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. 

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. 

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%).” 

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

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. 

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. 

Watching World Data

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

Location	Total Infections as of 11/18/22	New Infections on 11/18/22	Total Deaths	New Deaths on 11/18/22	% of Pop.Infected	SARS-CoV-2 Isolates Currently Known in Location	National/ State Mask Mandate	Currently in Lockdown
World	642,552,835(5,271,193 new infections in 14 days).	344,837	6,624,873(20,425 new deaths in last 14 days)	1,083	8.24%	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	No	No
USA	100,156,325(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.1	No	No
Brazil	35,039,614(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)	72	16.27%	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)	No	No
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)	No	No
United Kingdom	23,977,637(ranked #6) 49,596 new infections in 2 weeks.	–	196,241 (ranked #7) 1,537  new deaths in 2 weeks	–	35.00%	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)	No	No
California, USA	11,405,188(ranked #14 in the world; 51,292 new infections in the last 14 days).	2,217	97,239 (ranked #20 in world) 255 new deaths in the last 14 days	7	28.86%	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.1	No	No
Mexico	7,118,933(ranked #19) 5,801 new infections in 14 days).	–	330,444(ranked #5)29 new deaths in 14 days)	–	5.41%		No	No
South Africa	4,037,221(ranked #37; 7,484 new infections in 14 days).	598	102,371 (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)	No	No
Canada	4,377,070(ranked #33) 40,210 new infections in 14 days).	–	47,118(ranked #25 ) 749  new deaths in the last 14 days	–	11.40%		No	No
Poland	6,348,380(ranked #21; 14,789 new infections in 14 days).	359	118,267 (ranked #15)110 new deaths in the last 14 days	15	16.82%	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	No	No
Russia	21,525,567 (ranked #10), 71,900 new infections in 14 days).	5,546 (ranked #12)	391,333(ranked #4)874 new deaths in 14 days	60	14.76%		No	No
Peru	4,159,132(ranked #35, 25,059 new infections in 14 days).	3,357	217,229(ranked #6) 257 new deaths in the last 14 days	11	12.42%	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)	No	No
Iran	7,559,211(ranked #18; 1,189 new infections in last 14 days)	47	144,620(ranked #12) 33 new deaths in the last 14 days	3	8.78%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Spain	13,573,721(ranked #12;   44,078 new infections in 14 days).	3,168	115,641 (ranked #16)402 new deaths in 14 days	38	29.0%	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)	No	No
France	37,287,547(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.	74	56.29%  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.1.1	No	No
Germany	36,205,405(ranked #4; 381,634 new infections in 14 days.)	25,238 (ranked #5)	156,613 (ranked #11)2,078 new deaths in 14 days	203	43.16% 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.1.1	No	No
South Korea	26,462,319 (ranked #6 701,618 new infections in 14 days).	49,418(ranked #2)	29,925 (ranked #35) 609 new deaths in 14 days	63	51.55%2.37% increase in 14 days	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No
Vietnam	11,510,919 (ranked #13; 5,670 new infections in 14 days).	435	43,168(ranked #26)	1	11.63%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No
Netherlands	8,534,144 (ranked #16; 11,415 new infections in 14 days).	853	22,892 (ranked #41)	2	49.58%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinant	No	No
Denmark	3,143,261 (ranked #40) 6,511 new infections in 14 days.	290	7,470 (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) recombinant	No	No
Taiwan	8,130,219(ranked #17)292,561 new infections in 14 days	17,991 (ranked #7)	13,848 (ranked #58 764 new deaths in the last 14 days)	58	34.03% 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)	No	No
Japan	23,604,176(ranked #9)1,069,799 new infections in the last 14 days	84,375(ranked #1)	48,058(ranked #24) 1,160 new deaths in the last 14 days	99	18.79% 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*	No	No
Argentina	9,721,718 (ranked #15)	–	130,011(ranked #14)	–	21.12%		No	No
Italy	24,031,538 (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.		No	No
Chile	4,865,658(ranked #28) 88,450 new infections in14 days..	6,457 (ranked#11)	62,130(ranked #22)  398 new deaths in the last 14 days.	28	25.27% 0.46% of population infected in the last 14 days.		No	No
Colombia	6,312,657(ranked #22)	–	141,881(ranked #13)	–	12.25%		No	No
Australia	10,552,678(ranked #14) 833,801 new infections in 14 days.	10,925 (ranked #8)	15,967(ranked #55) 191 new deaths in 14 days.	14	40.48%  0.53% of population infected in last 14 days.		No	No
Turkey	16,976,729(ranked #11)57,091 new infections in 14 days.	–	101,327(ranked #19) 124 new deaths in 14 days..	–	19.84%		No	No
Indonesia	6,596,,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.	32	23.63%		No	No
Malaysia	4,963,216 (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.	5	14.95%		No	No
Hong Kong	2,020,885(ranked#47)	8,008 (ranked#9)	10,577 (ranked#65)	8	26.57%		No	No
China	279,431	2,388	5,226	–	–	–	–	–

What Our Team Is Reading This Week

• Covid-19 is a leading cause of death in children and young people ages 0-19 years in the United States (Preprint) https://doi.org/10.1101/2022.05.23.22275458 
• Post-COVID-19-associated morbidity in children, adolescents, and adults: A matched cohort study including more than 157,000 individuals with COVID-19 in Germany (PLOS Medicine) https://journals.plos.org/plosmedicine/article?id=10.1371%2Fjournal.pmed.1004122 
• Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies (Acta Pharmacologica Sinica) https://doi.org/10.1038/s41401-022-00998-0 
• Cognitive Deficits in Long Covid-19 (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMcibr2210069 
• Brain 18F-FDG PET imaging in outpatients with post-COVID-19 conditions: findings and associations with clinical characteristics (European Journal of Nuclear Medicine and Molecular Imaging) https://doi.org/10.1007/s00259-022-06013-2 
• Acute and postacute sequelae associated with SARS-CoV-2 reinfection (Nature) https://doi.org/10.1038/s41591-022-02051-3 
• Associations between indoor relative humidity and global COVID-19 outcomes (Journal of the Royal Society) https://doi.org/10.1098/rsif.2021.0865 
• Successful treatment of prolonged, severe COVID-19 lower respiratory tract disease in a B-cell ALL patient with an extended course of remdesivir and nirmatrelvir/ritonavir (Clinical Infectious Diseases) https://doi.org/10.1093/cid/ciac868 
• Impact of SARS-CoV-2 ORF6 and its variant polymorphisms on host responses and viral pathogenesis (Preprint) https://doi.org/10.1101/2022.10.18.512708 
• Anti-PF4 antibodies associated with disease severity in COVID-19 (PNAS) https://www.pnas.org/doi/10.1073/pnas.2213361119
• A multinational Delphi consensus to end the COVID-19 public health threat (Nature) ​​https://doi.org/10.1038/s41586-022-05398-2 
• Pfizer and BioNTech Announce Updated Clinical Data for Omicron BA.4/BA.5-Adapted Bivalent Booster Demonstrating Substantially Higher Immune Response in Adults Compared to the Original COVID-19 Vaccine https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-updated-clinical-data-omicron 
• Paxlovid and Long Covid (Ground Truths, Eric Topol) https://erictopol.substack.com/p/paxlovid-and-long-covid?utm_source=substack&utm_medium=email 
• Risk of Infection and Hospitalization Among Children and Adolescents in New York After Emergence of the SARS-CoV-2 Omicron Variant – Comment and Response (JAMA) https://jamanetwork.com/journals/jama/article-abstract/2797231 
• Myocarditis (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMra2114478 
• SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 47 (UK Health Security Agency) https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1115077/Technical-Briefing-47.pdf 
• Effectiveness of Monovalent mRNA Vaccines Against COVID-19–Associated Hospitalization Among Immunocompetent Adults During BA.1/BA.2 and BA.4/BA.5 Predominant Periods of SARS-CoV-2 Omicron Variant in the United States — IVY Network, 18 States, December 26, 2021–August 31, 2022 (MMWR) https://www.cdc.gov/mmwr/volumes/71/wr/mm7142a3.htm
  • “Three-dose monovalent mRNA VE estimates against COVID-19–associated hospitalization decreased with time since vaccination. Three-dose VE during the BA.1/BA.2 and BA.4/BA.5 periods was 79% and 60%, respectively, during the initial 120 days after the third dose and decreased to 41% and 29%, respectively, after 120 days from vaccination.”
• Saliva antibody-fingerprint of reactivated latent viruses after mild/asymptomatic COVID-19 is unique in patients with myalgic-encephalomyelitis/chronic fatigue syndrome (Frontiers in Immunology) https://doi.org/10.3389/fimmu.2022.949787 
• SARS-CoV-2 Nsp6 causes cardiac defects through MGA/MAX complex-mediated increased glycolysis (Preprint) https://doi.org/10.21203/rs.3.rs-1677754/v1 
• WHO’s Therapeutics and COVID-19 Living Guideline on mAbs needs to be reassessed (The Lancet) https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)01938-9/fulltext 
• SARS-CoV-2 disrupts host epigenetic regulation via histone mimicry (Nature) https://doi.org/10.1038/s41586-022-05282-z 
• Real-world effectiveness of molnupiravir and nirmatrelvir plus ritonavir against mortality, hospitalisation, and in-hospital outcomes among community-dwelling, ambulatory patients with confirmed SARS-CoV-2 infection during the omicron wave in Hong Kong: an observational study (The Lancet) https://doi.org/10.1016/S0140-6736(22)01586-0 
• An ACE2-dependent Sarbecovirus in Russian bats is resistant to SARS-CoV-2 vaccines (PLOS Pathogens) https://doi.org/10.1371/journal.ppat.1010828 
• Plasma cytokine levels reveal deficiencies in IL-8 and gamma interferon in Long-COVID (Preprint) https://doi.org/10.1101/2022.10.03.22280661 
• Lingering cardiac involvement in previously well people after mild COVID-19 (Nature Medicine) https://www.nature.com/articles/s41591-022-02002-y
• SARS-CoV-2 variants of concern and variants under investigation in England: technical briefing 46 (UK Health Security Agency) https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1109820/Technical-Briefing-46.pdf 
• Rapid initiation of nasal saline irrigation to reduce severity in high-risk COVID+ outpatients (Ear, Nose, and Throat Journal) https://doi.org/10.1177/01455613221123737 
• SARS-CoV-2 Omicron boosting induces de novo B cell response in humans (Preprint) https://doi.org/10.1101/2022.09.22.509040 
• Imprinted SARS-CoV-2 humoral immunity induces converging Omicron RBD evolution (Preprint) https://www.biorxiv.org/content/10.1101/2022.09.15.507787v2
  • Note: This is a frightening paper and if the conclusions are accurate humans in general are in trouble. From other papers the facts that HERV-M and EBV are activated  by SARS-CoV-2 infection does not bode well for humans moving forward.
• SARS-CoV-2 Omicron boosting induces de novo B cell response in humans (Preprint) https://www.biorxiv.org/content/10.1101/2022.09.22.509040v1 
• Evolution of antibody immunity following Omicron BA.1 breakthrough infection (Preprint) https://www.biorxiv.org/content/10.1101/2022.09.21.508922v1 
• SARS-CoV-2 Spike protein promotes vWF secretion and thrombosis via endothelial cytoskeleton-associated protein 4 (CKAP4) (Signal Transduction and Targeted Therapy) https://www.nature.com/articles/s41392-022-01183-9 
• Long-term neurologic outcomes of COVID-19 (Nature Medicine) https://www.nature.com/articles/s41591-022-02001-z 
• Pulmonary Dysfunction after Pediatric COVID-19 (Radiology) https://pubs.rsna.org/doi/10.1148/radiol.221250 
• Severe Respiratory Illnesses Associated with Rhinoviruses and/or Enteroviruses Including EV-D68 – Multistate, 2022 (CDC) https://emergency.cdc.gov/han/2022/han00474.asp 
• VACCINE INFORMATION FACT SHEET FOR RECIPIENTS AND CAREGIVERS ABOUT COMIRNATY (COVID-19 VACCINE, mRNA), THE PFIZER-BIONTECH COVID-19 VACCINE, AND THE PFIZER-BIONTECH COVID-19 VACCINE BIVALENT (ORIGINAL AND OMICRON BA.4/BA.5) TO PREVENT CORONAVIRUS DISEASE 2019 (COVID-19) FOR USE IN INDIVIDUALS 12 YEARS OF AGE AND OLDER https://labeling.pfizer.com/ShowLabeling.aspx?id=14472 
• Pfizer/BioNTech COVID-19 Omicron-Modified Bivalent Vaccine https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-09-01/07-covid-swanson-508.pdf 
• Coronavirus (COVID-19) Update: FDA Authorizes Moderna, Pfizer-BioNTech Bivalent COVID-19 Vaccines for Use as a Booster Dose (FDA) https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-moderna-pfizer-biontech-bivalent-covid-19-vaccines-use 
• Resistance of SARS-CoV-2 Omicron Subvariant BA.4.6 to Antibody Neutralization (Preprint) https://www.biorxiv.org/content/10.1101/2022.09.05.506628v1.full 
• SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 45, 9 September 2022 (UK Health Security Agency) https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1103869/Technical-Briefing-45-9September2022.pdf 
• SARS CoV-2 detected in neonatal stool remote from maternal COVID-19 during pregnancy (Pediatric Research) https://doi.org/10.1038/s41390-022-02266-7 
• SARS-CoV-2 variants of concern: spike protein mutational analysis and epitope for broad neutralization (Nature Communications) https://doi.org/10.1038/s41467-022-32262-8 
• Is SARS-CoV-2 an oncogenic virus? (Journal of Infection) https://doi.org/10.1016/j.jinf.2022.08.005 
• Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope (Cell) https://doi.org/10.1016/j.cell.2022.07.002 
• Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: an analysis of 2-year retrospective cohort studies including 1 284 437 patients (The Lancet Psychiatry) https://doi.org/10.1016/S2215-0366(22)00260-7 
• An Antibody from Single Human VH-rearranging Mouse Neutralizes All SARS-CoV-2 Variants Through BA.5 by Inhibiting Membrane Fusion (Science Immunology) https://doi.org/10.1126/sciimmunol.add5446 
• Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is common in post-acute sequelae of SARS-CoV-2 infection (PASC): Results from a post-COVID-19 multidisciplinary clinic (Preprint) https://doi.org/10.1101/2022.08.03.22278363 
• Evaluation of publication bias for 12 clinical trials of molnupiravir to treat SARS-CoV-2 infection in 13,694 patients (Preprint) https://www.researchsquare.com/article/rs-1913200/v1 
• Anti-neuronal antibodies against brainstem antigens are associated with COVID-19 (eBioMedicine) https://doi.org/10.1016/j.ebiom.2022.104211 
• Risk of SARS-CoV-2 Acquisition in Health Care Workers According to Cumulative Patient Exposure and Preferred Mask Type (JAMA Infectious Diseases) http://jamanetwork.com/article.aspx?doi=10.1001/jamanetworkopen.2022.26816 
• Coronavirus spike protein activated natural immune response, damaged heart muscle cells (AHA Basic Cardiovascular Sciences Meeting) https://newsroom.heart.org/news/coronavirus-spike-protein-activated-natural-immune-response-damaged-heart-muscle-cells 
• Distinguishing features of Long COVID identified through immune profiling (Preprint) https://doi.org/10.1101/2022.08.09.22278592 
• Virological characteristics of the SARS-CoV-2 Omicron BA.2.75 (Preprint) https://doi.org/10.1101/2022.08.07.503115 
• Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir (Preprint) https://doi.org/10.1101/2022.08.07.499047 
• Transmissible SARS-CoV-2 variants with resistance to clinical protease inhibitors (Preprint) https://doi.org/10.1101/2022.08.07.503099 
• Comparative pathogenicity of SARS-CoV-2 Omicron subvariants including BA.1, BA.2, and BA.5 (Preprint) https://doi.org/10.1101/2022.08.05.502758 
• Neuropathology and virus in brain of SARS-CoV-2 infected non-human primates (Nature Communications) https://doi.org/10.1038/s41467-022-29440-z 
• SARS-CoV-2 Brain Regional Detection, Histopathology, Gene Expression, and Immunomodulatory Changes in Decedents with COVID-19 (Journal of Neuropathology and Experimental Neurology) https://doi.org/10.1093/jnen/nlac056 
• Examination of SARS-CoV-2 In-Class Transmission at a Large Urban University With Public Health Mandates Using Epidemiological and Genomic Methodology (JAMA) http://jamanetwork.com/article.aspx?doi=10.1001/jamanetworkopen.2022.25430 
• Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection (Nature) https://doi.org/10.1038/nature04295 
• Impact of Pre-Existing Chronic Viral Infection and Reactivation on the Development of Long COVID (Preprint) https://doi.org/10.1101/2022.06.21.22276660 
• Notes from the Field: Increase in Pediatric Intracranial Infections During the COVID-19 Pandemic — Eight Pediatric Hospitals, United States, March 2020–March 2022 (MMWR) http://dx.doi.org/10.15585/mmwr.mm7131a4 
• Broadly neutralizing antibodies target the coronavirus fusion peptide (Science) https://doi.org/10.1126/science.abq3773
• Efficacy and Safety of a Recombinant Plant-Based Adjuvanted Covid-19 Vaccine (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2201300 
• Efficacy and Safety of the RBD-Dimer–Based Covid-19 Vaccine ZF2001 in Adults (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2202261 
• Risk of Reinfection, Vaccine Protection, and Severity of Infection with the BA.5 Omicron Subvariant: A Danish Nation-Wide Population-Based Study (Preprint) https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4165630 
• SARS-CoV-2 Omicron BA.5: Evolving tropism and evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern. (Preprint) https://doi.org/10.1101/2022.07.07.22277128 
• Brain imaging and neuropsychological assessment of individuals recovered from mild to moderate SARS-CoV-2 infection (Preprint) https://doi.org/10.1101/2022.07.08.22277420 
• Increased Risk of Herpes Zoster in Adults ≥50 Years Old Diagnosed With COVID-19 in the United States (Open Forum Infectious Diseases) https://doi.org/10.1093/ofid/ofac118 
• Neutralization sensitivity of Omicron BA.2.75 to therapeutic monoclonal antibodies (Preprint) https://doi.org/10.1101/2022.07.14.500041 
• Neutralizing antibody activity against 21 SARS-CoV-2 variants in older adults vaccinated with BNT162b2 (Nature Microbiology) https://doi.org/10.1038/s41564-022-01163-3 
• How COVID-19 affects microvessels in the brain (Brain) https://doi.org/10.1093/brain/awac211 
• Fine Analysis of Lymphocyte Subpopulations in SARS-CoV-2 Infected Patients: Differential Profiling of Patients With Severe Outcome (Frontiers in Immunology) https://doi.org/10.3389/fimmu.2022.889813 
• SARS-CoV-2 accelerated clearance using a novel nitric oxide nasal spray (NONS) treatment: A randomized trial (The Lancet Regional Health – Southeast Asia) https://doi.org/10.1016/j.lansea.2022.100036 
• Effectiveness of 2, 3, and 4 COVID-19 mRNA Vaccine Doses Among Immunocompetent Adults During Periods when SARS-CoV-2 Omicron BA.1 and BA.2/BA.2.12.1 Sublineages Predominated — VISION Network, 10 States, December 2021–June 2022 (MMWR) http://dx.doi.org/10.15585/mmwr.mm7129e1 
• Characterization of virologic rebound following nirmatrelvir-ritonavir treatment for COVID-19 (Clinical Infectious Diseases) https://doi.org/10.1093/cid/ciac512 
• Potential Autoimmunity Resulting from Molecular Mimicry between SARS-CoV-2 Spike and Human Proteins (Preprint) https://doi.org/10.1101/2021.08.10.455737 
• COVID-19 positive patients at higher risk of developing neurodegenerative disorders, new study shows (Medical Express) https://medicalxpress.com/news/2022-06-covid-positive-patients-higher-neurodegenerative.html 
• Evidence of previous SARS-CoV-2 infection in seronegative patients with long COVID (eBioMedicine) https://doi.org/10.1016/j.ebiom.2022.104129 
• SARS-CoV-2 infection induces inflammatory bone loss in golden Syrian hamsters (Nature Communications) https://doi.org/10.1038/s41467-022-30195-w 
• Persistent 129Xe MRI Pulmonary and CT Vascular Abnormalities in Symptomatic Individuals with Post-Acute COVID-19 Syndrome (Radiology) https://doi.org/10.1148/radiol.220492 
• ACE2-independent infection of T lymphocytes by SARS-CoV-2 (Signal Transduction and Targeted Therapy) https://doi.org/10.1038/s41392-022-00919-x 
• Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae (Preprint) https://doi.org/10.1101/2022.06.14.22276401 
• SARS-CoV-2 is detected in the gastrointestinal tract of asymptomatic endoscopy patients but is unlikely to pose a significant risk to healthcare personnel (Gastro Hep Adv) https://doi.org/10.1016/j.gastha.2022.06.002 
• Long COVID symptoms in SARS-CoV-2-positive children aged 0–14 years and matched controls in Denmark (LongCOVIDKidsDK): a national, cross-sectional study (Child & Adolescent Health) https://doi.org/10.1016/S2352-4642(22)00154-7 
• Age and sex-specific risks of myocarditis and pericarditis following Covid-19 messenger RNA vaccines (Nature Communications) https://doi.org/10.1038/s41467-022-31401-5 
• COVID-19 positive patients at higher risk of developing neurodegenerative disorders, new study shows https://medicalxpress.com/news/2022-06-covid-positive-patients-higher-neurodegenerative.html 
• Posttranslational modifications optimize the ability of SARS-CoV-2 spike for effective interaction with host cell receptors (Biophysics and Computational Biology) https://doi.org/10.1073/pnas.2119761119