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

I would expect the Omicron variant to continue to mutate just like Delta. There are now already three Omicron variants, BA.1, BA,2. and BA.3. We expect to see additional Omicron variants as this isolate spreads rapidly around the USA and the World. As of 12/22/21 the Omicron variant, which was first seen in South Africa on 11/08/21, is now in all 50 states, Puerto Rico and the District of Columbia. As of 1/14/22 Omicron has been identified on all seven continents and in at least 131 countries. 

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

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

In the United States as of 1/28/22, SARS-CoV-2 deaths have increased for the fifth time in ten 14-day periods. There were 599 more deaths per day than in the last 14-day period. In November 2021, SARS-CoV-2 was the third most common cause of death in the United States. 

In the last 14 days, the number of infections has decreased by 103,655 infections per day compared to the preceding 14-day period. Our infections per day have decreased for the first time over the last 12 weeks. Unless people get vaccinated, including their third dose of the vaccine, we will see further spread of the Omicron variants and increase in deaths in people who are not vaccinated, have waning immunity, the immunocompromised population and others with risk factors particularly those older than over the age of 64. SARS-CoV-2 is now in the top ten most common causes of death for children. Anyone over the age of 5 years can now get vaccinated in the United States at no cost. This should get done immediately. 

The new variant, B.1.1.529 (Omicron), was first seen in South Africa on 11/8/21 with multiple new mutations, deletions and an insertion that caused a doubling of new infections every 1.3 days in Gauteng, South Africa. In just 67 days, as of 1/14/22, Omicron has been found on seven continents, in 117 countries and all 50 states in the United States. Unlike Delta variants in South Africa, Omicron was infecting and hospitalizing patients in all age groups but particularly children under five years of age and adults greater than 60 years of age. Increased vaccinations, vaccines against new mutants, drugs against 3C-like protease like PAXLOVID^TM, increased mask usage and social distancing, which are part of the Biden SARS-CoV-2 plan, are all necessary to continue to stop further spread of mutants and reduce infections, hospitalizations, and deaths. Per CDC data ending in 1/29/22, the Delta variant accounts for 0.1% of new infections in the United States, while Omicron accounts for 99.9%. It’s worth noting that in the last 30 days, according to GISAID, the United States has only sequenced 0.617% of cases. 

On 1/28/22, the United States had 522,300 new infections with two states (Tennessee and Iowa) failing to report. There were also 2,732 deaths, with five other states failing to report deaths (Wyoming, Alaska, Connecticut, Colorado, and Oklahoma). Florida continues to consistently under-report daily infections and deaths. The number of hospitalized patients has been increasing in many areas, and now 24,384 patients are seriously or critically ill; that number was 25,636 two weeks ago. The number of critically ill patients has decreased by 1,252 in the last 14 days, while at least 33,575 new deaths occurred. The number of critically ill patients has decreased for the first time in fourteen 14-day periods but a large number of patients are still dying each day (average 2,398/day). 

As of 1/28/22, we have had 905,661 deaths and 76,271,402 SARS-CoV-2 infections in the United States. We have had 9,061,867 new infections in the last 14 days. We are adding an average of 4,530,933 infections every seven days. For the pandemic in the United States we are averaging one death for every 83.1 infections reported or over 12,032 deaths for each one million infections. As of 1/14/22, thirty-five states have had greater than 500,000 total infections, and 36 states have had greater than 5,000 total deaths. Fifteen states (North Carolina, Indiana, Tennessee, Massachusetts, Ohio, Michigan, Georgia, Illinois, New Jersey, Pennsylvania, Florida, Texas, New York, Arizona and California) have had greater than 20,000 deaths. Four states (Florida, Texas, New York, and California) have had greater than 60,000 deaths. 

On 11/20/20 in the United States, 3.70% of the population had a documented SARS-CoV-2 infection. California was ranked 41st in infection percentage at 2.77%. On 11/20/21 in North Dakota, 9.18% of the population was infected (ranked #1), and in South Dakota, 8.03% of the population was infected (ranked #2). As of 1/28/22, in the United States, 20.00% of the population has had a documented SARS-CoV-2 infection. In the last 14 months, 22.38% of our country became infected with SARS-CoV-2. In the last 2 weeks 2.38% of the country became infected. On 11/20/20, there were 260,331 (cumulative) deaths in the US from SARS-CoV-2. In the last 14 months, there were 663,330 new deaths from SARS-CoV-2. For ten of those months, vaccines have been available to all adults. During these ten months, 300,988 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 1/28/22, California was ranked 41st in infection percentage at 20.12% and 16.49% of Californians were infected in the last 13 months. As of 1/28/22 forty-two states have had greater than 20% of their population infected. Rhode Island was at 32.22% (ranked #1), North Dakota was at 29.00% (ranked #2), Alaska was at 28.05% (ranked #3), Utah was at 27.30% (ranked #4) and Tennessee was at 26.75% (ranked #5) and Florida was at 25.73% (ranked #8) of their population infected. Forty-nine states and the District of Columbia now have greater than 14% of their population infected. Only one state has less than 14% of their population infected: Maine (12.86%). Maine and the US Virgin Islands remain the safest places to visit in the United States.

The table below shows that if we rank the US states with the highest death rates per million population within the world rankings, we see that Mississippi, Arizona and New Jersey have the eighth highest COVID-19 deaths per million in the world. Alabama is at ninth with Louisiana and New York tied at tenth, followed by  Arkansas and Massachusetts tied at 11th and Rhode Island and Florida tied at 13th. The United States as a whole ranks 18th in the world for deaths per million population (2,734 deaths per million). California ranks 38th in the USA (and 39th in the world). If we look at the death rates per million in South Korea (130), Iceland (133), Japan (148), and Israel (922), they suggest that treatment outcomes are somehow different in these four countries. The same phenomenon can be seen in Scandinavia, where the death rate in Sweden is 1,551 per million, compared to 262 per million in Norway and 350 per million in Finland. The United States should take a closer look at how countries with low death rates (like South Korea, Iceland, Japan, Finland, and Norway) are preventing COVID-19 infections and treating COVID-19 patients. 

State or Country	COVID-19 Deaths per million population	Rank in USA	Ranked within World
Mississippi	3,639	1st	8th tied
New Jersey	3,526	3rd	8th tied
Louisiana	3,362	5th	10th tied
New York	3,336	6th	10th tied
Alabama	3,477	4th	9th
Arizona	3,572	2nd	8th tied
Massachusetts	3,179	11th	11th tied
Rhode Island	3,117	14th	13th tied
Arkansas	3,186	10th	11th tied
Florida	3,010	18th	13th tied
California	2,020	38th	39th
USA	2,734		18th
Peru	6,083		1st
Bosnia-Herzegovina	4,405		3rd
North Macedonia	4,002		6th
Hungary	4,285		4th
Montenegro	4053		5th
Bulgaria	4,809		2nd
Gibraltar	2,970		13th
Czechia	3,459		8th
Brazil	2,909		15th
San Marino	3,172		11th
Georgia	3,739		7th
Sweden	1,551		36th
Israel	922		88th
Canada	875		93rd
Finland	350		132nd
Norway	262		137th
Japan	148		154th
Iceland	133		159th
South Korea	130		160th

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 ofMolnupiravir) 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). 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). 

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

Date	Paxlovid	Molnupiravir	Sotrovimab	Evusheld
1/24/22-1/30/22	99,980	399,980	52,260	74,976

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

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

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.

A New Possible Indication for an Older FDA-Approved Antiviral Drug 

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

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

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

The Threat of SARS-CoV-2 Variants

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

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

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

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

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

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

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

Omicron cases sequenced as of 2/1/22:

Map of Omicron sequenced transmissions:

Delta cases sequenced as of 2/1/22: 

Map of Delta sequenced transmissions:

B.1.640 cases sequenced as of 2/1/22:

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 1/28/22	New Infections on 1/28/22	Total Deaths	New Deaths on 1/28/22	% of Pop.Infected	SARS-CoV-2 Isolates Currently Known in Location	National/ State Mask Mandate?	Currently in Lockdown?
World	324,182,263(25,715,028 new infections in 14 days; a new record for the pandemic for 14 days).	3,233,868	5,547,390(94,398 new deaths in last 14 days)	7,852	4.16%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines) Mu/B.1.621 (Colombia)C.1.2 (South Africa 2% of isolates in July 2021)R1 (Japan)Omicron/B.1.1.529 + BA.1 + BA.2 + BA.3 (South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)	No	No
USA	66,209,535 (ranked #1) 10,513,035 new infections in the last 14 days; new record for the pandemic for 14 days).	827,132 (ranked #1)	872,086 (ranked #1)25,181 new deaths in the last 14 days.	2,303	20.00% (3.32% increase in 14 days, new record for the pandemic for a 14 day period).	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan)         Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)	No	No
Brazil	22,927,203(ranked #3)	111,376	620,847(ranked #2)	238	10.67%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
India	40,854,851(ranked #2) increased by 4,003,889 infections in 2 weeks).	231,142	493, 218(ranked #3)	852	2.91%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)APTK India VOI 32421Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Iota/B.1.526 (USA-NYC) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)	No	No
United Kingdom	16,333,980(ranked #4; was #6 twenty weeks ago; increased by 3,396,094 infections in 2 weeks; a new pandemic record for 14 days).	89,176	155,317 (ranked #7 in world)	277	23.86%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)C.1.2 (South Africa)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)	No	No
California, USA	5,363,784(ranked #12 in the world;  1,241,751 new infections; a new pandemic record for 14 days).	118,324	77,928 (ranked #20 in world)	131	16.79%(3.12% increase in 14 days)	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Mexico	4,257,740(ranked #14; 570,706 new infections in 14 days).	48,150	304,863(ranked #5)	495	3.68%	B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
South Africa	3,552,043(ranked #19; 46,245  new infections in 14 days).	3,789	94,734 (ranked #17)	133	5.94%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)       C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)	No	No
Canada	3,007,264(ranked #23, was 26th four weeks ago; 289,282 new infections in 14 days).	9,088	33,489(ranked #29)	116	7.85% .	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)	No	No
Poland	4,752,700(ranked #14 ;471,218 new infections in 14 days).	57,262	104,907 (ranked #15)	271	12.57%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3	No	No
Turkey	10,339,097(ranked #7, 1,004,596 new infections in 14 days, a new pandemic record for 14 days).	93,586	86,871 (ranked #19)	210	13.22%	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)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)	No	No
Russia	10,747,125(ranked #6)	23,820	319,911(ranked #4 in world)	739	7.35%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)R1 (Japan) B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Argentina	6,932,972(ranked #11; 1,278,504 new infections in 14 days, a new pandemic record for 14 days).	139,853	117,901 (ranked #13 in world)	93	15.12% (2.78 % increase in two weeks, a new pandemic record for 14 days).	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gama/P.1 (Brazil)Delta/B.1.617.2 (India)Lambda/C.37 (Peru)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Colombia	5,157,440(ranked #13, 318,469 new infections in 14 days.)	34,923	130,731 (ranked #11 in world)	106	10.58%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Epsilon/B.1.427 + B.1.429 (USA)*Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Peru	2,296,831(ranked #23, 215,958 new infections in 14 days).	39,080	203,302(ranked #6)	47	7.46%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Indonesia	4,269,740(ranked #15)	850	144,163 (ranked #8)	8	1.53%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Eta/B.1.525 (Nigeria/UK)Theta/P.3 (Philippines) Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Iran	6,217,320(ranked 12th; was 12th  twenty weeks ago)	2,539	132,026 (ranked #10)	24	7.25%	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	8,093,036(ranked 9th;   1,798,291 new infections in 14 days, a new pandemic record for 14 days).	162,506	90,759 (ranked #18)	139	17.29% (3.84% increase in two weeks, a new pandemic record for 14 days).	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	13,569,675 (ranked #5)	329,371	126,721 (ranked #12)	191	20.71	Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)	No	No

What Our Team Is Reading This Week

• SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 35 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1050999/Technical-Briefing-35-28January2022.pdf 
• Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants (Nature) https://www.nature.com/articles/s41586-022-04466-x_reference.pdf 
• Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time (Preprint) https://www.medrxiv.org/content/10.1101/2022.01.14.22269235v1 
• Syncytin, envelope protein of human endogenous retrovirus (HERV): no longer ‘fossil’ in human genome (Animal Cells and Systems) https://doi.org/10.1080/19768354.2021.2019109 
• Host Chitinase 3-like-1 is a Universal Therapeutic Target for the Delta, Omicron and Other SARS-CoV-2 Viral Variants in COVID 19 (Preprint) https://www.biorxiv.org/content/10.1101/2022.01.21.477274v1 
• COVID-19 reinfections among naturally infected and vaccinated individuals (Nature) https://www.nature.com/articles/s41598-022-05325-5 
• Duration of Protection against Mild and Severe Disease by Covid-19 Vaccines (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2115481 
• Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants (Preprint) https://www.medrxiv.org/content/10.1101/2022.01.25.22269794v1 
• COVID-19 and the Common Cold—Preexisting Coronavirus Antibodies May Hinder SARS-CoV-2 Immunity (JAMA) https://jamanetwork.com/journals/jama/fullarticle/2788621?guestAccessKey=0bbad800-e651-496b-8046-d124bbc63a5a&term=01262022&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jama&utm_content=olf&utm_term=012622 
• Viral dynamics and duration of PCR positivity of the SARS-CoV-2 Omicron variant https://dash.harvard.edu/handle/1/37370587 
• Emergence in Southern France of a new SARS-CoV-2 variant of probably Cameroonian origin harbouring both substitutions N501Y and E484K in the spike protein (Preprint) https://doi.org/10.1101/2021.12.24.21268174 
• A living WHO guideline on drugs for covid-19 (BMJ) https://doi.org/10.1136/bmj.m3379 
• Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis (Science) ​​https://doi.org/10.1126/science.abj8222 
• Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection (Nature) https://www.nature.com/articles/s41590-021-01113-x 
• An upper bound on one-to-one exposure to infectious human respiratory particles (PNAS) https://www.pnas.org/content/118/49/e2110117118 
• Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies (Nature) https://doi.org/10.1038/d41586-021-03796-6 
• Frequent Occurrence of SARS-CoV-2 Transmission among Non-close Contacts Exposed to COVID-19 Patients (Journal of Korean Medical Science) https://doi.org/10.3346/jkms.2021.36.e233 
• Serial Screening for SARS-CoV-2 in Rectal Swabs of Symptomatic COVID-19 Patients (Journal of Korean Medical Science) https://doi.org/10.3346/jkms.2021.36.e301 
• Saliva swabs are the preferred sample for Omicron detection (Preprint) https://doi.org/10.1101/2021.12.22.21268246 
• SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing: Update on hospitalisation and vaccine effectiveness for Omicron VOC-21NOV-01 (B.1.1.529) 31 December 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1044481/Technical-Briefing-31-Dec-2021-Omicron_severity_update.pdf 
• Characteristics and Clinical Outcomes of Children and Adolescents Aged <18 Years Hospitalized with COVID-19 — Six Hospitals, United States, July–August 2021 (MMWR) https://www.cdc.gov/mmwr/volumes/70/wr/mm705152a3.htm 
• The SARS-CoV-2 variant, Omicron, shows rapid replication in human primary nasal epithelial cultures and efficiently uses the endosomal route of entry. (Preprint) https://drive.google.com/file/d/1vam2PVMWvfRBczqs_uZbnUixGja1QPZD/view 
• Initial Assessment of SARS-CoV-2 Omicron Variant in Exhaled Breath Aerosol (Preprint) https://mfr.osf.io/render?url=https%3A%2F%2Fosf.io%2Fdscy3%2Fdownload 
• Multisystem Involvement in Post-acute Sequelae of COVID-19 (PASC) (Annals of Neurology) https://doi.org/10.1002/ana.26286 
• Taiwan rejects US CDC guidance on 5-day quarantine (Taiwan News) https://www.taiwannews.com.tw/en/news/4393548 
• Risk assessment for SARS-CoV-2 variant: Omicron VOC-21NOV-01 (B.1.1.529) (UK Health Security Agency) https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1041896/15-december-2021-risk-assessment-for-SARS_Omicron_VOC-21NOV-01_B.1.1.529.pdf 
• HKUMed finds Omicron SARS-CoV-2 can infect faster and better than Delta in human bronchus but with less severe infection in lung https://www.med.hku.hk/en/news/press/20211215-omicron-sars-cov-2-infection 
• mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant (Preprint) https://www.medrxiv.org/content/10.1101/2021.12.14.21267755v1/ 
• “Breakthrough” COVID-19 Hospitalizations Among Fully Vaccinated Patients Occur Most Often among Older Adults and Involve People with Chronic Health Conditions (KFF) https://www.kff.org/coronavirus-covid-19/press-release/breakthrough-covid-19-hospitalizations-among-fully-vaccinated-patients-occur-most-often-among-older-adults-and-involve-people-with-chronic-health-conditions/ 
• Discovery Health, South Africa’s largest private health insurance administrator, releases at-scale, real-world analysis of Omicron outbreak based on 211 000 COVID-19 test results in South Africa, including collaboration with the South Africa https://www.discovery.co.za/corporate/news-room#/documents/press-release-dot-pdf-417948 
• SARS-CoV-2 variants of concern and variants under investigation in England, Technical Briefing 31 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1040076/Technical_Briefing_31.pdf 
• Minimal cross-over between mutations associated with Omicron variant of SARS-CoV-2 and CD8+ T cell epitopes identified in COVID-19 convalescent individuals (Preprint) https://www.biorxiv.org/content/10.1101/2021.12.06.471446v1 
• COVID-19 vaccines dampen genomic diversity of SARS-CoV-2: Unvaccinated patients exhibit more antigenic mutational variance (Preprint) https://www.medrxiv.org/content/10.1101/2021.07.01.21259833v1 
• SARS-CoV-2 B.1.1.529 variant (Omicron) evades neutralization by sera from vaccinated and convalescent individuals (Preprint) https://www.medrxiv.org/content/10.1101/2021.12.08.21267491v1 
• Myocarditis after Covid-19 Vaccination in a Large Health Care Organization (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2110737 
• Myocarditis after BNT162b2 mRNA Vaccine against Covid-19 in Israel (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2109730 
• Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2116185 
• Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial (Science) https://www.science.org/doi/10.1126/science.abm3425 
• Dissecting the early COVID-19 cases in Wuhan (Science) https://www.science.org/doi/10.1126/science.abm4454 
• Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis (The Lancet) https://doi.org/10.1016/S2666-5247(21)00267-6 
• An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19 (Science) ​​https://doi.org/10.1126/science.abl4784 
• Pfizer’s Novel Covid-19 Oral Antiviral Treatment Candidate Reduced Risk Of Hospitalization Or Death By 89% In Interim Analysis Of Phase 2/3 Epic-Hr Study https://www.pfizer.com/news/press-release/press-release-detail/pfizers-novel-covid-19-oral-antiviral-treatment-candidate 
• The county’s indoor mask mandate is triggered: masks will be required starting Nov. 5. (Monterey County Weekly) https://www.montereycountyweekly.com/blogs/news_blog/the-countys-indoor-mask-mandate-is-triggered-masks-will-be-required-starting-nov-5/article_1c375fd4-3b54-11ec-9dd8-d3ac853c92cc.html 
• Community transmission and viral load kinetics of the SARS-CoV-2 delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: a prospective, longitudinal, cohort study (The Lancet) https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00648-4/fulltext 
  • “Vaccination reduces the risk of delta variant infection and accelerates viral clearance. Nonetheless, fully vaccinated individuals with breakthrough infections have peak viral load similar to unvaccinated cases and can efficiently transmit infection in household settings, including to fully vaccinated contacts. Host–virus interactions early in infection may shape the entire viral trajectory.”
• Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2107934 
• COVID vaccine makers brace for a variant worse than Delta (Nature) https://www.nature.com/articles/d41586-021-02854-3 
• SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 27 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1029715/technical-briefing-27.pdf 
• SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 26 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1028113/Technical_Briefing_26.pdf 
• Heterologous SARS-CoV-2 Booster Vaccinations – Preliminary Report (Preprint) https://doi.org/10.1101/2021.10.10.21264827 
• An objective systematic comparison of the most common adverse events of COVID-19 vaccines (Preprint) https://doi.org/10.1101/2021.10.11.21264830 
• LSU Health Shreveport has discovered a new variant of COVID-19 in Louisiana (Shreveport Times) https://www.shreveporttimes.com/story/news/local/2021/10/13/new-covid-variant-reported-louisiana-lsu-health/8437214002/ 
• Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2114583 
• Pandemics Throughout History (Frontiers in Microbiology) https://dx.doi.org/10.3389%2Ffmicb.2020.631736 
• A novel B.1.1.523 SARS-CoV-2 variant that combines many spike mutations linked to immune evasion with current variants of concern (Preprint) https://www.biorxiv.org/content/10.1101/2021.09.16.460616v1 
• Pediatric COVID-19 Cases in Counties With and Without School Mask Requirements — United States, July 1–September 4, 2021 (MMWR) http://dx.doi.org/10.15585/mmwr.mm7039e3 
• Association Between K–12 School Mask Policies and School-Associated COVID-19 Outbreaks — Maricopa and Pima Counties, Arizona, July–August 2021 (MMWR) http://dx.doi.org/10.15585/mmwr.mm7039e1 
• Distribution of SARS-CoV-2 Variants in a Large Integrated Health Care System — California, March–July 2021 (MMWR) http://dx.doi.org/10.15585/mmwr.mm7040a4 
• Charlson Comorbidity Index (CCI) https://www.mdcalc.com/charlson-comorbidity-index-cci 
• Decreased Incidence of Infections Caused by Pathogens Transmitted Commonly Through Food During the COVID-19 Pandemic — Foodborne Diseases Active Surveillance Network, 10 U.S. Sites, 2017–2020 (MMWR) http://dx.doi.org/10.15585/mmwr.mm7038a4 
• Will Covid Overwhelm Our Vaccines? (Forbes) https://www.forbes.com/sites/williamhaseltine/2021/10/08/will-covid-overwhelm-our-vaccines/?sh=29b94be17cff 
• Anti-Covid Drugs Are Coming, But At What Cost? (Forbes) https://www.forbes.com/sites/williamhaseltine/2021/10/08/anti-covid-drugs-are-coming-but-at-what-cost/?sh=7add6fa377a1 
• Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2107659 
• Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2105290?query=featured_coronavirus 
• Mix-and-match COVID vaccines trigger potent immune response (Nature) https://www.nature.com/articles/d41586-021-01359-3 
• Is the R.1 variant in the Bay Area? What to know about the highly mutated COVID strain (SF Chronicle) https://www.sfchronicle.com/health/article/Is-the-R-1-variant-in-the-Bay-Area-What-to-know-16483185.php 
• Closest known relatives of virus behind COVID-19 found in Laos (Nature) https://www.nature.com/articles/d41586-021-02596-2 
• Children of America, You’ve Been Gaslit at Lunchtime (Psychology Today) https://www.psychologytoday.com/us/blog/compassion-works/202109/children-america-you-ve-been-gaslit-lunchtime 
• Who’s dying in California from COVID-19? (CalMatters) https://calmatters.org/health/coronavirus/2021/09/covid-california-deaths/ 
• The continuous evolution of SARS-CoV-2 in South Africa: a new lineage with rapid accumulation of mutations of concern and global detection (Preprint) https://www.medrxiv.org/content/10.1101/2021.08.20.21262342v1.full 
• Is This The Next Variant Of Concern— C.1.2? (Haseltine for Forbes) https://www.forbes.com/sites/williamhaseltine/2021/09/03/is-this-the-next-variant-of-concern–c12/?sh=2860a8094680 
• Personal protective equipment does not sufficiently protect against virus aerosol unless combined with advanced air purification or ventilation techniques | medRxiv https://www.medrxiv.org/content/10.1101/2021.09.02.21263008v1
• Israel’s home COVID-19 tests keep 180,000 students in school – Israel News – Haaretz.com https://www.haaretz.com/israel-news/.premium-israel-s-home-covid-19-tests-keep-180-000-students-in-school-1.10182409
• JCI – The autoimmune signature of hyperinflammatory multisystem inflammatory syndrome in children https://www.jci.org/articles/view/151520
• Patterns of SARS-CoV-2 aerosol spread in typical classrooms – ScienceDirect https://www.sciencedirect.com/science/article/pii/S0360132321005680
• Starr, T.N., Czudnochowski, N., Liu, Z. et al. SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape. Nature 597, 97–102 (2021). https://doi.org/10.1038/s41586-021-03807-6