COVID-19

SARS-CoV-2 Update 2/10/23

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

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

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

XBB.1.5 Variant Continues to Dominate in the United States

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

CDC

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

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

XBB.1.5 Proportion of Sequenced Isolates in the USA

12/3/2212/10/2212/17/2212/24/2212/31/221/7/231/14/231/21/231/28/232/04/232/11/23
2.3%4.4%7.4%11.8%20.1%30.4%43.0%49.1%61.3%65.9%74.7%

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

12/3/2212/10/2212/17/2212/24/2212/31/221/7/231/14/231/21/231/28/232/04/232/11/23
53.5%57.4%58.6%60.3%59.2%53.2%44.7%40.2%31.1%27.4%21.4%

Percent of isolates identified as XBB.1.5 by Region

Region
Week ending in12345678910
12/31/2275.3%72.2%32.7%19.0%6.0%21.5%8.1%2.1%9.2%2.5%
1/14/2381.7%82.7%49.0%31.1%14%24.9%8.8%15%15.8%8.1%
1/28/2389.3%91.1%72.5%52.1%36.5%42.8%24.4%32.5%35.1%20.3%
2/11/2393.8%95.2%85.8%72.4%60.4%63.4%53.1%60.9%56.9%37.4%
CDC

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

Troubling Variant News from the UK

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

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

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

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

UK Health Security Agency
UK Health Security Agency

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

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

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

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

A Deeper Dive into U.S. COVID Data

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

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

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

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

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

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

Watching World Data

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

LocationTotal Infections as of 2/10/23New Infections on 2/10/23Total DeathsNew Deaths on 2/10/23% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World677,294,111(2,779,648 new infections in the last 14 days with an average of 198,546 infections per day).135,5096,780755(52,474 new deaths in the last 14 days with an average of 3,748 deaths per day.)8888.68%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines) Mu/B.1.621 (Colombia)C.1.2 (South Africa 2% of isolates in July 2021)R1 (Japan)Omicron/B.1.1.529 + BA.1 + BA.2 + BA.3 (South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)Four new recombinants 12/31 to 3/22)BA.2.12.1 (USA)BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)BF.7BJ.1XBB (new recombinant India)BQ.1BQ.1.1BS.1BN.1XBB.1XBB.1.5CH.1.1  NoNo
USA104,760,445(ranked #1) 653,533 new infections in the last 14 days with an average of 46,681 infections/day
12,107(ranked #7)
39 states failed to report infections on 2/10/23.
1,139,979(ranked #1) 7,743 new deaths reported in the last 14 days or an average of 553 deaths/ day. 159
38 states failed to report deaths on 2/10/23.
31.29%
B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan)         Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)Recombinant Delta AY.119.2- Omicron BA.1.1 (Tennessee, USA 12/31/21)\BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)BA.4.6 (USA 7/22)BF.7BJ.1XBB (new recombinant India)BQ.1BQ.1.1BN.1XBB.1XBB.1.5CH.1.1NoNo
Brazil36,930,339(ranked #5) 124,372 new infections in the last 14 days. 12,716 (ranked#5)697,662(ranked #2; 1,777 new deaths in the last 14 days)4217.14%
NoNo
India 44,682,530(ranked #2).
530,739(ranked #3) 3.17%
Unchanged in 8 weeks
NoNo
United Kingdom
24,293,752(ranked #9) 34,506 new infections in the last 2 weeks.204,898 (ranked #7) 1,669 new deaths in the last 2 weeks35.46%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)C.1.2 (South Africa)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)XD (AY.4/BA.1) recombinantXF (Delta/BA.1) recombinantXE (BA.1/BA.2) recombinantBA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)NoNo
California, USA12,011,521(ranked #12 in the world; 50,447 new infections in the last 14 days).1,459100,345 (ranked #20 in world; 452  new deaths in the last 14 days2230.39%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)BQ.1BQ.1.1BN.1XBBXBB.1XBB.1.5CH.1.1NoNo
Mexico7,400,848(ranked #19) 47,218 new infections in 14 days).– 332,850(ranked #5) 834 new deaths in the last 14 days)5.62%NoNo
South Africa4,057,211(ranked #38; 1,927 new infections in the last 14 days).102,595 (ranked #18) no new deaths in the last 14 days).6.67%

B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)       C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)NoNo
Canada4,560,962(ranked #34) 21,733 new infections in 14 days).50,629(ranked #24) 494  new deaths in the last 14 days.11.88% NoNo
Russia22,047,525 (ranked #10), 77,539 new infections in 14 days).12,392 (ranked #6)395,484(ranked #4)582 new deaths in 14 days3715.12%NoNo
Peru4,483,236(ranked #35, 2,408 new infections in 14 days). 200219,229(ranked #6) 500 new deaths in the last 14 days.113.31%NoNo
Spain13,748,918(ranked #12; 37,667 new infections in 14 days).1,119 (ranked #13)118,876 (ranked #16) 542 new deaths in 14 days.3629.42%
NoNo
France39,,559,127 (ranked #3)3,336 (ranked #9)164,537 (ranked #10) 457  new deaths in 14 days.4460.31%  a 0.07% increase in 14 days.NoNo
Germany37,739,472(ranked #4; 167,840 new infections in 14 days.)13,420 (ranked #4)166,763 (ranked #9)1,322 new deaths in 14 days. 10345.19%0.20% increase in 14 daysNoNo
South Korea30,325,483 (ranked #7; 218,129 new infections in 14 days).13,504(ranked #3)33,697 (ranked #34) 365 new deaths in 14 days.1759.07%0.42% increase in 14 daysNoNo
Netherlands8,586,372 (ranked #17; 4,951 new infections in 14 days).39622,992 (ranked #41)49.88%NoNo
Taiwan9,773,627(ranked #16); 345,147  new infections in 14 days16,964 (ranked #2)16,964 (ranked #56; 760 new deaths in the last 14 days)
7040.91%
1.45% of population has been infected in the last 14 days
NoNo
Japan32,908,240(ranked #6)543,390 new infections in the last 14 days28,615(ranked #1)70,377(ranked #20)
3,327 new deaths in the last 14 days for an average of 238  deaths per day.
19226.20%
0.43-% of the population infected in the last 14 days.
NoNo
Australia11,330,342(ranked #14) 34,876 new infections in 14 days.2,491 (ranked #10)19,070(ranked #49) 455 new deaths in 14 days.3543.46% 
0.14-% of the population infected in last 14 days.
NoNo
Hong Kong2,880,518(ranked# 41) 62,811 new infections in the last 14 days.25013,412 (ranked#60)132 new deaths in the last 14 days.537.88%
0.15% of the population infected in the last 14 days.
NoNo
China503,302 

What Our Team Is Reading This Week

COVID-19

SARS-CoV-2 Update 1/14/23

In 2022, multiple new Omicron variants BA.1, BA.2, BA.4, and BA.5 assaulted the world’s population of humans and other animals. By the time multiple companies made and tested Omicron BA.1 vaccines, BA.1 was no longer the dominant variant; in fact, it was no longer present. On August 31, 2022, the FDA allowed rapid introduction of an Omicron BA.5 bivalent vaccine. 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. A new variant, CH.1.1 (BA.2.75.3.4.1.1.1.1) caused 5.9% of infections in the world from December 25 to January 14, 2023 and, from December 26 to January 1, 19.5% of infections in the United Kingdom. 

On January 13, the World Health Organization (WHO) updated its recommendations on mask wearing to specify that, given the global spread of COVID-19, masks should be worn “irrespective of the local epidemiological situation,” meaning that masks are now recommended for everyone, not just people in areas with high levels of transmission. Here are our 14-day moving average determinations for SARS-CoV-2 for the United States. We use the WORLDOMETERS aggregators data set to make any projections since it includes data from the Department of Veterans Affairs, the U.S. Military, federal prisons and the Navajo Nation.

XBB.1.5 Variant Continues to Dominate

During the week ending in 1/14/22, the CDC estimates that based on genomic surveillance, XBB.1.5 accounted for 43% of infections, followed by BQ.1.1 at 28.8%, BQ.1 at 15.9%, XBB at 3.9%, BA.5 at 2.6%, BN.1 at 2.1%, BF.7 at 1.4%, and BA.2.75 at 1.3%. The remaining variants made up less than 1% each: BA.5.2.6 (0.5%), BA.2 (0.2%), BF.11 (0.2%), BA.4.6 (0.1%), and BA.2.75.2 (0.1%). We are keeping our eye on BA.2.75, as the CDC is likely lumping in its descendant, CH.1, and its subvariants under this label. 

CDC

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

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

XBB.1.5 Proportion of Sequenced Isolates in the USA

12/3/2212/10/2212/17/2212/24/2212/31/221/7/231/14/23
2.3%4.4%7.4%11.8%20.1%30.4%43.0%

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

12/3/2212/10/2212/17/2212/24/2212/31/221/7/231/14/23
53.5%57.4%58.6%60.3%59.2%53.2%44.7%

Percent of isolates identified as XBB.1.5 by Region

Region
Week ending in12345678910
12/31/2275.3%72.2%32.7%19.0%6.0%21.5%8.1%2.1%9.2%2.5%
1/14/2381.7%82.7%49.0%31.1%14%24.9%8.8%15%15.8%8.1%
CDC

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

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

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

From Daniele Focosi, M.D., Ph.D. @dfocosi on Twitter, January 9, 2023

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

A Deeper Dive into U.S. COVID Data

On 1/13/23, the United States had 19,397 documented new infections. There were also 193 deaths. Thirty-seven states did not report their infections, and 37 states didn’t report their deaths. In the United States on 1/13/23 the number of hospitalized patients (44,806)  has increased  (+10.98% compared to the previous 14 days) and was 40,374 on December 30. On 1/13/22 there were 5,449 patients who were seriously or critically ill (a 6.1% increase); that number was 5,135 two weeks ago. The number of critically ill patients has increased by 315 in the last 14 days, while at least 7,064 new deaths occurred. The number of critically ill patients has increased for the 11th time in thirty-five 14-day periods. Patients are still dying each day (average 505/day). 

As of 1/13/23, we have had 1,125,020 deaths and 103,482,187 SARS-CoV-2 infections in the United States. We have had 971,709 new infections in the last 14 days. We are adding an average of 485,855 new infections every seven days. For the pandemic in the United States we are averaging one death for every 91.98 infections or over 10,872 deaths for each one million infections. As of 1/13/22, 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. Nine states have over 4,000 deaths per million population: Mississippi (4,406), Arizona (4,465), Alabama (4,246), West Virginia (4,340), New Mexico (4,240), Tennessee (4,186), Arkansas (4,225), Michigan (4,105) and New Jersey (4,016). Eighteen states (Alabama, Virginia, Missouri, North Carolina, Indiana, Tennessee, Massachusetts, Ohio, Michigan, Georgia, Illinois, New Jersey, Pennsylvania, Florida, Texas, New York, Arizona and California) have had greater than 20,000 deaths. Nine states have had greater than 40,000 deaths: Florida (84,170 deaths), Texas (92,600 deaths), New York (75,909 deaths), Pennsylvania (49,263 deaths), Georgia (41,648 deaths), Ohio (41,001 deaths) , Illinois (40,678 deaths), Michigan (41,001), and  California (98,954 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 (26 months), there were 857,919 new deaths from SARS-CoV-2. For twenty-two of those months, vaccines have been available to all adults. During these twenty-two months, 552,821 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 1/13/23, California was ranked 32nd in the USA in infection percentage at 29.99%. In California, 26.02% of the people were infected in the last 22 months. As of 1/13/23, 31 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.                   

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

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

Watching World Data

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

LocationTotal Infections as of 1/13/23New Infections on 1/13/23Total DeathsNew Deaths on 1/13/23% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World670,816,950319,9876,728,2701,6078.60%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  NoNo
USA103,482,187 (ranked #1)
19,397 (ranked #5)
37 states and D,C. failed to report infections on 12/2/22.
1,125,020 (ranked #1) 193
37 states  and D.C. failed to report deaths on 1/13/23.
30.90%
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.1NoNo
Brazil36,623,217(ranked #5) 20,548 (ranked#4)695,334 (ranked #2)7917.00%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)NoNo
India 44,681,884 (ranked #2)
530,726(ranked #3) 3.17%
Unchanged in 4 weeks
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)NoNo
United Kingdom
24,243,576 (ranked #9)202,157 (ranked #7) 470 new deaths in 2 weeks35.39%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)NoNo
California, USA11,852,546 (ranked #13 in the world)1,51698,954 (ranked #20 in world)
2529.99%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.1NoNo
Mexico7,303,600 (ranked #19) 5,686 (ranked #11)331,452(ranked #5)455.55%NoNo
South Africa4,051,243 (ranked #37; 4,347 new infections in 14 days).183102,568 (ranked #18) 0 new deaths in 14 days)
Unchanged in 4 weeks
6.66%


Unchanged in 4 weeks
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)NoNo
Canada4,508275 (ranked #34)49,566 (ranked #24 ) 11.74% NoNo
Poland6,732,901 (ranked #21)324118,640 (ranked #15) 87 new deaths in the last 14 days716.88%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 NoNo
Russia21,846,722 (ranked #10)5,978 (ranked #12)394,209(ranked #4)4714.98%NoNo
Peru4,473,821(ranked #35)627 218,490(ranked #6) 1313.28%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)NoNo
Iran7,562,446 (ranked #18)75144,723 (ranked #12) 18.78%
Unchanged in 4 weeks
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)NoNo
Spain13,711,251 (ranked #12)9,871 (ranked #7)117,759 (ranked #16) new deaths in 14 days7629.34%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)NoNo
France39,442,176 (ranked #3)6,238 (ranked #9)163,347 (ranked #10)10160.13% B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinantBQ.1.1NoNo
Germany37,605,135 (ranked #4)10,609 (ranked #6)163,775 (ranked #9)15044.83%
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)GKA (AY.4/BA.1) recombinantBQ.1.1NoNo
South Korea29,737,769 (ranked #7)39,726 (ranked #2)32,867 (ranked #34) 6657.93%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)NoNo
Vietnam11,526,089 (ranked #13)5543,186(ranked #26)11.64%
Unchanged in 4 weeks
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
Netherlands8,576,523 (ranked #17)22,989 (ranked #41)49.83%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)GKA (AY.4/BA.1) recombinantNoNo
Denmark3,171,515 (ranked #40)  1907,982 (ranked #76)1154.35%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) recombinantNoNo




Taiwan9,167,795 (ranked #16)21,721 (ranked #3)15,755 (ranked #56)
5338.37%
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Japan31,176,281(ranked #6)144,077 (ranked #1)61,761(ranked #23)
48024.82%
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.2*BA.5*NoNo
Argentina10,004,679 (ranked #15)130,249(ranked #14)21.74%NoNo
Italy25,363,742 (ranked #8) 185,993(ranked #8) 42.08%
NoNo
Chile5,081,862 (ranked #27)3,289 (ranked#14)63,466(ranked #22) 
2926.39%
NoNo
Colombia6,349,971 (ranked #22) 142,259(ranked #13)12.32%
NoNo
Australia11,247,412 (ranked #14) 5,985 (ranked #10)17,712(ranked #50) 5943.14% 
NoNo
Turkey17,042,722 (ranked #11)101,492 (ranked #19)   19.91%
Unchanged in 4 weeks
NoNo


Indonesia6,725,458 (ranked #20)363160,719 (ranked #11)   478 new deaths in the last 14 days.824.09%NoNo
Malaysia5,032,146 (ranked #28) 32036,908 (ranked #29) 315.16%NoNo


Hong Kong2,817,707(ranked#41) 8,260 (ranked #8)12,693 (ranked#60) 345 new deaths in the last 14 days.7137.05%
NoNo
China503,302 (ranked #91)

What Our Team Is Reading This Week

COVID-19

SARS-CoV-2 Update

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

SARS-CoV-2 infections per day in the United States have increased for the 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. On 11/19/22 the CDC estimates that BA.5 accounted for 24% of infections (a 28.4% drop from 10/21/22), BQ.1 accounted for 25.5% (a 16.1% increase since 10/21/22), BQ.1.1 accounted for 24.2% (a 17.0% increase since 10/21/22), BA.4.6 accounted for 4.4% (a 5.1% decrease from 10/21/22), BF.7 accounted for 7.8% (a 1.2% decrease from 10/21/22),  and BA.2.75.2 accounted for 0.8%. A new variant BN.1 accounted for 5.1% of isolates on 11/19/22.  In the week ending November 19, 2022 BQ isolates accounted for 49.7% of infections (a 14.4% 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. 

CDC
CDC

The total percentage of BQ variant infections in the region that includes New York and New Jersey was 52.3% two weeks ago and is now 64.8%. BA.5 accounts for 14% of infections, BN.7 accounts for 5.6%, and a new isolate, BN.1, accounts for 2.2% of isolates. BA.5.2.6 isolates now account for 1.9% of infections. The BA.2.75 lineages account for 3.2% of infections. 

CDC

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

Data on the rapid spread of a dangerous variant category, the BQ variants, was withheld by the CDC in their weekly reports until three weeks ago. The data on BQ.1 and BQ.1.1, the last being a variant with five significant spike protein mutations leading to escape from immunity from prior infections or vaccination. In addition, our monoclonal antibody therapies do not work for these isolates. Infections and hospitalizations in New York are rapidly increasing, secondary to BQ variants. BQ variants have been found in all 10 regions in the United States. Since New York has been a harbinger of things to come throughout the pandemic, we expect the pattern of increased infections, hospitalizations and deaths to continue in many states. These emerging BQ variants are descendants of BA.5. It’s troubling that, despite the availability of a BA.5 bivalent SARS-CoV-2 vaccine, few people are getting vaccinated. As of November 17, 2022, the CDC reports that the Pfizer Omicron BA.5 mRNA booster was administered to 22,681,194 people and the Moderna Omicron BA.5 mRNA booster was administered to 12,715,605 people. In total, 35,396,799 people in the United States (5 years and up) have received the bivalent vaccine. That’s only 15.5% of people who received the primary series and 10.6% of the overall population.  

Children under the age of 5 have not been approved to receive either Omicron BA.5 mRNA boosters. Sadly, in children between 0 and 5 years of age only 1.5 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 1,360 children have died of COVID-19, and another 74 have died of multisystem inflammatory syndrome (MIS-C). Worldwide, according to UNICEF, over 16,100 children and young adults aged 0-20 have died of COVID-19. 

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

VariantSublineage ofSpike MutationsGlobal SequencesUK Sequences
BF.7BA.5.2.1R346T11,9222,644
BQ.1BA.5L452RN460KK444T2,4903,207
BQ.1.1BA.5N460KK444TR346T2,304(35 countries)1,272
BS.1BA.2.3.2R346TL452RN460KG476S79 2

In Monterey County during the pandemic we have had 96,339 reported SARS-CoV-2 infections, 2,983 hospitalizations and 795 reported deaths as of 11/18/22. The Monterey County Health Department reports that, as of 11/21/22, 3.1% 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 55% 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. 

Monterey County Health Department

On 11/18/22, the United States had 22,851 documented new infections. There were also 160 deaths. Thirty-four states did not report their infections, and 36 states didn’t report their deaths. In the United States on 11/18/22 the number of hospitalized patients (27,868)  has increased slightly (+2% compared to the previous 14 days) in many areas and was 27,395 on November 5. On 11/18/22 there were 3,362 patients who were seriously or critically ill; that number was 3,146 two weeks ago. The number of critically ill patients has increased by 216 in the last 14 days, while at least 4,401 new deaths occurred. The number of critically ill patients has increased for the seventh time in thirty-one 14-day periods. Patients are still dying each day (average 314/day). Two new Omicron variants BQ.1 and BQ.1.1 are causing increased numbers of infections and hospitalizations in New York and the rest of the country. BA.2.75, BA.4.6, BA.5, BF.7 and BN.1 and other variants are still causing infections. In Singapore a different Omicron BA.2 variant, XBB, has caused rapidly increasing infections and now has been named a designated variant along with BQ.1 in the October 28 UK Health Security Agency Technical Briefing. Past infections with a BA.1, BA.2 or BA.5 variants will not prevent infections with any of the newer variants. Monoclonal antibodies are not effective against newer BQ variants and other spike protein mutated variants. 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.

As of 11/18/22, we have had 1,102,439 deaths and 100,156,325 SARS-CoV-2 infections in the United States. We have had 553,847 new infections in the last 14 days. We are adding an average of 276,934 new infections every seven days. For the pandemic in the United States we are averaging one death for every 90.84 infections or over 11,007 deaths for each one million infections. As of 11/18/22, thirty-nine 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 33 states have greater than 3,000 deaths per million population. Seven states have over 4,000 deaths per million population: Mississippi (4,374), Arizona (4,348), Alabama (4,205), West Virginia (4,230), New Mexico (4,147), Tennessee (4,134), and Arkansas (4,153). . 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 (91,854 deaths), New York (73,831 deaths), Pennsylvania (48,126 deaths), Georgia (40,915 deaths), Ohio (40,391 deaths) , Illinois (40,198 deaths), and  California (97,239 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 835,338 new deaths from SARS-CoV-2. For twenty of those months, vaccines have been available to all adults. During these twenty months, 530,340 people have died of SARS-CoV-2 infections. Clearly, a vaccine-only approach is not working anywhere, especially not in the United States. In addition to getting more people vaccinated, most of the hospitalizations and deaths could have been prevented by proper masking (N95 or better), social distancing, and treatment with oral antiviral agents like Paxlovid. We recommend all of these precautions and treatments to every patient in our clinic, and we have only lost one patient to COVID in 2.5 years. 

As of 11/18/22, California was ranked 33rd in the USA in infection percentage at 28.86%. In California, 24.89% of the people were infected in the last 20 months. As of 11/18/22, 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 1,459 for the last 14 days, which is a 178 deaths-per-day decrease over the previous 14 days. The United States accounts for 21.52% (314 per day) of all deaths per day in the world over the last two weeks. Worldwide infections per day were 376,514 the last two weeks. The United States accounts for 10.51% of those infections (or 39,561 infections per day). 

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

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

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

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

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

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

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

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

Watching World Data

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.

LocationTotal Infections as of 11/18/22New Infections on 11/18/22Total DeathsNew Deaths on 11/18/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World642,552,835(5,271,193 new infections in 14 days).344,8376,624,873(20,425 new deaths in last 14 days)1,0838.24%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  NoNo
USA100,156,325(ranked #1) 553,847 new infections in the last 14 days or 39,561/day.
22,851(ranked #6)
34 states and D,C. failed to report infections on 11/18/22.
1,102,439(ranked #1) 4,401 new deaths reported in the last 14 days or 388/day. 160
36 states  and D.C. failed to report deaths on 11/18/22.
29.91%
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.1NoNo
Brazil35,039,614(ranked #5) 149,371 new infections in the last 14 days. 30,438 (ranked#4)688,958(ranked #2; 574 new deaths in 14 days)7216.27%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)NoNo
India 44,669,527(ranked #2); 10,080  new infections in 2 weeks.576
530,533(ranked #3) 47 new deaths in 2 weeks.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)NoNo
United Kingdom
23,977,637(ranked #6) 49,596 new infections in 2 weeks.196,241 (ranked #7) 1,537  new deaths in 2 weeks35.00%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)NoNo
California, USA11,405,188(ranked #14 in the world; 51,292 new infections in the last 14 days).2,21797,239 (ranked #20 in world)
255 new deaths in the last 14 days
728.86%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.1NoNo
Mexico7,118,933(ranked #19) 5,801 new infections in 14 days).330,444(ranked #5)29 new deaths in 14 days)5.41%NoNo
South Africa4,037,221(ranked #37; 7,484 new infections in 14 days).598102,371 (ranked #18) 8 new deaths in 14 days)6.64%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)NoNo
Canada4,377,070(ranked #33) 40,210 new infections in 14 days).47,118(ranked #25 ) 749  new deaths in the last 14 days11.40% NoNo
Poland6,348,380(ranked #21; 14,789 new infections in 14 days). 359118,267 (ranked #15)110 new deaths in the last 14 days1516.82%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 NoNo
Russia21,525,567 (ranked #10), 71,900 new infections in 14 days).5,546 (ranked #12)391,333(ranked #4)874 new deaths in 14 days6014.76%NoNo
Peru4,159,132(ranked #35, 25,059 new infections in 14 days). 3,357217,229(ranked #6) 257 new deaths in the last 14 days1112.42%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)NoNo
Iran7,559,211(ranked #18; 1,189 new infections in last 14 days)47144,620(ranked #12) 33 new deaths in the last 14 days38.78%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)NoNo
Spain13,573,721(ranked #12;   44,078 new infections in 14 days).3,168115,641 (ranked #16)402 new deaths in 14 days3829.0%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)NoNo
France37,287,547(ranked #3; 367,483 new infections in the last 14 days).37,177 (ranked #3)158,163 (ranked #10)886 new deaths in 14 days.7456.29%  a 0.56% 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.1.1NoNo
Germany36,205,405(ranked #4; 381,634 new infections in 14 days.)25,238 (ranked #5)156,613 (ranked #11)2,078 new deaths in 14 days 20343.16%
0.46% 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.1.1NoNo
South Korea26,462,319 (ranked #6 701,618 new infections in 14 days).49,418(ranked #2)29,925 (ranked #35) 609 new deaths in 14 days6351.55%2.37% increase in 14 daysB2 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)NoNo
Vietnam11,510,919 (ranked #13; 5,670 new infections in 14 days).43543,168(ranked #26)111.63%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)NoNo
Netherlands8,534,144 (ranked #16; 11,415 new infections in 14 days).85322,892 (ranked #41)249.58%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
Denmark3,143,261 (ranked #40) 6,511 new infections in 14 days. 2907,470 (ranked #78  83 new deaths in the last 14 days)53.86%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo




Taiwan8,130,219(ranked #17)292,561 new infections in 14 days17,991 (ranked #7)13,848 (ranked #58 764 new deaths in the last 14 days)
5834.03%
1.22% 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)NoNo
Japan23,604,176(ranked #9)1,069,799 new infections in the last 14 days84,375(ranked #1)48,058(ranked #24)
1,160 new deaths in the last 14 days
9918.79%
0.85% 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.2*BA.5*NoNo
Argentina9,721,718 (ranked #15)130,011(ranked #14)21.12%NoNo
Italy24,031,538 (ranked #7) 389,527 new infections in the last 14 days.    180,581(ranked #8) 
1,145 new deaths in the last 14 days
39.87%
0.64% of population infected in last 14 days.
NoNo
Chile4,865,658(ranked #28) 88,450 new infections in14 days..6,457 (ranked#11)62,130(ranked #22) 
398 new deaths in the last 14 days.
2825.27%
0.46% of population infected in the last 14 days.
NoNo
Colombia6,312,657(ranked #22)141,881(ranked #13)12.25%

NoNo
Australia10,552,678(ranked #14) 833,801 new infections in 14 days.10,925 (ranked #8)15,967(ranked #55) 191 new deaths in 14 days.1440.48% 
0.53% of population infected in last 14 days.
NoNo
Turkey16,976,729(ranked #11)57,091 new infections in 14 days.101,327(ranked #19) 124 new deaths in 14 days..19.84%NoNo


Indonesia6,596,,812 (ranked #20) 83,899 new infections in last 14 days.6,699 (ranked #10)159,323 (ranked #9)   555 new deaths in the last 14 days.3223.63%NoNo
Malaysia4,963,216 (ranked #27) 44,299 new infections in the last 14 days.3,037 (ranked #17)36,588 (ranked #29) 124 new deaths in the last 14 days.514.95%NoNo


Hong Kong2,020,885(ranked#47)8,008 (ranked#9)10,577 (ranked#65)826.57%NoNo
China279,4312,3885,226

What Our Team Is Reading This Week

COVID-19

SARS-CoV-2 Update

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. 

CDC
CDC

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

CDC

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

CDC

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.”

VariantSublineage ofSpike MutationsGlobal SequencesUK Sequences
BF.7BA.5.2.1R346T9,809 (1,752 from Belgium)663
BQ.1.1BA.5N460KK444TR346T326(20 countries)60
BJ.1BA.513 non- synonymous spike mutations, 7 in RBD and including4 predicted immune escape locations123 (10 countries, most cases in India)1
BS.1BA.2.3.2R346TL452RN460KG476S25 (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. 

Monterey County Health Department

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

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

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

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

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

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

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

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

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

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.

LocationTotal Infections as of 10/21/22New Infections on 10/21/22Total DeathsNew Deaths on 10/21/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World632,432,678(4,347,443 new infections in 14 days).349,3516,581,530(21,965 new deaths in last 14 days)1,1898.11%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  NoNo
USA99,055,537(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)NoNo
Brazil34,822,174(ranked #4) 64,917 new infections in the last 14 days. 3,400687,581(ranked #2; 732 new deaths in 14 days)3716.16%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)NoNo
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.43.17%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)NoNo
United Kingdom
23,855,522(ranked #7) 120,249 new infections in 2 weeks.192,682 (ranked #7) 1,794  new deaths in 2 weeks34.82%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)NoNo
California, USA11,332,345(ranked #14 in the world; 39,798 new infections in the last 14 days).99896,721 (ranked #20 in world)
303 new deaths in the last 14 days
1428.65%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)NoNo
Mexico7,106018(ranked #19) 4,587 new infections in 14 days).453330,321(ranked #5)181 new deaths in 14 days)155.40%NoNo
South Africa4,025,375(ranked #37; 4,587 new infections in 14 days).416102,257 (ranked #18) 63 new deaths in 14 days)116.62%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)NoNo
Canada4,314,718(ranked #33) 43,827 new infections in 14 days).3,06746,025(ranked #25)631  new deaths in the last 14 days4911.23% NoNo
Poland6,333,591 (ranked #21; 22,629  new infections in 14 days). 1,170118,015 (ranked #15)272 new deaths in the last 14 days2416.78%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 NoNo
Russia21,354,915(ranked #10), 190,973 new infections in 14 days).9,761 (ranked #8)389,359(ranked #4)1,368 new deaths in 14 days9314.64%NoNo
Peru4,152,019(ranked #32, 3,858 new infections in 14 days). 314216,877(ranked #6) 177 new deaths in the last 14 days12.32%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)NoNo
Iran7,555,694(ranked #17; 4,672 new infections in last 14 days)139144,540(ranked #12) 69 new deaths in the last 14 days48.78%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)NoNo
Spain13,488,015(ranked #12;   46,047 new infections in 14 days).3,630114,858 (ranked #16)390 new deaths in 14 days3128.87%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)NoNo
France36,524,605 (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.8155.69%  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) recombinantNoNo
Germany35,172,693(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 20441.93%
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) recombinantNoNo
South Korea25,244,255 (ranked #6 310,499 new infections in 14 days).24,709(ranked #8)28,952 (ranked #37) 338 new deaths in 14 days3049.18%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)NoNo
Vietnam11,496,354 (ranked #13; 10,933 new infections in 14 days).58243,159 (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)NoNo
Netherlands8,494,705 (ranked #16; 33,354 new infections in 14 days).95222,683 (ranked #41)549.35%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) recombinantNoNo
Denmark3,131,149(ranked #40) 12,835 new infections in 14 days. 6527,248 (ranked #79 126 new deaths in the last 14 days)1353.66%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) recombinantNoNo




Taiwan7,379,205(ranked #18)569,950 new infections in 14 days37,265 (ranked #3)12,206 (ranked #59 937 new deaths in the last 14 days)
7830.89%
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)NoNo
Japan21,926,231(ranked #9)463,493 new infections in the last 14 days31,593(ranked #5)46,152(ranked #25)
831 new deaths in the last 14 days
6717.45%
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.2*BA.5*NoNo

What Our Team Is Reading This Week

COVID-19

SARS-CoV-2 Update

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 second time in four 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 14 deaths per day. The number of infections per day has decreased by 19,313.  The CDC estimates that BA.5 accounted for 83.1%, BA.4.6 accounted for 11.9%, BF.7 accounted for 2.3%, BA.4 accounted for 1.4%, BA.2.12.1 accounted for 0.0% of isolates, BA.2 accounted for 0.0%, BA.1.1 accounted for 0.0%, and B.1.1.529 accounted for 0% in the week ending September 10. The rise in BA.4.6 cases is especially concerning because the September 9 UK Security Agency Technical Briefing says that, “Pseudoviral neutralisation assays performed on BA.4.6 show that titres are reduced 2-fold, compared to neutralisation of BA.4 or BA.5 using sera from triple dosed recipients of the Pfizer BNT162b2 vaccine.” The same briefing also states that BA.4.6 has a growth advantage relative to BA.5. 

CDC

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

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

NY Times

The Omicron variant has continued to mutate just like Delta. The list of variants was not updated in the last four weeks, but as of six weeks ago, there are now 276 Omicron sub-variants that have been assigned Pango lineages, including 123 sub-lineages of BA.2, one sub-lineage of BA.3, 15 sub-lineages of BA.4, and 45 sub-lineages of BA.5. The BF lineage (new fourteen weeks ago) now has 21 sublineages.. The BE lineage (also new fourteen weeks ago), with BE.1 first detected in South Africa, Austria and England, now has 7 sublineages. There are also new lineages from fourteen weeks ago: BC.1 (Japan), BC.2 (Peru), BD.1 (UK), BG.1 (Peru), BG.2 (US, Denmark, Canada), BG.3 (Peru), BG.4 (Israel). In the last six weeks, the BG lineage has expanded to include BG.5 (USA) and BG.6 (Peru). Lastly, two new sublineages were added in the past six weeks: BH.1 (India) and BK.1 (USA and Canada). 

In Monterey County, as of 9/24/22, 1.1% of 0-4 year-olds and 39.9% of 5-11 year-olds have received the first two doses of vaccine, while 73.1% of 12-17 year-olds have received two doses. Only 53.6% of Monterey County residents have received a third dose of the vaccine. On June 17, The FDA authorized both the Pfizer and Moderna vaccines for use in children ages 6 months to four years. We believe children under 5 should be vaccinated as soon as possible. All Monterey County residents should get up to date on COVID-19 vaccinations as soon as possible. 

Monterey County Health Department

On 9/23/22, the United States had 33,238 documented new infections. There were also 259 deaths. Twenty-six states did not report their infections, and 30 states didn’t report their deaths. In the United States the number of hospitalized patients has decreased slightly in many areas and was 30,273 on September 24, a decrease of 6,417 hospitalizations compared to the previous 14 days. On 9/14/22 there are 3,176 patients who are seriously or critically ill; that number was 3,829 two weeks ago. The number of critically ill patients has decreased by 653 in the last 14 days, while at least 5,228 new deaths occurred. The number of critically ill patients has decreased for the fourth time in twenty-eight 14-day periods. Patients are still dying each day (average 375/day). Omicron BA.4, BA.4.6 and BA.5 variants are still causing infections. Past infections with a BA.1 or BA.2 variant will not prevent infections with BA.4, BA.4.6 or BA.5. Evusheld may not prevent BA.4.6 infections.

As of 9/23/22, we have had 1,081,566 deaths and 97,880,451 SARS-CoV-2 infections in the United States. We have had 854,450 new infections in the last 14 days. We are adding an average of 427,225 new infections every seven days. For the pandemic in the United States we are averaging one death for every 90.48 infections or over 11,050 deaths for each one million infections. As of 9/23/22, 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. Vermont, at 1,152 deaths per million, and Hawaii, 1,186 deaths per million, are the states with the lowest death rates. Six states have over 4,000 deaths per million population: Mississippi (4,327), Arizona (4,304), Alabama (4,160), West Virginia (4,119), New Mexico (4,079) and Tennessee (4,057). 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. Four states have had greater than 70,000 deaths: Florida (81,139 deaths), Texas (91,159 deaths), New York (72,058 deaths), and  California (95,970 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 (22 months), there were 820,435 new deaths from SARS-CoV-2. For eighteen of those months, vaccines have been available to all adults. During these eighteen months, 509,469 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 9/23/22, California was ranked 32nd in the USA in infection percentage at 28.40%. In California, 24.43% of people were infected in the last 19 months. As of 9/23/22, 43 states have had greater than 25% of their population infected. No state has less than 20% of their population infected. Below are the variant proportions for Region 9, which includes California, Nevada, and Arizona. 

CDC

Worldwide, average deaths per day are 1,737 for the last 14 days, which is a 340 deaths-per-day decrease over the previous 14 days. The United States accounts for 21.58% (375 per day) of all deaths per day in the world over the last two weeks. Worldwide infections per day were 474,827. The United States accounts for 12.854% of those infections (or 61,032 infections per day). 

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

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

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

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

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

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

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

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

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.

LocationTotal Infections as of 9/23/22New Infections on 9/23/22Total DeathsNew Deaths on 9/23/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World619,585,969(6,647,575  new infections in 14 days).410,5586,538,850(24,324 new deaths in last 14 days)1,3127.94%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)  NoNo
USA97,880,451(ranked #1) 854,450 new infections in the last 14 days.
33,238(ranked #5)
26 states failed to report infections on 9/23/22.
1,081,566(ranked #1) 5,228 new deaths reported in the last 14 days. 259
30 states failed to report deaths on 9/23/22.
29.57%
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)NoNo
Brazil34,666,387(ranked #4) 129,467 new infections in the last 14 days. 6,861685,816(ranked #2; 950 new deaths in 14 days)9116.05%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)NoNo
India 44,563,337(ranked #2); 73,054 new infections in 2 weeks.4,912
528,487(ranked #3) 348 new deaths in 2 weeks.383.16%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)NoNo
United Kingdom
23,621,952(ranked #7) 67,433 new infections in 2 weeks.189,919 (ranked #7) 893  new deaths in 2 weeks34.39%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)NoNo
California, USA11,228,790(ranked #14 in the world; 100,708 new infections in the last 14 days).1,61995,970 (ranked #20 in world)
616 new deaths in the last 14 days
1328.40%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)NoNo
Mexico7,080,152(ranked #18) 27,224 new infections in 14 days).4,147330,017(ranked #5)312 new deaths in 14 days)685.36%NoNo
South Africa4,017,163(ranked #37; 3,113 new infections in 14 days).152102,169 (ranked #18) 40 new deaths in 14 days)6.58%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)       C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)NoNo
Canada4,233,468(ranked #33) 35,767 new infections in 14 days).2,47744,992(ranked #24)
618new deaths in the last 14 days
3611.60% NoNo
Poland6,268,049 (ranked #21; 61,157 new infections in 14 days). 4,438117,431 (ranked #15)1916.60%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 NoNo
Russia20,694,894(ranked #10), 734,599 new infections in 14 days).53,335 (ranked #2)386,551(ranked #4)1,386 new deaths in 14 days10414,16%NoNo
Peru4,140,129(ranked #34, 16,694 new infections in 14 days). 1,150216,446(ranked #6)1712.17%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)NoNo
Iran7,546,276(ranked #17; 8,495 new infections in last 14 days)421144,367(ranked #12)8.73%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)


NoNo
Spain13,393,196(ranked #12;   34,671 new infections in 14 days).-(ranked #18)113,845(ranked #16)676 new deaths in 14 days28.61%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)NoNo
France35,050,133 (ranked #3; 367,940 new infections in the last 14 days).38,464 (ranked #6)154,854 (ranked #10)
386  new deaths in 14 days
3053.44%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) recombinantNoNo
Germany32,905,086(ranked #5; 452,824 new infections in 14 days.).50,800 (ranked #3)149,368 (ranked #11)
1,139  new deaths in 14 days
9339.22%
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) recombinantNoNo
South Korea24,535,940 (ranked #6 601,906 new infections in 14 days).39,972(ranked #8)28,009 (ranked #37) 
628 new deaths in 14 days
5947.80%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)NoNo
Vietnam11,467,619 (ranked #13; 32,147 new infections in 14 days).1,92843,146 (ranked #26)11.58%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Netherlands8,413,532 (ranked #16; 16,553 new infections in 14 days).1,75622,633 (ranked #41)148.98%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) recombinantNoNo
Denmark3,097,088 (ranked #40) 7,517 new infections in 14 days6407,021 (ranked #79)53.22%53.07%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo




Taiwan6,132,744(ranked #22)
518,546 new infections in 14 days
42,420 (ranked #4)10,702 (ranked #63)
5925.67%
2.17% 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)NoNo
Japan20,840,785(ranked #9)
958,392 new infections in the last 14 days
61,478(ranked #1)44,071(ranked #25)
1,970 new deaths in the last 14 days
12016.59%
0.76% 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)BA.2*BA.5*NoNo

What Our Team Is Reading This Week