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.

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.

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

12/04/2022 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.

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SARS-CoV-2 infections per day in the United States have increased for the second time in 16 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 decreased by 54 deaths per day. Many states are not reporting deaths or infections in a timely manner. The number of infections per day has increased by 494. In late November of this year, the National Institutes of Health launched MakeMyTestCount.org, a website that allows users to anonymously report the results of at-home COVID tests. Unfortunately, it has thus far not been widely publicized.

Drug-Evading Mutants Continue to Dominate the Variant Soup

On 12/3/22 the CDC estimates that BA.5 accounted for 13.8% of infections (a 38.6% drop from 10/21/22), BQ.1 accounted for 30.9% (a 21.5% increase since 10/21/22), BQ.1.1 accounted for 31.9% (a 24.77% increase since 10/21/22), BA.4.6 accounted for 2.3% (a 7.2% decrease from 10/21/22), BF.7 accounted for 6.3% (a 2.7% decrease from 10/21/22), BN.1 accounted for 4.6% of isolates (a 0.5% decrease since 1/19/22), and BA.2.75.2 accounted for 0.5%. In the last two weeks, three isolates were added to the CDC’s reporting: XBB (5.5% of isolates), BA.5.2.6 (1.8%), and BF.11 (0.9%). In the week ending December 3, 2022, BQ isolates accounted for 62.8% of infections (a 27.5% increase in infections caused by these BQ variants since 10/21/22). 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.

The total percentage of BQ variant infections in the region that includes New York and New Jersey was 64.8% two weeks ago and is now 72.4%. BA.5 accounts for 6.9% of infections, BF.7 accounts for 4.2%, BN.1 accounts for 2.4%, BA.5.2.6 accounts for 1.5%, and BA.2.75 lineages account for 1.3% of infections. Curiously, no XBB isolates are currently being reported in Region 2.

The total percentage of BQ variant infections in the region that includes California, Nevada, Arizona, and Hawaii was 36.9% two weeks ago and is now 62.6%. BA.5.2.6 isolates now account for 1.6% of cases. The BA.2.75 lineages account for 1.3%. BF.7 accounts for 5.5%, BN.1 accounts for 6.0%, and BA.2 isolates account for 1.9%. Again, CDC is not reporting XBB in Region 9.

Data on the rapid spread of a dangerous variant category, the BQ variants, was withheld by the CDC in their weekly reports until five 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. Similarly, the XBB variant wasn’t present in the CDC’s variant proportions reporting two weeks ago, but the December 3 iteration adds XBB going back at least three weeks.

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, November 4, 2022

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 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.

The November 25 UK Health Security Agency Technical Briefing identifies lineages BA.5, BA.5.2.35, BA.5.7, BQ.1, BQ.1.1, XBB, and BN1 (BA.2.75.5.1) as isolates of concern.

Variant	Sublineage of	Mutations	Global Sequences outside UK	UK Sequences
BQ.1	BA.5	L452R, N460K, K444T	33,206 (81 countries)	9,285 (> 40% of all sequenced samples)
BQ.1.1	BA.5	N460K, K444T, R346T	17,621 (70 countries)	4,715
BA.5.2.35	BA.5.2	R346T, 2 synonymous single nucleotide polymorphisms (SNPs) G28423C and C7006T	447	848
BN.1	BA.2.75.5	R346T, F490S	1,127	190
XBB	Recombinant of BJ.1 and BM.1.1.1 (both descended from BA.2), approximate break point between spike mutations G446S and N460K	E: T11A, Spike: V83A, H146Q, Q183E, F486S, F490S. Spike mutations inherited from BJ.1 are G339H, R346T, V445P, G446S and from BM.1.1.1 are N460K, F486V, F490S, and R493Q	4,831 (51 countries)	345

Disappointing Vaccine Uptake, Especially Among Children

Our monoclonal antibody therapies do not work for these isolates, but these emerging BQ variants are descendants of BA.5, so the new BA.5 bivalent vaccine should offer some protection, when combined with an N95 mask. It’s troubling that, despite the availability of this vaccine, few people are getting vaccinated. As of November 30, 2022, the CDC reports that 39,719,443 people in the United States (5 years and up) have received the bivalent vaccine. That’s only 17.4% of people who received the primary series and 12% of the overall population.

Children under the age of 5 have not been approved to receive either Omicron BA.5 mRNA booster. Sadly, in children between 0 and 5 years of age only 1.61 million have received at least one dose of any SARS-CoV-2 mRNA vaccine based on the original Wuhan isolate. In the United States, at least 1,372 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.

In Monterey County, during the pandemic we have had 96,851 reported SARS-CoV-2 infections, 3,022 hospitalizations and 797 reported deaths as of 12/3/22. The Monterey County Health Department reports that, as of 12/3/22, 3.3% of 0-4 year-olds and 40.1% of 5-11 year-olds have received the first two doses of vaccine, while 73.3% of 12-17 year-olds have received two doses. Only 55.1% 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.

Mask Up to Protect Against Additional Viral Threats This Winter

In a new preprint on respiratory syncytial virus (RSV) in young children, researchers from Case Western University write, “Among RSV-infected children in 2022, 19.2% had prior documented COVID-19 infection, significantly higher than the 9.7% among uninfected children, suggesting that prior COVID-19 could be a risk factor for RSV infection or that there are common risk factors for both viral infections.” Wearing a well-fitting, high-filtration mask not only protects against COVID but also protects against other viruses like RSV, influenza, and measles. The recent surge in respiratory infections among children that has overwhelmed hospitals around the country is most certainly a result of the removal of mask mandates throughout the United States. A new study of COVID infection data in Massachusetts public schools from February to June 2022, after many districts rescinded mask mandates, shows that “the lifting of masking requirements was associated with an additional 44.9 cases per 1000 students and staff,” compared to in schools where mask requirements were upheld. The authors explain that the districts which kept mask requirements in place were ones that tended to have less updated buildings and whose student populations had a greater percentage of low-income families, students with disabilities, English learners, and Black and Latinx students. As such, they conclude, “we believe that universal masking may be especially useful for mitigating effects of structural racism in schools, including potential deepening of educational inequities.” This is something that we’ve been saying since the beginning of the pandemic; removing nonpharmaceutical interventions always disproportionately harms the most vulnerable members of our society.

The state of Ohio has had 54 cases of measles this year, 50 of which were in the Columbus area, and 20 of which have required hospitalization. All of the infected were unvaccinated. Arstechnica reports, “Nine of the cases are in babies under the age of 1 year, who are typically not yet eligible for vaccination. Twenty-six cases are in infants ages 1 to 2 years—who are eligible for their first dose. Ten cases are in toddlers ages 3 to 5—some of whom would have been eligible for their second dose—and there are five cases in children between the ages of 6 and 17.”

As of December 1, the CDC has reported 76 cases of measles in the United States in five (undisclosed) jurisdictions. We’re certain that with no COVID mitigations for holiday travel, the measles will not remain in Ohio.

A Deeper Dive into U.S. COVID Data

On 12/2/22, the United States had 32,724 documented new infections. There were also 149 deaths. Thirty-four states did not report their infections, and 38 states didn’t report their deaths. In the United States on 12/2/22 the number of hospitalized patients (34,646) has increased (+24% compared to the previous 14 days) and was 27,868 on November 18. On 12/2/22 there were 4,005 patients who were seriously or critically ill (a 20% increase); that number was 3,362 two weeks ago. The number of critically ill patients has increased by 643 in the last 14 days, while at least 4,168 new deaths occurred. The number of critically ill patients has increased for the eighth time in thirty-two 14-day periods. Patients are still dying each day (average 298/day).

As of 11/18/22, we have had 1,106,607 deaths and 100,787,799 SARS-CoV-2 infections in the United States. We have had 631,454 new infections in the last 14 days. We are adding an average of 315,727 new infections every seven days. For the pandemic in the United States we are averaging one death for every 91.08 infections or over 10,980 deaths for each one million infections. As of 12/02/22, 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, and 33 states have greater than 3,000 deaths per million population. Eight states have over 4,000 deaths per million population: Mississippi (4,380), Arizona (4,362), Alabama (4,212), West Virginia (4,256), New Mexico (4,150), Tennessee (4,145), Arkansas (4,168) and Michigan (4,014). 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 (82,875 deaths), Texas (91,934 deaths), New York (74,288 deaths), Pennsylvania (48,387 deaths), Georgia (41,070 deaths), Ohio (40,558 deaths) , Illinois (40,339 deaths), Michigan (40,085), and California (97,515 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 (24 months), there were 839,506 new deaths from SARS-CoV-2. For twenty of those months, vaccines have been available to all adults. During these twenty months, 534,508 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 12/02/22, California was ranked 33rd in the USA in infection percentage at 29.06%. In California, 25.09% of the people were infected in the last 21 months. As of 12/2/22, 28 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.

Worldwide, average deaths per day are 1,444 for the last 14 days. The United States accounts for 20.63% (298 per day) of all deaths per day in the world over the last two weeks. Worldwide infections per day were 482,580 the last two weeks. The United States accounts for 9.34% of those infections (or 45,104 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.

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 12/2/22	New Infections on 12/2/22	Total Deaths	New Deaths on 12/2/22	% of Pop.Infected	SARS-CoV-2 Isolates Currently Known in Location	National/ State Mask Mandate	Currently in Lockdown
World	649,308,956(6,756,121 new infections in 14 days).	429,743	6,645,094(20,221 new deaths in last 14 days)	1,029	8.33%	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)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.1BN.1*	No	No
USA	100,787,779(ranked #1) 631,454 new infections in the last 14 days or 45,104/day.	32,724(ranked #5) 34 states and D,C. failed to report infections on 12/2/22.	1,106,607(ranked #1) 4,168 new deaths reported in the last 14 days or 388/day.	149 38 states and D.C. failed to report deaths on 12/2/22.	30.10%	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)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)BQ.1BQ.1.1BN.1*	No	No
Brazil	35,375,733(ranked #5) 336,119 new infections in the last 14 days.	399251 (ranked#4)	690,129(ranked #2; 1,171 new deaths in 14 days)	131	16.42%	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)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)	No	No
India	44,674,195(ranked #2); 4,668 new infections in 2 weeks.	211	530,627(ranked #3) 94 new deaths in 2 weeks.	3	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	24,024,746(ranked #6) 47,109 new infections in 2 weeks.	–	197253 (ranked #7) 1,102 new deaths in 2 weeks	–	35.07%	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	11,483,568(ranked #14 in the world; 78,380 new infections in the last 14 days).	4,819	97,515 (ranked #20 in world) 176 new deaths in the last 14 days	14	29.06%	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.1*	No	No
Mexico	7,132,792(ranked #19) 13,859 new infections in 14 days).	–	330,525(ranked #5)81 new deaths in 14 days)	–	5.42%		No	No
South Africa	4,042,221(ranked #37; 5,299 new infections in 14 days).	312	102,464 (ranked #18) 93 new deaths in 14 days)	–	6.65%	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	4,408,276(ranked #34) 31,206 new infections in 14 days).	–	47,781(ranked #25 ) 663 new deaths in the last 14 days	–	11.48%		No	No
Poland	6,353,850 (ranked #21; 5,470 new infections in 14 days).	542	118,332 (ranked #15)65 new deaths in the last 14 days	4	16.83%	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	21,597,613 (ranked #10), 72,046 new infections in 14 days).	6,785 (ranked #11)	392,060(ranked #4)727 new deaths in 14 days	58	14.81%		No	No
Peru	4,266,251(ranked #36, 107,119 new infections in 14 days).	13,868 (ranked#9)	217,428(ranked #6) 199 new deaths in the last 14 days	14	12.66%	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	7,559,737(ranked #18; 526 new infections in last 14 days)	31	144,634(ranked #12) 14 new deaths in the last 14 days	1	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	13,612,052(ranked #12; 38,331 new infections in 14 days).	2,758	116,081 (ranked #16)440 new deaths in 14 days	30	29.13%	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	37,916,052 (ranked #3; 628,505 new infections in the last 14 days).	69,253 (ranked #2)	159,026 (ranked #10)863 new deaths in 14 days.	76	57.81% a 1.52% 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) recombinantBQ.1.1	No	No
Germany	36,530,020(ranked #4; 324,615 new infections in 14 days.)	30,420 (ranked #6)	158,108 (ranked #11)1,486 new deaths in 14 days	166	43.54% 0.38% 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) recombinantBQ.1.1	No	No
South Korea	27,155,813 (ranked #6 693,494 new infections in 14 days).	57,079(ranked #3)	30,568 (ranked #35) 643 new deaths in 14 days	62	52.90%1.35% 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	11,516,489 (ranked #13; 5,570new infections in 14 days).	581	43,176(ranked #26)	1	11.63%	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
Netherlands	8,543,838 (ranked #16; 9,694 new infections in 14 days).	959	22,916 (ranked #41)	3	49.64%	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)GKA (AY.4/BA.1) recombinant	No	No
Denmark	3,148,210 (ranked #40) 4,949 new infections in 14 days.	610	7,537(ranked #78 67 new deaths in the last 14 days)	5	53.95%	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)GKA (AY.4/BA.1) recombinant	No	No
Taiwan	8,329,000(ranked #17)198,781 new infections in 14 days	15,643 (ranked #7)	14,387 (ranked #58 539 new deaths in the last 14 days)	53	34.86% 0.83% 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	24,911,367(ranked #7)1,307,161 new infections in the last 14 days	118,201(ranked #1)	49,826(ranked #23) 1,768 new deaths in the last 14 days	182	19.83% 1.04% of the population 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)BA.2BA.5	No	No
Argentina	9,727,247 (ranked #15)5,529 new infections in the last 14 days.	–	130,025(ranked #14)	–	21.14%		No	No
Italy	24,327,664 (ranked #8) 96,126 new infections in the last 14 days.	–	181,733(ranked #8) 1,152 new deaths in the last 14 days	–	40.36% 0.49% of population infected in last 14 days.		No	No
Chile	4,925,051(ranked #28) 59,393 new infections in14 days..	5,041 (ranked#13)	62,484(ranked #22) 354 new deaths in the last 14 days.	26	25.28% 0.31% of population infected in the last 14 days.		No	No
Colombia	6,318,021(ranked #22) 5,364 new infections in the last 14 days.	3,252	141,811(ranked #13)	16	12.26%		No	No
Australia	10,725,239(ranked #14) 172,561 new infections in 14 days.	14,741 (ranked #8)	16,187(ranked #55) 220 new deaths in 14 days.	16	41.14% 0.66% of population infected in last 14 days.		No	No
Turkey	17,005,537(ranked #11)28,808 new infections in 14 days.	–	101,400(ranked #19) 73 new deaths in 14 days..	–	19.87%		No	No
Indonesia	6,669,821 (ranked #20) 73,009 new infections in last 14 days.	4,977 (ranked #14)	159,884 (ranked #9) 561 new deaths in the last 14 days.	54	23.89%		No	No
Malaysia	4,994,543 (ranked #27) 31,327 new infections in the last 14 days.	2,375	36,695 (ranked #29) 107 new deaths in the last 14 days.	11	15.05%		No	No
Hong Kong	2,128,382(ranked#46) 107,497 new infections in the last 14 days.	10,137 (ranked #10)	10,762 (ranked#64)185 new deaths in the last 14 days.	15	27.98% 1.41% of population infected in the last 14 days.		No	No
China	323,686 (ranked #103) 44,255 new infections in 14 days	4,150 (ranked#15)	–	–	–	–	–	–

What Our Team Is Reading This Week

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
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

COVID-19

SARS-CoV-2 Update

10/25/2022 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 decreased for the fourth time in 12 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 in the United States have decreased by 81 deaths per day; however, many states are not reporting deaths in a timely manner. The number of infections per day has decreased by 8,524. The CDC estimates that BA.5 accounted for 62.2% (a 17% drop from 10/7/22), BQ.1 accounted for 9.4%, BQ.1.1 accounted for 7.2%, BA.4.6 accounted for 11.3%, BF.7 accounted for 6.7%, BA.2.75 accounted for 1.6%, BA.2.27.2 accounted for 1.3%, and BA.4 accounted for 0.4%, in the week ending October 22.

The total percentage of BQ variant infections in the region that includes New York and New Jersey is 28.4%.

The total percentage of BQ variant infections in the region that includes Pennsylvania, Delaware, Maryland, West Virginia, and Virginia is 17.8%.

The total percentage of BQ variant infections in the region that includes California, Nevada, Arizona, and Hawaii is 13.6%.

Data on the rapid spread of a dangerous variant category, the BQ variants, was withheld by the CDC in their weekly reports until last week. 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. We can expect this pattern to continue in many states, since New York has been a harbinger of things to come throughout the pandemic.

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 October 19, the CDC reports that 19.4 million people have received the bivalent vaccine. That’s only 8.5% of people who received the primary series and 5% of the overall population.

There has been no new UK Health Security Agency Technical Briefing since October 7. The October 7 Technical Briefing says, “From UK data, BQ.X, BA.2.75.2 and BF.7 are the most concerning variants in terms of both growth and neutralisation data at present; there is also supportive animal model data for BA.2.75.”

Variant	Sublineage of	Spike Mutations	Global Sequences	UK Sequences
BF.7	BA.5.2.1	R346T	9,809 (1,752 from Belgium)	663
BQ.1.1	BA.5	N460KK444TR346T	326(20 countries)	60
BJ.1	BA.5	13 non- synonymous spike mutations, 7 in RBD and including4 predicted immune escape locations	123 (10 countries, most cases in India)	1
BS.1	BA.2.3.2	R346TL452RN460KG476S	25 (15 from Japan)	0

Data from UK Health Security Agency

In Monterey County, as of 10/22/22, 2.1% of 0-4 year-olds and 40.1% of 5-11 year-olds have received the first two doses of vaccine, while 73.3% of 12-17 year-olds have received two doses. Only 54.1% 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 10/21/22, the United States had 19,652 documented new infections. There were also 190 deaths. Thirty-four states did not report their infections, and 36 states didn’t report their deaths. In the United States the number of hospitalized patients has decreased slightly (-1% compared to the previous 14 days) in many areas and was 26,810 on October 22. On 10/21/22 there were 2,707 patients who are seriously or critically ill; that number was 2,753 two weeks ago. The number of critically ill patients has decreased only by 47 in the last 14 days, while at least 4,951 new deaths occurred. The number of critically ill patients has decreased for the fifth time in twenty-nine 14-day periods. Patients are still dying each day (average 354/day). Omicron BA.4, BA.4.6, BA.5, and BF.7 variants are still causing infections. A new variant BQ.1.1, descended from Omicron BA.5, is causing increasing numbers of infections and hospitalizations in New York. In Singapore a different Omicron BA.2 variant, XBB, is causing rapidly increasing infections. Past infections with a BA.1, BA.2 or BA.5 variants will not prevent infections with any of the newer variants.

As of 10/21/22, we have had 1,092,606 deaths and 99,055,537 SARS-CoV-2 infections in the United States. We have had 532,369 new infections in the last 14 days. We are adding an average of 266,185 new infections every seven days. For the pandemic in the United States we are averaging one death for every 90.65 infections or over 11,030 deaths for each one million infections. As of 10/21/22, 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 (4,350), Arizona (4,330), Alabama (4,186), West Virginia (4,178), New Mexico (4,111), Tennessee (4,103) and Arkansas (4,114). . 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. Seven states have had greater than 40,000 deaths: Florida (82,065 deaths), Texas (91,584 deaths), New York (72,694 deaths), Pennsylvania (47,582 deaths), Georgia (40,552 deaths), Ohio (40,111 deaths) and California (96,721 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 825,605 new deaths from SARS-CoV-2. For nineteen of those months, vaccines have been available to all adults. During these eighteen months, 520,509 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 10/21/22, California was ranked 33rd in the USA in infection percentage at 28.65%. In California, 24.68% of people were infected in the last 19 months. As of 10/21/22, 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 1,569 for the last 14 days, which is a 97 deaths-per-day increase over the previous 14 days. The United States accounts for 22.56% (354 per day) of all deaths per day in the world over the last two weeks. Worldwide infections per day were 310,532. The United States accounts for 12.04% of those infections (or 37,384 infections per day).

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

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.

From Professor Marc Johnson, molecular virologist @SolidEvidence on Twitter and Daniele Focosi, M.D., Ph.D. @dfocosi on Twitter

Watching World Data

Location	Total Infections as of 10/21/22	New Infections on 10/21/22	Total Deaths	New Deaths on 10/21/22	% of Pop.Infected	SARS-CoV-2 Isolates Currently Known in Location	National/ State Mask Mandate	Currently in Lockdown
World	632,432,678(4,347,443 new infections in 14 days).	349,351	6,581,530(21,965 new deaths in last 14 days)	1,189	8.11%	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	99,055,537(ranked #1) 532,369 new infections in the last 14 days.	19,652(ranked #7) 34 states failed to report infections on 10/21/22.	1,092,606(ranked #1) 4,951 new deaths reported in the last 14 days.	190 36 states failed to report deaths on 10/21/22.	29.58%	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	34,822,174(ranked #4) 64,917 new infections in the last 14 days.	3,400	687,581(ranked #2; 732 new deaths in 14 days)	37	16.16%	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	44,640,748(ranked #2); 31,991 new infections in 2 weeks.	2,112	528,957(ranked #3) 199 new deaths in 2 weeks.	4	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	23,855,522(ranked #7) 120,249 new infections in 2 weeks.	–	192,682 (ranked #7) 1,794 new deaths in 2 weeks	–	34.82%	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	11,332,345(ranked #14 in the world; 39,798 new infections in the last 14 days).	998	96,721 (ranked #20 in world) 303 new deaths in the last 14 days	14	28.65%	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	7,106018(ranked #19) 4,587 new infections in 14 days).	453	330,321(ranked #5)181 new deaths in 14 days)	15	5.40%		No	No
South Africa	4,025,375(ranked #37; 4,587 new infections in 14 days).	416	102,257 (ranked #18) 63 new deaths in 14 days)	11	6.62%	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	4,314,718(ranked #33) 43,827 new infections in 14 days).	3,067	46,025(ranked #25)631 new deaths in the last 14 days	49	11.23%		No	No
Poland	6,333,591 (ranked #21; 22,629 new infections in 14 days).	1,170	118,015 (ranked #15)272 new deaths in the last 14 days	24	16.78%	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	21,354,915(ranked #10), 190,973 new infections in 14 days).	9,761 (ranked #8)	389,359(ranked #4)1,368 new deaths in 14 days	93	14.64%		No	No
Peru	4,152,019(ranked #32, 3,858 new infections in 14 days).	314	216,877(ranked #6) 177 new deaths in the last 14 days	–	12.32%	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	7,555,694(ranked #17; 4,672 new infections in last 14 days)	139	144,540(ranked #12) 69 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	13,488,015(ranked #12; 46,047 new infections in 14 days).	3,630	114,858 (ranked #16)390 new deaths in 14 days	31	28.87%	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	36,524,605 (ranked #3; 758,248 new infections in the last 14 days).	49,087 (ranked #2)	156,337 (ranked #10)803 new deaths in 14 days.	81	55.69% a 2.17% 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	35,172,693(ranked #4; 1,224,661 new infections in 14 days.)	49,087 (ranked #2)	152,482 (ranked #11)1,947 new deaths in 14 days	204	41.93% 1.71% 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	25,244,255 (ranked #6 310,499 new infections in 14 days).	24,709(ranked #8)	28,952 (ranked #37) 338 new deaths in 14 days	30	49.18%	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	11,496,354 (ranked #13; 10,933 new infections in 14 days).	582	43,159 (ranked #26)	–	11.61%	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	8,494,705 (ranked #16; 33,354 new infections in 14 days).	952	22,683 (ranked #41)	5	49.35%	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	3,131,149(ranked #40) 12,835 new infections in 14 days.	652	7,248 (ranked #79 126 new deaths in the last 14 days)	13	53.66%	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	7,379,205(ranked #18)569,950 new infections in 14 days	37,265 (ranked #3)	12,206 (ranked #59 937 new deaths in the last 14 days)	78	30.89% 2.53% 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	21,926,231(ranked #9)463,493 new infections in the last 14 days	31,593(ranked #5)	46,152(ranked #25) 831 new deaths in the last 14 days	67	17.45%	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)BA.2BA.5	No	No

What Our Team Is Reading This Week

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

COVID-19

SARS-CoV-2 Update

06/19/2022 davidcwrightmd

SARS-CoV-2 infections per day have been increasing in the United States for 8 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 19 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 64.2% of isolates, BA.2 accounted for 14.2%, BA.5 accounted for 13.3%, BA.4 accounted for 8.3%, and B.1.1.529 accounted for 0% in the week ending June 11.

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.

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.

European Centre for Disease Prevention and Control

The Omicron variant will continue to mutate just like Delta. There are now 157 Omicron sub-variants (an increase of 57 in the last two weeks) that have been assigned Pango lineages, including 92 sub-lineages of BA.2 (an increase of 42 in two weeks), one sub-lineage of BA.3, three sub-lineages of BA.4, and five sub-lineages of BA.5. There are also two new lineages: BF.1, detected in England, Denmark, Spain and Scotland, and BE.1, detected in South Africa, Austria and England. Curiously, the UK Health Security Agency, which usually releases updates every two weeks, has not released a new Technical Briefing on SARS-CoV-2 variants since May 20.

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.

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.

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 6/19/22, only 38.9% of 5-11 year-olds have received the first two doses of vaccine, while 80.8% 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 6/17/22, the United States had 81,733 documented new infections. There were also 200 deaths. Twenty-one states did not report their infections, and 32 states didn’t report their deaths. In the United States the number of hospitalized patients had been increasing in many areas. Now there are 3.006 patients who are seriously or critically ill; that number was 2,683 two weeks ago. The number of critically ill patients has increased by 323 in the last 14 days, while at least 4,896 new deaths occurred (an increase of 19 deaths per day from the previous 14 days). The number of critically ill patients has increased for the fourth time in twenty-one 14-day periods. Patients are still dying each day (average 350/day). Omicron BA.2, BA.4, 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 6/17/22, we have had 1,038,265 deaths and 87,968,819 SARS-CoV-2 infections in the United States. We have had 1,518,216 new infections in the last 14 days. We were adding an average of 759,108 infections every seven days. For the pandemic in the United States we are averaging one death for every 84.72 infections or over 11,803 deaths for each one million infections. As of 6/17/22, thirty-seven 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 69,000 deaths. California and Texas have each had greater than 88,000 deaths with California having 92,181 deaths (20th most deaths in the world).

As of 6/17/22, in the United States, 26.27% of the population has had a documented SARS-CoV-2 infection. In the last 18 months, 23.52% 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 778,134 new deaths from SARS-CoV-2. For fifteen of those months, vaccines have been available to all adults. During these fifteen months, 467,168 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 6/17/22, California was ranked 35th in the USA in infection percentage at 25.03%. In California, 21.06% of people were infected in the last 18 months. As of 6/17/22, 35 states have had greater than 25% of their population infected.

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

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.

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 6/17/22	New Infections on 6/17/22	Total Deaths	New Deaths on 6/17/22	% of Pop.Infected	SARS-CoV-2 Isolates Currently Known in Location	National/ State Mask Mandate	Currently in Lockdown
World	543,620,349(8,989,675 new infections in 14 days).	497,265	6,339,387(20,374 new deaths in last 14 days)	1,091	6.97%	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	87,968,819(ranked #1) 1,518,216 new infections in the last 14 days.	81,733(ranked #1) 21 states failed to report infections.	1,038,265(ranked #1) 4,896 new deaths in the last 14 days.	200 32 states failed to report deaths.	26.27%	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.2.12.1BA.4 (South Africa)BA.5 (South Africa)*	No	No
Brazil	31,673,375(ranked #3) 535,896 new infections in the last 14 days.	28,672 (ranked #6)	668,968(ranked #2; 1,949 new deaths in 14 days)	76	14.69%	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	43,283,793(ranked #2); 101,921 new infections in 2 weeks.	13,216	524,840(ranked #3)	–	3.07%	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	22,472,503(ranked #6) 166,610 new infections in 2 weeks.	12,054	179,537 (ranked #7)	65	32.76%	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)*	No	No
California, USA	9,892,097(ranked #13 in the world; 233,150 new infections in the last 14 days).	14,603	92,181 (ranked #20 in world)	45	25.03%	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.2.12.1BA.4 (South Africa)BA.5 (South Africa)*	No	No
Mexico	5,852,596(ranked #21) 70,191 new infections in 14 days).	9,406	325,340(ranked #5)	69	4.48%	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	3,984,646(ranked #30; 19,224 new infections in 14 days).	971	105,589 (ranked #18)	5	6.55%	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	3,910,211(ranked #32) 30,111 new infections in 14 days).	782	41,723(ranked #25)	6	10.18% .	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	6,010,919 (ranked #20; 2,724 new infections in 14 days).	48	116,390 (ranked #15)	–	15.91%	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	15,085,742(ranked #10, 12,995 new infections in 14 days).	————	98,996 (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	18,391,797(ranked #7), 47,833 new infections in 14 days).	3,373	380,333(ranked #4 in world)	63	12.59%	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	9,313,453(ranked #13; 82,880 new infections in 14 days).	———–	128,984 (ranked #14)	——–	20.24%	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	6,131,657(ranked #18, 26,642 new infections in 14 days).	–	139,908 (ranked #13)	–	11.80%	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	3,596,374(ranked #35, 12,974 new infections in 14 days).	1,400	213,374(ranked #6)	13	10.61%	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	7,234,523(ranked 17th; 1,909 new infections in last 14 days)	156	141,361(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	12,563,399(ranked 11th; 160,154 new infections in 14 days).	16,090	107,482 (ranked #17)	81	26.85%	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	30,079,458 (ranked #4; 483,566 new infections in the last 14 days).	50,605 (ranked #3)	149,039 (ranked #10)	43	45.88%	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	27,124,459(ranked #5; 613,531 new infections in 14 days.).	28,471 (ranked #7)	140,292 (ranked #12)	–	32.17%	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	18,263,643 (ranked #8 121,808 new infections in 14 days).	7,186(ranked #17)	21,416 (ranked #39)	9	35.56%	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	10,736,408 (ranked #12; 12,735 new infections in 14 days).	723	43,083 (ranked #24)	–	10.83%	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	8,122,258 (ranked #15; 32,021 new infections in 14 days).	3,855	22,343 (ranked #41)	1	47.19%	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	2,996,713 (ranked #39) 10,405 new infections in 14 days	995	6,421 (ranked #81)	–	51.38%	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
North Korea (DPRK)	4,581,420 (ranked #24; 663,840 new infections in 14 days)	23,160 (ranked #8)	73	–	17.62%	Omicron/B.1.1.529 South Africa November 2021)	No	No
Taiwan	3,190,746(ranked #38)	55,220 (ranked #2)	4,868 (ranked #89)	154 (ranked #2)	13.34%	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	9,108,323(ranked #14)	15,802(ranked #10)	30,980(ranked #31)	17	7.24%	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

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

COVID-19

SARS-CoV-2 Update

12/18/2021 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.

SARS-CoV-2 infections are 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 Delta variants and 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 already two Omicron variants, BA.1 and BA.2. We expect to see additional Omicron variants as this isolate spreads rapidly around the USA and the World. As of 12/18/21 the Omicron variant, which was first seen in South Africa on 11/08/21, is now in 40 states, Puerto Rico and the District of Columbia. It has also been identified in at least 70 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. That’s 33 days ago and still no word from the FDA on approval. No deaths occurred in their study in the treatment group. We are averaging over 1,000 deaths per day in the USA and Russia. If the drug were available and just 90% effective in preventing deaths, each country could prevent over 900 deaths per day. If the FDA takes another 30 days for approval and drug distribution doesn’t occur rapidly then that’s at least 27,000 additional deaths in each country that could have been prevented. For now only masking (N95 rated masks, please!), social distancing and vaccination will have any effect on these variants.

In the United States, SARS-CoV-2 deaths have increased for the second time in six 14-day periods. There were 113 more deaths per day than in the last 14-day period. In the last 14 days, the number of infections has increased by 41,127 infections per day compared to the preceding 14-day period. Our infections per day have increased for the third time over the last 14 weeks. With travel and multiple holidays and events occurring in the next 60 days, we expect the infections to continue to increase. Unless people get vaccinated and get their third dose of the vaccine, we will see further spread of Delta variants like AY4.2 and an increase in deaths particularly in people with risk factors and over the age of 55. Anyone over the age of 5 years can now get vaccinated in the United States at no cost. This should get done immediately.

A 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 is causing a doubling of new infections every 1.3 days in Gauteng, South Africa. In just 40 days, as of 12/17/21, Omicron has been found in 70 countries and 40 states in the United States. Unlike Delta variants in South Africa, Omicron is 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, 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. The Delta variants still account for 97% of new infections in the United States. Omicron accounted for 3% of infections by 12/11/21.

On 12/17/21, the United States had 163,707 new infections with two states failing to report (Iowa and Maryland). There were also 1,653 deaths (with five other states failing to report deaths). Florida continues to consistently under-report daily infections and deaths. The number of hospitalized patients has been increasing in many areas, and now 15,602 patients are seriously or critically ill; that number was 13,714 two weeks ago. The number of critically ill patients has increased by 1,888 in the last 14 days, while at least 18,603 new deaths occurred. The number of critically ill patients has increased for the third time in twelve 14-day periods and a large number of patients are still dying each day (average 1,329/day).

As of 12/17/21, we have had 826,719 deaths and 51,510,281 SARS-CoV-2 infections in the United States. We have had 1,932,232 new infections in the last 14 days. We are adding an average of 966,166 infections every seven days. For the pandemic in the United States we are averaging one death for every 62.3 infections reported or over 16,050 deaths for each one million infections. As of 12/17/21, thirty-one states have had greater than 500,000 total infections, and 36 states have had greater than 5,000 total deaths. Eleven states (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 50,000 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 12/17/21, in the United States, 15.45% of the population has had a documented SARS-CoV-2 infection. In the last 13 months, 11.75% 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 13 months, there were 566,388 new deaths from SARS-CoV-2. For ten of those months, vaccines have been available to all adults. During these ten months, 221,946 people have died of SARS-CoV-2 infections. Many of these hospitalizations and deaths could have been prevented by vaccination, proper masking, and social distancing.

As of 12/17/21, California was ranked 42nd in infection percentage at 12.80% and 10.04% of Californians were infected in the last 13 months. And now let’s look at the top 27 infected states, all greater than 16%, which is not a list that you’d like to be on in 2021. North Dakota was at 22.17% (ranked #1), Alaska was at 20.39% (ranked #2), Tennessee was at 19.71% (ranked #3), Rhode Island was at 19.70% (ranked #4), South Dakota was at 19.62% (ranked #5), Wyoming 19.60% (ranked #6), , Utah at 19.26% (ranked #7), Iowa was at 18.93% (ranked #8), Kentucky was at 18.48% (ranked #9), Arizona was at 18.28% (ranked #10), Montana was at 18.22% (ranked #11), South Carolina was at 18.18% (ranked #12), Wisconsin was at 18.10% (ranked #13), Arkansas was at 17.97% (ranked #14), Florida was at 17.59% (ranked #15), Indiana was at 17.55% (ranked#16), Mississippi was at 17.55% (ranked #17), Idaho was at 17.53% (ranked #18), West Virginia was at 17.49% (ranked #19), Alabama was at 17.47% (ranked #20), Oklahoma was at 17.30% (ranked #21), Minnesota was at 17.15% (ranked#22), Kansas was at 16.93%(ranked #23), Nebraska was at 16.27% (ranked #24), Louisiana was at 16.79% (ranked #25), Delaware was at 16.74%(ranked #26) and Michigan at 16.01% of the population infected (ranked #27). Forty-two states now have greater than 12% of their population infected. Only one state has less than 7% of their population infected: Hawaii (6.43%). Hawaii and the US Virgin Islands still remain the safest places in the United States. Hawaii had its first patient with an Omicron (B.1.1.529) SARS-CoV-2 infection two weeks ago.

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 has the fifth highest COVID-19 deaths per million in the world. New York, New Jersey and Arizona would be tied at the 9th highest number of deaths per million in the world, followed by Louisiana at 10th, Arkansa at 11th, Arizona, Florida at 12th, Massachusetts and Rhode Island tied at 14th. The United States as a whole ranks 20th in the world for deaths per million population (2,495 deaths per million). California ranks 35th in the USA (and 36th in the world). If we look at the death rates per million in South Korea (89), Iceland (105), Japan (146), and Israel (882), 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 1,491 per million, compared to 219 per million in Norway and 260 per million in Finland. The United States should take 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	3,479	1st	5th
New Jersey	3,228	3rd	9th tied
Louisiana	3,210	5th	10th
New York	3,033	6th	9th tied
Alabama	3,333	2nd	7th
Arizona	3,227	4th	9th tied
Massachusetts	2,870	11th	14th tied
Rhode Island	2,824	13th	14th tied
Arkansas	2,959	7th	11th
Florida	2,896	9th	12th
California	1,920	35th	36th
USA	2,495		20th
Peru	6,007		1st
Bosnia-Herzegovina	4,036		3rd
North Macedonia	3,741		6th
Hungary	3,899		4th
Montenegro	3,776		5th
Bulgaria	4,356		2nd
Gibraltar	2,969		10th
Czechia	3,264		7th
Brazil	2,875		13th
San Marino	2,762		14th
Georgia	3,261		8th
Sweden	1,491		56th
Israel	882		87th
Canada	785		94th
Finland	260		135th
Norway	219		139th
Japan	146		153rd
Iceland	105		163rd
South Korea	89		167th

A New Drug for SARS-CoV-2 Treatment

Pfizer has developed a reversible inhibitor of C3-like protease of SARS-CoV-2. The drug inhibits this key enzyme that is crucial for virus production. The compound, called Compound 6, 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. I had anticipated that the drug would be approved in the next 7 days. In my opinion, this agent, if approved, will markedly alter the course of every coronavirus infection throughout the world.

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):

Omicron cases sequenced as of 12/17/21:

Source: GISAID

Delta cases sequenced as of 12/17/21:

Source: GISAID

Map of Delta sequenced transmissions:

Source: GISAID

B.1.640 cases sequenced as of 12/17/21:

Source: GISAID

Gamma cases sequenced as of 12/17/21:

Source: GISAID

Mu cases sequenced as of 12/17/21:

Source: GISAID

Watching World Data

Location	Total Infections as of 12/17/21	New Infections on 12/17/21	Total Deaths	New Deaths on 12/17/21	% of Pop.Infected	SARS-CoV-2 Isolates Currently Known in Location	National/ State Mask Mandate?	Currently in Lockdown?
World	273,960,234(8,798,529 new infections in 14 days).	730,090	5,360,728(102,682 new deaths in last 14 days;	7,297	3.51%	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 (South Africa November 2021)B.1.640 (Congo/France)*	No	No
USA	51,510,281 (ranked #1) 1,932,232 new infections in the last 14 days)	163,707 (ranked #1)	826,719 (ranked #1)18,603 new deaths in the last 14 days)	1,653	15.45%	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)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 (South Africa November 2021)B.1.640 (Congo/France)*	No	No
Brazil	22,209,020(ranked #3)	4,079	617,647(ranked #2)	126	10.34%	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 (South Africa November 2021)	No	No
India	34,732,592(ranked #2)	6,543	476,897(ranked #3)	38	2.48%	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 (South Africa November 2021)B.1.640 (Congo/France)*	No	No
United Kingdom	11,190,354(ranked #4; was #6 sixrteen weeks ago)	93,045	147,048(ranked #7 in world)	111	16.35%	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)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 (South Africa November 2021)B.1.640 (Congo/France)*	No	No
California, USA	5,067,329(ranked #14 in world)	9,125	75,935(ranked #20 in world)	113	12.82%	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 (South Africa November 2021)*	No	No
Mexico	3,927,265(ranked #15)	2,627	297,356(ranked #4)	169	3.00%	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 (South Africa November 2021)*	No	No
South Africa	3,276,529(ranked #18) Exponential growth of Omicron occurring in South Africa. Children under 5 are infected.Quadrupling of daily infections in last four days.	20,713 on 12/17/21,16,055 on 12/3/21,11,535 on 12/2/21,8,561 on 12/1/21,4,373 on 11/30/21,789 on 11/19/21339 on 11/5/21	90,297	35	5.42%	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 South Africa, November 2021)B.1.640 (Congo/France)	No	No
Canada	1,864,891(ranked #27)	6,892	30,624	12	4.87%	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 (South Africa November 2021)B.1.640 (Congo/France)*	Yes, except Alberta Province	No
Poland	3,923,472(ranked #16)	20,027	90,872	566	10.38%	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 (South Africa November 2021)	No	No
Turkey	9,136,565(ranked #6)	18,141	80,053	190	10.66%	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 (South Africa November 2021)*	No	No
Russia	10,159,389(ranked #5)	27,743	295,104(ranked #5 in world)	1,080	6.95%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)R1(Japan) B.1.640 (Congo/France)Omicron/B.1.1.529 (South Africa November 2021)	No	No
Argentina	5,382,290(ranked #11)	5,648	116,892	18	11.75%	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)Gama/P.1 (Brazil)Delta/B.1.617.2 (India)Lambda/C.37 (Peru)Omicron/B.1.1.529 (South Africa November 2021)*	No	No
Colombia	5,103,269(ranked #13)	1,803	129,345	50	9.87%	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)Mu/B.1.621 (Colombia)	No	No
Peru	2,269,180(ranked #23)	——–	202,076(ranked #6)	——-	6.71%	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)	No	No
Indonesia	4,260,148(ranked #14)	291	143,986	7	1.53%	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 (Congo/France)Omicron/B.1.1.529 (South Africa November 2021)	No	No
Iran	6,157,650(ranked 9th; was 12th sixteen weeks ago)	2,196	130,992	46	7.20%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)	No	No
Spain	5,455,527(ranked 10th)	33,359	88,708	41	11.66%	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 South Africa November 2021)B.1.640 (Congo/France)*	No	No

What Our Team Is Reading This Week

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/
https://www.discovery.co.za/corporate/news-room#/documents/press-release-dot-pdf-417948
SARS-CoV-2 variants of concern and variants under investigation in England, Technical Briefing 31 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1040076/Technical_Briefing_31.pdf
Minimal cross-over between mutations associated with Omicron variant of SARS-CoV-2 and CD8+ T cell epitopes identified in COVID-19 convalescent individuals (Preprint) https://www.biorxiv.org/content/10.1101/2021.12.06.471446v1
COVID-19 vaccines dampen genomic diversity of SARS-CoV-2: Unvaccinated patients exhibit more antigenic mutational variance (Preprint) https://www.medrxiv.org/content/10.1101/2021.07.01.21259833v1
SARS-CoV-2 B.1.1.529 variant (Omicron) evades neutralization by sera from vaccinated and convalescent individuals (Preprint) https://www.medrxiv.org/content/10.1101/2021.12.08.21267491v1
Myocarditis after Covid-19 Vaccination in a Large Health Care Organization (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2110737
Myocarditis after BNT162b2 mRNA Vaccine against Covid-19 in Israel (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2109730
Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2116185
Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial (Science) https://www.science.org/doi/10.1126/science.abm3425
Dissecting the early COVID-19 cases in Wuhan (Science) https://www.science.org/doi/10.1126/science.abm4454
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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.

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 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

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. On May 22, 2021, the CDC reported that Alpha made up approximately 69% of COVID-19 cases in the previous two weeks.

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).

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.

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 524 total and 11 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 June 18, has had 2,023,179 infections and 189,933 deaths.

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.

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.

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	—

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 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).

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.

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.

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 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 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

COVID-19

SARS-CoV-2 Update

04/10/202104/10/2021 davidcwrightmd

It’s time for our next 14-day moving average determinations and projections for infections and deaths from SARS-CoV-2 for the United States and my thoughts on vaccines and mutant viruses. We use the WORLDOMETERS aggregators data set to make our projections of future total infections and deaths 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 fourth time in a 14-day period. There were 133 fewer deaths per day than in the last 14-day period. In the last 14 days, the number of infections has increased by 11,210 infections per day. This increase in infections over the last four 14-day periods is secondary to SARS CoV-2 mutants, to include the B.1.1.7 (UK isolate), a New York isolate B.1.526, the CAL.20C isolate, the South African isolate and the Brazilian isolates. 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 over Easter and Spring break as well as upgoing Memorial Day weekend, summer vacations and the July 4th holiday will all cause further increases. Vaccinations, increased mask usage and social distancing, which are a part of the Biden 100-day SARS-CoV-2 plan (day 80 of plan) will be necessary to stop spread of mutants and cause reductions in infections, hospitalizations and deaths in the future. On 4/09/21, 85,638 new infections occurred in the United States. There were also 929 deaths. The number of hospitalized patients is increasing, and only 9,078 patients are critically ill. The number of critically ill patients has increased by 468 in the last 14 days, while 13,006 new deaths occurred. The number of critically ill patients is increasing and a large number of patients are still dying each day.

As of 4/09/21, we have had 574,840 deaths and 31,802,772 SARS-CoV-2 infections in the United States. We have had 949,742 new infections in the last 14 days. We are adding 474,871 infections every 7 days. Each million infections usually results in at least 20,000 deaths. On 4/9/21, twenty-one states had greater than 500,000 total infections, and 32 states had greater than 5,000 total deaths.

For comparison, 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 4/09/21, in the United States, 9.60% of the population has had a documented SARS-CoV-2 infection. In the last 5 months nearly 6% of our country became infected with SARS-CoV-2.

As of 4/09/21, California was ranked 33rd in infection percentage at 9.34%. In North Dakota 13.71% of the population was infected (ranked #1) and in South Dakota 13.50% of the population was infected (ranked #2). Thirty-five states have greater than 9% of their population infected and 45 states have greater than 6% infected. Only one state has less than 3% of their population infected: Hawaii (2.15%).

New Mutants

A new mutant SARS-CoV-2 virus (lineage B.1.1.7), first seen in the UK in September, has now been found in multiple other countries. There are 3,170 reported cases in the USA as of 3/11/21. As of 3/25/21 there are 8,337 reported cases in the USA. This isolate has now been found in 50 states and the District of Columbia. This isolate (let’s call it Lineage B.1.1.7 or SARS-CoV-2 UK) 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 the B.1.1.7 variant compared to all other isolates. Due to air and other travel, this isolate will become the dominant isolate worldwide.

As of 3/11/21 B.1.351, also known as the South African isolate, had 108 reported cases and has occurred in 23 states and the District of Columbia. As of 3/25/21 there are 266 reported cases in 29 states and the District of Columbia. On 3/11/21 the P.1 isolate (Brazil) had 17 reported cases and has been found in 10 states. As of 3/25/21 there were 79 P1 isolates in 11 states. (This data is available at https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant-cases.html)

A disturbing report out of the UK has found a second mutation in B.1.1.7. This mutation, which occurs in the loop sequence has also been found in the South African (B.1.351) and Brazilian (P.1) variants. (The loop sequence is in the receptor binding motif in the receptor binding domain of the S1 sequence of the spike protein.) This mutation involves a change of one amino acid of the spike protein, number 484, from glutamic acid to lysine. This point mutation allows the virus to bind better to the ACE2 receptor, which increases infectivity. People who are exposed to one of these variants (versus the old B2 isolate) are more likely to be infected and are more likely to transmit the virus to others.

In our last three updates we summarized a research letter published in Clinical Infectious Diseases about a patient in the UK who was first infected in April with a B2 isolate and experienced only mild symptoms but was infected with the new B.1.1.7 variant in December and became critically ill. The patient described in this research letter was not protected by a natural infection with a B2 lineage SARS-CoV-2 isolate in April 2020 from having a potentially lethal second infection with a B.1.1.7 lineage variant in December 2020, suggesting that folks who have had a past SARS-CoV-2 infection should not expect to have any immunity to new variants such as B.1.1.7. All of the currently available vaccines were developed with spike protein from B2 lineages. Moderna, Pfizer, and AstraZeneca/Oxford are currently remaking their spike protein vaccines to address the mutations in the South African variant of SARS-CoV-2 because the AstraZeneca/Oxford vaccine did not work in a small trial in South Africa, where most of the patients had the South African mutant (B.1.351).

A California Mutant

A fourth mutant isolate of SARS-CoV-2, B.1.429 + B.1.427 (CAL.20C), has been identified in California. This isolate does not have any of the mutations mentioned above, but contains five mutations, three of which are in the spike protein, but not in the receptor binding motif. This mutant may be partially responsible for the massive increase in infections in California, to include infections of people who had already recovered from a SARS-CoV-2 infection earlier. In California to date, we have had 3,618,594 infections and 55,455 total deaths. California is averaging 249 deaths per day in the last 14 days. Currently, 9.15% of the population in California is infected. Nationally, we rank 29th in the percentage of people in the state infected. To my knowledge, only one privately held company is currently modifying their vaccine to cover the B.1.429 + B.1.427 mutant.

New Mutants Arrive in California

Stanford University announced this week that they have identified five infections with the Maharashtra India VOC 32421 (yet to be named) in the San Francisco Bay Area. Two additional isolates are PCR positive and pending sequencing. This isolate is a double-mutant responsible for up to 40% of the infections in India.

Many readers may now be familiar with the E484K mutation present in the South African isolate, the Brazilian isolate, the New York isolate (B.1.256), and the new Nigerian/UK double mutant. When vaccine manufacturers make booster vaccines to address these variants, they will only account for the E484K mutation. What sets this VOC from India apart from the other variants is that it has a different point mutation at 484 that involves a change of one amino acid of the spike protein, number 484, from glutamic acid to glutamine (E484Q). This point mutation, like E484K, probably allows the virus to bind to the ACE2 receptor and evade neutralizing antibodies directed against the original Wuhan sequence. A vaccine created to address E484K would not address this isolate.

The second mutation in Maharashtra India VOC 32421 is L452R, which is one of the same mutations seen in CAL.20C (B.1.429 + B.1.427). This mutation is also not being covered by any vaccine currently being made as a booster.

In India on 4/9/21, 144,829 new infections and 773 deaths occurred. India now has the third-highest number of infections in the world (13,202,783) and the fourth-highest number of deaths (168,467). India has a population of 1,390,456,911. At the present time, only 0.94% of the country has been infected with SARS-CoV-2. International travel and trade will continue to spread this highly infectious isolate to other parts of the world. This infection has now landed in California, our most-populous state.

Watching the Data

Location	Total Infections as of 4/9/21	New Infections on 4/9/21	Total Deaths	New Deaths on 4/9/21	% of Pop.Infected	SARS-CoV-2 Isolates Currently Known in Location	National/ State Mask Mandate?	Currently in Lockdown?
World	135,290,124	786,147*	2,927,750	13,317	1.73%	B2 lineageB.1.1.7 (UK)B.1.525 (Nigeria/UK)B.1.526 (USA-NYC)B.1.351 (SA)B.1.429 + B.1.427 (USA)**P.1 (Brazil)P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Maharashtra India VOC 32421	No	No
USA	31,802,772 (ranked #1)	85,638 (ranked #3)	574,840 (ranked #1)	929	9.56%	B2 lineageB.1.1.7 (UK)B.1.525 (Nigeria/UK)B.1.526 (USA-NYC)B.1.351 (SA)B.1.429 + B.1.427 (USA)**P.1 (Brazil)P.2 (Brazil)Maharashtra India VOC 32421	No	No
Brazil	13,375,414(ranked #2)	89,090(ranked #2)	348,934(ranked #2)	3,647	6.25%	B2 lineageB.1.1.7 (UK)B.1.351 (SA)P.1 (Brazil)P.2 (Brazil)	No	No
India	13,202,783(ranked #3)	144,829(ranked #1)	168,467(ranked #4)	773	0.94%	B2 lineageB.1.1.7 (UK)B.1.351 (SA)B.1.429 + B.1.427 (USA)**B.1.525 (Nigeria/UK)APTK India VOC 32421Maharashtra India VOC 32421	No	No
United Kingdom	4,365,456(ranked #6)	3,145	127,040	60	6.40%	B2 lineageB.1.1.7 (UK)B.1.525 (Nigeria/UK)B.1.351 (SA)B.1.429 + B.1.427 (USA)**P.1 (Brazil)	No	No
California, USA	3,694,147(ranked #9)	3,609	60,282	153	9.34%	B2 lineageB.1.1.7 (UK)B.1.351 (SA)B.1.429 + B.1.427 (USA)**P.2 (Brazil)Maharashtra India VOC 32421	No	No
Mexico	2,267,109(ranked #14)	5,140	206,146(ranked #3)	548	1.74%	B2 lineageB.1.1.7 (UK)B.1.429 + B.1.427 (USA)**P.1 (Brazil)	No	No
South Africa	1,556,242(ranked #20)	1,267	53,226	53	2.50%	B2 lineageB.1.1.7 (UK)B.1.351 (SA)	No	No
Canada	1,045,278(ranked #23)	9,255	23,251	40	2.59%	B2 lineageB.1.1.7 (UK)B.1.525 (Nigeria/UK)B.1.429 + B.1.427 (USA)**P.1 (Brazil)	Yes, except Alberta Province	No
Poland	2,528,042(ranked #11)	28,523	28,523	768	6.40%	B2 lineageB.1.1.7 (UK)B.1.525 (Nigeria/UK)B.1.351 (SA)	No	No
Turkey	3,745,657(ranked #7)	55,791	33,454	253	14.40%	B2 lineageB.1.1.7 (UK)B.1.525 (Nigeria/UK)B.1.351 (SA)B.1.429 + B.1.427 (USA)**P.1 (Brazil)	No	No

*This number is higher than it was 2 weeks ago. It was 630,055.

**Also referred to as CAL.20C

SARS-CoV-2 and Children

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 March 29, CDC reported 3,185 cases of MIS-C that meet the case definition and 33 deaths—that’s 568 new cases and 3 new deaths since the March 1 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 additional 1,000 cases, and only two months to add additional 1,185 cases. This suggests to us that B.1.1.7 is causing more MIS-C.

As of the APA’s April 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. 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 April 1, A total of 284 child deaths due to COVID-19 were reported in 43 states (an increase of 16 child deaths since March 18). In the United 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. 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 49 (+2) child deaths. Arizona reported 26 (+2), California 16 (+1), Colorado 12, Georgia 10, Illinois 17 (+1) , Maryland 10, Tennessee 11, and New York City 22 (+1).

The United Kingdom tracks hospitalizations by age group, and with the increased incidence of B.1.1.7 saw the number of child hospitalizations double from November 2020 to January 2021. This data likely influenced the decision to close school buildings and go into total lockdown there on January 4, 2021. 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.

The Road Ahead

We are just on Day 80 of the Biden-Harris administration.The President has made the pandemic a first priority and has now ordered enough vaccine to vaccinate everyone who wants a vaccination by July 2021. We have been averaging 3 million vaccinations a day for the last seven days after having opened mass vaccination sites in multiple cities and states. To date, 178,837,781 doses of vaccine have been administered. As of 4/9/21, in the U.S., 68,202,458 people are fully vaccinated, which accounts for 20.5% of the population. On April 16, all people in the U.S. over the age of 16 will be eligible to receive a vaccine. The Biden administration is on track to exceed its goal of administering 200 million doses of vaccine in the first 100 days of the administration. Pfizer and Moderna have applied for emergency use authorization to administer their mRNA vaccines to children aged 12-16. Testing is ongoing for children in younger age groups.

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 with vaccination should keep the pandemic from overwhelming our health care delivery system. New mutations like B.1.429 + B.1.427 (Cal.20C) and the UK, Brazillian, South African, and Indian variants will probably spread rapidly throughout the United States over the next 90 days as several states (including Texas, Florida, Iowa, Mississippi) open up everything and do away with masking and social distancing. We are seeing an increase of 11,000 new infections per day in the United States, compared to an increase of only 9 new infections per day two weeks ago. In the UK, B.1.1.7, has increased the number of infections, hospitalizations and deaths. This and other mutants may be doing the same thing in the USA.

The bad news is that all currently available vaccines are based on the Chinese spike protein sequence from 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.

I still feel the current approach of companies and governments of making new vaccines against just the South African variant is wrong. In Brazil, where the P.1 isolate is dominant, they’ve had 1,050,649 infections and 45,208 deaths in the last 14 days. In South Africa, the total number of infections ever is 1,556,242, and they’ve had 53,226 deaths. Brazil is on track to have more infections and deaths in the next month than South Africa has had for the entire pandemic. It makes no sense to make a vaccine based on the South African mutant and not make one for the Brazilian P.1 mutant.

The ideal approach to these spreading 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 each 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 so far, the highest number of tests per day has been 1,709,210, so we’re doing nearly 600,000 fewer tests per day. 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 are finally preparing to make more vaccine, 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 We’re Reading This Week

As Variants Have Spread, Progress Against the Virus in U.S. Has Stalled (NY Times) https://www.nytimes.com/interactive/2021/04/06/us/variants-cases-spread.html
Michigan’s COVID-19 case rate is 3rd worst in US, schools go virtual, hospitals fill up (Detroit Free Press) https://www.freep.com/story/news/health/2021/03/25/michigan-covid-19-case-rate-second-worst-in-nation/6986599002/?fbclid=IwAR1l2IDUy17HOyQicUpN68Tw4B7EwDxJem4rNufrQ6onRguaemNDvG5HGy4
Community Transmission of SARS-CoV-2 Associated with a Local Bar Opening Event — Illinois, February 2021 (MMWR) https://www.cdc.gov/mmwr/volumes/70/wr/mm7014e3.htm?s_cid=mm7014e3_x
New Double Mutant Coronavirus Variant From India Found In California For First Time (Deadline) https://deadline.com/2021/04/double-mutant-coronavirus-variation-india-discovered-in-california-1234727857/
The Checkup for April 9: 102 cases of P.1 variant reported in Massachusetts (Berkshire Eagle) https://www.berkshireeagle.com/news/local/the-checkup-for-april-9-102-cases-of-p-1-variant-reported-in-massachusetts/article_9839b294-997e-11eb-b1e3-77bddba543f5.html
Coronavirus at school: at Delacroix high school in Drancy, 20 students have already lost a parent from Covid (France Bleu) https://www.francebleu.fr/infos/sante-sciences/au-lycee-delacroix-de-drancy-20-eleves-ont-perdu-leur-parents-du-covid-l-etablissement-reste-ouvert-1616775074
100 new coronavirus cases at day care linked to UK variant outbreak (ABC News) https://abcnews.go.com/US/100-coronavirus-cases-day-care-linked-uk-variant/story?id=76738410
SARS-CoV-2 spike E484K mutation reduces antibody neutralisation – ScienceDirect https://www.sciencedirect.com/science/article/pii/S2666524721000689
168 Oregonians vaccinated for COVID-19 have contracted virus; 3 died (KVAL13) https://kval.com/news/local/168-oregonians-vaccinated-for-covid-19-have-contracted-virus-3-died
Tracking Variants in CA (CA Department of Public Health) https://www.cdph.ca.gov/Programs/CID/DCDC/Pages/COVID-19/COVID-Variants.aspx
COVID Data Tracker Weekly Review (CDC) https://www.cdc.gov/coronavirus/2019-ncov/covid-data/covidview/index.html
Children and COVID-19: State-Level Data Report (American Academy of Pediatrics) https://services.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/children-and-covid-19-state-level-data-report/

COVID-19

SARS-CoV-2 Update

03/28/2021 davidcwrightmd

In the United States, SARS-CoV-2 deaths have decreased for the third time in a 14-day period. There were 4,478 fewer deaths per day than in the last 14-day period. In the last 14 days, the number of infections has increased by 9 infections per day. This increase in infections over the last four 14-day periods may be secondary to SARS CoV-2 mutants B.1.1.7 (UK isolate), a New York isolate B.1.526, the CAL.20C isolate, the South African isolate and the Brazilian isolate. Increased mask usage and social distancing, which are a part of the Biden 100-day SARS-CoV-2 plan (day 66 of plan) will be necessary to stop spread of these mutants and cause further reductions in infections, hospitalizations and deaths. On 3/26/21, 76,976 new infections occurred in the United States. There were also 1,289 deaths. The number of hospitalized patients is decreasing, and only 8,610 patients are critically ill. The number of critically ill patients has decreased by 3,060 in the last 14 days, while 14,837 new deaths occurred. This still suggests that the number of critically ill patients is decreasing because a large number of patients are still dying each day.

As of 3/26/21, we have had 561,142 deaths and 30,853,032 SARS-CoV-2 infections in the United States. We have had 792,803 new infections in the last 14 days. We are adding 396,402 infections every 7 days. Each million infections usually results in at least 20,000 deaths. On 3/12/21, twenty states have had greater than 500,000 total infections, and 30 states had greater than 5,000 total deaths.

As of 3/12/21, in the United States 9.28% of the population has had a documented SARS-CoV-2 infection. In the last 4 months nearly 6% of our country became infected with SARS-CoV-2.

As of 3/26/21, California was ranked 31st in infection percentage at 9.25%. In North Dakota 13.43% of the population was infected (ranked #1) and in South Dakota 13.20% of the population was infected (ranked #2). Thirty-four states have greater than 9% of their population infected and 45 states have greater than 6% infected. Only two states have less than 3% of their population infected: Vermont (2.96%), and Hawaii (2.06%).

New Mutants

A California Mutant

Watching the Data

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

As of the AAP’s March 18 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. 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 March 18, A total of 268 child deaths due to COVID-19 were reported in 43 states (an increase of 15 child deaths since March 4). In the United 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. 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 47 (+3) child deaths. Arizona reported 24, California 15 (+1), Georgia 10, Illinois 16, Maryland 10, Pennsylvania 9 (+2), New Jersey 6 (+2) and New York City 21.

The Road Ahead

We are just on Day 66 of the Biden-Harris administration.The President has made the pandemic a first priority and has now ordered enough vaccine to vaccinate everyone who wants a vaccination by July 2021. We have been averaging 2.6 million vaccinations a day for the last seven days after having opened mass vaccination sites in multiple cities and states. To date, 138 million doses of vaccine have been administered. The new goal of the Biden administration is to administer 200 million doses of vaccine in the first 100 days of his administration.

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, Vermont and Hawaii are doing a better job handling the pandemic than many of our states. These interventions with vaccination should keep the pandemic from overwhelming our health care delivery system. New mutations like B.1.429 + B.1.427 (Cal.20C), the UK, Brazillian and South African variants will probably spread rapidly throughout the United States over the next 90 days as several states (including Texas, Florida, Iowa, Mississippi) open up everything and do away with masking and social distancing. We are starting to see increased numbers of infections occurring in the United States. In the last seven days, we’ve averaged 4,377 infections per day greater than the preceding seven days. In the UK, B.1.1.7, has increased the number of infections, hospitalizations and deaths. This mutant may be doing the same thing in the USA.

I still feel the current approach of companies and governments of making new vaccines against just the South African variant is wrong. In Brazil, where the P.1 isolate is dominant, they’ve had 1,039,036 infections and 32,046 deaths in the last 14 days. In South Africa, the total number of infections ever is 1,543,079, and they’ve had 56,602 deaths. Brazil is on track to have more infections and deaths in two weeks than South Africa has had for the entire pandemic. It makes no sense to make a vaccine based on the South African mutant and not make one for the Brazilian P.1 mutant.

The ideal approach to these spreading major mutations on at least four 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 each 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.

COVID-19

SARS-CoV-2 Update

03/14/2021 davidcwrightmd

In the United States, SARS-CoV-2 deaths have decreased for the second time in a 14-day period. There were 492 fewer deaths per day than in the last 14-day period. In the last 14 days, the number of infections has decreased by 14,033 infections per day. This decrease in infections over the last four 14-day periods may represent increased mask usage and social distancing, which are a part of the Biden 100-day SARS-CoV-2 plan (day 52 of plan). On 3/12/21, 66,785 new infections occurred in the United States. There were also 1,505 deaths. The number of hospitalized patients is decreasing, and only 11,670 patients are critically ill. The number of critically ill patients has decreased by 3,808 in the last 14 days, while 21,534 new deaths occurred. This suggests that the number of critically ill patients is decreasing because a large number of patients are dying.

As of 3/12/21, we have had 545,545 deaths and 29,993,423 SARS-CoV-2 infections in the United States. We have had 820,681 new infections in the last 14 days. We are adding 410,340 infections every 7 days. Each million infections usually results in at least 20,000 deaths. On 3/12/21, twenty states have had greater than 500,000 total infections, and 30 states had greater than 5,000 total deaths.

As of 3/12/21, in the United States 9.02% of the population has had a documented SARS-CoV-2 infection. In the last 3.5 months 5% of our country became infected with SARS-CoV-2.

As of 3/12/21, California was ranked 29th in infection percentage at 9.02%. In North Dakota 13.23% of the population was infected (ranked #1) and in South Dakota 12.92% of the population was infected (ranked #2). Thirty states have greater than 9% of their population infected and 44 states have greater than 6% infected. Only four states have less than 4% of their population infected: Oregon (3.77%), Maine (3.47%), Vermont (2.66%), and Hawaii (1.98%).

New Mutants

A new mutant SARS-CoV-2 virus (lineage B.1.1.7), first seen in the UK in September, has now been found in multiple other countries. There are 3,170 reported cases in the US as of 3/11/21. This isolate has now been found in 49 states and the District of Columbia. This isolate (let’s call it Lineage B.1.1.7 or SARS-CoV-2 UK) 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 the B.1.1.7 variant compared to all other isolates. Due to air and other travel, this isolate will become the dominant isolate worldwide.

B.1.351, also known as the South African isolate, has 108 reported cases and has occurred in 23 states and the District of Columbia. The P.1 isolate (Brazil) has 17 reported cases and has been found in 10 states. (This data is available at https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant-cases.html)

A California Mutant

Watching the Data

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

Source: https://www.cdc.gov/mis-c/cases/index.html

As of the APA’s March 4 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. 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 March 4, A total of 256 child deaths due to COVID-19 were reported in 43 states. In the United 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. 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 44 child deaths. Arizona reported 24, California 14, Georgia 10, Illinois 16, Maryland 10, and New York City 21.

The Road Ahead

We are just on Day 66 of the Biden-Harris administration.The President has made the pandemic a first priority and has now ordered enough vaccine to vaccinate everyone who wants a vaccination by July 2021. We are currently vaccinating two million people a day in the United States and may vaccinate another 80 million people over the next 34 days. 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, Vermont and Hawaii are doing a better job handling the pandemic than many of our states. These interventions with vaccination should keep the pandemic from overwhelming our health care delivery system. New mutations like B.1.429 + B.1.427 (Cal.20C), the UK, Brazillian and South African variants will probably spread rapidly throughout the United States over the next 90 days as several states (including Texas, Florida, Iowa, Mississippi) open up everything and do away with masking and social distancing. We should start seeing increased numbers of infections occurring in the United States over the next 30 days. At least one mutant from the UK, B.1.1.7, has increased the number of infections, hospitalizations and deaths. This mutant 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 Novavax vaccine should also be available in the second quarter of 2021. The current goal of the Biden administration in the US is to vaccinate everyone who wants a vaccine by July 1, 2021. If vaccine is available, another 180 million people could be vaccinated. That’s good news. We are averaging 2 million vaccinations a day after having opened mass vaccination sites in multiple cities and states.

I feel the current approach of companies and governments of making new vaccines against just the South African variant is wrong. The ideal approach to these spreading major mutations on at least four 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 each 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 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 are finally preparing to make more vaccine, 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.