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.

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

Drug-Evading Mutants Continue to Dominate the Variant Soup

On 12/3/22 the CDC estimates that BA.5 accounted for 13.8% of infections (a 38.6% drop from 10/21/22), BQ.1 accounted for 30.9% (a 21.5% increase since 10/21/22), BQ.1.1 accounted for 31.9% (a 24.77% increase since 10/21/22), BA.4.6 accounted for 2.3% (a 7.2% decrease from 10/21/22), BF.7 accounted for 6.3% (a 2.7% decrease from 10/21/22), BN.1 accounted for 4.6% of isolates (a 0.5% decrease since 1/19/22), and BA.2.75.2 accounted for 0.5%. In the last two weeks, three isolates were added to the CDC’s reporting: XBB (5.5% of isolates), BA.5.2.6 (1.8%), and BF.11 (0.9%). In the week ending December 3, 2022, BQ isolates accounted for 62.8% of infections (a 27.5% increase in infections caused by these BQ variants since 10/21/22). BQ.1.1 has five spike mutations that are different from BA.5. Four of these mutations allow escape from immunity from monoclonal antibodies, any prior infection (including Omicron BA.5), or any vaccine to include the bivalent Omicron BA.5 vaccine. 

CDC
CDC

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

CDC

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

Data on the rapid spread of a dangerous variant category, the BQ variants, was withheld by the CDC in their weekly reports until five weeks ago. The data on BQ.1 and BQ.1.1, the last being a variant with five significant spike protein mutations leading to escape from immunity from prior infections or vaccination. Similarly, the XBB variant wasn’t present in the CDC’s variant proportions reporting two weeks ago, but the December 3 iteration adds XBB going back at least three weeks. 

Two virologists collaborated on Twitter to create the figure below, which Professor Johnson titled “Convergent Evolution on Steroids.”  It shows the key mutations present in many of the currently-circulating Omicron subvariants and demonstrates that mutation at site 346 is becoming more and more common. 

From Daniele Focosi, M.D., Ph.D. @dfocosi on Twitter, November 4, 2022

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

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

VariantSublineage ofMutationsGlobal Sequences outside UKUK Sequences
BQ.1BA.5L452R, N460K, K444T33,206 
(81 countries)
9,285
(> 40% of all sequenced samples)
BQ.1.1BA.5N460K, K444T, R346T17,621
(70 countries)
4,715
BA.5.2.35BA.5.2R346T, 2 synonymous single nucleotide polymorphisms (SNPs) G28423C and C7006T447848
BN.1BA.2.75.5R346T, F490S 1,127190
XBBRecombinant of BJ.1 and BM.1.1.1 (both descended from BA.2), approximate break point between spike mutations G446S and N460KE: T11A, Spike: V83A, H146Q, Q183E, F486S, F490S. Spike mutations inherited from BJ.1 are G339H, R346T, V445P, G446S and from BM.1.1.1 are N460K, F486V, F490S, and R493Q4,831 
(51 countries)
345 

Disappointing Vaccine Uptake, Especially Among Children

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

Children under the age of 5 have not been approved to receive either Omicron BA.5 mRNA booster. Sadly, in children between 0 and 5 years of age only 1.61 million have received at least one dose of any SARS-CoV-2 mRNA vaccine based on the original Wuhan isolate. In the United States, at least 1,372 children have died of COVID-19, and another 74 have died of multisystem inflammatory syndrome (MIS-C). Worldwide, according to UNICEF, over 16,100 children and young adults aged 0-20 have died of COVID-19. 

In Monterey County, during the pandemic we have had 96,851 reported SARS-CoV-2 infections, 3,022 hospitalizations and 797 reported deaths as of 12/3/22. The Monterey County Health Department reports that, as of 12/3/22, 3.3% of 0-4 year-olds and 40.1% of 5-11 year-olds have received the first two doses of vaccine, while 73.3% of 12-17 year-olds have received two doses. Only 55.1% of Monterey County residents have received a third dose of the vaccine. The Monterey County Health Department does not publish data on how many residents have received the new BA.5 bivalent booster vaccine. On June 17, The FDA authorized both the Pfizer and Moderna vaccines for use in children ages 6 months to four years. We believe children under 5 should be vaccinated as soon as possible. All Monterey County residents should get up to date on COVID-19 vaccinations, including the bivalent BA.5 booster, as soon as possible.  

Monterey County Health Department

Mask Up to Protect Against Additional Viral Threats This Winter

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

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

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

A Deeper Dive into U.S. COVID Data

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

As of 11/18/22, we have had 1,106,607 deaths and 100,787,799 SARS-CoV-2 infections in the United States. We have had 631,454 new infections in the last 14 days. We are adding an average of 315,727 new infections every seven days. For the pandemic in the United States we are averaging one death for every 91.08 infections or over 10,980 deaths for each one million infections. As of 12/02/22, thirty-nine states have had greater than 500,000 total infections, and 38 states and Puerto Rico have had greater than 5,000 total deaths. Forty-six states have had greater than 2,000 deaths, and 33 states have greater than 3,000 deaths per million population. Eight states have over 4,000 deaths per million population: Mississippi (4,380), Arizona (4,362), Alabama (4,212), West Virginia (4,256), New Mexico (4,150), Tennessee (4,145), Arkansas (4,168) and Michigan (4,014). Eighteen states (Alabama, Virginia, Missouri, North Carolina, Indiana, Tennessee, Massachusetts, Ohio, Michigan, Georgia, Illinois, New Jersey, Pennsylvania, Florida, Texas, New York, Arizona and California) have had greater than 20,000 deaths. Eight states have had greater than 40,000 deaths: Florida (82,875 deaths), Texas (91,934 deaths), New York (74,288 deaths), Pennsylvania (48,387 deaths), Georgia (41,070 deaths), Ohio (40,558 deaths) , Illinois (40,339 deaths), Michigan (40,085), and  California (97,515 deaths, 20th most deaths in the world). 

On 11/20/20, there were 260,331 (cumulative) deaths in the US from SARS-CoV-2. Since 11/20/20 (24 months), there were 839,506 new deaths from SARS-CoV-2. For twenty of those months, vaccines have been available to all adults. During these twenty months, 534,508 people have died of SARS-CoV-2 infections. Clearly, a vaccine-only approach is not working anywhere, especially not in the United States. In addition to getting more people vaccinated, most of the hospitalizations and deaths could have been prevented by proper masking (N95 or better), social distancing, and treatment with oral antiviral agents like Paxlovid. We recommend all of these precautions and treatments to every patient in our clinic, and we have only lost one patient to COVID in 2.5 years. 

As of 12/02/22, California was ranked 33rd in the USA in infection percentage at 29.06%. In California, 25.09% of the people were infected in the last 21 months. As of 12/2/22, 28 states have had greater than 30% of their population infected. Fifty states, the District of Columbia and Puerto Rico have greater than 20% of their population infected.                            

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

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

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

Watching World Data

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

LocationTotal Infections as of 12/2/22New Infections on 12/2/22Total DeathsNew Deaths on 12/2/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World649,308,956(6,756,121 new infections in 14 days).429,7436,645,094(20,221 new deaths in last 14 days)1,0298.33%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines) Mu/B.1.621 (Colombia)C.1.2 (South Africa 2% of isolates in July 2021)R1 (Japan)Omicron/B.1.1.529 + BA.1 + BA.2 + BA.3 (South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)Four new recombinants 12/31 to 3/22)BA.2.12.1 (USA)BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)BF.7BJ.1XBBBQ.1BQ.1.1BS.1BN.1  NoNo
USA100,787,779(ranked #1) 631,454 new infections in the last 14 days or 45,104/day.
32,724(ranked #5)
34 states and D,C. failed to report infections on 12/2/22.
1,106,607(ranked #1) 4,168 new deaths reported in the last 14 days or 388/day. 149
38 states  and D.C. failed to report deaths on 12/2/22.
30.10%
B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan)         Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)Recombinant Delta AY.119.2- Omicron BA.1.1 (Tennessee, USA 12/31/21)\BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)BQ.1BQ.1.1BN.1NoNo
Brazil35,375,733(ranked #5) 336,119 new infections in the last 14 days. 399251 (ranked#4)690,129(ranked #2; 1,171 new deaths in 14 days)13116.42%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)NoNo
India 44,674,195(ranked #2); 4,668  new infections in 2 weeks.211
530,627(ranked #3) 94 new deaths in 2 weeks.33.17%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
24,024,746(ranked #6) 47,109 new infections in 2 weeks.197253 (ranked #7) 1,102  new deaths in 2 weeks35.07%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)C.1.2 (South Africa)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)XD (AY.4/BA.1) recombinantXF (Delta/BA.1) recombinantXE (BA.1/BA.2) recombinantBA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)NoNo
California, USA11,483,568(ranked #14 in the world; 78,380 new infections in the last 14 days).4,81997,515 (ranked #20 in world)
176  new deaths in the last 14 days
1429.06%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)BQ.1BQ.1.1BN.1NoNo
Mexico7,132,792(ranked #19) 13,859 new infections in 14 days).330,525(ranked #5)81 new deaths in 14 days)5.42%NoNo
South Africa4,042,221(ranked #37; 5,299 new infections in 14 days).312102,464 (ranked #18) 93 new deaths in 14 days)6.65%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)       C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)NoNo
Canada4,408,276(ranked #34) 31,206 new infections in 14 days).47,781(ranked #25 ) 663  new deaths in the last 14 days11.48% NoNo
Poland6,353,850 (ranked #21; 5,470 new infections in 14 days). 542118,332 (ranked #15)65 new deaths in the last 14 days416.83%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3 NoNo
Russia21,597,613 (ranked #10), 72,046 new infections in 14 days).6,785 (ranked #11)392,060(ranked #4)727 new deaths in 14 days5814.81%NoNo
Peru4,266,251(ranked #36, 107,119 new infections in 14 days). 13,868 (ranked#9)217,428(ranked #6) 199 new deaths in the last 14 days1412.66%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Iran7,559,737(ranked #18; 526 new infections in last 14 days)31144,634(ranked #12) 14 new deaths in the last 14 days18.78%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
Spain13,612,052(ranked #12;   38,331 new infections in 14 days).2,758116,081 (ranked #16)440 new deaths in 14 days3029.13%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
France37,916,052 (ranked #3; 628,505 new infections in the last 14 days).69,253 (ranked #2)159,026 (ranked #10)863  new deaths in 14 days.7657.81%  a 1.52% increase in 14 days.B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinantBQ.1.1NoNo
Germany36,530,020(ranked #4; 324,615 new infections in 14 days.)30,420 (ranked #6)158,108 (ranked #11)1,486  new deaths in 14 days 16643.54%
0.38% increase in 14 days
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantBQ.1.1NoNo
South Korea27,155,813 (ranked #6 693,494 new infections in 14 days).57,079(ranked #3)30,568 (ranked #35) 643  new deaths in 14 days6252.90%1.35% 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
Vietnam11,516,489 (ranked #13; 5,570new infections in 14 days).58143,176(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
Netherlands8,543,838 (ranked #16; 9,694 new infections in 14 days).95922,916 (ranked #41)349.64%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
Denmark3,148,210 (ranked #40) 4,949 new infections in 14 days. 6107,537(ranked #78  67 new deaths in the last 14 days)553.95%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo




Taiwan8,329,000(ranked #17)198,781 new infections in 14 days15,643 (ranked #7)14,387 (ranked #58 539 new deaths in the last 14 days)
5334.86%
0.83% of population has been infected in the last 14 days
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Japan24,911,367(ranked #7)1,307,161 new infections in the last 14 days118,201(ranked #1)49,826(ranked #23)
1,768 new deaths in the last 14 days
18219.83%
1.04% of the population infected in the last 14 days.
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)BA.2*BA.5*NoNo
Argentina9,727,247 (ranked #15)5,529 new infections in the last 14 days.130,025(ranked #14)21.14%NoNo
Italy24,327,664 (ranked #8) 96,126 new infections in the last 14 days.    181,733(ranked #8) 
1,152 new deaths in the last 14 days
40.36%
0.49% of population infected in last 14 days.
NoNo
Chile4,925,051(ranked #28) 59,393 new infections in14 days..5,041 (ranked#13)62,484(ranked #22) 
354 new deaths in the last 14 days.
2625.28%
0.31% of population infected in the last 14 days.
NoNo
Colombia6,318,021(ranked #22) 5,364 new infections in the last 14 days.3,252141,811(ranked #13)1612.26%
NoNo
Australia10,725,239(ranked #14) 172,561 new infections in 14 days.14,741 (ranked #8)16,187(ranked #55) 220 new deaths in 14 days.1641.14% 
0.66% of population infected in last 14 days.
NoNo
Turkey17,005,537(ranked #11)28,808 new infections in 14 days.101,400(ranked #19)   73 new deaths in 14 days..19.87%NoNo


Indonesia6,669,821 (ranked #20) 73,009 new infections in last 14 days.4,977 (ranked #14)159,884 (ranked #9)   561 new deaths in the last 14 days.5423.89%NoNo
Malaysia4,994,543 (ranked #27) 31,327 new infections in the last 14 days.2,37536,695 (ranked #29) 107 new deaths in the last 14 days.1115.05%NoNo


Hong Kong2,128,382(ranked#46) 107,497 new infections in the last 14 days.10,137 (ranked #10)10,762 (ranked#64)185 new deaths in the last 14 days.1527.98%
1.41% of population infected in the last 14 days.
NoNo
China323,686 (ranked #103) 44,255 new infections in 14 days4,150 (ranked#15)

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

CDC
CDC

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

CDC

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

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 2, 2022, the CDC reports that only 26,378,963 people have received the bivalent vaccine. The Pfizer Omicron BA.5 mRNA booster was administered to 16,748,737 people and the Moderna Omicron BA.5 mRNA booster was administered to 9,630,226 people. In total, 26.3 million people (5 years and up) have received the bivalent vaccine. That’s only 11.6% of people who received the primary series and 7.9% of the overall population.  

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

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

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
Data from UK Health Security Agency

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

Monterey County Health Department

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Watching World Data

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 11/04/22New Infections on 11/04/22Total DeathsNew Deaths on 11/04/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World637,281,842(4,849,164 new infections in 14 days).273,3336,604,448(22,918 new deaths in last 14 days)1,0918.17%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines) Mu/B.1.621 (Colombia)C.1.2 (South Africa 2% of isolates in July 2021)R1 (Japan)Omicron/B.1.1.529 + BA.1 + BA.2 + BA.3 (South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)Four new recombinants 12/31 to 3/22)BA.2.12.1 (USA)BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)BF.7BJ.1XBBBQ.1BQ.1.1BS.1  NoNo
USA99,602,478(ranked #1) 546,941 new infections in the last 14 days or 39,067/day.
19,652(ranked #6)
35 states and D,C. failed to report infections on 11/04/22.
1,098,038(ranked #1) 5,432 new deaths reported in the last 14 days or 388/day. 148
37 states  and D.C. failed to report deaths on 11/04/22.
29.74%
B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan)         Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)Recombinant Delta AY.119.2- Omicron BA.1.1 (Tennessee, USA 12/31/21)\BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)NoNo
Brazil34,890,243(ranked #5) 62,069 new infections in the last 14 days. 2,738688,384(ranked #2; 803 new deaths in 14 days)6816.20%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)NoNo
India 44,659,447(ranked #2); 18,699  new infections in 2 weeks.1,082
530,486(ranked #3) 1,529 new deaths in 2 weeks.73.17%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
23,930,041(ranked #7) 74,519 new infections in 2 weeks.194,704 (ranked #7) 2,022  new deaths in 2 weeks34.93%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)C.1.2 (South Africa)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)XD (AY.4/BA.1) recombinantXF (Delta/BA.1) recombinantXE (BA.1/BA.2) recombinantBA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)NoNo
California, USA11,353,896(ranked #13 in the world; 21,351 new infections in the last 14 days).1,43496,984 (ranked #20 in world)
303 new deaths in the last 14 days
728.73%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)NoNo
Mexico7,113,132(ranked #19) 7,114 new infections in 14 days).628330,415(ranked #5)94 new deaths in 14 days)55.40%NoNo
South Africa4,029,737(ranked #37; 4,362 new infections in 14 days).241102,363 (ranked #18) 106 new deaths in 14 days)526.63%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)       C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)NoNo
Canada4,336,860(ranked #33) 22,142 new infections in 14 days).46,389(ranked #25 ) 364  new deaths in the last 14 days11.29% NoNo
Poland6,333,591 (ranked #21; 9,506  new infections in 14 days). 693118,157 (ranked #15)142 new deaths in the last 14 days1416.80%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3 NoNo
Russia21,453667(ranked #10), 98,753 new infections in 14 days).6,149 (ranked #9)390,459(ranked #4)1,100 new deaths in 14 days7114.71%NoNo
Peru4,159,132(ranked #36, 7,113new infections in 14 days). 598216,972(ranked #6) 95 new deaths in the last 14 days512.34%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Iran7,558,002(ranked #17; 2,308 new infections in last 14 days)40144,587(ranked #12) 47 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
Spain13,529,643(ranked #12;   41,628 new infections in 14 days).2,551115,239 (ranked #16)381 new deaths in 14 days2328.95%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
France36,920,064 (ranked #3; 395,459 new infections in the last 14 days).29,438 (ranked #4)157,277 (ranked #10)940 new deaths in 14 days.7856.29%  a 0.60% increase in 14 days.B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinantNoNo
Germany35,823,771(ranked #4; 651,078 new infections in 14 days.)38,859 (ranked #2)154,535 (ranked #11)2,053 new deaths in 14 days 20742.70%
0.77% increase in 14 days
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
South Korea25,760,701 (ranked #6 516,446 new infections in 14 days).43,424(ranked #1)29,315 (ranked #36) 363 new deaths in 14 days3549.18%1.00% 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
Vietnam11,505,249 (ranked #13; 8,895 new infections in 14 days).33943,165(ranked #26)11.62%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Netherlands8,521,729 (ranked #16; 27,024 new infections in 14 days).1,22522,845 (ranked #41)349.51%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
Denmark3,138,750 (ranked #40) 7,601 new infections in 14 days. 3557,387 (ranked #78 139 new deaths in the last 14 days)1253.79%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo




Taiwan7,837,658(ranked #17)458,453 new infections in 14 days27,594 (ranked #5)13,084 (ranked #59 878 new deaths in the last 14 days)
7432.80%
1.91% of population has been infected in the last 14 days
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Japan22,534,377(ranked #9)608,146 new infections in the last 14 days34,064(ranked #5)46,898(ranked #24)
757 new deaths in the last 14 days
5917.94%
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)BA.2*BA.5*NoNo
Argentina9,718,875 (ranked #15)129,991(ranked #14)21.12%NoNo
Italy23,642,011 (ranked #8)     179,436(ranked #8)39,23%NoNo
Chile4,777,208(ranked #28)7,57061,737(ranked #22)1224.81%NoNo
Colombia6,310,332(ranked #14)141,850(ranked #13)12.25%NoNo
Australia9,718,875(ranked #14)15,618 (ranked #7)15,776(ranked #55)5939.95%NoNo
Turkey16,919,638(ranked #11)101,203(ranked #19)19.77%NoNo
Indonesia6,512,913 (ranked #20)5,303 (ranked #11)158,768 (ranked #9)3123,23%NoNo
Malaysia4,918,917 (ranked #29)4,360 (ranked #13)36,481 (ranked #29)114.75%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 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 third time in 10 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 increased by 60 deaths per day. The number of infections per day has decreased by 15,124. The CDC estimates that BA.5 accounted for 79.2%, BA.4.6 accounted for 13.6%, BF.7 accounted for 4.6%,  BA.2.75 accounted for 1.8% and BA.4 accounted for 0.8%, in the week ending October 8. The rise in BA.4.6 cases is especially concerning because the September 9 UK Health 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. The October 7 UK Health Security Agency 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.5N460K
K444T
R346T
326(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.2.3.2R346T
L452R
N460K
G476S
25 (15 from Japan)0
Data from 7 October 2022 UK Health Security Agency Technical Briefing

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 sixteen weeks ago) now has 21 sublineages. The BE lineage (also new sixteen weeks ago), with BE.1 first detected in South Africa, Austria and England, now has 7 sublineages. There are also new lineages from sixteen 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 eight weeks, the BG lineage has expanded to include BG.5 (USA) and BG.6 (Peru). Lastly, two new sublineages were added in the past eight weeks: BH.1 (India) and BK.1 (USA and Canada). 

In Monterey County, as of 10/7/22, 1.7% of 0-4 year-olds and 40.0% of 5-11 year-olds have received the first two doses of vaccine, while 73.2% of 12-17 year-olds have received two doses. Only 53.9% 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 10/07/22, the United States had 23,524 documented new infections. There were also 229 deaths. Thirty states did not report their infections, and 33 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 10/07/22 there are 2,753 patients who are seriously or critically ill; that number was 3,176 two weeks ago. The number of critically ill patients has decreased by 423 in the last 14 days, while at least 6,089 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 435/day). Omicron BA.4, BA.4.6, BA.5, and BF.7 variants are still causing infections. Past infections with a BA.1 or BA.2 variant will not prevent infections with any of the newer variants. 

As of 10/07/22, we have had 1,087,655 deaths and 98,523,168 SARS-CoV-2 infections in the United States. We have had 642,717 new infections in the last 14 days. We are adding an average of 321,358 new infections every seven days. For the pandemic in the United States we are averaging one death for every 90.58 infections or over 11,040 deaths for each one million infections. As of 10/07/22, 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 1,167 deaths per million, and Hawaii, 1,196 deaths per million, are the states with the lowest death rates. Seven states have over 4,000 deaths per million population: Mississippi (4,344), Arizona (4,315), Alabama (4,175), West Virginia (4,157), New Mexico (4,099), Tennessee (4,087) and Arkansas (4,068). . 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. Six states have had greater than 40,000 deaths: Florida (81,566 deaths), Texas (91,394 deaths), New York (72,346 deaths), Pennsylvania (47,323 deaths), Georgia (40,374 deaths) and  California (96,418 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 820,654 new deaths from SARS-CoV-2. For nineteen of those months, vaccines have been available to all adults. During these eighteen months, 515,558 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 10/07/22, California was ranked 32nd in the USA in infection percentage at 28.57%. In California, 24.60% of people were infected in the last 19 months. As of 9/23/22, 23 states have had greater than 30% 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 1,480 for the last 14 days, which is a 257 deaths-per-day decrease over the previous 14 days. The United States accounts for 29.39% (435 per day) of all deaths per day in the world over the last two weeks. Worldwide infections per day were 464,233. The United States accounts for 9.89% of those infections (or 45,908 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 10/07/22New Infections on 10/07/22Total DeathsNew Deaths on 10/07/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World626,085,235(6,488,266 new infections in 14 days).458,5976,559,565(20,715 new deaths in last 14 days)1,2558.03%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
USA98,523,168(ranked #1) 642,717 new infections in the last 14 days.
23,524(ranked #6)
30 states failed to report infections on 10/08/22.
1,087,655(ranked #1) 6,089 new deaths reported in the last 14 days. 229
33 states failed to report deaths on 10/07/22.
29.40%
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
Brazil34,757,257(ranked #4) 90,870 new infections in the last 14 days. 7,149686,849(ranked #2; 1,033 new deaths in 14 days)9016.09%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 44,609,257(ranked #2); 45,920 new infections in 2 weeks.2,797
528,778(ranked #3) 291 new deaths in 2 weeks.243.16%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
23,735,273(ranked #7) 13,321 new infections in 2 weeks.190,888 (ranked #7) 969  new deaths in 2 weeks34.55%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, USA11,292,547(ranked #14 in the world; 63,757 new infections in the last 14 days).1,32196,418 (ranked #20 in world)
616 new deaths in the last 14 days
1028.57%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)NoNo
Mexico7,090,965(ranked #18) 27,224 new infections in 14 days).330,139(ranked #5)122 new deaths in 14 days)5.37%NoNo
South Africa4,020,788(ranked #37; 3,113 new infections in 14 days).359102,194 (ranked #18) 25 new deaths in 14 days)6.59%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
Canada4,270,891(ranked #33) 37,423 new infections in 14 days).2,75645,394(ranked #24)392 new deaths in the last 14 days2611.09% NoNo
Poland6,310,962 (ranked #21; 42,913 new infections in 14 days). 2,618117,743 (ranked #15)312 new deaths in the last 14 days4116.71%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
Russia21,163,942(ranked #10), 469,048 new infections in 14 days).22,268 (ranked #7)387,991(ranked #4)1,386 new deaths in 14 days10414.48%NoNo
Peru4,148,161(ranked #34, 8,032 new infections in 14 days). 339216,700(ranked #6) 254 new deaths in the last 14 days5512.19%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
Iran7,551,022(ranked #17; 4,746 new infections in last 14 days)166144,471(ranked #12) 104 new deaths in the last 14 days28.73%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
Spain13,441,941(ranked #12;   48,745 new infections in 14 days).3,615114,468 (ranked #16)623 new deaths in 14 days6828.72%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
France35,766,357 (ranked #3; 716,224 new infections in the last 14 days).Double the new infections of the previous 14 days61,121 (ranked #2)155,534 (ranked #10)676 new deaths in 14 days.5353.52%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinantNoNo
Germany33,948,632(ranked #5; 1,043,546 new infections in 14 days.).More than double the new infections of the previous 14 days.122,265 (ranked #1)150,535 (ranked #11)1,167 new deaths in 14 days12940.22%
1% 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 Korea24,933,756 (ranked #6 397,816 new infections in 14 days).22,529(ranked #8)28,614 (ranked #37) 505 new deaths in 14 days4148.53%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
Vietnam11,485,361 (ranked #13; 17,742 new infections in 14 days).70243,152 (ranked #26)111.56%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Netherlands8,441,351 (ranked #16; 22,819 new infections in 14 days).22,663 (ranked #41)149.01%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
Denmark3,118,314 (ranked #40) 21,226 new infections in 14 days. Has more than doubled new infections  last 14 days.8727,121 (ranked #79 100 new deaths in the last 14 days)953.41%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




Taiwan6,782,455(ranked #19)649,711 new infections in 14 days50,570 (ranked #3)11,369 (ranked #62 667 new deaths in the last 14 days)
5228.36%
2.69% 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
Japan21,489,738(ranked #9)648,953 new infections in the last 14 days29,443(ranked #5)45,321(ranked #25)
1,970 new deaths in the last 14 days
7317.10%
0.51% 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

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

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.2.12.1 accounted for 0.1% of isolates, BA.2 accounted for 1.0%, BA.5 accounted for 87.5%, BA.4 accounted for 2.2%, BA.4.6 accounted for 9.2%, 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 two weeks, but as of four 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 twelve weeks ago) now has 21 sublineages.. The BE lineage (also new twelve weeks ago), with BE.1 first detected in South Africa, Austria and England, now has 7 sublineages.. There are also new lineages from twelve 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 four weeks, the BG lineage has expanded to include BG.5 (USA) and BG.6 (Peru). Lastly, two new sublineages were added in the past four weeks: BH.1 (India) and BK.1 (USA and Canada). 

In Monterey County, as of 9/11/22, 0.6% of 0-4 year-olds and 39.7% of 5-11 year-olds have received the first two doses of vaccine, while 73.0% of 12-17 year-olds have received two doses. Only 53.4% 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 9/09/22, the United States had 50,822 documented new infections. There were also 317 deaths. Twenty-six states did not report their infections, and 29 states didn’t report their deaths. In the United States the number of hospitalized patients has decreased slightly in many areas and was 36,690 on September 6, a decrease of 1,949 hospitalizations compared to the previous 14 days. On 9/09/22 there are 3,829 patients who are seriously or critically ill; that number was 3,992 two weeks ago. The number of critically ill patients has decreased by 153 in the last 14 days, while at least 6,495 new deaths occurred. The number of critically ill patients has decreased for the third time in twenty-seven 14-day periods. Patients are still dying each day (average 464/day). Omicron BA.4, BA.4.6 (a new USA variant) and BA.5 variants causing infections should continue to increase and critically ill patients may increase. Deaths usually lag two to four weeks behind exponential increase in 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 9/09/22, we have had 1,075,338 deaths and 97,026,001 SARS-CoV-2 infections in the United States. We have had 1,055,994 new infections in the last 14 days. We are adding an average of 527,997 new infections every seven days. For the pandemic in the United States we are averaging one death for every 90.23 infections or over 11,083 deaths for each one million infections. As of 9/09/22, thirty-eight states have had greater than 500,000 total infections, and 37 states have had greater than 5,000 total deaths. Forty-six states have had greater than 2,000 deaths, and 46 states have greater than 2,000 deaths per million population. Vermont, at 1,146 deaths per million, and Hawaii, 1,169 deaths per million, are the states with the lowest death rates. Five states have over 4,000 deaths per million population: Mississippi (4,308), Arizona (4,281), Alabama (4,134), West Virginia (4,088), New Mexico (4,046( and Tennessee (4,032). 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 (80,384 deaths), Texas (90,860 deaths), New York (71,730 deaths), and  California (95,354 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 815,207 new deaths from SARS-CoV-2. For eighteen of those months, vaccines have been available to all adults. During these eighteen months, 504,241 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 9/09/22, California was ranked 32nd in the USA in infection percentage at 28.16%. In California, 24.19% of people were infected in the last 19 months. As of 9/09/22, 42 states have had greater than 25% of their population infected. No state has less than 20% of their population infected. 

Worldwide, average deaths per day are 2,077 for the last 14 days, which is a 322 deaths-per-day decrease over the previous 14 days. The United States accounts for 15.95% (464 per day) of all deaths per day in the world over the last two weeks. Worldwide infections per day were 584,902. The United States accounts for 12.899% of those infections (or 75,428 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. 

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 9/09/22New Infections on 9/09/22Total DeathsNew Deaths on 9/09/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World612,988,394(8,188,628  new infections in 14 days).492,2846,514,526(29,079 new deaths in last 14 days)1,7167.86%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
USA97,026,001(ranked #1) 1,055,994 new infections in the last 14 days.
50,822(ranked #4)
26 states failed to report infections on 9096/22.
1,076,338(ranked #1) 6,495  new deaths reported in the last 14 days. 317
29 states failed to report deaths on 9/09/22.
26.72%*
*Not updated for 10 weeks by Worldometer.
B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan)         Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)Recombinant Delta AY.119.2- Omicron BA.1.1 (Tennessee, USA 12/31/21)\BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)NoNo
Brazil34,536.920(ranked #4) 195,011 new infections in the last 14 days. 14,005 (ranked #9)684,866(ranked #2; 1,402 new deaths in 14 days)8216.01%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 44,490,283(ranked #2); 101,587 new infections in 2 weeks.9,938 (ranked #11)
528,139(ranked #3) 631 new deaths in 2 weeks.363.16%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
23,554,519(ranked #7) 61,644 new infections in 2 weeks.189,026 (ranked #7) 1,265 new deaths in 2 weeks34.30%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*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, USA11,128,082(ranked #14 in the world; 75,216 new infections in the last 14 days).2,19195,354 (ranked #20 in world)
395 new deaths in the last 14 days
1428.16%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
Mexico7,052,928(ranked #18) 51,338 new infections in 14 days).2,973329,705(ranked #5)426 new deaths in 14 days)305.34%NoNo
South Africa4,014,050(ranked #36; 3,418 new infections in 14 days).329102,129 (ranked #18) 45 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
Canada4,197,701(ranked #33) 39,219 new infections in 14 days).2,62644,374(ranked #24)
550 new deaths in the last 14 days
3410.93% NoNo
Poland6,206,982 (ranked #21; 44,320 new infections in 14 days). 4,553117,233 (ranked #15)1416.44%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
Russia19,960,295(ranked #9), 648,322 new infections in 14 days).52,106 (ranked #4)385,165(ranked #4)1,255 new deaths in 14 days9613.68%NoNo
Peru4,123,435(ranked #34, 28,783 new infections in 14 days). 2,399216,045(ranked #6)4212.24%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
Iran7,537,781(ranked #17; 16,788 new infections in last 14 days)700144,135(ranked #12)278.76%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
Spain13,367,647(ranked #12;   34,671 new infections in 14 days).2,975(ranked #18)113,130 (ranked #16)676 new deaths in 14 days6928.61%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
France34,682,193 (ranked #3; 235,339 new infections in the last 14 days).19,087 (ranked #7)154,468 (ranked #10)
621 new deaths in 14 days
3152.88%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinantNoNo
Germany32,452,250(ranked #5; 410,902 new infections in 14 days.).30,166 (ranked #6)148,229 (ranked #11)
1,125 new deaths in 14 days
8238.68%
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 Korea23,933,949 (ranked #6 1,130,964 new infections in 14 days).69,389(ranked #2)27,381 (ranked #37) 
968 new deaths in 14 days
6846.62%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Vietnam11,435,472 (ranked #13; 36,072 new infections in 14 days).1,21943,126 (ranked #25)11.55%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
Netherlands8,396,979 (ranked #15; 15,970 new infections in 14 days).1,21922,613 (ranked #41)148.78%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) 7,970 new infections in 14 days6146,968 (ranked #79)353.07%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




Taiwan5,614,198(ranked #22)
445,249 new infections in 14 days
34,231 (ranked #5)10,225 (ranked #64)
5523.50%
1.89% 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
Japan19,882,393(ranked #10)
1,918,596 new infections in the last 14 days
112,404(ranked #1)42,101(ranked #26)
3,904 new deaths in the last 14 days
26115.83%
1.52% 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

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 first time in two weeks; however, there is still widespread underreporting by states, a failure to capture positive home tests, and a decreased PCR screening program in most states. Deaths per day in the United States have decreased by 31 deaths per day. The number of infections have decreased by 19,061 infections per day.  The CDC estimates that BA.2.12.1 accounted for 0.2% of isolates, BA.2 accounted for 0%, BA.5 accounted for 88.7%, BA.4 accounted for 3.6%, BA.4.6 accounted for 7.5%, and B.1.1.529 accounted for 0% in the week ending August 27.

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.

NY Times

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

The Omicron variant has continued to mutate just like Delta. There are now 276 Omicron sub-variants (an increase of 46 in the last two weeks) that have been assigned Pango lineages, including 123 sub-lineages of BA.2 (an increase of 7 in two weeks), one sub-lineage of BA.3, 15 sub-lineages of BA.4 (an increase of one in two weeks), and 45 sub-lineages of BA.5 (an increase of 21 in two weeks). The BF lineage (new ten weeks ago) now has 21 sublineages, an increase of 10 in two weeks. The BE lineage (also new ten weeks ago), with BE.1 first detected in South Africa, Austria and England, now has 7 sublineages, an increase of 3 in two weeks. There are also new lineages from ten 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 two weeks, the BG lineage has expanded to include BG.5 (USA) and BG.6 (Peru). Lastly, two new sublineages were added in the past two weeks: BH.1 (India) and BK.1 (USA and Canada). 

In Monterey County, as of 8/28/22, 0.5% of 0-4 year-olds and 39.4% of 5-11 year-olds have received the first two doses of vaccine, while 72.9% of 12-17 year-olds have received two doses. Only 53.4% of Monterey County residents have received a third dose of the vaccine. On June 17, The FDA authorized both the Pfizer and Moderna vaccines for use in children ages 6 months to four years. We believe children under 5 should be vaccinated as soon as possible. We would anticipate, with the start of school on August 5 and the low vaccination rates in our county, that we’ll have a marked increase in the number of infected patients. All Monterey County residents should get up to date on COVID-19 vaccinations as soon as possible. 

Monterey County Health Department

On 8/26/22, the United States had 63,798 documented new infections. There were also 312 deaths. Twenty-four states did not report their infections, and 28 states didn’t report their deaths. In the United States the number of hospitalized patients has decreased slightly in many areas and was 38,630 on August 27, a decrease of 9% compared to the previous 14 days. Now there are 3,992 patients who are seriously or critically ill; that number was 4,490 two weeks ago. The number of critically ill patients has decreased by 498 in the last 14 days, while at least 6,692 new deaths occurred. The number of critically ill patients has decreased for the second time in twenty-six 14-day periods. Patients are still dying each day (average 478/day). Omicron BA.4, BA.4.6 (a new USA variant) and BA.5 variants causing infections should continue to increase and critically ill patients may increase. Deaths usually lag two to four weeks behind exponential increase in infections. Past infections with a BA.1 or BA.2 variant will not prevent infections with BA.4, BA.4.6 or BA.5. 

As of 8/26/22, we have had 1,068,843 deaths and 95,970,007 SARS-CoV-2 infections in the United States. We have had 1,326,375 new infections in the last 14 days. We are adding an average of 663,188 infections every seven days. For the pandemic in the United States we are averaging one death for every 89.78 infections or over 11,137 deaths for each one million infections. As of 8/26/22, thirty-eight states have had greater than 500,000 total infections, and 37 states have had greater than 5,000 total deaths. Forty-six states have had greater than 2,000 deaths, and 42 states have greater than 2,000 deaths per million population. Vermont, at 1,153 deaths per million, and Hawaii, 1,133 deaths per million, are the states with the lowest death rates. 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 (79,568 deaths), Texas (90,539 deaths), New York (71,422 deaths), and  California (94,959 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 (21 months), there were 808,712 new deaths from SARS-CoV-2. For seventeen of those months, vaccines have been available to all adults. During these seventeen months, 497,746 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 8/26/22, California was ranked 32nd in the USA in infection percentage at 27.97%. In California, 24.0% of people were infected in the last 19 months. As of 8/26/22, 41 states have had greater than 25% of their population infected. No state has less than 20% of their population infected. 

Worldwide, average deaths per day are 2,399 for the last 14 days, which is a 55 deaths-per-day decrease over the previous 14 days. The United States accounts for 19.92% (478 per day) of all deaths per day in the world over the last two weeks. Worldwide infections per day were 774,366. The United States accounts for 12.23% of those infections (or 94,741 infections per day). 

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 8/26/22New Infections on 8/26/22Total DeathsNew Deaths on 8/26/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World604,789,766(10,841,118 new infections in 14 days).689,1946,485,447(33,589 new deaths in last 14 days)1,9277.75%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
USA95,970,007(ranked #1) 1,326,375 new infections in the last 14 days.
63,798(ranked #3)
24 states failed to report infections on 8/26/22.
1,068,843(ranked #1) 6,692  new deaths reported in the last 14 days. 312
30 states failed to report deaths on 8/26/22.
26.72%*
*Not updated for 8 weeks by Worldometer.
B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan)         Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)Recombinant Delta AY.119.2- Omicron BA.1.1 (Tennessee, USA 12/31/21)\BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)NoNo
Brazil34,368,909(ranked #4) 220,778 new infections in the last 14 days. 18,270 (ranked #8)683,464(ranked #2; 2,147 new deaths in 14 days)13615.92%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 44,398,696(ranked #2); 159,324 new infections in 2 weeks.9,520 (ranked #12)
527,597(ranked #3) 631 new deaths in 2 weeks.413.15%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
23,492,875(ranked #6) 72,049 new infections in 2 weeks.187,761 (ranked #7) 1,674 new deaths in 2 weeks34.22%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, USA11,052,866(ranked #14 in the world;  156,070 new infections in the last 14 days).11,37494,959 (ranked #20 in world)
640 new deaths in the last 14 days
5527.97%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
Mexico7,001,590(ranked #18) 7,728 new infections in 14 days).7,281(ranked #16)329,289(ranked #5)693 new deaths in 214 days)645.31%B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
South Africa4,010,632(ranked #36; 2,607 new infections in 14 days).247102,084 (ranked #18) 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
Canada4,158,491(ranked #33) 48,560 new infections in 14 days).3,27043,797(ranked #24)3910.81% B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
Poland6,162,662 (ranked #21; 48,822 new infections in 14 days). 3,847117,007 (ranked #15)4016.32%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
Russia19,311,973(ranked #9), 487,691 new infections in 14 days).46,452 (ranked #4)383,910(ranked #4)899 new deaths in 14 days8113.22%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)R1 (Japan) B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Peru4,094,652(ranked #34, 80,821 new infections in 14 days). 3,286215,566(ranked #6)4212.05%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
Iran7,520,993(ranked #17; 55,414 new infections in last 14 days)2,019143,647(ranked #12)358.71%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
Spain13,332,976(ranked #12;   38,737 new infections in 14 days).3,064(ranked #26)112,454 (ranked #16)787 new deaths in 14 days7028.49%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
France34,446,854 (ranked #3; 254,935 new infections in the last 14 days).18,116 153,857 (ranked #10)
793 new deaths in 14 days
5152.52%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinantNoNo
Germany32,041,348(ranked #5; 506,005 new infections in 14 days.).33,226 (ranked #5)147,104 (ranked #11)
1,406 new deaths in 14 days
10137.98%
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
South Korea22,802,985 (ranked #7 1,691,145 new infections in 14 days).101,064(ranked #2)26,413 (ranked #37) 8144.39%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
Vietnam11,399,400 (ranked #13; 36,860 new infections in 14 days).3,19543,110 (ranked #25)11.48%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
Netherlands8,381,009 (ranked #16; 18.445 new infections in 14 days).1,15622,594 (ranked #41)248.68%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
Denmark3,089,118 (ranked #40) 12,476 new infections in 14 days6806,893 (ranked #79)552.93%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)GKA (AY.4/BA.1) recombinantNoNo




Taiwan5,168,949(ranked #23)
322,462 new infections in 14 days
26,713 (ranked #6)9,773 (ranked #65)
4521.61%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
Japan17,983,797(ranked #10)
2,897,493 new infections in the last 14 days
227,139(ranked #1)38,197(ranked #27)
3,660 new deaths in the last 14 days
31014.31%
2.31% 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

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

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

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

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

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

Monterey County Public Health

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

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

  1. Facility/Provider Name for Registration
  2. Provider Type (Hospital, Pharmacy, Etc)
  3. Shipping Address
  4. Contact Name(s)
  5. Contact Email(s)
  6. Contact Phone Number(s)

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

Watching World Data

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 8/12/22New Infections on 8/12/22Total DeathsNew Deaths on 8/12/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World593,948,648(13,178,472 new infections in 14 days).792,5726,451,858(34,360 new deaths in last 14 days)2,2417.61%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines) Mu/B.1.621 (Colombia)C.1.2 (South Africa 2% of isolates in July 2021)R1 (Japan)Omicron/B.1.1.529 + BA.1 + BA.2 + BA.3 (South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)Four new recombinants 12/31 to 3/22)BA.2.12.1 (USA)BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)NoNo
USA94,643,632(ranked #1) 1,589,448 new infections in the last 14 days.
85,116(ranked #3)
22 states failed to report infections on 8/12/22.
1,062,151(ranked #1) 7,131  new deaths reported in the last 14 days. 335
28 states failed to report deaths on 8/12/22..
26.72%*
*Not updated for 6 weeks by Worldometer.
B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan)         Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)Recombinant Delta AY.119.2- Omicron BA.1.1 (Tennessee, USA 12/31/21)\BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)NoNo
Brazil34,148,131(ranked #3) 352,939 new infections in the last 14 days. 23,552 (ranked #7)681,317(ranked #2; 2,942 new deaths in 14 days)29215.82%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)NoNo
India 44,239.372(ranked #2); 239,234 new infections in 2 weeks.15,815 (ranked#11)
526,966(ranked #3) 654 new deaths in 2 weeks.683.14%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)APTK India VOI 32421Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Iota/B.1.526 (USA-NYC) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India)NoNo
United Kingdom*
*No reported data for 8/12/22
23,420,826(ranked #6) 116,347 new infections in 2 weeks.186,087 (ranked #7) 2,134 new deaths in 2 weeks34.12%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)C.1.2 (South Africa)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)XD (AY.4/BA.1) recombinantXF (Delta/BA.1) recombinantXE (BA.1/BA.2) recombinantBA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)NoNo
California, USA10,896,796(ranked #14 in the world;  198618 new infections in the last 14 days).13,30694,319 (ranked #20 in world)
615 new deaths in the last 14 days
5027.57%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)NoNo
Mexico6,903,862(ranked #18) 192,015 new infections in 14 days).13,313(ranked #12)328,596(ranked #5)1,071 new deaths in 214 days)715.23%B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
South Africa4,007,925(ranked #33; 3,370 new infections in 14 days).313101,982 (ranked #18) Not updated in last 2 weeks.6.58%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)       C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)NoNo
Canada4,109,931(ranked #33) 87,572 new infections in 14 days).3,60343,583(ranked #24)3710.69% B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
Poland6,113,840 (ranked #21; 48,508 new infections in 14 days). 4,223116,751 (ranked #15)1416.19%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3 NoNo
Russia18,824,282(ranked #9), 247,309 new infections in 14 days).27,810383,011(ranked #4 in world)5712.88%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)R1 (Japan) B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Peru4,013,831(ranked #34, 118,345 new infections in 14 days). 10,882214,890(ranked #6)7211.82%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Iran7,465,579(ranked #17; 88,785 new infections in last 14 days)6,404142,806(ranked #12)548.65%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)


NoNo
Spain13,294,139(ranked #12;   67,560 new infections in 14 days).4,528(ranked #22)111,667 (ranked #16)11028.41%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
France34,191,919 (ranked #3; 405,153 new infections in the last 14 days).22,638 (ranked #9)153,064 (ranked #10)
1,101 new deaths in 14 days
7452.13%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) recombinantNoNo
Germany31,535,343(ranked #5; 682,031 new infections in 14 days.).45,859 (ranked #4)145,698 (ranked #11)
1,726 new deaths in 14 days
13737.38%
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
South Korea21,111,840 (ranked #8 1,491,323 new infections in 14 days).128,671(ranked #2)25,499 (ranked #37) 5841.10%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Vietnam11,362,540 (ranked #13; 586,056 new infections in 14 days).2,19243,096 (ranked #25)111.45%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)NoNo
Netherlands8,362,564 (ranked #16; 31,241 new infections in 14 days).1,88222,542 (ranked #41)448.57%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
Denmark3,076,642 (ranked #40) 16,658 new infections in 14 days1,3236,792 (ranked #80)1252.72%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo




Taiwan4,846,477(ranked #24)
300,841 new infections in 14 days
21,965 (ranked #10)9,373 (ranked #67)
3120.27%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Japan15,086,304(ranked #11)
2,908,192 new infections in the last 14 days
224,929(ranked #1)34,537(ranked #30)
2,251 new deaths in the last 14 days
21412.00%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)BA.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 have been increasing in the United States for 16 consecutive weeks despite underreporting by states and the failure to capture positive home tests and a decreased screening program in most states. Deaths per day had been decelerating at a rapid rate in the United States but are now increased by 65 more deaths per day. The number of infections have increased as the Omicron BA.2.12.1, BA.2, BA.4, and BA.5 variants of SARS CoV-2 have spread across the nation. The CDC estimates that BA.2.12.1 accounted for 5.0% of isolates, BA.2 accounted for 0.3%, BA.5 accounted for 89.1%, BA.4 accounted for 12.9%, and B.1.1.529 accounted for 0% in the week ending July 23.

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

Unless people continue to wear masks and get vaccinated, including their third dose of the vaccine, we will see further spread of the Omicron variants and increase in deaths in people who are not vaccinated, those who have waning immunity, the immunocompromised population, and others with risk factors, particularly those older over the age of 64. SARS-CoV-2 is now in the top ten most common causes of death for children. Anyone over the age of 5 years can now get vaccinated in the United States at no cost. This should get done immediately. 

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

Monterey County Health Department
Monterey County Health Department

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

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

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

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

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

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

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

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

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 Intramuscular Prophylaxis of SARS-CoV-2 Immunocompromised Patients

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

  1. Facility/Provider Name for Registration
  2. Provider Type (Hospital, Pharmacy, Etc)
  3. Shipping Address
  4. Contact Name(s)
  5. Contact Email(s)
  6. Contact Phone Number(s)

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

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

Watching World Data

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 7/29/22New Infections on 7/29/22Total DeathsNew Deaths on 7/29/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World580,770,176(14,426,888 new infections in 14 days).905,4056,417,498(31,678 new deaths in last 14 days)2,8087.45%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines) Mu/B.1.621 (Colombia)C.1.2 (South Africa 2% of isolates in July 2021)R1 (Japan)Omicron/B.1.1.529 + BA.1 + BA.2 + BA.3 (South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)Four new recombinants 12/31 to 3/22)BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)NoNo
USA93,054,184(ranked #1) 1,883,613 new infections in the last 14 days.
99,081(ranked #4)
22 states failed to report infections.
1,055,020(ranked #1) 6,327 new deaths in the last 14 days. 28628 states failed to report deaths.26.72%*
*Not updated for four weeks by Worldometers
B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan)         Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)Recombinant Delta AY.119.2- Omicron BA.1.1 (Tennessee, USA 12/31/21)\BA.2BA.2.12.1 (United States)BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India)NoNo
Brazil33,795,192(ranked #3) 545,075 new infections in the last 14 days. 42,816 (ranked #8)678,375(ranked #2; 3,230 new deaths in 14 days)22815.66%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
India 44,000,138(ranked #2); 270,067 new infections in 2 weeks.20,408
526,312(ranked #3)543.12%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)APTK India VOI 32421Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Iota/B.1.526 (USA-NYC) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2.75 (India)NoNo
United Kingdom*
*No reported data for 7/29/22
23,304,479(ranked #6) 229,119 new infections in 2 weeks.183,953 (ranked #7) 
2,373 new deaths in 2 weeks
33.95%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)C.1.2 (South Africa)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)XD (AY.4/BA.1) recombinantXF (Delta/BA.1) recombinantXE (BA.1/BA.2) recombinantBA.2BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India)NoNo
California, USA10,698,178(ranked #14 in the world;  317,309 new infections in the last 14 days).18,71593,704 (ranked #20 in world)
687 new deaths in the last 14 days
5127.07%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa)BA.5 (South Africa)NoNo
Mexico6,711,847(ranked #18) 337,971 new infections in 14 days).24,893(ranked #9)327,525(ranked #5)1135.09%B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
South Africa4,004,555(ranked #33; 4,704 new infections in 14 days).354101,982 (ranked #18)56.58%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)       C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)NoNo
Canada4,012,359(ranked #32) 4,896 new infections in 14 days).43,583(ranked #24)10.44% .B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
Poland6,065,332 (ranked #21; 35,385 new infections in 14 days). 3,391116,556 (ranked #15)916.06%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3 NoNo
Russia18,576,973(ranked #9), 96,039 new infections in 14 days).11,422382,352(ranked #4 in world)3912.71%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)R1 (Japan) B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Peru3,895,486(ranked #37, 181,125 new infections in 14 days). 6,467214,195(ranked #6)4111.48%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Iran7,376,794(ranked 17th; 106,771 new infections in last 14 days)7,849141,891(ranked #12)548.55%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)


NoNo
Spain13,226,579(ranked 11th;   136,103 new infections in 14 days).7,783(ranked #18)110,719 (ranked #16)10928.26%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
France33,786,766 (ranked #4; 967,865 new infections in the last 14 days).45,515 (ranked #6)151,983 (ranked #10)
1,407 new deaths in 14 days
8951.52%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinantNoNo
Germany30,853,312(ranked #5; 1,170,323 new infections in 14 days.).66,003 (ranked #4)143,972 (ranked #11)
1,437 new deaths in 14 days
11736.58%
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
South Korea19,620,517 (ranked #9 940,375 new infections in 14 days).85,275(ranked #3)24,999 (ranked #38) 3538.20%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Vietnam10,776,484 (ranked #13; 17,339 new infections in 14 days).1,80343,093 (ranked #25)110.86%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)NoNo
Netherlands8,331,315 (ranked #18; 57,081 new infections in 14 days).3,23822,492 (ranked #41)448.40%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
Denmark3,059,984 (ranked #39) 20,125 new infections in 14 days1,0376,639 (ranked #81)1152.44%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo




Taiwan4,545,636(ranked #29)
330,436 new infections in 14 days
23,289 (ranked #10)8,833 (ranked #69)
916 new deaths in 14 days
5719.01%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Japan12,118,112(ranked #12)
2,117,392 new infections in the last 14 days
230,055(ranked #1)32,286(ranked #30)1169.64%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo

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