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 and deaths per day had been decelerating at a rapid rate in the United States. The rate of decline has lessened as the increased infection rate and infectivity of the Omicron BA.1 variant of SARS CoV-2. The outbreak is still caused by variants of concern Omicron BA.1.1, BA.1, BA.2 and to a lesser degree BA.3 (particularly in Poland). Omicron variants are 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 63 Omicron sub-variants that have been assigned Pango lineages, including 18 sub-lineages of BA.2, which is rapidly spreading in the United States and makes up greater than 85.9% of isolates as of 4/9/22, according to the CDC

An additional problem may be the development of recombinant SARS-CoV-2 isolates. A recombinant isolate occurs when two isolates infect the same cell and, in the process of viral reproduction, exchange nucleic acids, creating a new isolate that is a recombination of parts from the genomes of both isolates. A recombinant isolate of Delta AY.4.2.2 and Omicron BA.1.1 was recently reported in the UK. As of 3/25/22 four different recombinant variants of SARS-CoV-2 have been reported by the UK Health Security Agency. 

According to the UK Health Security Agency’s Technical Briefing from 3/25/22: “There are currently 3 recombinant lineages being monitored as part of horizon scanning: XD, XE, and XF (Figure 6). XD and XF are Delta and BA.1 recombinants. XE is a BA.1 and BA.2 recombinant and has 3 mutations that are not present in all BA.1 or BA.2 sequences: NSP3 C3241T and V1069I, and NSP12 C14599T. XF and XE are associated with UK sequenced samples. XD is predominantly associated with France. XD contains the unique mutation NSP2:E172D.”

As of 4/5/22 the UK Health Security Agency reports 1,179 sequences of the XE recombinant in the UK data. The figure below shows a breakdown of XE data by gender and age group. We can see there were more XE infections in children and young adults than there were in the 70+ age groups. 

UK Health Security Agency
UK Health Security Agency

The US recombinant isolate, Delta AY.119.2-Omicron BA.1.1, has a Omicron spike sequence from amino acid 158 through amino acid 339 and was recently found in four states (Tennessee [original isolate 12/31/21], Pennsylvania [3 isolates], New Jersey [4 isolates] and Massachusetts [one isolate]; see table below.) 

Lacek et al.

We do not know yet whether any recombinant isolates will rapidly spread or have enhanced morbidity and mortality. 

We expect to see additional Omicron variants, recombinant variants and probably new pandemic SARS- CoV-2 lineages as uncontrolled infection continues in multiple continents and countries. 

As of 3/27/21 the Omicron variants, which were first seen in South Africa on 11/08/21, are now in all 50 states, Puerto Rico and the District of Columbia. As of 4/10/22 Omicron has been identified on all seven continents and in at least 179 countries.

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. 

Vaccination will not prevent you from getting an Omicron variant infection. For now only masking (N95 rated masks, please!) and social distancing will have any effect on acquisition of infection with 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). 

According to a KFF analysis of CDC data, in January 2022, SARS-CoV-2 was in the top four causes of death in the United States for all age groups, including children. It was the number one cause of death in people aged 45-84.

In the last 14 days, the number of infections has decreased by 873 infections per day compared to the preceding 14-day period. Our infections per day have decreased for the fourth time in the last 14 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. 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 4/10/22, only 35.9% of 5-11 year-olds have received the first two doses of vaccine, while 78.9% of 12-17 year-olds have received two doses.

Omicron Subvariant BA.2 Is Here and Dominant

Per CDC data ending in 4/9/22, the Delta variant accounted for 0.0% of new infections in the United States, while Omicron BA1.1 accounted for 13.1%, Omicron B.1.1.529 accounts for 1.0%, and Omicron subvariant BA.2 accounted for 85.9%. It’s worth noting that in the last 30 days, according to GISAID, the United States has only sequenced 3.67% of cases. 

and differences between the three Omicron family viruses. ACCESS HEALTH INTERNATIONAL

Nextstrain

On 4/8/22, the United States had 35,285 new infections. There were also 404 deaths. In the United States the number of hospitalized patients has been decreasing in many areas, and now only 1,716 patients are seriously or critically ill; that number was 2,548 two weeks ago. The number of critically ill patients has decreased by 832 in the last 14 days, while at least 8,467 new deaths occurred (a decrease of 1,587 deaths from the previous 14 days). The number of critically ill patients has decreased for the sixth time in eighteen 14-day periods. Patients are still dying each day (average 605/day). Omicron BA.2 infections should continue to increase but critically ill patients, and deaths may continue to decrease in the next two weeks if Omicron BA.2 continues to cause less severe disease and does not infect large numbers of previously BA.1 infected patients. There have already been reports out of Israel of patients infected with BA.1 being later reinfected with BA.2. 

As of 4/08/22, we have had 1,011,665 deaths and 82,034,738 SARS-CoV-2 infections in the United States. We have had 433,848 new infections in the last 14 days. We were adding an average of 266,924 infections every seven days. For the pandemic in the United States we are averaging one death for every 81.0 infections reported for each death or over 12,332 deaths for each one million infections. As of 4/8/22, thirty-six states have had greater than 500,000 total infections, and 36 states have had greater than 5,000 total deaths. Sixteen states (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 68,000 deaths. California and Texas have each had greater than 85,000 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 4/8/22, in the United States, 24.52% of the population has had a documented SARS-CoV-2 infection. In the last 16 months, 21.83% 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 16 months, there were 751,534 new deaths from SARS-CoV-2. For thirteen of those months, vaccines have been available to all adults. During these thirteen months, 440,568 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 4/8/22, California was ranked 38th in infection percentage at 23.10%. In California 19.42% of Californians were infected in the last 16 months. As of 3/11/22 forty-three states have had greater than 20% of their population infected. Rhode Island was at 34.30% (ranked #1), Alaska was at 32.89% (ranked #2), North Dakota was at 31.50% (ranked #3), Tennessee was at 29.61% (ranked #4), Kentucky was at 29.52% (ranked #5), Utah was at 28.96% (ranked #6), South Carolina was at 28.54% (ranked #7), West Virginia was at 27.81% (ranked #8), Arizona was at 27.67% (ranked #9), Arkansas was at 27.61% (ranked #10) and Florida was at 27.51% (ranked #11) of their population infected. Forty-three states now have greater than 20% of their population infected. 

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 Alabama had the eighth highest death rate, New Jersey and Arkansas have the ninth highest COVID-19 deaths per million in the world. Louisiana had the tenth, New York was at eleventh,  Florida was at 12th and Rhode Island was at thirteenth. The United States as a whole ranks 18th in the world for deaths per million population (3,056 deaths per million). California ranks 39th in the USA (and 37th in the world). If we look at the death rates per million in South Korea (365), Iceland (296), Japan (227), and Israel (1,132), 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 1,809 per million, compared to 485 per million in Norway and 600 per million in Finland. The United States should have taken a closer look at how countries with low death rates (like South Korea, Iceland, Japan, Finland, and Norway) were preventing COVID-19 infections and treating COVID-19 patients. 

State or Country COVID-19 Deaths per million populationRank in USARanked within World
Mississippi4,171 1st8th tied
New Jersey  3,7486th9th tied
Louisiana3,6958th10th 
New York 3,52411th11th tied 
Alabama3,9523rd8th tied
Arizona4,0782nd8th tied
Rhode Island  3,327  19th13th
Arkansas3,7457th9th tied
Florida3,42417th12th 
California2,26439th37th
USA3,05618th
Peru6,2881st
Bosnia-Herzegovina  4,8483rd
Hungary4,7544th
Montenegro4,3086th
Bulgaria5,3512nd
Czechia3,7089th
Brazil3,07215th
Georgia4,2177th
Sweden1,80957th
Israel1,13285th
Canada99192nd
Finland600120th
Norway485127th
Japan227151st
Iceland296145th
South Korea365138th

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 

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. Sotrovimab is not effective against the BA.2 Omicron variant of SARS-CoV-2. On 3/25/22, the FDA revoked emergency use authorization for sotrovimab to treat COVID-19 infections in 8 states, Puerto Rico, and the Virgin Islands. They justified this decision with the reasoning that, according to the CDC, BA.2 accounts for more than 50% of cases in HH2 regions 1 and 2. We decided to look at data from Walgreens’ COVID-19 Index, which is updated every few days. 

Omicron Subvariant Trends by State (from Walgreens COVID-19 Index) for 3/24/22 and 4/08/22

Bebtelovimab is a new 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 we think that bebtelovimab rather than sotrovimab should be used for SARS-CoV-2 in all states based on the above Walgreen data sets from 3/24/22 and 4/08/22.

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. 

The Threat of SARS-CoV-2 Variants

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

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

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

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

Source: World Health Organization

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

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

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

According to the UK Health Security Agency Technical Briefing from 2/25/22, “A putative Delta and Omicron recombinant has been identified in the UK, with likely parental lineages AY.4.2.2 and BA.1.1 and a breakpoint in non-structural protein 3 (nsp3). The presence of 34 genomes sampled between 7 January 2022 and 14 February 2022 suggest that this recombinant is able to transmit.” GISAID has also begun publishing data about a recombinant of Delta AY.4 and Omicron BA.1, first identified in France. According to GISAID data, this variant has also been detected in Denmark, Germany, the Netherlands, and the United States. Forbes 

We will need to monitor for this Delta-Omicron recombinant variant in the United States as well. 

Omicron cases sequenced as of 4/10/22:

GISAID

GISAID

Map of Omicron sequenced transmissions:

GISAID

Delta cases sequenced as of 4/10/22: 

GISAID

Map of Delta sequenced transmissions:

GISAID

GKA (AY.4/BA.1) cases sequenced as of 4/10/22:

GISAID

B.1.640 cases sequenced as of 4/10/22:

GISAID

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 4/8/22New Infections on 4/8/22Total DeathsNew Deaths on 4/8/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World497,520,253(17,964,695 new infections in 14 days).1,087,7306,198,662(56,243 new deaths in last 14 days)3,6346.38%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)NoNo
USA82,034,738(ranked #1) 433,848 new infections in the last 14 days.35,285(ranked #8)1,011,665(ranked #1)8,467 new deaths in the last 14 days. 40424.52%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)NoNo
Brazil30,123,963(ranked #3) 497,143 new infections in the last 14 days. 34,576 (ranked #11)658,626(ranked #2)25913.85%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
India43,018,032(ranked #2); 321,706 new infections in 2 weeks.1,150521,686(ranked #3)823.06%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)NoNo
United Kingdom21,549,830(ranked #6; was #6 thirty weeks ago; 858,707 new infections in 2 weeks.25,305(ranked 11th in the world).169,759 (ranked #7 in world)34731.45%(1.25% increase in the last 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)*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) recombinantNoNo
California, USA9,130,644(ranked #13 in the world;  44,240 new infections in the last 14 days).3,78989,461 (ranked #20 in world)5423.10%(0.14% 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)NoNo
Mexico5,643,963(ranked #20) 71,541 new infections in 14 days).32,216 (ranked #9)323,508(ranked #5)1054.79%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 Africa3,730,066(ranked #29; 19,300 new infections in 14 days).1,377100,084 (ranked #18)96.15%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)NoNo
Canada3,560,840(ranked #32, was 26th fourteen weeks ago; 285,094 new infections in 14 days).8,55737,977(ranked #26)429.29% .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
Poland5,976,364(ranked #19; 43,262 new infections in 14 days). 1,330115,594 (ranked #15)5815.82%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
Turkey14,946,379(ranked #10, 170,745 new infections in 14 days).7,12098,342 (ranked #19)3117.39% (0.20% of the country was infected in the last 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)*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)NoNo
Russia17,969,431(ranked #7), 254,031 new infections in 14 days).14,311371,169(ranked #4 in world)28012.30%; 0.17% of the country was infected in the last 14 days.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
Argentina9,051,243(ranked #13; 27,431 new infections in 14 days).1,993128,194 (ranked #14 in world)3619.70% (0.05 % increase in two weeks).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)NoNo
Colombia6,087,443(ranked #17, 4,500 new infections in 14 days).320139,703 (ranked #12 in the world)1011.79%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)NoNo
Peru3,550,791(ranked #33, 6,453 new infections in 14 days). 551212,438(ranked #6)1810.51%, a 0.02% increase in 14 days).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
Indonesia6,030,168(ranked #18; 38,481 new infections in 14 days)1,755155,556 (ranked #9)472.77%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)
NoNo
Iran7,186,992 39,585 new infections in last 14 days(ranked 15th; was 12th  thirty weeks ago)3,184140,528 (ranked #11)368.36%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
Spain11,627,487(ranked 11th;   175,811 new infections in 14 days).16,278103,104 (ranked #17)11924.85%, a 0.38% increase in 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)NoNo
France26,698,031 (ranked #4; 1,918,149 new infections in the last 14 days).148,768 (ranked #3)143,141 (ranked #10)13940.74%, a 2.93% increase in the last 14 days, a new pandemic record for 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
Germany22,534,061(ranked #5; 2,515,596 new infections in 14 days.).169,454 (ranked #2)132,141 (ranked #13)33626.74%, a 2.98% increase 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)GKA (AY.4/BA.1) recombinantNoNo
Hungary1,868,007 (ranked #43; 27,649 new infections in 14 days).
2,40045,721 (ranked #23)3719.42%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
Romania2,870,486(ranked #38; 34,737 new infections in 14 days).1,70965,179 (ranked#20)915.00%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)NoNo
South Korea14,983,694 (ranked 9th) ; 3,821,462 new infections in 14 days).205,289(ranked#1)18,754 (ranked #44); 4,460 new deaths in 14 days, a new pandemic record for 14 days in South Korea).37329.18%; a 7.45% 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)NoNo
Ukraine4,982,249(ranked #21; 29,336 new infections in 14 days),2,025108,818 (ranked #16)2011.51%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)NoNo
Vietnam10,135,789(ranked #12; 1,319,338 new infections in 14 days).39,334(ranked #7)42,768 (ranked #24)3510.25%, (a 1.34% 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)NoNo
Netherlands7,971,855 (ranked #14; 271,140 new infections in 14 days).10,903 (ranked #10)22,080 (ranked #39)1446.34%, (a 1.57% 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
Denmark2,932,847, (ranked #37) 43,559 new infections in 14 days2,5035,861 (ranked #84)2450.32%, (a 0.74% 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

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 and deaths per day have been decelerating at a rapid rate in the United States.Infections are and many other countries but are increasing rapidly in a handful of countries in Europe and Asia . The outbreak is still caused by variants of concern Omicron BA.1.1, BA.1, BA.2 and to a lesser degree BA.3 (particularly in Poland). Omicron variants are 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 four Omicron variants, BA.1, BA.1.1, BA.2 and BA.3. BA.2 is rapidly spreading in the United States and makes up 55.11% of isolates as of 3/23/22.

An additional problem may be the development of recombinant SARS-CoV-2 isolates from patients in Europe and the United States. A recombinant isolate occurs when two isolates infect the same cell and, in the process of viral reproduction, exchange nucleic acids, creating a new isolate that is a recombination of parts from the genomes of both isolates. A recombinant isolate of Delta AY.4.2.2 and Omicron BA.1.1 was recently reported in the UK. As of 3/25/22 four different recombinant variants of SARS-CoV-2 have been reported: three in the UK, one in France, and one in the United States.

According to the UK Health Security Agency’s Technical Briefing from 3/25/22: “There are currently 3 recombinant lineages being monitored as part of horizon scanning: XD, XE, and XF (Figure 6). XD and XF are Delta and BA.1 recombinants. XE is a BA.1 and BA.2 recombinant and has 3 mutations that are not present in all BA.1 or BA.2 sequences: NSP3 C3241T and V1069I, and NSP12 C14599T. XF and XE are associated with UK sequenced samples. XD is predominantly associated with France. XD contains the unique mutation NSP2:E172D.”

UK Health Security Agency

The US recombinant isolate, Delta AY.119.2-Omicron BA.1.1, has a Omicron spike The US recombinant isolate, Delta AY.119.2-Omicron BA.1.1, has a Omicron spike sequence from amino acid 158 through amino acid 339 and was recently found in four states (Tennessee [original isolate 12/31/21], Pennsylvania [3 isolates], New Jersey [4 isolates] and Massachusetts [one isolate]; see table below.) 

Lacek et al. https://doi.org/10.1101/2022.03.19.484981

We do not know yet whether any recombinant isolates will rapidly spread or have enhanced morbidity and mortality. 

We expect to see additional Omicron variants, recombinant variants and probably new pandemic SARS- CoV-2 lineages as uncontrolled infection continues in multiple continents and countries. 

As of 3/27/21 the Omicron variants, which were first seen in South Africa on 11/08/21, are now in all 50 states, Puerto Rico and the District of Columbia. As of 3/27/22 Omicron has been identified on all seven continents and in at least 176 countries.

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 from the CVS in Salinas and on Fremont Boulevard in north Monterey. 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 PAXLOVIDTM from the Salinas CVS pharmacy and the north Monterey pharmacy and successfully treated ten patients in the last six weeks. We have also treated two patients with Molnupiravir due to our inability at that time to obtain PAXLOVIDTM. Molnupiravir does not appear to be in short supply in the United States. You can just send your electronic prescription to a participating CVS pharmacy. You probably should call in advance to check on drug availability and their participation.

In the absence of obtaining intravenous Sotrovimab or Bebtelovimab, only oral PAXLOVIDTM and Molnupiravir are available to treat SARS-CoV-2 as an outpatient. Vaccination will not prevent you from getting an Omicron variant infection. For now only masking (N95 rated masks, please!) and social distancing 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 2/25/22, SARS-CoV-2 deaths have decreased for the first time in twelve 14-day periods. There were 2,568 fewer 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 12,614 infections per day compared to the preceding 14-day period. Our infections per day have decreased for the third time in 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. In Monterey County, only 35% of 5-11 year olds have received the first dose of vaccine.

The 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 165 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 PAXLOVIDTM, 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. 

Omicron Subvariant BA.2 Is Here and Dominant

Two cases of BA.2 have been reported in Monterey county in the last two weeks. Walgeens data on 3/23/22 showed that 55.1% of infections in the USA were BA.2. Per CDC data ending in 3/26/22, the Delta variant accounts for 0.0% of new infections in the United States, while Omicron BA1.1 accounts for 40.4%, Omicron B.1.1.529 accounts for 4.7%, and Omicron subvariant BA.2 accounts for 54.9%. It’s worth noting that in the last 30 days, according to GISAID, the United States has only sequenced 2.596% of cases. 

Omicron subvariant BA.2 has been detected in every region of the United States, and the proportion of BA.2 continues to increase. BA.2 also contains 17 mutations that set it apart from BA.1 (ten of which are also different from those in BA. 3. 

FIGURE 3: Venn diagram showing the similarities and differences between the three Omicron family viruses. ACCESS HEALTH INTERNATIONAL

Nextstrain

On 3/25/22, the United States had 31,927 new infections. There were also 692 deaths. In the United States the number of hospitalized patients has been decreasing in many areas, and now 2,548 patients are seriously or critically ill; that number was 4,604 two weeks ago. The number of critically ill patients has decreased by 2,056 in the last 14 days, while at least 10,154 new deaths occurred (a decrease of 10,690 deaths from the previous 14 days). The number of critically ill patients has decreased for the fifth time in seventeen 14-day periods. Patients are still dying each day (average 725/day). Infections, critically ill patients, and deaths should markedly decrease in the next two weeks if Omicron BA.2 causes less severe disease and does not infect large numbers of previously BA.1 infected patients. However, there have already been reports out of Israel of patients infected with BA.1 being later reinfected with BA.2. 

As of 3/11/22, we have had 1,003,198 deaths and 81,600,890 SARS-CoV-2 infections in the United States. We have had 445,930 new infections in the last 14 days. We were adding an average of 222,965 infections every seven days. For the pandemic in the United States we are averaging one death for every 81.4 infections reported or over 12,294 deaths for each one million infections. As of 3/11/22, thirty-six 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 68,000 deaths. California and Texas have each had greater than 85,000 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 3/25/22, in the United States, 24.57% of the population has had a documented SARS-CoV-2 infection. In the last 16 months, 21.85% of our country became infected with SARS-CoV-2. In the last 2 weeks 0.3% 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 16 months, there were 743,067 new deaths from SARS-CoV-2. For thirteen of those months, vaccines have been available to all adults. During these thirteen months, 432,101 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 3/25/22, California was ranked 38th in infection percentage at 22.98%. In California 19.28% of Californians were infected in the last 16 months. As of 3/11/22 forty-three states have had greater than 20% of their population infected. Rhode Island was at 33.99% (ranked #1), Alaska was at 32.59% (ranked #2),North Dakota was at 31.45% (ranked #3), Tennessee was at 29.57% (ranked #4), Kentucky was at 29.35% (ranked #5), Utah was at 28.92% (ranked #6), South Carolina was at 28.49% (ranked #7), West Virginia was at 27.74% (ranked #8), Arkansas was at 27.58% (ranked #9), Arizona was at 27.43% (ranked #10) and Florida was at 27.40% (ranked #11) of their population infected. 43 states now have greater than 20% of their population infected. 

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 Alabama had the eighth highest death rate, New Jersey and Arkansas have the ninth highest COVID-19 deaths per million in the world. Louisiana had the tenth, New York was at eleventh,  Florida was at 16th and Rhode Island was at fourteenth. The United States as a whole ranks 18th in the world for deaths per million population (2,971 deaths per million). California ranks 38th in the USA (and 37th in the world). If we look at the death rates per million in South Korea (278), Iceland (281), Japan (218), and Israel (1,122), 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 1,778 per million, compared to 426 per million in Norway and 537 per million in Finland. The United States should have taken a closer look at how countries with low death rates (like South Korea, Iceland, Japan, Finland, and Norway) were preventing COVID-19 infections and treating COVID-19 patients. 

State or Country COVID-19 Deaths per million populationRank in USARanked within World
Mississippi4,158 1st8th tied
New Jersey  3,7395th9th tied
Louisiana3,6738th10th tied 
New York 3,51810th11th 
Alabama3,9233rd8th tied
Arizona3,9682nd8th tied
Rhode Island  3,245  21st14th
Arkansas3,7147th9th tied
Florida3,40016th12th tied
California2,24538th37th
USA3,00018th
Peru6,2801st
Bosnia-Herzegovina  4,8383rd
Hungary4,7064th
Montenegro4,2956th
Bulgaria5,3112nd
Czechia3,6789th
Brazil3,06115th
Georgia4,2007th
Sweden1,77857th
Israel1,12284th
Canada97690th
Finland537124th
Norway426130th
Japan218151st
Iceland281145th
South Korea278144th

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 

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. Sotrovimab is not effective against the BA.2 Omicron variant of SARS-CoV-2. On 3/25/22, the FDA revoked emergency use authorization for sotrovimab to treat COVID-19 infections in 8 states, Puerto Rico, and the Virgin Islands. They justified this decision with the reasoning that, according to the CDC, BA.2 accounts for more than 50% of cases in HH2 regions 1 and 2. We decided to look at data from Walgreens’ COVID-19 Index, which is updated every few days. 

Walgreens COVID-19 Index

Omicron Subvariant Trends by State (from Walgreens COVID-19 Index) as of 3/24/22

StateBA.1 / BA1.1BA.2
California**40%60%
Texas**17.2%82.8%
Florida**29.73%70.27%
New York*21.30%78.7%
Pennsylvania**23.53%76.47%
New Jersey*20.39%79.61%
Massachusetts*20.73%79.63%
Maine*55.88%44.12%
New Hampshire*66.67%33.33%
Rhode Island*18.18%81.82%
Vermont*50%50%
Connecticut*36.36%63.64%
Michigan**40%60%
Wisconsin**40.28%59.72%
Minnesota**23.33%76.67%
Illinois**38.83%61.17%
Ohio**30.33%66.67%
Colorado**45.16%54.84%
Utah**33.33%66.67%
Nevada**33.72%66.28%
Arizona**47.06%52.94%
New Mexico71.43%28.57%
Washington**0%100%
Oregon**28.57%71.43%
Idaho**0%100%
Alaska**0%100%
Hawaii**0%100%

*FDA announced on 3/25/22 that sotrovimab is no longer authorized for use in these states.

**Other States in bold that have more than 50% BA.2 (Walgreens data set). 

Bebtelovimab is a new 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. If you are planning on using a monoclonal antibody to treat a SARS-CoV-2 infection concurrently we think that bebtelovimab rather than sotrovimab should be used for SARS-CoV-2 in most states based on the above Walgreens data set.

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. 

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, with the exception of sotrovimab, 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):

WHO

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):

WHO

Omicron cases sequenced as of 3/31/22:

GISAID
GISAID

Map of Omicron sequenced transmissions:

GISAID

Delta cases sequenced as of 3/31/22: 

GISAID

Map of Delta sequenced transmissions:

GISAID

GKA (AY.4/BA.1) cases sequenced as of 3/31/22:

GISAID

B.1.640 cases sequenced as of 3/31/22:

GISAID

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 3/25/22New Infections on 3/25/22Total DeathsNew Deaths on 3/25/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask Mandate?Currently in Lockdown?
World479,555.558(24,498,608 new infections in 14 days; an increase of 2,743,044 infections from the preceding 14 days).1,558,4706,142,419(85,092 new deaths in last 14 days)4,6156.15%%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)NoNo
USA81,600,890
(ranked #1) 445,930 new infections in the last 14 days.
31,927
(ranked#12)
1,003,198
(ranked #1)10,154 new deaths in the last 14 days. 
69224.57%
(0.30% increase in 14 days). 
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)NoNo
Brazil29,802,257(ranked #3) 497,143 new infections in the last 14 days. 34,576 (ranked #11)658,626(ranked #2)25913.85%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
India43,018,032(ranked #2); increased by 30,158 infections in 2 weeks.1,1605200,885(ranked #3)953.06%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)NoNo
United Kingdom20,691,123(ranked #5; was #6 twenty-eight weeks ago; increased by 1,160,638 infections in 2 weeks.39,925(ranked 8th in the world).164,454 (ranked #7 in world)17230.20%(1.69% increase in the last 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)*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) recombinantNoNo
California, USA9,086,404(ranked #12 in the world;  52,561 new infections in the last 14 days).3,65588,700 (ranked #20 in world)9922.99%(0.13% 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)NoNo
Mexico5,643,963(ranked #20) 52,092 new infections in 14 days).3,658320,432(ranked #5)1554.29%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 Africa3,710,766(ranked #27; 18,804 new infections in 14 days).1,55799,939 (ranked #18)76.12%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)NoNo
Canada3,275,746(ranked #33, was 26th twelve weeks ago; 160,773 new infections in 14 days).6,67637,411(ranked #26)458.96% .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
Poland5,933,102(ranked #19; 133,106 new infections in 14 days). 8,236114,736 (ranked #15)11015.70%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
Turkey14,775,634(ranked #8, 261,860 new infections in 14 days).15,30397,666 (ranked #19)6817.19% (1.29% of the country was infected in the last 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)*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)NoNo
Russia17,715,390(ranked #7), 473,347 new infections in 14 days).25,382366,618(ranked #4 in world)39812.13%; 0.33% of the country was infected in the last 14 days.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
Argentina9,023,812(ranked #12; 135,839 new infections in 14 days).2,572127,846 (ranked #14 in world)6619.65% (0.12 % increase in two weeks).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)NoNo
Colombia6,082,943(ranked #17, 7,287 new infections in 14 days).366139,544 (ranked #12 in the world)1311.73%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)NoNo
Peru3,544,338(ranked #30, 9,651 new infections in 14 days). 548212,050(ranked #6)2810.49%, a 0.02% increase in 14 days).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
Indonesia5,991,687(ranked #18; 103.677 new infections in 14 days)4,857154,463 (ranked #9)1202.15%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)
NoNo
Iran7,147,407 29,863 new infections in last 14 days(ranked 15th; was 12th  twenty-eight weeks ago)1,530139,917 (ranked #11)528.32%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
Spain11,451,676(ranked 10th;   227,702 new infections in 14 days).24,298102,392 (ranked #17)11324.47%, a 0.48% increase in 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)NoNo
France24,779,882 (ranked #4; 1,398,603 new infections in the last 14 days).143,571 (ranked #3)141,564 (ranked #10)12137.81%, a 2.13% increase in the last 14 days, a new pandemic record for 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
Germany20,018,465(ranked #6; 3,136,520 new infections in 14 days, a new pandemic record for 14 days).276,746 (ranked#2)128,757 (ranked #13).30023.76%, a 3.72% increase in the last 14 days, a new pandemic record for 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
Hungary1,839,358 (ranked #43; 14,996 new infections in 14 days).
2,43945,258 (ranked #22)3819.12%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
Romania2,835,749(ranked #37; 48,124 new infections in 14 days).3,72564,873 (ranked#20)3314.91%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
South Korea11,162,232 (ranked 11th; 5,239,608 new infections in 14 days, a new pandemic world record for 14 days in one country).339,396(ranked#1)14,294 (ranked#54; 4,439 new deaths in 14 days, a new pandemic record for 14 days in South Korea).39221.73%; a 10.43% increase in 14 days, a new pandemic world record for one country in a 14 day period).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
Ukraine4,952,913(ranked #21; 58,582 new infections in 14 days),3,630107,811 (ranked #16)3211.44%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)NoNo
Vietnam8,816,431(ranked #13; 3,082,003 new infections in 14 days, a new pandemic record for Vietnam).109,666(ranked#4)42,196 (ranked #24)518.91%, (a 4.11% increase in 14 days, a new pandemic record for Vietnam in a 14 day period).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
Netherlands7,700,715 (ranked #14; 644,901 new infections in 14 days).34,989 (ranked #10)21,871 (ranked #39)2044.77%, (a 3.75% 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
Denmark2,889,288 (ranked #37, 92,868 new infections in 14 days).5,3515,542 (ranked #84)2449.58%, (a 1.59% 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

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 have been decelerating at a rapid rate in the United States and many other countries but are increasing rapidly in a handful of countries in Europe and Asia. The outbreak is still caused by variants of concern Omicron BA.1.1, BA.1, BA.2 and to a lesser degree BA.3 (particularly in Poland). Omicron variants are 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 four Omicron variants, BA.1, BA.1.1, BA.2 and BA.3. A recombinant isolate of Delta AY.4.2.2 and Omicron BA.1.1 has recently been reported in the UK. We expect to see additional Omicron variants as these isolates spread rapidly around the USA and the World. As of 3/11/21 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 3/11/22 Omicron has been identified on all seven continents and in at least 165 countries

Omicron has 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 from the CVS in Salinas and on Fremont Boulevard in north Monterey. 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 PAXLOVIDTM from the Salinas CVS pharmacy and the north Monterey pharmacy and successfully treated four patients in the last four weeks. We have also treated a fifth patient from Turlock with PAXLOVIDTM . We  have also treated two patients with Molnupiravir due to our inability at that time to obtain PAXLOVIDTM . Molnupiravir does not appear to be in short supply in the United States. You can just send your electronic prescription to a participating CVS pharmacy. You probably should call in advance to check on drug availability and their participation.

In the absence of obtaining intravenous Sotrovimab or Bebtelovimab, only oral PAXLOVIDTM and Molnupiravir are available to treat SARS-CoV-2 as an outpatient. Vaccination will not prevent you from getting an Omicron variant infection. For now only masking (N95 rated masks, please!) and social distancing 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 2/25/22, SARS-CoV-2 deaths have decreased for the first time in twelve 14-day periods. There were 2,568 fewer 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 44,468 infections per day compared to the preceding 14-day period. Our infections per day have decreased for the second time over the last 8 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.In Monterey County, only 35% of 5-11 year olds have received the first dose of vaccine.

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 165 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 PAXLOVIDTM, 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. 

Omicron Subvariant BA.2 Is Coming

Per CDC data ending in 3/5/22, the Delta variant accounts for 0.0% of new infections in the United States, while Omicron BA1.1 accounts for 73.7%, Omicron B.1.1.529 accounts for 14.7%, and Omicron subvariant BA.2 accounts for 11.6%. It’s worth noting that in the last 30 days, according to GISAID, the United States has only sequenced 3.042% of cases. 

Omicron subvariant BA.2 has been detected in every region of the United States, and the proportion of BA.2 continues to increase. BA.2 also contains 17 mutations that set it apart from BA.1 (ten of which are also different from those in BA. 3. 

FIGURE 3: Venn diagram showing the similarities and differences between the three Omicron family viruses. ACCESS HEALTH INTERNATIONAL

Nextstrain

On 3/11/22, the United States had 39,254 new infections. There were also 1,022 deaths. Florida continues to consistently under-report daily infections and deaths. In the United States the number of hospitalized patients has been decreasing in many areas, and now 4,604 patients are seriously or critically ill; that number was 8,981 two weeks ago. The number of critically ill patients has decreased by 4,357 in the last 14 days, while at least 20,844 new deaths occurred (a decrease of 11,267 deaths from the previous 14 days). The number of critically ill patients has decreased for the fourth time in sixteen 14-day periods but a large number of patients are still dying each day (average 1,489/day). Infections, critically ill patients, and deaths should markedly decrease in the next two weeks if Omicron BA.2 causes less severe disease and does not infect large numbers of previously BA.1 infected patients. However, there are reports out of Israel of patients infected with BA.1 being later reinfected with BA.2. 

As of 3/11/22, we have had 993,044 deaths and 81,154,960 SARS-CoV-2 infections in the United States. We have had 622,653 new infections in the last 14 days. We were adding an average of 311,277 infections every seven days. For the pandemic in the United States we are averaging one death for every 81.7 infections reported or over 12,236 deaths for each one million infections. As of 3/11/22, thirty-six 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 68,000 deaths. California and Texas have each had greater than 85,000 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 3/11/22, in the United States, 24.09% of the population has had a documented SARS-CoV-2 infection. In the last 16 months, 21.55% of our country became infected with SARS-CoV-2. In the last 2 weeks 0.18% 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 16 months, there were 732,913 new deaths from SARS-CoV-2. For twelve of those months, vaccines have been available to all adults. During these twelve months, 421,947 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 3/11/22, California was ranked 37th in infection percentage at 22.86%. In California 19.16% of Californians were infected in the last 16 months. As of 3/11/22 forty-three states have had greater than 20% of their population infected. Rhode Island was at 33.77% (ranked #1), Alaska was at 32.19% (ranked #2),North Dakota was at 31.38% (ranked #3), Tennessee was at 29.51% (ranked #4), Kentucky was at 29.02% (ranked #5), Utah was at 28.86% (ranked #6) and Florida was at 27.32% (ranked #10) of their population infected. All 50 states and the District of Columbia now have greater than 16% of their population infected. 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 had the sixth highest death rate, Arizona, Alabama and New Jersey have the eighth highest COVID-19 deaths per million in the world. Louisiana, Arkansas and New York tied at tenth, Massachusetts is at 11th, Florida is at 12th and Rhode Island is at fourteenth. The United States as a whole ranks 18th in the world for deaths per million population (2,971 deaths per million). California ranks 38th in the USA (and 37th in the world). If we look at the death rates per million in South Korea (192), Iceland (229), Japan (204), and Israel (1,111), 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 1,741 per million, compared to 319 per million in Norway and 478 per million in Finland. The United States should have taken 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 populationRank in USARanked within World
Mississippi4,118  1st6th
New Jersey  3,7254th8th tied
Louisiana3,6337th10th tied 
New York 3,50410th10th tied
Alabama3,8413rd8th tied
Arizona3,8592nd8th tied
Massachusetts3,44611th11th
Rhode Island  3,229  19th14th
Arkansas3,6008th10th tied
Florida3,34518th12th tied
California2,21538th37th
USA2,97118th
Peru6,2651st
Bosnia-Herzegovina  4,8103rd
North Macedonia  4,7395th
Hungary4,6424th
Montenegro4,2856th
Bulgaria5,2582nd
Gibraltar2,99917th
Czechia3,6429th
Brazil3,04315th
San Marino3,28912th
Georgia4,1517th
Sweden1,74157th
Israel1,11184th
Canada96290th
Finland478125th
Norway319141st
Japan204151st
Iceland229147th
South Korea192154th

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). 

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

DatePaxlovidMolnupiravirSotrovimabBebtelovimabEvusheld
1/24/22-1/30/2299,980399,98052,26074,976
1/31/22-2/6/220052,10474,960
2/7/22-2/13/2299,940399,84052,24848,74549,264
2/14/22-2/20/220052,24948,79549,992
2/21/22-2/27/22148,980349,77652,19449,00049,922
2/28/22-3/6/220046,98651,99049,992
3/7/22-3/13/22175,000174,96052,24249,000199,992

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.

Bebtelovimab is a new 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.

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. 

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):

World Health Organization

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

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

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

World Health Organization

According to the UK Health Security Agency Technical Briefing from 2/25/22, “A putative Delta and Omicron recombinant has been identified in the UK, with likely parental lineages AY.4.2.2 and BA.1.1 and a breakpoint in non-structural protein 3 (nsp3). The presence of 34 genomes sampled between 7 January 2022 and 14 February 2022 suggest that this recombinant is able to transmit.” GISAID has also begun publishing data about a recombinant of Delta AY.4 and Omicron BA.1, first identified in France. According to GISAID data, this variant has also been detected in Denmark, Germany, the Netherlands, and the United States.

GISAID

Map of Omicron sequenced transmissions:

GISAID

Delta cases sequenced as of 3/13/22: 

GISAID

Map of Delta sequenced transmissions:

GISAID

Source: GISAID

New recombinant GKA (AY.4/BA.1) cases sequenced as of 3/13/22:

GISAID

B.1.640 cases sequenced as of 3/13/22:

GISAID

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 3/11/22New Infections on 3/11/22Total DeathsNew Deaths on 3/11/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask Mandate?Currently in Lockdown?
World455,056,951(21,755,564 new infections in 14 days; an increase of 7,152,177 infections from the preceding 14 days).1,694,1006,057,327(100,832 new deaths in last 14 days)6,0205.83%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)NoNo
USA81,154,960
(ranked #1) 622,653 new infections in the last 14 days.
39,254
(ranked #12)
993,044
(ranked #1)20,844 new deaths in the last 14 days. 
1,02224.27%
(0.18% increase in 14 days). 
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)NoNo
Brazil29,305,114(ranked #3)  725,872 new infections in the last 14 days. 55,211 (ranked #8)654,612(ranked #2)46513.62%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
India42,987,875(ranked #2); increased by 83,131 infections in 2 weeks.3,615515,833(ranked #3)883.06%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)NoNo
United Kingdom19,530,485(ranked #5; was #6 twenty-six weeks ago; increased by 725,720 infections in 2 weeks.72,828(ranked 4th in the world).161,738 (ranked #7 in world)11428.51%(1.05% increase in the last 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)*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)NoNo
California, USA9,033,843(ranked #10 in the world;  76,635 new infections in the last 14 days).5,15387,397 (ranked #20 in world)14322.86%(0.23% 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)NoNo
Mexico5,591,871(ranked #19) 118,390 new infections in 14 days).8,098320,607(ranked #5)1974.26%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 Africa3,691,962(ranked #24; 32,291 new infections in 14 days).1,67199,709 (ranked #18)286.09%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)NoNo
Canada3,275,746(ranked #31, was 26th ten weeks ago; 81,263 new infections in 14 days).6,17536,855(ranked #26)488.76% .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
Poland5,799,996(ranked #17; 162,350 new infections in 14 days). 11,637113,307 (ranked #15)12115.35%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
Turkey14,513,774(ranked #8, 600,149 new infections in 14 days).25,40196,217 (ranked #19)12316.90% (0.69% of the country was infected in the last 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)*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)NoNo
Russia17,242,043(ranked #6), 1,190,015 new infections in 14 days).50,743359,585(ranked #4 in world)67411.80%; 0.81% of the country was infected in the last 14 days.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
Argentina8,887,973(ranked #11; 1,——— new infections in 14 days).5,615127,051 (ranked #13 in world)4219.53% (0.16 % increase in two weeks).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)NoNo
Colombia6,075,656(ranked #14, 16,941 new infections in 14 days).782139,255 (ranked #11 in the world)3511.72%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)NoNo
Peru3,534,687(ranked #29, 109,793 new infections in 14 days). 72,828211,423(ranked #6)5910.47%, a 0.32% increase in 14 days).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
Indonesia5,5864,010(ranked #15; 359,592 new infections in 14 days)16,110151,703 (ranked #9)2902.10%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)
NoNo
Iran7,117,544 93,640 new infections in last 14 days(ranked 12th; was 12th  twenty-six weeks ago)3,953138,711 (ranked #12)1398.29%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
Spain11,223,974(ranked 10th;   246,450 new infections in 14 days).19,849101,135 (ranked #17)5823.99%, a 0.53% increase in 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)NoNo
France23,381,279 (ranked #4; 788,170 new infections).72,399140,029 (ranked #10)14935.68%, a 1.20% increase in the last 14 days.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)NoNo
Germany16,881,945(ranked #7)245,342 (ranked #2)125,911 (ranked #14)24220.04%NoNo
Hungary1,814,362 (ranked #43)2,06844,653 (ranked #22)5018.86%NoNo
Romania2,787,625(ranked #37)2,97464,292 (ranked#20)4914.65%NoNo
South Korea5,822,626 (ranked 16th)282,976(ranked #1)9,85522911.34%NoNo
Ukraine4,894,331(ranked #21)5,858106,985 (ranked #16)8611.30%NoNo
Vietnam5,734,428(ranked #18)177,976(ranked #3)41,228 (ranked #24)715.80%NoNo
Netherlands7,055,814 (ranked #13)69,165 (ranked #6)21,688 (ranked #39)1341.02%NoNo
Denmark2,796,420 (ranked #13)13,0365,076 (ranked #85)2747.99%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 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 146 countries

Omicron has 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 only been able to obtain PAXLOVIDTM 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 PAXLOVIDTM from the Salinas CVS pharmacy and successfully treated two patients in the last four weeks. Last week we treated a third patient from Turlock with PAXLOVIDTM . Two weeks ago we treated our first patient with Molnupiravir due to our inability at that time to obtain PAXLOVIDTM . Molnupiravir was obtained from the Monterey CVS and does not appear to be in short supply in the United States. You can just send your electronic prescription to a participating CVS pharmacy. You probably should call in advance to check on drug availability and their participation.

In the absence of obtaining intravenous Sotrovimab, only oral PAXLOVIDTM 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 2/11/22, SARS-CoV-2 deaths have increased for the sixth time in eleven 14-day periods. There were 2,459 more deaths per day than in the last 14-day period. Part of this increase is presumably a catch-up of unreported or late reported cases of SARS-CoV-2 deaths over the last eight weeks. 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 increased by 282,707 infections per day compared to the preceding 14-day period. Part of this increase is probably due to late reporting of infections over the last 8 weeks. Our infections per day have increased for the first time over the last 4 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. In Monterey County, only 35% of 5-11 year olds have received the first dose of vaccine.

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 PAXLOVIDTM, 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. 

Omicron Subvariant BA.2 Is Coming

Per CDC data ending in 2/5/22, the Delta variant accounts for 0.0% of new infections in the United States, while Omicron (B.1.1.529/BA.1) accounts for 96.4% and Omicron subvariant BA.2 accounts for 3.6%. It’s worth noting that in the last 30 days, according to GISAID, the United States has only sequenced 0.599% of cases. 

Omicron subvariant BA.2 has been detected in every region of the United States. BA.2 also contains 17 mutations that set it apart from BA.1 (ten of which are also different from those in BA. 3.

FIGURE 3: Venn diagram showing the similarities and differences between the three Omicron family viruses. ACCESS HEALTH INTERNATIONAL

Nexstrain

On 2/11/22, the United States had 149,318 new infections. There were also 1,917 deaths. Florida continues to consistently under-report daily infections and deaths. The number of hospitalized patients has been decreasing in many areas, and now 16,791 patients are seriously or critically ill; that number was 24,384 two weeks ago. The number of critically ill patients has decreased by 7,593 in the last 14 days, while at least 68,003 new deaths occurred. The number of critically ill patients has decreased for the second time in fifteen 14-day periods but a large number of patients are still dying each day (average 4,857/day). Infections, critically ill patients, and deaths should markedly decrease in the next two weeks if Omicron BA.2 causes less severe disease and does not infect large numbers of previously BA.1 infected patients. However, there are reports out of Israel of patients infected with BA.1 being later reinfected with BA.2. 

As of 2/11/22, we have had 905,661 deaths and 79,228,628 SARS-CoV-2 infections in the United States. We have had 13,018,093 new infections in the last 14 days. We were adding an average of 6,509,047 infections every seven days. For the pandemic in the United States we are averaging one death for every 84.2 infections reported or over 11,866 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 65,000 deaths. California and Texas have each had greater than 80,000 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 2/11//22, in the United States, 23.66% of the population has had a documented SARS-CoV-2 infection. In the last 14 months, 20.94% of our country became infected with SARS-CoV-2. In the last 2 weeks 3.60% 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 15 months, there were 679,958 new deaths from SARS-CoV-2. For eleven of those months, vaccines have been available to all adults. During these eleven months, 368,991 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 2/11/22, California was ranked 39th in infection percentage at 22.24%. In California 18.54% of Californians were infected in the last 14 months. As of 2/11/22 forty-two states have had greater than 20% of their population infected. Rhode Island was at 33.21% (ranked #1), North Dakota was at 30.79% (ranked #2), Alaska was at 30.68% (ranked #3), Tennessee was at 28.78% (ranked #4), Utah was at 28.41% (ranked #5) and Florida was at 26.93% (ranked #8) of their population infected. Forty-nine states and the District of Columbia now have greater than 15% of their population infected. Only one state has less than 14% of their population infected: Maine (13.96%). 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, Alabama and New Jersey have the eighth highest COVID-19 deaths per million in the world. Louisiana, Arkansas and New York tied at tenth, followed by  Arkansas and Massachusetts tied at 11th and Rhode Island and Florida tied at 13th and Massachusetts at 14th. The United States as a whole ranks 18th in the world for deaths per million population (2,819 deaths per million). California ranks 38th in the USA (and 37th in the world). If we look at the death rates per million in South Korea (137), Iceland (157), Japan (158, and Israel (1,012), 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 1,614 per million, compared to 276 per million in Norway and 391 per million in Finland. The United States should have taken 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 populationRank in USARanked within World
Mississippi3,884  1st8th tied
New Jersey  3,8453rd8th tied
Louisiana3,4805th10th tied
New York 3,4356th10th tied
Alabama3,5844th7th 
Arizona3,7322nd8th tied
Massachusetts3,30710th14th
Rhode Island  3,187  15th13th tied
Arkansas3,30611th10th tied
Florida3,13518th13th tied
California2,00338th37th
USA2,81918th
Peru6,1691st
Bosnia-Herzegovina  4,6133rd
North Macedonia  4,1796th
Hungary4,4034th
Montenegro4,1095th
Bulgaria4,9992nd
Gibraltar2,99914th
Czechia3,5149th
Brazil2,96415th
San Marino3,20212th
Georgia3,8877th
Sweden1,61456th
Israel1,01285th
Canada92490th
Finland391131st
Norway276138th
Japan158156th
Iceland157157th
South Korea137161st

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). 

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

DatePaxlovidMolnupiravirSotrovimabEvusheld
1/24/22-1/30/2299,980399,98052,26074,976
1/31/22-2/6/220052,10474,960
2/7/22-2/13/2299,940399,84052,24849,264

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):

Source: World Health Organization

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

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

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

Omicron cases sequenced as of 2/13/22:

GISAID

Map of Omicron sequenced transmissions:

Delta cases sequenced as of 2/13/22: 

GISAID

Map of Delta sequenced transmissions:

GISAID

B.1.640 cases sequenced as of 2/13/22:

GISAID

Watching World Data

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

LocationTotal Infections as of 2/11/22New Infections on 2/11//22Total DeathsNew Deaths on 2/11/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask Mandate?Currently in Lockdown?
World408,698,709(84,516446 new infections in 14 days; a new record for the pandemic for 14 days).2,334,2425,820,065(272,575 new deaths in last 14 days)11,1935.24%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)NoNo
USA79,228,628*
(ranked #1) 13,018,093 new infections in the last 14 days; new record for the pandemic for 14 days).
*JHU reported 77,683,119 infections
149,318
(ranked #4)
940,089**
(ranked #1)68,003 new deaths in the last 14 days; a new pandemic record for 14 days.
** JHU reported 918,924 deaths. 
1,91723.66%
(3.66% increase in 14 days: a 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)NoNo
Brazil27,291,515(ranked #3)  4,364,312 infections in 14 days; a new pandemic record for 14 days. 166,003637,232(ranked #2)1,12112.69%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
India42,586,628(ranked #2); increased by 1,731,777 infections in 2 weeks.50,407508,012(ranked #3)8043.03%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)NoNo
United Kingdom18,219,990(ranked #5; was #6 twenty-two weeks ago; increased by 1,886,010 infections in 2 weeks.58,724159,351 (ranked #7 in world)19326.61%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)NoNo
California, USA8,791,317(ranked #10 in the world;  3,427,523 new infections; a new pandemic record for 14 days).23,37382,694 (ranked #20 in world)23322.24%(5.45% increase in 14 days;  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)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)NoNo
Mexico5,226,269(ranked #16) 968,529 new infections in 14 days).34,261311,554(ranked #5)9273.98%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 Africa3,637,673(ranked #20; 85,630 new infections in 14 days).2,86296,851 (ranked #17)1466.01%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)NoNo
Canada3,180,827(ranked #26, was 26th six weeks ago; 173,563 new infections in 14 days).10,18935,371(ranked #26)1408.31% .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
Poland5,348,888(ranked #15;596,188 new infections in 14 days; a new pandemic record for 14 days). 36,483107,756 (ranked #15)28914.15%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
Turkey12,748,341(ranked #7, 2,409,244 new infections in 14 days, a new pandemic record for 14 days).95,99589,994 (ranked #19)25314.85%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)NoNo
Russia13,731,794;(ranked #6), 2,984,669 new infections in 14 days; a new pandemic record for 14 days).203,949338,813(ranked #4 in world)7229.40%; a 2.05% increase in 14 days; a new pandemic record for 14 days.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
Argentina6,932,972(ranked #11; 1,278,504 new infections in 14 days, a new pandemic record for 14 days).139,853117,901 (ranked #13 in world)9315.12% (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)NoNo
Colombia6,007,991(ranked #13, 850,551 new infections in 14 days; a new pandemic record for 14 days).5,421136,764 (ranked #10 in world)18111.60%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)NoNo
Peru3,424,894(ranked #22, 1,128,063 new infections in 14 days; a new pandemic record for 14 days). 13,693207,965(ranked #6)22810.15%, a 2.96% increase in 14 days; a new pandemic record for 14 days.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
Indonesia4,708,043(ranked #17)40,489144,958 (ranked #9)1001.69%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)
NoNo
Iran6,761,855(ranked 12th; was 12th  twenty-two weeks ago)31,247133,437 (ranked #11)1437.88%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
Spain10,604,200(ranked 10th;   2,511,164 new infections in 14 days, a new pandemic record for 14 days).49,00495,995 (ranked #18)38922.66% (5.37% 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)NoNo
France21,503,659 (ranked #4; 7,993,984 new infections in 14 days; a new pandemic record for 14 days).1,31,376134,536 (ranked #11)329 32.82%, a 12.11% increase in 14 days; a new 14 day pandemic record.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)NoNo

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