.1 was recently reported in the UK. As of 3/25/22 four different recombinant variants of SARS-CoV-2 have been reported by the UK Health Security Agency.

According to the UK Health Security Agency’s Technical Briefing from 3/25/22: “There are currently 3 recombinant lineages being monitored as part of horizon scanning: XD, XE, and XF (Figure 6). XD and XF are Delta and BA.1 recombinants. XE is a BA.1 and BA.2 recombinant and has 3 mutations that are not present in all BA.1 or BA.2 sequences: NSP3 C3241T and V1069I, and NSP12 C14599T. XF and XE are associated with UK sequenced samples. XD is predominantly associated with France. XD contains the unique mutation NSP2:E172D.” As of 5/17/22 the UK Health Security Agency reports 2,049 sequences of the XE recombinant in the UK data.

Unless people continue to wear masks and get vaccinated, including their third dose of the vaccine, we will see further spread of the Omicron variants and increase in deaths in people who are not vaccinated, have waning immunity, the immunocompromised population and others with risk factors particularly those older over the age of 64. SARS-CoV-2 is now in the top ten most common causes of death for children. Anyone over the age of 5 years can now get vaccinated in the United States at no cost. This should get done immediately.In Monterey County, as of 7/3/22, only 0.6% of 0-4 year-olds and 43.2% of 5-11 year-olds have received the first two doses of vaccine, while 78.7% of 12-17 year-olds have received two doses. On June 17, The FDA authorized both the Pfizer and Moderna vaccines for use in children ages 6 months to four years. We believe children under 5 should be vaccinated as soon as possible.

On 7/1/22, the United States had 102,788 documented new infections. There were also 283 deaths. Twenty-one states did not report their infections, and 27 states didn’t report their deaths. In the United States the number of hospitalized patients had been increasing in many areas. Now there are 3,400 patients who are seriously or critically ill; that number was 3,006 two weeks ago. The number of critically ill patients has increased by 394 in the last 14 days, while at least 5,106 new deaths occurred (an increase of 8 deaths per day from the previous 14 days). The number of critically ill patients has increased for the fifth time in twenty-two 14-day periods. Patients are still dying each day (average 358/day). Omicron BA.2, BA.2.12.1, BA.4, and BA.5 variants causing infections should continue to increase and critically ill patients may continue to increase. Deaths, which usually lag two to four weeks behind exponential increase in infections, are increasing now. Past infections with a BA.1 or BA.2 variant will not prevent infections with BA.2.12.1, BA.4, or BA.5.

As of 7/1/22, we have had 1,043,281 deaths and 89,507,083 SARS-CoV-2 infections in the United States. We have had 1,538,264 new infections in the last 14 days. We are adding an average of 769,312 infections every seven days. For the pandemic in the United States we are averaging one death for every 86.2 infections or over 11,656 deaths for each one million infections. As of 7/1/22, thirty-eight states have had greater than 500,000 total infections, and 36 states have had greater than 5,000 total deaths. Seventeen states (Virginia, Missouri, North Carolina, Indiana, Tennessee, Massachusetts, Ohio, Michigan, Georgia, Illinois, New Jersey, Pennsylvania, Florida, Texas, New York, Arizona and California) have had greater than 20,000 deaths. Four states (Florida, Texas, New York, and California) have had greater than 70,000 deaths. California and Texas have each had greater than 89,000 deaths with California having 92,621 deaths (20th most deaths in the world).

As of 7/1/22, in the United States, 26.72% of the population has had a documented SARS-CoV-2 infection. In the last 18 months, 23.97% of our country became infected with SARS-CoV-2. On 11/20/20, there were 260,331 (cumulative) deaths in the US from SARS-CoV-2. In the last 18 months, there were 783,150 new deaths from SARS-CoV-2. For fifteen of those months, vaccines have been available to all adults. During these fifteen months, 472,184 people have died of SARS-CoV-2 infections. Most of the hospitalizations and deaths could have been prevented by vaccination, proper masking, and social distancing.

As of 7/1/22, California was ranked 35th in the USA in infection percentage at 25.69%. In California, 21.72% of people were infected in the last 18 months. As of 7/1/22, 36 states have had greater than 25% of their population infected.

Worldwide, average deaths per day are 1,470 for the last 14 days. The United States has 24.35% (358 per day) of all deaths per day in the world over the last two weeks. Worldwide infections per day were 712,693. The United States accounts for 15.42% of those infections (or 109,902 infections per day).

FDA-Approved Oral Drug Treatments for SARS-CoV-2

Pfizer has developed PAXLOVID™, an oral reversible inhibitor of C3-like protease of SARS-CoV-2. The drug inhibits this key enzyme that is crucial for virus production. The compound, also called Compound 6 (PF-07321332), is part of the drug combination PAXLOVID™ (PF-07321332; ritonavir), which just successfully completed a Phase 2-3 trial in humans in multiple countries. The preliminary results were announced on 11/5/21 by Pfizer. The results show that 89% of the hospitalizations and deaths were prevented in the drug treatment arm. The drug was administered twice a day for five days. No deaths occurred in the treatment group, and ten deaths occurred in the placebo group. The study was stopped by an independent data safety monitoring board, and the FDA concurred with this decision. Pfizer applied for an Emergency Use Authorization for this drug on 11/15/21. This drug was approved on 12/23/21. We have only been able to obtain PAXLOVID™ for two patients who we successfully treated with this drug obtained from CVS in Salinas (East Alisal Street; phone number 831-424-0026). They were expecting another shipment on 1/28/22. In my opinion, this agent, if more widely available, could markedly alter the course of every coronavirus infection throughout the world.

FDA Approved Intramuscular Prophylaxis of SARS-CoV-2 Immunocompromised Patients

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Watching World Data

Location	Total Infections as of 7/1/22	New Infections on 7/1/22	Total Deaths	New Deaths on 7/1/22	% of Pop.Infected	SARS-CoV-2 Isolates Currently Known in Location	National/ State Mask Mandate	Currently in Lockdown
World	553,598,056(9,977,707 new infections in 14 days).	825,008	6,359,972(20,585 new deaths in last 14 days)	1,503	7.10%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines) Mu/B.1.621 (Colombia)C.1.2 (South Africa 2% of isolates in July 2021)R1 (Japan)Omicron/B.1.1.529 + BA.1 + BA.2 + BA.3 (South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)Four new recombinants 12/31 to 3/22)BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)*	No	No
USA	89,507,083(ranked #1) 1,538,264 new infections in the last 14 days.	102,788(ranked #2) 21 states failed to report infections.	1,043,281(ranked #1) 5,016 new deaths in the last 14 days.	283 27 states failed to report deaths.	26.72%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan) Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)Recombinant Delta AY.119.2- Omicron BA.1.1 (Tennessee, USA 12/31/21)\BA.2BA.2.12.1 (United States)BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India)*	No	No
Brazil	32,434,063(ranked #3) 760,688 new infections in the last 14 days.	75,612 (ranked #5)	671,700(ranked #2; 2,732 new deaths in 14 days)	234	15.04%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
India	43,488,519(ranked #2); 204,726 new infections in 2 weeks.	17,237	525,168(ranked #3)	29	3.09%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)Eta/B.1.525 (Nigeria/UK)APTK India VOI 32421Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Iota/B.1.526 (USA-NYC) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2.75 (India)*	No	No
United Kingdom	22,741,065(ranked #6) 268,562 new infections in 2 weeks.	20,720	180,417 (ranked #7) 880 new deaths in 2 weeks	87	33.15%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)C.1.2 (South Africa)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)XD (AY.4/BA.1) recombinantXF (Delta/BA.1) recombinantXE (BA.1/BA.2) recombinantBA.2BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India)*	No	No
California, USA	10,154,345(ranked #12 in the world; 262,248 new infections in the last 14 days).	23,524	92,620 (ranked #20 in world) 439 new deaths in the last 14 days	60	25.69%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa)BA.5 (South Africa)*	No	No
Mexico	6,034,602(ranked #20) 182,006 new infections in 14 days).	24,537(ranked #9)	325,716(ranked #5)	47	4.58%	B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)*	No	No
South Africa	3,994,223(ranked #31; 9,577 new infections in 14 days).	380	101,804 (ranked #18)	16	6.56%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India) C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)	No	No
Canada	3,946,087(ranked #32) 35,876 new infections in 14 days).	–	42,010(ranked #25)	–	10.27% .	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)*	No	No
Poland	6,015,634 (ranked #21; 4,715 new infections in 14 days).	643	116,429 (ranked #15)	5	15.92%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3	No	No
Turkey	15,123,331(ranked #10, 37,582 new infections in 14 days).	————	99,032 (ranked #19)	———	17.51%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)*	No	No
Russia	18,433,394(ranked #8), 41,597 new infections in 14 days).	3,155	381,165(ranked #4 in world)	53	12.62%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)R1 (Japan) B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Argentina	9,367,172(ranked #14; 53,619 new infections in 14 days).	———–	129,070 (ranked #14)	——–	20.35%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gama/P.1 (Brazil)Delta/B.1.617.2 (India)Lambda/C.37 (Peru)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)*	No	No
Colombia	6,175,181(ranked #18, 43,424 new infections in 14 days).	–	140,070 (ranked #14)	–	11.88%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Epsilon/B.1.427 + B.1.429 (USA)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)*	No	No
Peru	3,629,796(ranked #38, 33,432 new infections in 14 days).	4,706	235,526(ranked #6)	29	10.71%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Iran	7,238,589(ranked 17th; 4,066 new infections in last 14 days)	463	141,390(ranked #11)	1	8.40%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Spain	12,818,184(ranked 11th; 254,785 new infections in 14 days).	28,048(ranked #8)	108,111 (ranked #17)	89	27.39%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)	No	No
France	31,208,925 (ranked #4; 1,129,467 new infections in the last 14 days).	125,066 (ranked #1)	149,585 (ranked #10)	52	47.60%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinant	No	No
Germany	28,392,629(ranked #5; 1,268,170 new infections in 14 days.).	98,669 (ranked #3)	141,292 (ranked #12)	103	33.67%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinant	No	No
South Korea	18,368,857 (ranked #9 105,214 new infections in 14 days).	9,516(ranked #17)	24,555 (ranked #39)	8	35.76%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No
Vietnam	10,747,397 (ranked #12; 10,989 new infections in 14 days).	927	43,087 (ranked #24)	–	10.84%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No
Netherlands	8,190,255 (ranked #15; 67,997 new infections in 14 days).	6,083	22,380 (ranked #41)	2	47.58%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinant	No	No
Denmark	3,016,049 (ranked #39) 19,336 new infections in 14 days	1,455	6,471 (ranked #81)	2	51.70%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinant	No	No
North Korea (DPRK)	4,744,430 (ranked #24; 163,010 new infections in 14 days)	4,570	73	–	18.24%	Omicron/B.1.1.529 South Africa November 2021)	No	No
Taiwan	3,803,029(ranked #38) 612,283 new infections in 14 days	35,780 (ranked #6)	6,772 (ranked #79)	121	15.91%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No
Japan	9,329,520(ranked #14) 221,197 new infections in the last 14 days	23,523(ranked #10)	31,281(ranked #31)	15	7.42%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No

What Our Team Is Reading This Week

Characterization of virologic rebound following nirmatrelvir-ritonavir treatment for COVID-19 (Clinical Infectious Diseases) https://doi.org/10.1093/cid/ciac512
Potential Autoimmunity Resulting from Molecular Mimicry between SARS-CoV-2 Spike and Human Proteins (Preprint) https://doi.org/10.1101/2021.08.10.455737
COVID-19 positive patients at higher risk of developing neurodegenerative disorders, new study shows (Medical Express) https://medicalxpress.com/news/2022-06-covid-positive-patients-higher-neurodegenerative.html
Evidence of previous SARS-CoV-2 infection in seronegative patients with long COVID (eBioMedicine) https://doi.org/10.1016/j.ebiom.2022.104129
SARS-CoV-2 infection induces inflammatory bone loss in golden Syrian hamsters (Nature Communications) https://doi.org/10.1038/s41467-022-30195-w
Persistent 129Xe MRI Pulmonary and CT Vascular Abnormalities in Symptomatic Individuals with Post-Acute COVID-19 Syndrome (Radiology) https://doi.org/10.1148/radiol.220492
ACE2-independent infection of T lymphocytes by SARS-CoV-2 (Signal Transduction and Targeted Therapy) https://doi.org/10.1038/s41392-022-00919-x
Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae (Preprint) https://doi.org/10.1101/2022.06.14.22276401
SARS-CoV-2 is detected in the gastrointestinal tract of asymptomatic endoscopy patients but is unlikely to pose a significant risk to healthcare personnel (Gastro Hep Adv) https://doi.org/10.1016/j.gastha.2022.06.002
Long COVID symptoms in SARS-CoV-2-positive children aged 0–14 years and matched controls in Denmark (LongCOVIDKidsDK): a national, cross-sectional study (Child & Adolescent Health) https://doi.org/10.1016/S2352-4642(22)00154-7
Age and sex-specific risks of myocarditis and pericarditis following Covid-19 messenger RNA vaccines (Nature Communications) https://doi.org/10.1038/s41467-022-31401-5
COVID-19 positive patients at higher risk of developing neurodegenerative disorders, new study shows https://medicalxpress.com/news/2022-06-covid-positive-patients-higher-neurodegenerative.html
Posttranslational modifications optimize the ability of SARS-CoV-2 spike for effective interaction with host cell receptors (Biophysics and Computational Biology) https://doi.org/10.1073/pnas.2119761119
Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2 (The Lancet) https://doi.org/10.1016/S0140-6736(22)00941-2
Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum (Cell) https://doi.org/10.1016/j.cell.2022.06.005
Immunomodulatory treatment in postural tachycardia syndrome: A case series (European Journal of Neurology) https://doi.org/10.1111/ene.14711
Long COVID-19 Liver Manifestation in Children (JPGN) https://journals.lww.com/jpgn/abstract/9900/long_covid_19_liver_manifestation_in_children.84.aspx
Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C (Nature Communications) https://doi.org/10.1038/s41467-022-30649-1
C.D.C. Dismisses Airborne Transmission of Monkeypox. Some Experts Disagree. (NY Times) https://www.nytimes.com/2022/06/10/health/monkeypox-airborne.html
Omicron BA.1 breakthrough infection drives cross-variant neutralization and memory B cell formation against conserved epitopes (Science Immunology) https://doi.org/10.1126/sciimmunol.abq2427
SARS-CoV-2 Infection and Persistence Throughout the Human Body and Brain (National Institutes of Health) https://videocast.nih.gov/watch=45296?jwsource=twi
Long COVID is associated with extensive in-vivo neuroinflammation on [18F]DPA-714 PET (Preprint) https://doi.org/10.1101/2022.06.02.22275916
Unexpected worsening of progressive multifocal leucoencephalopathy following COVID-19 pneumonia (Journal of Neurovirology) https://doi.org/10.1007%2Fs13365-021-00980-2
Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5 (Preprint) https://doi.org/10.1101/2022.05.26.493539
During the Omicron Wave, Death Rates Soared for Older People (NY Times with CDC data) https://www.nytimes.com/2022/05/31/health/omicron-deaths-age-65-elderly.html
PD-1 blockade counteracts post–COVID-19 immune abnormalities and stimulates the anti–SARS-CoV-2 immune response (JCI Insight) https://insight.jci.org/articles/view/146701
Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance (Nature Reviews Clinical Oncology) https://doi.org/10.1038/s41571-019-0218-0
Herpesvirus infections and post-COVID-19 manifestations: a pilot observational study (Observational Research) https://doi.org/10.1007/s00296-022-05146-9
An early warning system for emerging SARS-CoV-2 variants (Nature Medicine) https://doi.org/10.1038/s41591-022-01836-w
SARS-CoV-2 Omicron Variant is as Deadly as Previous Waves After Adjusting for Vaccinations, Demographics, and Comorbidities (Preprint) https://doi.org/10.21203/rs.3.rs-1601788/v1
Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1 (Preprint) https://www.medrxiv.org/content/10.1101/2022.04.25.22274187v1
COVID-19 Associated Hepatitis in Children (CAH-C) during the second wave of SARS-CoV-2 infections in Central India: Is it a complication or transient phenomenon. (Preprint) https://doi.org/10.1101/2021.07.23.21260716
Liver and Gastrointestinal Involvement in Patients With COVID-19: A Retrospective Study https://www.cureus.com/articles/90062-liver-and-gastrointestinal-involvement-in-patients-with-covid-19-a-retrospective-study
Cortical Grey Matter Volume Loss links to Neurological Sequelae in post COVID-19 “Long Haulers” (Preprint) https://doi.org/10.21203/rs.3.rs-1582065/v1
Virological characteristics of the SARS-CoV-2 Omicron BA.2 spike (Cell) https://doi.org/10.1016/j.cell.2022.04.035
Continued Emergence and Evolution of Omicron in South Africa: New BA.4 and BA.5 lineages https://www.krisp.org.za/manuscripts/MEDRXIV-2022-274406v1-deOliveira.pdf
Molecular consequences of SARS-CoV-2 liver tropism (Nature Metabolism) https://doi.org/10.1038/s42255-022-00552-6
China CDC shares latest COVID-19 data (GISAID) https://www.gisaid.org/resources/gisaid-in-the-news/china-shares-latest-11-apr-2022/#c920
Persistent COVID-19 symptoms in a community study of 606,434 people in England (Nature) https://www.nature.com/articles/s41467-022-29521-z
Brain Inflammation and Intracellular α-Synuclein Aggregates in Macaques after SARS-CoV-2 Infection (Viruses) https://www.mdpi.com/1999-4915/14/4/776
Antibody Resistance of SARS-CoV-2 Omicron BA.1, BA.1.1, BA.2 and BA.3 Sub-lineages (Preprint) https://www.biorxiv.org/content/10.1101/2022.04.07.487489v1
Infectious viral load in unvaccinated and vaccinated individuals infected with ancestral, Delta or Omicron SARS-CoV-2 (Nature Medicine) https://www.nature.com/articles/s41591-022-01816-0
Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain (Preprint) https://www.biorxiv.org/content/10.1101/2022.01.07.475453v1
Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study (BMJ) https://www.bmj.com/content/377/bmj-2021-069590
SARS-CoV-2 Infection Induces Ferroptosis of Sinoatrial Node Pacemaker Cells (Circulation Research) https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.121.320518
SARS-CoV-2 variants of concern and variants under investigation in England (UK Health Security Agency) https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1063424/Tech-Briefing-39-25March2022_FINAL.pdf
Neutralization of Omicron BA.1, BA.2, and BA.3 SARS-CoV-2 by 3 doses of BNT162b2 vaccine (Preprint) https://doi.org/10.1101/2022.03.24.485633
COVID-19-Associated Encephalitis: Two Case Reports https://www.cureus.com/articles/86903-covid-19-associated-encephalitis-two-case-reports
First evidence that an emerging mammalian alphacoronavirus is able to infect an avian species (Transboundary and Emerging Diseases) https://doi.org/10.1111/tbed.14535
SARS-CoV-2 co-infection with influenza viruses, respiratory syncytial virus, or adenoviruses (The Lancet) https://doi.org/10.1016/S0140-6736(22)00383-X
Evidence for SARS-CoV-2 Delta and Omicron co-infections and recombination (Preprint) https://www.medrxiv.org/content/10.1101/2022.03.09.22272113v1
Culture and identification of a “Deltamicron” SARS-CoV-2 in a three cases cluster in southern France (Preprint) https://www.medrxiv.org/content/10.1101/2022.03.03.22271812v1.full
Mandatory masking in schools reduced COVID-19 cases during Delta surge (NIH press release) https://www.nih.gov/news-events/news-releases/mandatory-masking-schools-reduced-covid-19-cases-during-delta-surge
School Masking Policies and Secondary SARS-CoV-2 Transmission (Pediatrics) https://publications.aap.org/pediatrics/article/doi/10.1542/peds.2022-056687/185379/School-Masking-Policies-and-Secondary-SARS-CoV-2
Transmission of SARS-CoV-2 delta variant (AY.127) from pet hamsters to humans, leading to onward human-to-human transmission: a case study (The Lancet) https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00326-9/fulltext
COVID-19 Variant Dashboard – USA by Raj Rajnarayanan https://public.tableau.com/app/profile/raj.rajnarayanan/viz/USAVariantDB/VariantDashboard
SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 38 (UK Health Security Agency) https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1060337/Technical-Briefing-38-11March2022.pdf
SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 37 (UK Health Security Agency) https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1057359/Technical-Briefing-37-25February2022.pdf
Engineered extracellular vesicles antagonize SARS-CoV-2 infection by inhibiting mTOR signaling (Biomaterials and Biosystems) https://www.sciencedirect.com/science/article/pii/S2666534422000046?via%3Dihub
Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study (Preprint) https://doi.org/10.21203/rs.3.rs-1385593/v1
Dynamics of the Delta and Omicron variants of SARS-CoV-2 in the United States: the battle of supremacy in the presence of vaccination, mask usage and antiviral treatment (Preprint) https://doi.org/10.21203/rs.3.rs-1420446/v1
Virological characteristics of SARS-CoV-2 BA.2 variant (Preprint) https://www.biorxiv.org/content/10.1101/2022.02.14.480335v1
Transmission of SARS-CoV-2 Omicron VOC subvariants BA.1 and BA.2: Evidence from Danish Households (Preprint) https://www.medrxiv.org/content/10.1101/2022.01.28.22270044v1
Waning 2-Dose and 3-Dose Effectiveness of mRNA Vaccines Against COVID-19–Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominance — VISION Network, 10 States, August 2021–January 2022 (MMWR) https://www.cdc.gov/mmwr/volumes/71/wr/mm7107e2.htm?s_cid=mm7107e2_e&ACSTrackingID=USCDC_921-DM75599&ACSTrackingLabel=MMWR%20Early%20Release%20-%20Vol.%2071%2C%20February%2011%2C%202022&deliveryName=USCDC_921-DM75599
SARS-CoV-2 B.1.1.529 (Omicron) Variant Transmission Within Households — Four U.S. Jurisdictions, November 2021–February 2022 (MMWR) https://www.cdc.gov/mmwr/volumes/71/wr/mm7109e1.htm?s_cid=mm7109e1_w
Pediatric Emergency Department Visits Before and During the COVID-19 Pandemic — United States, January 2019–January 2022 (MMWR) https://www.cdc.gov/mmwr/volumes/71/wr/mm7108e1.htm?s_cid=mm7108e1_w#F2_down
Birth Of The Omicron Family: BA.1, BA.2, BA.3. Each As Different As Alpha Is From Delta. (Forbes) https://www.forbes.com/sites/williamhaseltine/2022/01/26/birth-of-the-omicron-family-ba1-ba2-ba3-each-as-different-as-alpha-is-from-delta/?sh=403de4ee3da9
Take a look at SARS-CoV-2’s family tree. It’s full of surprises (NPR) https://www.npr.org/sections/goatsandsoda/2022/02/09/1047616658/take-a-look-at-sars-cov-2s-family-tree-its-full-of-surprises
SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 35 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1050999/Technical-Briefing-35-28January2022.pdf
Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants (Nature) https://www.nature.com/articles/s41586-022-04466-x_reference.pdf
Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time (Preprint) https://www.medrxiv.org/content/10.1101/2022.01.14.22269235v1
Syncytin, envelope protein of human endogenous retrovirus (HERV): no longer ‘fossil’ in human genome (Animal Cells and Systems) https://doi.org/10.1080/19768354.2021.2019109
Host Chitinase 3-like-1 is a Universal Therapeutic Target for the Delta, Omicron and Other SARS-CoV-2 Viral Variants in COVID 19 (Preprint) https://www.biorxiv.org/content/10.1101/2022.01.21.477274v1
COVID-19 reinfections among naturally infected and vaccinated individuals (Nature) https://www.nature.com/articles/s41598-022-05325-5
Duration of Protection against Mild and Severe Disease by Covid-19 Vaccines (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2115481
Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants (Preprint) https://www.medrxiv.org/content/10.1101/2022.01.25.22269794v1
COVID-19 and the Common Cold—Preexisting Coronavirus Antibodies May Hinder SARS-CoV-2 Immunity (JAMA) https://jamanetwork.com/journals/jama/fullarticle/2788621?guestAccessKey=0bbad800-e651-496b-8046-d124bbc63a5a&term=01262022&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jama&utm_content=olf&utm_term=012622
Viral dynamics and duration of PCR positivity of the SARS-CoV-2 Omicron variant https://dash.harvard.edu/handle/1/37370587

COVID-19

SARS-CoV-2 Update

02/28/202203/09/2022 davidcwrightmd

SARS-CoV-2 infections have been accelerating at a rapid rate in the United States and many other countries including the United Kingdom, France, Germany, and Italy. This is caused by the Omicron variant of concern. Omicron is at least four times as infectious as the already highly infectious Delta variants. UK scientists have found that the household secondary attack rate for Omicron is 21.6%, compared to 10.7% with Delta, meaning people infected with Omicron are twice as likely to infect household members as they would be if infected with Delta. They also estimate a “three- to eight-fold increased risk of reinfection with the Omicron variant.”

I would expect the Omicron variant to continue to mutate just like Delta. There are now already three Omicron variants, BA.1, BA,2. and BA.3. We expect to see additional Omicron variants as this isolate spreads rapidly around the USA and the World. As of 12/22/21 the Omicron variant, which was first seen in South Africa on 11/08/21, is now in all 50 states, Puerto Rico and the District of Columbia. As of 1/14/22 Omicron has been identified on all seven continents and in at least 146 countries.

Omicron has mutations which decrease the effectiveness of current vaccines and monoclonal antibodies. The effectiveness of the new Pfizer drug, PAXLOVID^TM, should not be compromised by any of the current mutations in Omicron or Delta variants. Pfizer completed their filing with the FDA on 11/15/21. The FDA approved PAXLOVID^TM on December 22 , 2021.The FDA approved Merck’s drug Molnupiravir on December 23, 2021. On 12/23/21 CVS announced by fax it was selected by the Government to distribute oral PAXLOVID^TM and Molnupiravir. On 12/27/21 another fax from CVS listed which CVS pharmacies in California would have these drugs. Monterey County covers 3,771 square miles with a population of 434,061. Three CVS pharmacies in Monterey, Salinas, and Soledad are the only listed pharmacies in our county. I have only been able to obtain PAXLOVID^TM from the CVS in Salinas which is awaiting another shipment. Fresno County covers 6,011 square miles with a population of 999,101. Four CVS pharmacies in Fresno County are the only listed pharmacies. We obtained PAXLOVID^TM from the Salinas CVS pharmacy and successfully treated two patients in the last four weeks. Last week we treated a third patient from Turlock with PAXLOVID^TM. Two weeks ago we treated our first patient with Molnupiravir due to our inability at that time to obtain PAXLOVID^TM . Molnupiravir was obtained from the Monterey CVS and does not appear to be in short supply in the United States. You can just send your electronic prescription to a participating CVS pharmacy. You probably should call in advance to check on drug availability and their participation.

In the absence of obtaining intravenous Sotrovimab, only oral PAXLOVID^TM and Molnupiravir are available to treat SARS-CoV-2 as an outpatient. For now only masking (N95 rated masks, please!), social distancing and vaccination will have any effect on these variants. Furthermore, we do not believe that a 5-day quarantine or isolation period is sufficient for any COVID-19 infection. The Taiwanese CDC agrees with both our recommendations on quarantine period and masking. In fact, the Taiwanese CDC has recommended N95 masking since the beginning of the pandemic (and made these masks universally available to their population). Taiwan has one of the lowest death rates per million during the course of the pandemic (see graph below).

In the United States as of 2/25/22, SARS-CoV-2 deaths have decreased for the first time in twelve 14-day periods. There were 2,568 fewer deaths per day than in the last 14-day period. In November 2021, SARS-CoV-2 was the third most common cause of death in the United States.

In the last 14 days, the number of infections has decreased by 836,157 infections per day compared to the preceding 14-day period. Our infections per day have decreased for the first time over the last 6 weeks. Unless people get vaccinated, including their third dose of the vaccine, we will see further spread of the Omicron variants and increase in deaths in people who are not vaccinated, have waning immunity, the immunocompromised population and others with risk factors particularly those older than over the age of 64. SARS-CoV-2 is now in the top ten most common causes of death for children. Anyone over the age of 5 years can now get vaccinated in the United States at no cost. This should get done immediately.In Monterey County, only 35% of 5-11 year olds have received the first dose of vaccine.

The new variant, B.1.1.529 (Omicron), was first seen in South Africa on 11/8/21 with multiple new mutations, deletions and an insertion that caused a doubling of new infections every 1.3 days in Gauteng, South Africa. In just 67 days, as of 1/14/22, Omicron has been found on seven continents, in 117 countries and all 50 states in the United States. Unlike Delta variants in South Africa, Omicron was infecting and hospitalizing patients in all age groups but particularly children under five years of age and adults greater than 60 years of age. Increased vaccinations, vaccines against new mutants, drugs against 3C-like protease like PAXLOVID^TM, increased mask usage and social distancing, which are part of the Biden SARS-CoV-2 plan, are all necessary to continue to stop further spread of mutants and reduce infections, hospitalizations, and deaths.

Omicron Subvariant BA.2 Is Coming

Per CDC data ending in 2/19/22, the Delta variant accounts for 0.0% of new infections in the United States, while Omicron (B.1.1.529/BA.1) accounts for 96.2% and Omicron subvariant BA.2 accounts for 3.8%. It’s worth noting that in the last 30 days, according to GISAID, the United States has only sequenced 1.582% of cases.

Omicron subvariant BA.2 has been detected in every region of the United States. BA.2 also contains 17 mutations that set it apart from BA.1 (ten of which are also different from those in BA. 3.

On 2/25/22, the United States had 76,258 new infections with two states not reporting (Iowa and Tennessee). There were also 1,853 deaths with 9 other states not reporting. Florida continues to consistently under-report daily infections and deaths. In the United States the number of hospitalized patients has been decreasing in many areas, and now 8,981 patients are seriously or critically ill; that number was 16,791 two weeks ago. The number of critically ill patients has decreased by 7,811 in the last 14 days, while at least 32,111 new deaths occurred. The number of critically ill patients has decreased for the third time in fifteen 14-day periods but a large number of patients are still dying each day (average 2,294/day). Infections, critically ill patients, and deaths should markedly decrease in the next two weeks if Omicron BA.2 causes less severe disease and does not infect large numbers of previously BA.1 infected patients. However, there are reports out of Israel of patients infected with BA.1 being later reinfected with BA.2.

As of 2/24/22, we have had 972,190 deaths and 80,532,307 SARS-CoV-2 infections in the United States. We have had 1,303,679 new infections in the last 14 days. We were adding an average of 651,840 infections every seven days. For the pandemic in the United States we are averaging one death for every 82.8 infections reported or over 12,072 deaths for each one million infections. As of 2/25/22, thirty-six states have had greater than 500,000 total infections, and 36 states have had greater than 5,000 total deaths. Fifteen states (North Carolina, Indiana, Tennessee, Massachusetts, Ohio, Michigan, Georgia, Illinois, New Jersey, Pennsylvania, Florida, Texas, New York, Arizona and California) have had greater than 20,000 deaths. Four states (Florida, Texas, New York, and California) have had greater than 65,000 deaths. California and Texas have each had greater than 80,000 deaths.

On 11/20/20 in the United States, 3.70% of the population had a documented SARS-CoV-2 infection. California was ranked 41st in infection percentage at 2.77%. On 11/20/21 in North Dakota, 9.18% of the population was infected (ranked #1), and in South Dakota, 8.03% of the population was infected (ranked #2). As of 2/25//22, in the United States, 24.09% of the population has had a documented SARS-CoV-2 infection. In the last 15 months, 21.37% of our country became infected with SARS-CoV-2. In the last 2 weeks 0.43% of the country became infected. On 11/20/20, there were 260,331 (cumulative) deaths in the US from SARS-CoV-2. In the last 15 months, there were 712,069 new deaths from SARS-CoV-2. For eleven of those months, vaccines have been available to all adults. During these eleven months, 401,103 people have died of SARS-CoV-2 infections. Most of the hospitalizations and deaths could have been prevented by vaccination, proper masking, and social distancing.

As of 2/11/22, California was ranked 39th in infection percentage at 22.69%. In California 18.99% of Californians were infected in the last 15 months. As of 2/24/22 forty-three states have had greater than 20% of their population infected. Rhode Island was at 33.55% (ranked #1), Alaska was at 31.55% (ranked #2),North Dakota was at 31.20% (ranked #3), Tennessee was at 29.91% (ranked #4), Utah was at 28.75% (ranked #5) and Florida was at 27.21% (ranked #9) of their population infected. All 50 states and the District of Columbia now have greater than 16% of their population infected. The table below shows that if we rank the US states with the highest death rates per million population within the world rankings, we see that Mississippi, Arizona, Alabama and New Jersey have the eighth highest COVID-19 deaths per million in the world. Massachusetts, Arkansas and New York tied at tenth, Louisiana is at 11th and Rhode Island and Florida tied at 13th. The United States as a whole ranks 18th in the world for deaths per million population (2,907 deaths per million). California ranks 40th in the USA (and 38th in the world). If we look at the death rates per million in South Korea (152), Iceland (177), Japan (181), and Israel (1,084), they suggest that treatment outcomes are somehow different in these four countries. The same phenomenon can be seen in Scandinavia, where the death rate in Sweden is 1,677 per million, compared to 291 per million in Norway and 426 per million in Finland. The United States should have taken a closer look at how countries with low death rates (like South Korea, Iceland, Japan, Finland, and Norway) are preventing COVID-19 infections and treating COVID-19 patients.

State or Country	COVID-19 Deaths per million population	Rank in USA	Ranked within World
Mississippi	4,035	1st	8th tied
New Jersey	3,717	4th	8th tied
Louisiana	3,572	5th	11th
New York	3,482	8th	10th tied
Alabama	3,709	3rd	8th tied
Arizona	3,837	2nd	8th tied
Massachusetts	3,391	11th	10th tied
Rhode Island	3,215	19th	13th tied
Arkansas	3,454	9th	10th tied
Florida	3,238	18th	13th tied
California	2,152	40th	38th
USA	2,907		18th
Peru	6,230		1st
Bosnia-Herzegovina	4,746		3rd
North Macedonia	4,311		5th
Hungary	4,528		4th
Montenegro	4,257		5th
Bulgaria	5,183		2nd
Gibraltar	2,999		14th
Czechia	3,583		9th
Brazil	3,014		14th
San Marino	3,289		12th
Georgia	4,037		7th
Sweden	1,677		56th
Israel	1,084		83rd
Canada	952		90th
Finland	426		126th
Norway	291		139th
Japan	181		153rd
Iceland	177		156th
South Korea	152		161st

FDA-Approved Oral Drug Treatments for SARS-CoV-2

Pfizer has developed PAXLOVID™, an oral reversible inhibitor of C3-like protease of SARS-CoV-2. The drug inhibits this key enzyme that is crucial for virus production. The compound, also called Compound 6 (PF-07321332), is part of the drug combination PAXLOVID™ (PF-07321332; ritonavir), which just successfully completed a Phase 2-3 trial in humans in multiple countries. The preliminary results were announced on 11/5/21 by Pfizer. The results show that 89% of the hospitalizations and deaths were prevented in the drug treatment arm. The drug was administered twice a day for five days. No deaths occurred in the treatment group, and ten deaths occurred in the placebo group. The study was stopped by an independent data safety monitoring board, and the FDA concurred with this decision. Pfizer applied for an Emergency Use Authorization for this drug on 11/15/21. This drug was approved on 12/23/21. We have only been able to obtain PAXLOVID™ for two patients who we successfully treated with this drug obtained from CVS in Salinas (East Alisal Street; phone number 831-424-0026). They were expecting another shipment on 1/28/22. In my opinion, this agent, if more widely available, could markedly alter the course of every coronavirus infection throughout the world.

Total Doses of All Four COVID-19 Drugs Provided to the United States, by Week

Date	Paxlovid	Molnupiravir	Sotrovimab	Bebtelovimab	Evusheld
1/24/22-1/30/22	99,980	399,980	52,260	—	74,976
1/31/22-2/6/22	0	0	52,104	—	74,960
2/7/22-2/13/22	99,940	399,840	52,248	48,745	49,264
2/14/22-2/20/22	0	0	52,249	48,795	49,992
2/21/22-2/27/22	148,980	349,776	52,194		49,922

FDA-Approved Intravenous Monoclonal Antibody Treatment for Non-Hospitalized SARS-CoV-2 Patients

Sotrovimab is a human monoclonal antibody made by Vir Technology and Glaxo-SmithKline which received a FDA EUA approval on May 26,1921 for intravenous drug treatment for non-hospitalized SARS-CoV-2 infected patients. According to the FDA, “The data supporting this EUA for sotrovimab are based on an interim analysis from a phase 1/2/3 randomized, double-blind, placebo-controlled clinical trial in 583 non-hospitalized adults with mild-to-moderate COVID-19 symptoms and a positive SARS-CoV-2 test result. Of these patients, 291 received sotrovimab and 292 received a placebo within five days of onset of COVID-19 symptoms. The primary endpoint was progression of COVID-19 (defined as hospitalization for greater than 24 hours for acute management of any illness or death from any cause) through day 29. Hospitalization or death occurred in 21 (7%) patients who received placebo compared to 3 (1%) patients treated with sotrovimab, an 85% reduction.” Sotrovimab is given intravenously in a single 500 mg dose. Supplies of this drug are also very limited and currently are only available at hospitals. In order to get this drug, we will probably have to go through the same process outlined below for Evusheld.

Bebtelovimab is a new monoclonal antibody treatment for mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options approved or authorized by FDA are not accessible or clinically appropriate. The authorized dose of Bebtelovimab is 175 mg, given as an intravenous injection over at least 30 seconds. The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for this drug on 2/11/22.

FDA Approved Intramuscular Prophylaxis of SARS-CoV-2 Immunocompromised Patients

Facility/Provider Name for Registration
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A New Possible Indication for an Older FDA-Approved Antiviral Drug

Remdesivir was the first FDA-approved Emergency Use Authorization drug for the treatment of SARS-CoV-2 infected patients. In their January 2021 paper in Nature Communications, Kokic et al explained the mechanism of Remdesivir’s action on SARS-CoV-2: “The active form of remdesivir acts as a nucleoside analog and inhibits the RNA-dependent RNA polymerase (RdRp) of coronaviruses including SARS-CoV-2. Remdesivir is incorporated by the RdRp into the growing RNA product and allows for addition of three more nucleotides before RNA synthesis stalls. Addition of the fourth nucleotide following Remdesivir incorporation into the RNA product is impaired by a barrier to further RNA translocation. This translocation barrier causes retention of the RNA 3ʹ-nucleotide in the substrate-binding site of the RdRp and interferes with entry of the next nucleoside triphosphate, thereby stalling RNA-dependent RNA polymerase. In the structure of the Remdesivir-stalled state, the 3ʹ-nucleotide of the RNA product is matched and located with the template base in the active center, and this may impair proofreading by the viral 3ʹ-exonuclease.”

A recent study by Gottlieb et al of intravenous Remdesivir to prevent disease progression, whose design was similar to the study designs used for PAXLOVID™ and Molnupiravir, was published in the New England Journal of Medicine on 1/27/22. The study resulted in an 87% lower risk of hospitalization or death than in the placebo group with a similar adverse events occurrence (42.3% and 46.3% respectively). The FDA may allow approval of outpatient intravenous Remdesivir over three days (200 mg IV on day one followed by 100 mg IV daily on days two and three) in high risk non-hospitalized SARS-CoV-2 infected patients.

With the exception of Evusheld, all of the therapies listed above can be used in Omicron-infected patients. Other previously approved monoclonal antibodies will not work for Omicron.

The Threat of SARS-CoV-2 Variants

In response to the need for “easy-to-pronounce and non-stigmatising labels,” at the end of May, the World Health Organization assigned a letter from the Greek alphabet to each SARS-CoV-2 variant. GISAID, Nextstrain, and Pango will continue to use the previously established nomenclature. For our purposes, we’ll be referring to each variant by both its Greek alphabet letter and the Pango nomenclature.

The WHO has sorted variants into two categories: Variants of Concern (VOC) and Variants of Interest (VOI). The criteria for Variants of Concern are as follows:

Increase in transmissibility or detrimental change in COVID-19 epidemiology; or
Increase in virulence or change in clinical disease presentation; or
Decrease in effectiveness of public health and social measures or available diagnostics, vaccines, therapeutics.

The WHO categorizes the following five variants as Variants of Concern (VOC):

Source: World Health Organization

The criteria for Variants of Interest (VOI) are as follows:

has been identified to cause community transmission/multiple COVID-19 cases/clusters, or has been detected in multiple countries; OR
is otherwise assessed to be a VOI by WHO in consultation with the WHO SARS-CoV-2 Virus Evolution Working Group.

The WHO categorizes the following six variants as Variants of Interest (VOI):

According to the UK Health Security Agency Technical Briefing from 2/25/22, “A putative Delta and Omicron recombinant has been identified in the UK, with likely parental lineages AY.4.2.2 and BA.1.1 and a breakpoint in non-structural protein 3 (nsp3). The presence of 34 genomes sampled between 7 January 2022 and 14 February 2022 suggest that this recombinant is able to transmit.” We will need to monitor for this Delta-Omicron recombinant variant in the United States as well.

Omicron cases sequenced as of 2/27/22:

Map of Omicron sequenced transmissions:

Delta cases sequenced as of 2/27/22:

Map of Delta sequenced transmissions:

B.1.640 cases sequenced as of 2/27/22:

Watching World Data

Location	Total Infections as of 2/25/22	New Infections on 2/25//22	Total Deaths	New Deaths on 2/25/22	% of Pop.Infected	SARS-CoV-2 Isolates Currently Known in Location	National/ State Mask Mandate?	Currently in Lockdown?
World	433,301,387(14,603,060 new infections in 14 days).	1,614,434	5,956,495(136,430 new deaths in last 14 days)	8,503	5.55%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines) Mu/B.1.621 (Colombia)C.1.2 (South Africa 2% of isolates in July 2021)R1 (Japan)Omicron/B.1.1.529 + BA.1 + BA.2 + BA.3 (South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)*	No	No
USA	80,532,307* (ranked #1) 1,303.679 new infections in the last 14 days. *JHU reported 77,683,119 infections	76,258 (ranked #6)	972,200 (ranked #1)68,003 new deaths in the last 14 days. JHU reported 918,924 deaths.	1,853	24.09% (0.43% increase in 14 days).	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan) Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)*	No	No
Brazil	28,679242(ranked #3) 1,378,727 infections.	89,247 (ranked #4)	648,160(ranked #2)	674	13.33%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
India	42,904,744(ranked #2); increased by 318,116 infections in 2 weeks.	10,399	513,512(ranked #3)	254	3.05%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)Eta/B.1.525 (Nigeria/UK)APTK India VOI 32421Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Iota/B.1.526 (USA-NYC) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)*	No	No
United Kingdom	18,804,765(ranked #5; was #6 twenty-four weeks ago; increased by 684,775infections in 2 weeks.	31,933	161,224 (ranked #7 in world)	120	27.46%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)C.1.2 (South Africa)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)*	No	No
California, USA	8,957,208(ranked #11 in the world; 165,891 new infections).	13,481	85,127 (ranked #20 in world)	227	22.69%(0.45% increase in 14 days)	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)*	No	No
Mexico	5,473,481(ranked #17) 247,200 new infections in 14 days).	18,252	317,303(ranked #5)	362	4.17%	B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)*	No	No
South Africa	3,669,671(ranked #20; 31,998 new infections in 14 days).	2,111	99,145 (ranked #18)	137	6.06%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India) C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)	No	No
Canada	3,275,746(ranked #27, was 26th eight weeks ago; 94,919 new infections in 14 days).	6,050	36,448(ranked #26)	71	8.55% .	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)*	No	No
Poland	5,637,646(ranked #15; 288,758 new infections in 14 days).	16,724	111,056(ranked #15)	198	14.92%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3	No	No
Turkey	13,913,625(ranked #8, 1,165,284 new infections in 14 days).	71,736	93,805 (ranked #19)	266	16.21% (1.36% of the country was infected in the last 14 days.)	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gamma/P.1 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)*	No	No
Russia	16,052,028;(ranked #6), 2,320,234 new infections in 14 days; a new pandemic record for 14 days).	123,460	349,365(ranked #4 in world)	787	10.99%; 1,54% of the country was infected in the last 14 days.	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)R1 (Japan) B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Argentina	8,887,973(ranked #11; 1,955,001 new infections in 14 days, a new pandemic record for 14 days).	139,853	125,958(ranked #13 in world)	86	19.37% (4.25 % increase in two weeks, a new pandemic record for 14 days).	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)Gama/P.1 (Brazil)Delta/B.1.617.2 (India)Lambda/C.37 (Peru)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)*	No	No
Colombia	6,058,715(ranked #13, 50,724 new infections in 14 days).	2,159	136,764 (ranked #10 in world)	181	11.70%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Epsilon/B.1.427 + B.1.429 (USA)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)*	No	No
Peru	3,424,894(ranked #22, 81,181 new infections in 14 days).	13,693	207,965(ranked #6)	228	10.15%, a 2.96% increase in 14 days; a new pandemic record for 14 days.	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Indonesia	5,504,418(ranked #16; 796, 375 new infections in 14 days)	46,643	147,844 (ranked #9)	258	1.97%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Eta/B.1.525 (Nigeria/UK)Theta/P.3 (Philippines) Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Iran	7,023,904 262,099 new infections in last 14 days(ranked 12th; was 12th twenty-four weeks ago)	11,972	136,166 (ranked #12)	214	8.18%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Spain	10,977,524(ranked 10th; 373,324 new infections in 14 days).	27,527	99,410 (ranked #17)	248	23.46%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)*	No	No
France	22,593,109(ranked #4; 1,089,450 new infections).	58,138	137,958 (ranked #11)	188	34.48%, a 1.66% increase in 14 days.	Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)	No	No

What Our Team Is Reading This Week

SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 37 (UK Health Security Agency) https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1057359/Technical-Briefing-37-25February2022.pdf
Virological characteristics of SARS-CoV-2 BA.2 variant (Preprint) https://www.biorxiv.org/content/10.1101/2022.02.14.480335v1
Transmission of SARS-CoV-2 Omicron VOC subvariants BA.1 and BA.2: Evidence from Danish Households (Preprint) https://www.medrxiv.org/content/10.1101/2022.01.28.22270044v1
Waning 2-Dose and 3-Dose Effectiveness of mRNA Vaccines Against COVID-19–Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominance — VISION Network, 10 States, August 2021–January 2022 (MMWR) https://www.cdc.gov/mmwr/volumes/71/wr/mm7107e2.htm?s_cid=mm7107e2_e&ACSTrackingID=USCDC_921-DM75599&ACSTrackingLabel=MMWR%20Early%20Release%20-%20Vol.%2071%2C%20February%2011%2C%202022&deliveryName=USCDC_921-DM75599
SARS-CoV-2 B.1.1.529 (Omicron) Variant Transmission Within Households — Four U.S. Jurisdictions, November 2021–February 2022 (MMWR) https://www.cdc.gov/mmwr/volumes/71/wr/mm7109e1.htm?s_cid=mm7109e1_w
Pediatric Emergency Department Visits Before and During the COVID-19 Pandemic — United States, January 2019–January 2022 (MMWR) https://www.cdc.gov/mmwr/volumes/71/wr/mm7108e1.htm?s_cid=mm7108e1_w#F2_down
Birth Of The Omicron Family: BA.1, BA.2, BA.3. Each As Different As Alpha Is From Delta. (Forbes) https://www.forbes.com/sites/williamhaseltine/2022/01/26/birth-of-the-omicron-family-ba1-ba2-ba3-each-as-different-as-alpha-is-from-delta/?sh=403de4ee3da9
Take a look at SARS-CoV-2’s family tree. It’s full of surprises (NPR) https://www.npr.org/sections/goatsandsoda/2022/02/09/1047616658/take-a-look-at-sars-cov-2s-family-tree-its-full-of-surprises
SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 35 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1050999/Technical-Briefing-35-28January2022.pdf
Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants (Nature) https://www.nature.com/articles/s41586-022-04466-x_reference.pdf
Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time (Preprint) https://www.medrxiv.org/content/10.1101/2022.01.14.22269235v1
Syncytin, envelope protein of human endogenous retrovirus (HERV): no longer ‘fossil’ in human genome (Animal Cells and Systems) https://doi.org/10.1080/19768354.2021.2019109
Host Chitinase 3-like-1 is a Universal Therapeutic Target for the Delta, Omicron and Other SARS-CoV-2 Viral Variants in COVID 19 (Preprint) https://www.biorxiv.org/content/10.1101/2022.01.21.477274v1
COVID-19 reinfections among naturally infected and vaccinated individuals (Nature) https://www.nature.com/articles/s41598-022-05325-5
Duration of Protection against Mild and Severe Disease by Covid-19 Vaccines (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2115481
Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants (Preprint) https://www.medrxiv.org/content/10.1101/2022.01.25.22269794v1
COVID-19 and the Common Cold—Preexisting Coronavirus Antibodies May Hinder SARS-CoV-2 Immunity (JAMA) https://jamanetwork.com/journals/jama/fullarticle/2788621?guestAccessKey=0bbad800-e651-496b-8046-d124bbc63a5a&term=01262022&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jama&utm_content=olf&utm_term=012622
Viral dynamics and duration of PCR positivity of the SARS-CoV-2 Omicron variant https://dash.harvard.edu/handle/1/37370587
Emergence in Southern France of a new SARS-CoV-2 variant of probably Cameroonian origin harbouring both substitutions N501Y and E484K in the spike protein (Preprint) https://doi.org/10.1101/2021.12.24.21268174
A living WHO guideline on drugs for covid-19 (BMJ) https://doi.org/10.1136/bmj.m3379
Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis (Science) https://doi.org/10.1126/science.abj8222
Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection (Nature) https://www.nature.com/articles/s41590-021-01113-x
An upper bound on one-to-one exposure to infectious human respiratory particles (PNAS) https://www.pnas.org/content/118/49/e2110117118
Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies (Nature) https://doi.org/10.1038/d41586-021-03796-6
Frequent Occurrence of SARS-CoV-2 Transmission among Non-close Contacts Exposed to COVID-19 Patients (Journal of Korean Medical Science) https://doi.org/10.3346/jkms.2021.36.e233
Serial Screening for SARS-CoV-2 in Rectal Swabs of Symptomatic COVID-19 Patients (Journal of Korean Medical Science) https://doi.org/10.3346/jkms.2021.36.e301
Saliva swabs are the preferred sample for Omicron detection (Preprint) https://doi.org/10.1101/2021.12.22.21268246
SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing: Update on hospitalisation and vaccine effectiveness for Omicron VOC-21NOV-01 (B.1.1.529) 31 December 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1044481/Technical-Briefing-31-Dec-2021-Omicron_severity_update.pdf
Characteristics and Clinical Outcomes of Children and Adolescents Aged <18 Years Hospitalized with COVID-19 — Six Hospitals, United States, July–August 2021 (MMWR) https://www.cdc.gov/mmwr/volumes/70/wr/mm705152a3.htm
The SARS-CoV-2 variant, Omicron, shows rapid replication in human primary nasal epithelial cultures and efficiently uses the endosomal route of entry. (Preprint) https://drive.google.com/file/d/1vam2PVMWvfRBczqs_uZbnUixGja1QPZD/view
Initial Assessment of SARS-CoV-2 Omicron Variant in Exhaled Breath Aerosol (Preprint) https://mfr.osf.io/render?url=https%3A%2F%2Fosf.io%2Fdscy3%2Fdownload
Multisystem Involvement in Post-acute Sequelae of COVID-19 (PASC) (Annals of Neurology) https://doi.org/10.1002/ana.26286
Taiwan rejects US CDC guidance on 5-day quarantine (Taiwan News) https://www.taiwannews.com.tw/en/news/4393548
Risk assessment for SARS-CoV-2 variant: Omicron VOC-21NOV-01 (B.1.1.529) (UK Health Security Agency) https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1041896/15-december-2021-risk-assessment-for-SARS_Omicron_VOC-21NOV-01_B.1.1.529.pdf
HKUMed finds Omicron SARS-CoV-2 can infect faster and better than Delta in human bronchus but with less severe infection in lung https://www.med.hku.hk/en/news/press/20211215-omicron-sars-cov-2-infection
mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant (Preprint) https://www.medrxiv.org/content/10.1101/2021.12.14.21267755v1/
“Breakthrough” COVID-19 Hospitalizations Among Fully Vaccinated Patients Occur Most Often among Older Adults and Involve People with Chronic Health Conditions (KFF) https://www.kff.org/coronavirus-covid-19/press-release/breakthrough-covid-19-hospitalizations-among-fully-vaccinated-patients-occur-most-often-among-older-adults-and-involve-people-with-chronic-health-conditions/

COVID-19

SARS-CoV-2 Update

07/07/2021 davidcwrightmd

It’s time for our next 14-day moving average determinations for SARS-CoV-2 for the United States and my thoughts on vaccines and mutant viruses. We use the WORLDOMETERS aggregators data set to make any projections since it includes data from the Department of Veterans Affairs, the U.S. Military, federal prisons and the Navajo Nation.

In the United States, SARS-CoV-2 deaths have decreased for the eleventh time in a 14-day period. There were 30 fewer deaths per day than in the last 14-day period. In the last 14 days, the number of infections has decreased by 947 infections per day. Our infections per day are still high, probably secondary to SARS-CoV-2 mutant Delta/B.1.617.2. I would predict that the opening of schools, places of worship, bars, restaurants, indoor dining and travel all will contribute to further spread of SARS-CoV-2 mutants and rising numbers in infections, hospitalizations and deaths in the coming months. Increased traveling as well as summer vacations, and the July 4 holiday will all cause further increases. Vaccinations, increased mask usage and social distancing, which are a part of the Biden SARS-CoV-2 plan (day 188 of plan) will be necessary to stop spread of mutants and cause further reductions in infections, hospitalizations and deaths in the future. On 7/02/21, the United States had 18,399 new infections. There were also 322 deaths. The number of hospitalized patients is decreasing, but 3,866 patients are still seriously or critically ill. The number of critically ill patients has decreased by 294 in the last 14 days, while 3,785 new deaths occurred. The number of critically ill patients is decreasing for the sixth 14-day period, but a large number of patients are still dying each day (average 270/day).

As of 7/02/21, we have had 621,161 deaths and 34,580,198 SARS-CoV-2 infections in the United States. We have had 188,327 new infections in the last 14 days. We are adding an average of 94,163 infections every 7 days. Each million infections usually results in 10,000 to 20,000 deaths. On 7/02/21, thirty-two states have had greater than 500,000 total infections, and 33 states have had greater than 5,000 total deaths. Ten states (Ohio, Michigan, Georgia, Illinois, New Jersey, Pennsylvania, Florida, Texas, New York and California) have had greater than 20,000 deaths. Four states (Florida, Texas, New York and California) have had greater than 35,000 deaths. In the world, 42 other countries have greater than 500,000 infections and 60 other countries have greater than 5,000 deaths.

On 11/20/20 in the United States, 3.70% of the population had a documented SARS-CoV-2 infection. California was ranked 41st in infection percentage at 2.77%. In North Dakota 9.18% of the population was infected (ranked #1), and in South Dakota 8.03% of the population was infected (ranked #2).

As of 7/02/21, in the United States, 10.38% of the population has had a documented SARS-CoV-2 infection. In the last 9 months, 7% of our country became infected with SARS-CoV-2.

As of 7/02/21, California was ranked 38th in infection percentage at 9.66%. In North Dakota 14.53% of the population was infected (ranked #1), while Rhode Island was at 14.40% (ranked #2) and South Dakota was at 14.08% of the population infected (ranked #3). Thirty-three states have greater than 10% of their population infected and 42 states have greater than 9% of their population infected. Only one state has less than 3% of their population infected: Hawaii (2.67%).

The Threat of SARS-CoV-2 Variants

In a response for the need for “easy-to-pronounce and non-stigmatising labels,” at the end of May, the World Health Organization assigned a letter from the Greek alphabet to each SARS-CoV-2 variant. GISAID, Nextstrain, and Pango will continue to use the previously established nomenclature. For our purposes, we’ll be referring to each variant by both its Greek alphabet letter and the Pango nomenclature.

The WHO has sorted variants into two categories: Variants of Concern (VOC) and Variants of Interest (VOI). The criteria for Variants of Concern are as follows:

Increase in transmissibility or detrimental change in COVID-19 epidemiology; or
Increase in virulence or change in clinical disease presentation; or
Decrease in effectiveness of public health and social measures or available diagnostics, vaccines, therapeutics.

The WHO categorizes the following four variants as Variants of Concern (VOC):

The criteria for Variants of Interest (VOI) are as follows:

has been identified to cause community transmission/multiple COVID-19 cases/clusters, or has been detected in multiple countries; OR
is otherwise assessed to be a VOI by WHO in consultation with the WHO SARS-CoV-2 Virus Evolution Working Group.

The WHO categorizes the following six variants as Variants of Interest (VOI):

The two variants of concern that have garnered most of our attention recently are Alpha (B.1.1.7) and Delta (B.1.617.2). Alpha, first detected in the United Kingdom in September of 2020, has been detected in almost every country and all 50 states in the U.S. Up until this week, Alpha was the dominant variant in the United States, accounting for 60-70% of cases in May and early June.

Alpha is more infectious than other previously circulating B2 lineage isolates. There are two deletions and six other mutations in its spike protein. One mutation involves a change of one amino acid, an asparagine at position 501 in the receptor binding motif with a tyrosine. This enhances binding (affinity) to the ACE-2 receptor and may alone be responsible for the increased infectivity of this isolate. A study published March 10 in the British Medical Journal (BMJ) found that the risk of death increased by 64% in patients infected with Alpha compared to all other isolates (known at the time).

While Alpha continues to pose a threat, the increased prominence of the Delta variant (B.1.617.2), first identified in India, is a concern for several reasons.

First, there is some evidence to suggest that Delta is more transmissible than other variants, including Alpha. This may be due to a mutation, P681R, near the furin cleavage site, and/or due to a deletion in the N-terminal domain (NTD) of the spike protein. In Australia, public health officials have described a handful of cases where transmission of the Delta variant occurred after “fleeting encounters”— five to ten seconds of close contact between strangers in a public place like a gym or a restaurant.

Second, Delta leads to more severe infections. According to a recent study in Scotland, “Risk of COVID-19 hospital admission was approximately doubled in those with the Delta VOC when compared to the Alpha VOC.”

Lastly, there is evidence of reduced vaccine effectiveness with Delta. The variant appears to be particularly evasive in people who have had only one dose of vaccine. A Scottish study estimated the vaccine effect against Delta after one dose to be 30% for the Pfizer vaccine and 18% for the AstraZeneca vaccine. After two doses, it was 79% for Pfizer and 60% for AstraZeneca.

Considering these factors, it is not surprising that Delta is on track to overtake Alpha (B.1.1.7) as the dominant variant worldwide. In the past month, it accounted for 91% of isolations in India, 97% of isolations in the United Kingdom, 96% in Singapore, 90% in Russia, 99% in Israel, and 73% in Australia. In the United States, Delta is now the dominant variant; as of July 6, it accounted for 41.8% of isolations in the past four weeks, compared to 12.9% two weeks ago and 3.7% four weeks ago. This suggests the proportion of Delta cases is nearly doubling every week.

To predict the potential impact of Delta in the U.S., one need only look across the pond. COVID-19 cases in Scotland (where 51% of the population is fully vaccinated) reached a record high last week, overwhelming hospitals and causing some to cancel elective surgeries and most outpatient care. In England, average daily COVID-19 hospital admissions have increased by 52% in the last week. ONS data also reveal a shift in the proportion of young people being hospitalized for COVID-19, with the number of hospitalized 15-24 year-olds increasing steadily since May. Meanwhile, the UK plans to end social distancing and mask mandates on July 19. (My daughter says this is where I should insert a facepalm emoji.)

In Israel, where 56% of the population have received two doses of the Pfizer vaccine, the Delta variant accounts for approximately 99% of cases over the past month. Israel’s health ministry now reports that the Pfizer vaccine is only 64% effective in preventing infection, compared to data from May (before Delta became dominant in Israel) that suggested the vaccine was 94% effective. Israel dropped its mask mandate on June 18, with exceptions for air travel and long-term healthcare facilities, but reinstated the mandate on June 28 after two school outbreaks.

As of July 3, the CDC estimates that the Delta variant makes up 51% of US cases. The NY Times reports that nationwide, compared to the previous 14 days, COVID-19 cases are up 14%. One state getting hit particularly hard by Delta is Missouri, where Delta accounts for 73% of COVID-19 cases. As of July 5, new COVID-19 cases in Missouri were up 45% compared to the previous 14 days, hospitalizations were up 24%, and deaths were up 68%. Some Missouri hospitals have run out of ventilators. The NY Times reports that as of July 5, only 39% of Missouri residents have been fully vaccinated. In the 12-17 age group only 23% have been vaccinated. Missouri never implemented a state-wide mask mandate, and most local mask mandates were lifted at the end of May, along with distancing and capacity restrictions for businesses. All state workers in Missouri were directed to return to in-person work by May 17.

Keeping in mind the potential of variants to evade vaccines, I believe it’s important that we pay attention to instances of vaccine failure. Prior to April 30, 2021, the CDC reported all breakthrough infections. From January 1, 2021 to April 30, 2021, there were 10,262 breakthrough infections, 27% of which were asymptomatic and 995 of which were hospitalized. Of the hospitalized patients, 160 (16%) died.

Between May 1 and June 28, there were 4,686 breakthrough cases reported to the CDC that resulted in hospitalization or death. (The CDC no longer tracks breakthrough cases that do not result in hospitalization or death.) As of June 28, the CDC reports that 656 fully-vaccinated people have died of COVID-19. This means that 496 of those deaths occurred between May 1 and June 28. Whereas the period from January 1 to April 30 had an average of 40 COVID deaths per month in fully-vaccinated people, the period from May 1 to June 28 had an average of 248 deaths per month. This constitutes a 6-fold increase. We can’t say with certainty whether this increase in deaths is related to the rise in prevalence of the Delta variant, but there is certainly a correlation. Delta accounted for less than 1% of cases at the end of April, about 3% at the end of May, and an estimated 51% in the last two weeks of June.

Indeed, reports of fully-vaccinated people infected with the Delta variant may become more common. Author John Pavlovitz recently described his family’s experience. Pavlovitz, his wife, and their 16 year-old son were all fully vaccinated, while their 11 year-old daughter was not yet eligible. Their daughter developed COVID-19 symptoms and tested positive while the family was traveling, and it presumably spread to the other three family members when they returned home to quarantine together. (However, there’s really no way of knowing which family member was the index case. For all we know, one of the vaccinated family members could have been infected asymptomatically and passed the virus to the daughter.) Pavlovitz and his wife both developed COVID-19 symptoms, and their son had an asymptomatic infection. Pavlovitz admits that they should have been more careful to prevent household transmission. They apparently did not wear masks in the house, even after they learned their daughter was infected. They thought that since they’d been vaccinated, they didn’t have to worry about being infected.

The experience of the Pavlovitz family suggests that it is prudent for vaccinated people to follow the World Health Organization’s guidance on masking: everyone, regardless of vaccination status, should continue to wear a mask when gathering with folks from other households indoors, when in close contact with people who are unvaccinated, and when in close contact with people who may be infected. Some U.S. local public health agencies, like Los Angeles County, agree.

Variants of (Slightly Less) Concern

At 2,284 cases, the United States has the second highest number of isolations of the Beta variant (B.1.351, first identified in South Africa), and 6 of these were in the last four weeks. The Beta variant now accounts for only 0.1% of isolations in the U.S., down from 0.3% two weeks ago.

The United States still has the most isolations of the Gamma variant (P.1) in the world, with 18,391 overall and 527 in the past four weeks. Gamma accounted for 9.2% of isolations in the past month, down from 12.1% two weeks ago.

The WHO has also recently labeled the Lambda variant (C.37), which was first identified in Peru in August of 2020, as a variant of interest. The United States has the second largest number of isolations of Lambda, after Chile, with 635 total and 17 in the past four weeks. Lambda causes over 80% of infections in Peru which experienced a surge in new cases this spring and, as of July 6, has had 2,069,051 infections and 193,588 deaths. Peru averaged 2,426 new cases per day over the last week. Strangely, a number of South American countries (Peru, Argentina, Colombia) have stopped reporting new isolations of Lambda to GISAID.

COVID-19 in California

The following data were reported by the California Department of Public Health:

Date	Total Cases	New Cases	Total Deaths	New Deaths	Hospitalized	In ICU	Fully Vaccinated
6/4/21	3,687,736	1,047	62,179	87	1,062	260	17,662,712
6/5/21	3,688,893	1,157	62,242	63	1,042	243	17,813,305
6/6/21	3,689,994	1,101	62,470	228	1,035	221	17,947,342
6/7/21	3,690,868	874	62,473	3	1,011	219	18,011,744
6/8/21	3,691,660	792	62,479	6	1,015	228	18,100,412
6/9/21	3,692,506	846	62,499	20	1,030	231	18,240,912
6/10/21	3,693,362	856	62,538	39	1,001	234	18,431,265
6/11/21	3,694,498	1,136	62,593	55	982	233	18,542,484
6/12/21	3,695,530	1,032	62,508	-85	955	240	18,637,504
6/13/21	3,696,472	942	62,512	4	915	241	18,694,365
6/14/21	3,697,299	827	62,505	-7	939	239	18,731,215
6/15/21	3,697,927	628	62,515	10	977	251	18,875,034
6/16/21	3,698,626	699	62,534	19	981	242	18,970,053
6/17/21	3,699,455	829	62,565	31	956	232	19,074,396
6/18/21	3,700,750	1,295	62,622	57	951	233	19,164,548
6/19/21	3,702,237	1,487	62,661	39	1,271		19,164,548
6/20/21	3,702,882	645	62,689	28	1,249		19,164,548
6/21/21	3,704,005	1,123	62,693	4	929	238	19,343,396
6/22/21	3,704,640	635	62,701	8	949	243	19,398,536
6/23/21	3,705,427	787	62,741	40	978	287	19,454,555
6/24/21	3,706,846	1,419	62,822	81	955	274	19,541,124
6/25/21	3,708,861	2,015	62,890	68	959	274	19,621,174
6/26/21	3,711,928	3,067	62,959	69			19,621,174
6/27/21	3,712,795	867	62,990	31			19,621,174
6/28/21	3,714,051	1,256	62,994	4	980	290	19,880,275
6/29/21	3,714,813	762	62,999	5	1,050	288	19,941,886
6/30/21	3,710,454	2,013	63,023	24	1,089	307	20,014,043
7/1/21	3,712,152	1,698	63,096	73	1,090	300	20,073,302
7/2/21	3,713,944	1,792	63,141	45	1,071	295	20,073,302
7/3/21	3,715,377	1,433*	63,165	24	1,071	295	20,073,302
7/4/21	3,716,810	1,433	63,189	24	1,071	295	20,073,302
7/5/21	3,718,243	1,433	63,213	24	1,071	295	20,073,302
7/6/21	3,719,674	1,433	63,238	24	1,153	298	20,240,207
7/7/21	3,721,006	1,332	63,259	21	1,228	299	20,296,653

*Data for 7/3/21-7/6/21 were reported in bulk on 7/6/21. We’ve divided the new cases evenly among the four days.

California dropped its mask mandate and most public space capacity limits on June 15. Over the past two weeks, daily new cases in California have hovered between 635 and 3,067. The two-week high for daily new cases occurred on June 26. More than 1,200 Californians are still hospitalized with COVID-19, with nearly 300 of those in the ICU. Since the beginning of July, 236 Californians have died of COVID-19.

Age of Confirmed COVID-19 Cases

Date	0-17 yrs Total	0-17 New Cases	18-49 yrs Total	18-49 New Cases	50-64 yrs Total	50-64 New Cases	65+ yrs Total	65+ New Cases	Unknown Total	Unknown New Cases
6/4/21	480,556	170	2,114,286	621	700,579	150	390,021	111	2,294	-5
6/5/21	480,743	187	2,114,961	675	700,764	185	390,135	114	2,290	-4
6/6/21	480,976	233	2,115,563	602	700,952	188	390,210	75	2,293	3
6/7/21	481,150	174	2,116,061	498	701,074	122	390,290	80	2,293	0
6/8/21	481,286	136	2,116,510	449	701,212	138	390,359	69	2,293	0
6/9/21	481,433	147	2,116,998	488	701,346	134	390,436	77	2,293	0
6/10/21	481,576	143	2,117,480	482	701,491	145	390,522	86	2,293	0
6/11/21	481,772	196	2,118,129	649	701,671	180	390,637	115	2,289	-4
6/12/21	481,965	193	2,118,723	594	701,826	155	390,722	85	2,294	5
6/13/21	482,126	161	2,119,276	553	701,972	146	390,812	90	2,286	-8
6/14/21	482,291	165	2,119,756	480	702,101	129	390,866	54	2,285	-1
6/15/21	482,406	115	2,120,111	355	702,212	111	390,912	46	2,286	1
6/16/21	482,524	118	2,120,523	412	702,312	100	390,983	71	2,284	-2
6/17/21	482,663	139	2,121,032	509	702,429	117	391,045	62	2,286	2
6/18/21	482,875	212	2,121,782	750	702,635	206	391,170	125	2,288	2
6/21/21	483,430	555	2,123,729	1,947	703,148		391,407		2,291
6/22/21	483,563	133	2,124,094	365	703,245	97	391,455	48	2,283	-8
6/23/21	483,694	131	2,124,566	472	703,375	130	391,507	52	2,285	2
6/24/21	483,875	181	2,125,416	850	703,600	225	391,652	145	2,303	18
6/25/21	484,111	236	2,126,605	1,189	703,957	357	391,870	218	2,318	15
6/28/21	484,900	789	2,129,631	3,026	704,847	890	392,338	468	2,355	37
6/29/21	485,075	175	2,130,090	459	704,938	91	392,372	34	2,338	-17
7/1/21	484,868	0	2,128,890	0	704,243	0	391,847	0	2,304	-34
7/2/21	485,148	280	2,130,049	1,159	704,468	225	391,977	130	2,302	-2
7/3/21	485,404	256	2,130,959	911	704,658	189	392,053	76	2,302	0
7/4/21	485,660	256	2,131,870	911	704,847	189	392,129	76	2,302	0
7/5/21	485,916	256	2,132,781	911	705,036	189	392,205	76	2,302	0
7/6/21	486,172	256	2,133,692	911	705,225	189	392,281	76	2,304	2
7/7/21	486,371	199	2,134,547	855	705,414	189	392,368	87	2,306	2

An examination of cases broken down by age group reveals that the 18-49 age group continues to have the highest rate of infection. There was a marked increase in new daily cases in this age group from June 15 to June 18, with moderate increases for the other three age groups.

Despite the availability of vaccines for children 12 and up, in California, we have not seen a marked decrease in the number of new cases in children over the past two weeks. From June 19 to July 2, the 0-17 age group averaged 276 new infections per day, a 69% increase compared to the previous 14-day period. (The daily average for June 4-18 was 163.) As of June 30, the California Department of Public Health reports 4 COVID-19 deaths in children under the age of 5 and 19 deaths in children ages 5-17. To date, 486,371 children in California have been infected with COVID-19. The US Census Bureau estimates that there are 8,890,250 children in California, so approximately 5.4% of children have had a documented case of COVID-19.

Watching World Data

Location	Total Infections as of 7/02/21	New Infections on 7/02/21	Total Deaths	New Deaths on 7/02/21	% of Pop.Infected	SARS-CoV-2 Isolates Currently Known in Location	National/ State Mask Mandate?	Currently in Lockdown?
World	183,836,958(5,248,302 new infections in 14 days)	437,548	3,979,868(113,224 new deaths in 14 days)	8,495	2.35%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines)	No	No
USA	34,580,198 (ranked #1)	18,399	621,161 (ranked #1)	322	10.38%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)	No	No
Brazil	18,687,469(ranked #3)	65,165(ranked #1)	522,068(ranked #2)	1,879	8.72%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)	No	No
India	30,501,189(ranked #2)	47,252(ranked #2)	401,068(ranked #3)	787	2.18%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)APTK India VOC 32421Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)	No	No
United Kingdom	4,855,169(ranked #7)	27,125	128,189	27	7.11%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)	No	No
California, USA	3,700,750(ranked #13 in world)	1,295	62,622	57	9.66%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)	No	No
Mexico	2,525,350(ranked #15)	6,081	233,248(ranked #4)	201	1.93%	B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)	No	No
South Africa	2,019,826(ranked #19)	24,270	621,322	303	3.36%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)	No	No
Canada	1,416,317(ranked #24)	1,007	26,338	43	3.72%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)	Yes, except Alberta Province	No
Poland	2,880,4107(ranked #14)	96	75,065	21	7.61%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)	No	No
Turkey	5,435,831(ranked #6)	4,891	49,829	27	6.37%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Lambda/C.37 (Peru)	No	No
Russia	5,561,360(ranked #5)	23,218	136,565	679	3.80%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)	No	No
Argentina	4,512,439(ranked #8)	20,888	95.382	610	9.69%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gama/P.1 (Brazil)Delta/B.1.617.2 (India)Lambda/C.37 (Peru)	No	No
Colombia	4,512,302(ranked #9)	28,005	107,723	5586	8.35%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)	No	No
Peru	2,060,344(ranked #18)	2,790	192,902(ranked #5)	215	6.16%	B2 lineageAlpha/B.1.1.7 (UK)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)	No	No
Indonesia	2,228,938(ranked #17)	25,830	59,534	539	10.8%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Eta/B.1.525 (Nigeria/UK)Theta/P.3 (Philippines) Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)	No	No

*Also referred to as CAL.20C

SARS-CoV-2, Children, and MIS-C/PIMS

I’m pleased to see that COVID-19 cases and MIS-C (PIMS) cases in children in the US are finally getting national attention. The CDC now tracks total MIS-C cases and deaths in children and young adults up to 20 years old in the United States. As of June 28, CDC reported 4,196 cases of MIS-C that meet the case definition and 37 deaths—that’s 178 new cases and one new death since the June 2 report. The CDC notes, “As of October 1, the number of cases meeting the case definition for multisystem inflammatory syndrome in children (MIS-C) in the United States surpassed 1,000. As of February 1, this number surpassed 2,000, and exceeded 3,000 as of April 1.” This means it took seven months to reach 1,000 MIS-C cases, only four months to reach an additional 1,000 cases, and only two months to add an additional 1,185 cases. This suggests to us that variants are causing more MIS-C.

Date of Reporting	Total MIS-C Patients	Change Since Last Report	Total MIS-C Deaths	Change Since Last Report
6/28/2021	4196	+178	37	+1
6/2/2021	4018	+276	36	+1
5/3/2021	3742	+557	35	-1
3/29/2021	3185	+568	36	+3
3/1/2021	2617	—	33	—

Schools in the United States have been open throughout the pandemic, with teachers and education support professionals demonstrating their extraordinary ability to adapt in adverse circumstances. Teachers all over the country reinvented their teaching, taking their classrooms online in order to provide safe and remote learning experiences for students. The so-called “reopening” of schools, which more accurately refers to the opening of school buildings, as schools never closed, has been highly politicized, with many governors issuing mandates for in-person instruction, even as case counts, hospitalizations, and deaths in their states rose exponentially. The CDC has maintained that transmission risk in schools is minimal, provided that adequate safety measures are taken; however, we know that many states have not properly enforced universal masking (and some are repealing mask mandates this week), and we know that many school facilities are not equipped with the proper air handling systems. With more school buildings opening, there is a growing body of research that suggests that COVID-19 transmission can and does happen in schools.

After recommending for months that school buildings be open, in mid-February (a year into the pandemic), The American Academy of Pediatrics, in collaboration with the Children’s Hospital Association, finally began tracking data on COVID-19 in children at the state and national level. Data reporting by states is still voluntary, and every state is different in its willingness to collect and disclose data on infections, hospitalizations, deaths, and testing rates in children.

As of the APA’s July 1 report, only 11 states provide age distribution for testing. This makes it difficult to hold states accountable for testing each age group in proportion to its population. We’ve seen a trend in states where testing data with age distribution is available that children are tested at lower rates than adults. Hospitalization data by age group is only available in 24 states and New York City, so we only understand the severity of COVID-19 infections in children for about half the country. Age distribution for cases is provided by 49 states, New York City, the District of Columbia, Puerto Rico, and Guam. Age distribution for deaths is provided in 43 states, New York City, Puerto Rico, and Guam. It’s worth noting that New York State does not provide age data for cases, testing, hospitalizations, and deaths. Two states, Florida and Utah, only report cases in children aged 0-14, so the number of cases, hospitalizations, and deaths in children ages 15-17 is unknown in these states.

As of July 1, children represented 14.2% of all COVID-19 cases reported to APA. A total of 335 child deaths due to COVID-19 were reported in 43 states. The following states do not report child mortality due to COVID-19: Michigan, Montana, New Mexico, New York, Rhode Island, South Carolina, and West Virginia.

If we truly want to keep children safe, especially as many school buildings open for in-person instruction, we need to collect more complete data in every state on child testing rates, cases, hospitalizations, and deaths.

Vaccinating America’s Children

The New York Times reports that nationally, 55.6% of people 12 and up are fully vaccinated, while 58.4% of people 18 and up are fully vaccinated, according to the CDC. Only 47.5% of the total population is fully vaccinated.

Some states are falling far behind when it comes to getting children—and the general population—fully vaccinated. Alabama and Mississippi have only fully vaccinated 33% of their population. Vermont, Maine, Massachusetts, and Connecticut have fully vaccinated more than 60% of their population, with Vermont having the highest vaccination rate at 74%. California has fully vaccinated 51% of their population.

The Road Ahead

President Biden has made the pandemic a first priority and has now ordered enough vaccines to vaccinate everyone who wants a vaccination by the end of this month. As of 7/7/21, the CDC reports that 182.8 million people (approximately 55.1% of the population) have had one dose of any vaccine. 157.9 million people (47.6% of the population) are fully vaccinated. The rate of people who are fully vaccinated has increased by less than 3% in the past two weeks.

As of May 10, all people in the U.S. over the age of 12 are eligible to receive a vaccine. The Biden administration has already exceeded its goal of administering 200 million doses of vaccine in the first 100 days of the administration. The Pfizer-BioNtech is already approved for ages 12-15 and the Moderna vaccine should be approved in June 2021. Moderna has applied for emergency use authorization to administer their mRNA vaccines to children aged 12-15. Testing is ongoing for children in younger age groups and may be approved for ages 2-11 by the end of September 2021.

Testing, wearing masks, social distancing and washing our hands frequently should no longer be political issues. These are non-pharmaceutical interventions used by most successful countries and some states to protect their citizens and their economies. New Zealand, Taiwan, and Australia are three countries that have done this successfully. In the United States, Hawaii is doing a better job handling the pandemic than many of our states. These interventions and vaccination should keep the pandemic from overwhelming our health care delivery systems world-wide. New mutations like Epsilon/B.1.427 + B.1.429 and the Alpha, Beta, Gamma, and Delta variants will probably spread rapidly throughout the United States over the next 90 days as many states (ex. Texas, Florida, Iowa, Mississippi, Wyoming and South Carolina) open up everything and do away with masking and social distancing. We will probably see increased new infections per day in the United States. In the UK, Alpha/B.1.1.7, has increased the number of infections, hospitalizations and deaths. This and other mutants may do the same thing in the USA.

The Pfizer and Moderna RNA vaccines and the Johnson & Johnson single dose vaccination adenovirus vaccine are all being used to immunize people in the USA. The Oxford-AstraZeneca vaccine and the Novavax vaccine may be available in the fourth quarter of 2021.

The bad news is that all currently available vaccines are based on the spike protein sequence identified in China in December 2019. Mutated isolates, as discussed above, may overtake our ability to produce new vaccines and vaccinate the populace. Like Influenza vaccines, we may have to reformulate vaccines based on active, worldwide surveillance at least every 4 to 6 months. The FDA is currently putting together a guidance document for how to develop booster vaccines for SARS-CoV-2 mutations. A surrogate marker of protection like antibody to the mutated Receptor Binding Domains of SARS-CoV-2 should be considered for vaccine approval.

The ideal approach to addressing the major mutations on at least five continents would be to make vaccines against each of the mutations. I’d get all of the vaccine companies and contract production companies on a call and “suggest” that two companies at least make and mass produce one of the four mutations. The government would pay the cost and buy at least 200 million doses in advance for each variant at say $40 a dose. The total cost to purchase the vaccine (800 million doses) would only be 32 billion dollars. Give each company a billion dollars each for development costs (another 8 billion dollars). Spend another two billion dollars for syringes and you’ve got enough booster doses to vaccinate 200 million people for all 4 variants. 42 billion dollars would be a small price to pay to catch up with the current mutations. Even if you had to do this every two years, it would be well worth the dollars spent.

We are not doing adequate numbers of PCR or antigen detection assays in the United States. According to JHU, in January of 2021, we were doing up to 2,307,949 tests per day. In March 2021, the highest number of tests per day was 1,709,210, and in April, the highest number of tests per day was 2,008,319. Currently, we’re doing 444,718 tests per day (7-day moving average); that’s 1,563,601 fewer tests per day than the April high.

We still need to perform more virus isolations and perform more DNA sequencing of viruses in each country, state, populous city, and county if we are to rapidly identify new mutations. In December 2020, WHO asked countries to increase their sequencing rates, and the European Commission asked member states to set a goal of 10%. The CDC then set a goal of 5% for the United States. At the end of June 2021, the United States had a SARS-CoV-2 genome sequencing rate of 1.69%, whereas the United Kingdom had a genome sequencing rate of 10.2%. I’m more hopeful that we will have the facilities, the equipment, and the trained staff needed to perform this work. As a nation we still need to make and distribute more vaccines to other countries, new vaccines directed against mutants, and the necessary rapid tests and protective equipment needed by medical staff, first responders, essential workers and especially teachers and students. I’m still hopeful we can work together on our and the world’s infectious disease problems.

What Our Team Is Reading This Week

85 teens, staffers get coronavirus at summer camp that didn’t require masks or check vaccine status (Washington Post) https://www.washingtonpost.com/health/2021/06/30/illinois-summer-camp-coronavirus-outbreak/
Nosocomial Outbreak of COVID-19 in a Hematologic Ward (Infection & Chemotherapy) https://icjournal.org/DOIx.php?id=10.3947/ic.2021.0046#F1
Missouri becomes hot spot for Delta variant fueling hospitalizations while vaccination efforts lag (CNN) https://www.cnn.com/2021/06/24/us/missouri-covid-19-delta-variant-vaccine/index.html
COVID-19: Latest Oklahoma case count reveals 737 breakthrough infections as state virus totals rise 36% (Tulsa World) https://tulsaworld.com/news/state-and-regional/covid-19-latest-oklahoma-case-count-reveals-737-breakthrough-infections-as-state-virus-totals-rise/article_82f01d30-d8f1-11eb-9b5a-bba9b4f7b185.html
First case of delta-plus, ‘double-whammy’ variant of COVID, detected in Louisiana (NOLA.com) https://www.nola.com/news/coronavirus/article_9d92b250-d9d3-11eb-82ec-8f68de6a04d4.html
Delta variant triggers dangerous new phase in the pandemic (Science) https://www.sciencemag.org/news/2021/06/delta-variant-triggers-dangerous-new-phase-pandemic
Increased transmissibility and global spread of SARS-CoV-2 variants of concern as at June 2021 (Eurosurveillance) https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.24.2100509
What we know about the ‘fleeting’ spread of the COVID-19 Delta variant in Sydney (ABC News) https://www.abc.net.au/news/2021-06-24/covid-delta-kappa-variant-spread-in-fleeting-moment-nsw-vic/100238680
Covid in Scotland: Raigmore Hospital at capacity amid rising cases (BBC) https://www.bbc.com/news/uk-scotland-highlands-islands-57735232
SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness (The Lancet) https://doi.org/10.1016/S0140-6736(21)01358-1
Drop in childhood vaccinations during pandemic may raise risk of other outbreaks when schools reopen, CDC says (Washington Post) https://www.washingtonpost.com/health/2021/06/10/childhood-vaccination-falloff-increased-risk-disease-outbreaks/
CDC COVID-19 State and County Forecasts, July 5, 2021 https://www.cdc.gov/coronavirus/2019-ncov/downloads/science/forecasting/cases/july2021/Consolidated-Cases-Forecasts-2021-07-05.pdf
Vaccination Is Making America Forget a Basic Pandemic Rule (The Atlantic) https://www.theatlantic.com/health/archive/2021/06/individualism-still-spoiling-pandemic-response/619133/
Gangrene, Hearing Loss Show Delta Variant May Be More Severe (Bloomberg) https://www.bloomberg.com/news/articles/2021-06-07/gangrene-hearing-loss-point-to-delta-variant-being-more-severe

COVID-19

SARS-CoV-2 Update

06/22/202106/26/2021 davidcwrightmd

In the United States, SARS-CoV-2 deaths have decreased for the tenth time in a 14-day period. There were 170 fewer deaths per day than in the last 14-day period. In the last 14 days, the number of infections has decreased by 4,978 infections per day. Our infections per day are still high, probably secondary to SARS-CoV-2 mutants, to include the Alpha/B.1.1.7 isolate, the Iota/B.1.526 isolate, the Epsilon/B.1.427 + B.1.429 isolate, the Beta/B.1.351 isolate, the Gamma/P.1 and Zeta/P.2 isolates, and the new isolate, Deta/B.1.617+. I would predict that the opening of schools, places of worship, bars, restaurants, indoor dining and travel all will contribute to further spread of multiple SARS-CoV-2 mutants and rising numbers in infections, hospitalizations and deaths in the coming months. Increased traveling as well as summer vacations, and the July 4 holiday will all cause further increases. Vaccinations, increased mask usage and social distancing, which are a part of the Biden SARS-CoV-2 plan (day 150 of plan) will be necessary to stop spread of mutants and cause further reductions in infections, hospitalizations and deaths in the future. On 6/18/21, the United States had 13,389 new infections. There were also 393 deaths. The number of hospitalized patients is decreasing, but 4,160 patients are still seriously or critically ill. The number of critically ill patients has decreased by 1,378 in the last 14 days, while 4,200 new deaths occurred. The number of critically ill patients is decreasing for the fifth 14-day period, but a large number of patients are still dying each day (average 300/day).

As of 6/18/21, we have had 616,920 deaths and 34,393,269 SARS-CoV-2 infections in the United States. We have had 201,569 new infections in the last 14 days. We are adding an average of 100,785 infections every 7 days. Each million infections usually results in 10,000 to 20,000 deaths. On 6/18/21, twenty-two states have had greater than 500,000 total infections, and 33 states have had greater than 5,000 total deaths. Ten states (Ohio, Michigan, Georgia, Illinois, New Jersey, Pennsylvania, Florida, Texas, New York and California) have had greater than 20,000 deaths. Four states (Florida, Texas, New York and California) have had greater than 35,000 deaths. In the world, 42 other countries have greater than 500,000 infections and 58 other countries have greater than 5,000 deaths.

As of 6/18/21, in the United States, 10.33% of the population has had a documented SARS-CoV-2 infection. In the last 8 months, over 7% of our country became infected with SARS-CoV-2.

As of 6/18/21, California was ranked 36th in infection percentage at 9.63%. In North Dakota 14.50% of the population was infected (ranked #1), while Rhode Island was at 14.38% (ranked #2) and South Dakota was at 14.06% of the population infected (ranked #3). Thirty-one states have greater than 10% of their population infected and 42 states have greater than 9% of their population infected. Only one state has less than 3% of their population infected: Hawaii (2.62%).

The Threat of SARS-CoV-2 Variants

The WHO has sorted variants into two categories: Variants of Concern (VOC) and Variants of Interest (VOI). The criteria for Variants of Concern are as follows:

Increase in transmissibility or detrimental change in COVID-19 epidemiology; or
Increase in virulence or change in clinical disease presentation; or
Decrease in effectiveness of public health and social measures or available diagnostics, vaccines, therapeutics.

The WHO categorizes the following four variants as Variants of Concern (VOC):

The criteria for Variants of Interest (VOI) are as follows:

has been identified to cause community transmission/multiple COVID-19 cases/clusters, or has been detected in multiple countries; OR
is otherwise assessed to be a VOI by WHO in consultation with the WHO SARS-CoV-2 Virus Evolution Working Group.

The WHO categorizes the following six variants as Variants of Interest (VOI):

The two variants of concern that have garnered most of our attention recently are Alpha (B.1.1.7) and Delta (B.1.617.2). Alpha, first detected in the United Kingdom in September of 2020, has been detected in almost every country and all 50 states in the U.S. On May 22, 2021, the CDC reported that Alpha made up approximately 69% of COVID-19 cases in the previous two weeks.

The Delta variant (B.1.617.2), first identified in India, is on track to overtake Alpha (B.1.1.7) as the dominant variant worldwide. In the past month, it accounted for 96% of isolations in India, 87% of isolations in the United Kingdom, 92% in Singapore, 84% in Russia, 40% in Israel, and 33% in Australia. In the United States, Delta accounted for 12.9% of isolations in the past four weeks, compared to 3.7% two weeks ago. This suggests the proportion of Delta cases is nearly doubling every week. At this rate, Delta will become the dominant variant in the U.S. by mid-July.

On 4/10/21, the CDC stopped providing data to the public on the number of reported cases of all variants of SARS-CoV-2, both nationally and by state. This data used to be available at https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant-cases.html. The CDC claims that the data is available in its COVID-19 Data Tracker, but only percentages, not actual case numbers, are available, and the data ends on May 22, 2021.

Luckily, GISAID is still reporting variant data. The United States has had 3,145 isolations of the Alpha variant (B.1.1.7) in the last four weeks and there have been a total of 181,209 cases of Alpha/B.1.1.7 identified in the US to date. (See chart below.)

For the Delta (B.1.617.2) variant, only India and the United Kingdom have more isolated cases than in the United States, which has 3,564 total cases, 916 of which were identified in the last four weeks. The UK, in the last 7 days, has had 58,830 new infections and 78 new deaths. The preceding week had 44,009 new infections and 55 deaths. We know that this is because of the increase in prevalence of the Delta variant. According to Public Health England, “numbers of the Delta (VOC-21APR-02) variant in the UK have risen by 33,630 since last week to a total of 75,953. The most recent data show 99% of sequenced and genotyped cases across the country are the Delta variant.” In the United States the prevalence of the Delta variant increased from 4% of isolates to 10% of isolates in one week.

At 2,130 cases, the United States has the fourth highest number of isolations of the Beta variant (B.1.351, first identified in South Africa), and 21 of these were in the last four weeks.

And the United States still has now the most isolations of the Gamma variant (P.1) in the world, with 16,208 overall and 735 in the past four weeks.

COVID-19 in California

The following data were reported by the California Department of Public Health:

Date	Total Cases	New Cases	Total Deaths	New Deaths	Hospitalized	In ICU	Fully Vaccinated
6/4/21	3,687,736	1,047	62,179	87	1,062	260	17,662,712
6/5/21	3,688,893	1,157	62,242	63	1,042	243	17,813,305
6/6/21	3,689,994	1,101	62,470	228	1,035	221	17,947,342
6/7/21	3,690,868	874	62,473	3	1,011	219	18,011,744
6/8/21	3,691,660	792	62,479	6	1,015	228	18,100,412
6/9/21	3,692,506	846	62,499	20	1,030	231	18,240,912
6/10/21	3,693,362	856	62,538	39	1,001	234	18,431,265
6/11/21	3,694,498	1,136	62,593	55	982	233	18,542,484
6/12/21	3,695,530	1,032	62,508	-85	955	240	18,637,504
6/13/21	3,696,472	942	62,512	4	915	241	18,694,365
6/14/21	3,697,299	827	62,505	-7	939	239	18,731,215
6/15/21	3,697,927	628	62,515	10	977	251	18,875,034
6/16/21	3,698,626	699	62,534	19	981	242	18,970,053
6/17/21	3,699,455	829	62,565	31	956	232	19,074,396
6/18/21	3,700,750	1,295	62,622	57	951	233	19,164,548

California dropped its mask mandate and most public space capacity limits on June 15. Over the past two weeks, daily new cases in California have hovered between 792 and 1,295. The two-week high for daily new cases occurred on June 18. More than 900 Californians are still hospitalized with COVID-19, with more than 200 of those in the ICU.

Age of Confirmed COVID-19 Cases in California

Date	0-17 yrs Total	0-17 New Cases	18-49 yrs Total	18-49 New Cases	50-64 yrs Total	50-64 New Cases	65+ yrs Total	65+ New Cases	Unknown Total	Unknown New Cases
6/4/21	480,556	170	2,114,286	621	700,579	150	390,021	111	2,294	-5
6/5/21	480,743	187	2,114,961	675	700,764	185	390,135	114	2,290	-4
6/6/21	480,976	233	2,115,563	602	700,952	188	390,210	75	2,293	3
6/7/21	481,150	174	2,116,061	498	701,074	122	390,290	80	2,293	0
6/8/21	481,286	136	2,116,510	449	701,212	138	390,359	69	2,293	0
6/9/21	481,433	147	2,116,998	488	701,346	134	390,436	77	2,293	0
6/10/21	481,576	143	2,117,480	482	701,491	145	390,522	86	2,293	0
6/11/21	481,772	196	2,118,129	649	701,671	180	390,637	115	2,289	-4
6/12/21	481,965	193	2,118,723	594	701,826	155	390,722	85	2,294	5
6/13/21	482,126	161	2,119,276	553	701,972	146	390,812	90	2,286	-8
6/14/21	482,291	165	2,119,756	480	702,101	129	390,866	54	2,285	-1
6/15/21	482,406	115	2,120,111	355	702,212	111	390,912	46	2,286	1
6/16/21	482,524	118	2,120,523	412	702,312	100	390,983	71	2,284	-2
6/17/21	482,663	139	2,121,032	509	702,429	117	391,045	62	2,286	2
6/18/21	482,875	212	2,121,782	750	702,635	206	391,170	125	2,288	2

New daily COVID-19 cases in the 0-17 age group hovered between 115 and 233. It’s worth noting that new cases did not steadily decrease among this or any age group over the past 14 days.

Despite the availability of vaccines for children 12 and up, in California, we have not seen a marked decrease in the number of new cases in children over the past two weeks. There have been an average of 166 new infections in children per day for the past 14 days, with 212 new infections on June 12. As of June 18, in California, 482,875 children have been infected. The US Census Bureau estimates that there are 8,890,250 children in California, so approximately 5.4% of children have been infected with COVID-19.

Watching World Data

Location	Total Infections as of 6/18/21	New Infections on 6/18/21	Total Deaths	New Deaths on 6/18/21	% of Pop.Infected	SARS-CoV-2 Isolates Currently Known in Location	National/ State Mask Mandate?	Currently in Lockdown?
World	178,588,656	401,096	3,866,644	8,524	2.29%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines)	No	No
USA	34,393,269 (ranked #1)	13,389	616,920 (ranked #1)	393	10.33%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)	No	No
Brazil	17,802,176(ranked #3)	98,135(ranked #1)	498,621(ranked #2)	2,449	8.31%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)	No	No
India	29,822,764(ranked #2)	60,800(ranked #2)	385,167(ranked #3)	1,269	2.14%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)APTK India VOC 32421Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)	No	No
United Kingdom	4,610,893(ranked #7)	10.476	127,956	11	6.75%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)	No	No
California, USA	3,700,750(ranked #13 in world)	1,295	62,622	57	9.67%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)	No	No
Mexico	2,467,643(ranked #15)	4,253	230,792(ranked #4)	168	1.89%	B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)	No	No
South Africa	1,796,589(ranked #19)	10,510	58,441	118	2.99%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)	No	No
Canada	1,407,269(ranked #23)	1,016	26,023	11	3.69%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)	Yes, except Alberta Province	No
Poland	2,878,466(ranked #14)	190	74,782	48	7.61%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)	No	No
Turkey	5,359,,728(ranked #5)	5,575	49,071	59	6.28%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Lambda/C.37 (Peru)	No	No
Russia	5,281,309(ranked #6)	17,262	128,445	453	3.61%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)	No	No
Argentina	4,242,763(ranked #9)	20,363	88,247	458	9.30%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gama/P.1 (Brazil)Delta/B.1.617.2 (India)Lambda/C.37 (Peru)	No	No
Colombia	3,886,614(ranked #10)	28,790	98,746	590	7.56%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)	No	No
Peru	2,023,179(ranked #17)	3,463	189,933(ranked #5)	176	6.05%	B2 lineageAlpha/B.1.1.7 (UK)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)	No	No

*Also referred to as CAL.20C

SARS-CoV-2, Children, and MIS-C/PIMS

I’m pleased to see that COVID-19 cases and MIS-C (PIMS) cases in children in the US are finally getting national attention. The CDC now tracks total MIS-C cases and deaths in children and young adults up to 20 years old in the United States. As of June 2, CDC reported 4,018 cases of MIS-C that meet the case definition and 36 deaths—that’s 276 new cases and one new death since the May 3 report. The CDC notes, “As of October 1, the number of cases meeting the case definition for multisystem inflammatory syndrome in children (MIS-C) in the United States surpassed 1,000. As of February 1, this number surpassed 2,000, and exceeded 3,000 as of April 1.” This means it took seven months to reach 1,000 MIS-C cases, only four months to reach an additional 1,000 cases, and only two months to add an additional 1,185 cases. This suggests to us that Alpha/B.1.1.7 is causing more MIS-C.

Date of Reporting	Total MIS-C Patients	Change Since Last Report	Total MIS-C Deaths	Change Since Last Report
6/2/2021	4018	+276	36	+1
5/3/2021	3742	+557	35	-1
3/29/2021	3185	+568	36	+3
3/1/2021	2617	—	33	—

As of the APA’s June 10 report, only 11 states provide age distribution for testing. This makes it difficult to hold states accountable for testing each age group in proportion to its population. We’ve seen a trend in states where testing data with age distribution is available that children are tested at lower rates than adults. Hospitalization data by age group is only available in 24 states and New York City, so we only understand the severity of COVID-19 infections in children for about half the country. Age distribution for cases is provided by 49 states, New York City, the District of Columbia, Puerto Rico, and Guam. Age distribution for deaths is provided in 43 states, New York City, Puerto Rico, and Guam. It’s worth noting that New York State does not provide age data for cases, testing, hospitalizations, and deaths. Two states, Florida and Utah, only report cases in children aged 0-14, so the number of cases, hospitalizations, and deaths in children ages 15-17 is unknown in these states.

As of June 10, children represented 14.1% of all COVID-19 cases reported to APA. A total of 330 child deaths due to COVID-19 were reported in 43 states (an increase of 3 child deaths in one week). The following states do not report child mortality due to COVID-19: Michigan, Montana, New Mexico, New York, Rhode Island, South Carolina, and West Virginia. Texas only reports age data for 3% of confirmed COVID-19 cases, so state-level data from Texas is extremely limited for assessing the incidence of COVID-19 in children. Even considering this, Texas reported 54 (+1) child deaths. Arizona reported 33, California 23, Colorado 15, Florida 7, Georgia 10, Illinois 20 (+1), Maryland 10, Tennessee 10, Massachusetts 8, Pennsylvania 11, and New York City 25 (+1).

The New York Times reports that nationally, 52% of people 12 and up are fully vaccinated, while 55% of people 18 and up are fully vaccinated, according to the CDC. Only 45% of the total population is fully vaccinated.

Some states are falling far behind when it comes to getting children—and the general population—fully vaccinated. Mississippi, Alabama, Arkansas, Wyoming, Louisiana, and Tennessee have fully vaccinated less than 35% of their population. Vermont, Maine, Massachusetts, Connecticut, Rhode Island, New Hampshire, New Jersey, Maryland, Washington, New Mexico, New York, Oregon, and Hawaii have fully vaccinated more than 50% of their population, with Vermont having the highest vaccination rate at 64%. California has fully vaccinated 48% of their population.

The Road Ahead

We are on Day 150 of the Biden-Harris administration.The President has made the pandemic a first priority and has now ordered enough vaccines to vaccinate everyone who wants a vaccination by July 2021. As of 6/18/21, the CDC reports that 176.7 million people (approximately 53.2% of the population) have had one dose of any vaccine. 149.1 million people (44.9% of the population) are fully vaccinated. The rate of people who are fully vaccinated has only increased by 3% in the past two weeks.

We still need to perform more virus isolations and perform more DNA sequencing of viruses in each country, state, populous city, and county if we are to rapidly identify new mutations. I’m more hopeful that we will have the facilities, the equipment, and the trained staff needed to perform this work. As a nation we still need to make and distribute more vaccines to other countries, new vaccines directed against mutants, and the necessary rapid tests and protective equipment needed by medical staff, first responders, essential workers and especially teachers and students. I’m still hopeful we can work together on our and the world’s infectious disease problems.

What Our Team Is Reading This Week

SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness (The Lancet) https://doi.org/10.1016/S0140-6736(21)01358-1
Trajectory of Growth of SARS-CoV-2 Variants in Houston, Texas, January through May 2021 Based on 12,476 Genome Sequences (Preprint) https://www.medrxiv.org/content/10.1101/2021.05.20.21257552v3
Evolution of enhanced innate immune evasion by the SARS-CoV-2 B.1.1.7 UK variant (Preprint) https://doi.org/10.1101/2021.06.06.446826
How the ‘Alpha’ Coronavirus Variant Became So Powerful (NY Times) https://www.nytimes.com/2021/06/07/health/covid-alpha-uk-variant.html
Drop in childhood vaccinations during pandemic may raise risk of other outbreaks when schools reopen, CDC says (Washington Post) https://www.washingtonpost.com/health/2021/06/10/childhood-vaccination-falloff-increased-risk-disease-outbreaks/
CDC COVID-19 State and County Forecasts, June 7, 2021 https://www.cdc.gov/coronavirus/2019-ncov/downloads/science/forecasting/cases/june2021/Consolidated-Cases-Forecasts-2021-06-07.pdf
Vaccination Is Making America Forget a Basic Pandemic Rule (The Atlantic) https://www.theatlantic.com/health/archive/2021/06/individualism-still-spoiling-pandemic-response/619133/
Pandemics End When We Stop Caring About Their Victims (The Atlantic) https://www.theatlantic.com/ideas/archive/2021/06/pandemics-end-when-we-stop-caring-about-their-victims/619127/
A fully vaccinated cruise set sail in the Caribbean. Two passengers just tested positive for covid. (Washington Post) https://www.washingtonpost.com/travel/2021/06/10/cruise-covid-celebrity-vaccine/
Gangrene, Hearing Loss Show Delta Variant May Be More Severe (Bloomberg) https://www.bloomberg.com/news/articles/2021-06-07/gangrene-hearing-loss-point-to-delta-variant-being-more-severe
Southern California hospitals don’t require vaccines as condition of employment (Daily News) https://www.dailynews.com/2021/06/11/southern-california-hospitals-dont-require-vaccines-as-condition-of-employment/
Increased Interseasonal Respiratory Syncytial Virus (RSV) Activity in Parts of the Southern United States (CDC) https://emergency.cdc.gov/han/2021/han00443.asp
Novavax’s coronavirus vaccine is 90 percent effective, study finds (Washington Post) https://www.washingtonpost.com/health/2021/06/14/novavax-coronavirus-vaccine-effective/
NIH study suggests coronavirus may have been in U.S. as early as December 2019 (Washington Post) https://www.washingtonpost.com/health/when-was-coronavirus-first-in-us/2021/06/15/1aaa6b56-cd2d-11eb-8cd2-4e95230cfac2_story.html
Many Post-Covid Patients Are Experiencing New Medical Problems, Study Finds (NY Times) https://www.nytimes.com/2021/06/15/health/covid-19-patients.html
‘This gives hope’: A third COVID-19 vaccine dose can boost protection for organ transplant recipients (Science Magazine) https://www.sciencemag.org/news/2021/06/gives-hope-third-covid-19-vaccine-dose-can-boost-protection-organ-transplant-recipients
A Deadly Super-Fungus Has Emerged in Brazil, Aided by Covid-19 (Gizmodo) https://gizmodo.com/a-deadly-super-fungus-has-emerged-in-brazil-aided-by-c-1847102045
Covid-19: Irish scientists discover link to life threatening blood clots (BBC) https://www.bbc.com/news/world-europe-57484740?piano-modal