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

SARS-CoV-2 infections per day have been increasing in the United States for 4 consecutive weeks despite underreporting by states and the failure to capture positive home tests and a decreased screening program in most states. The number of infections per day in the United States has increased by 59.7% in the last 2 weeks and 118.5% from 4 weeks ago. Deaths per day had been decelerating at a rapid rate in the United States but are now flattening out. The rate of decline has lessened as the increased infection rate and infectivity of the Omicron BA.1, BA.2 and particularly BA.2.12.1 variant of SARS CoV-2 have spread across the nation. The CDC estimates that BA.2.12.1 accounted for 36.5% of isolates in the week ending April 30.

Something to look out for is the rise of infections in South Africa from 25,393 infections in the 2 weeks ending on 4/22/22 to 71,869 infections in the last 14 days ending 5/6/22, a 283% increase. This is probably secondary to new Omicron mutants BA.4 and BA.5, which, according to NICD, became the dominant variants in South Africa in April, comprising 58% of isolates. According to the UK Health Security Agency, “BA.4 shares all mutations/deletions with the BA.2 lineage except the following: S: 69/70 deletion, R408 (WT, wild type)*, L452R, F486V, Q493 (WT); ORF 7b: L11F; N: P151S; synonymous SNP G12160A” and “BA.5 shares all mutations/deletions with the BA.2 lineage except the following: S: 69/70 deletion, R408 (WT), L452R, F486V, Q493 (WT); ORF6: D61 (WT); M: D3N; synonymous SNPs: G12160A, A27038G, and C27889T.” As of 5/8/22, the United States has sequenced 20 cases of BA.4 and 6 cases of BA.5. 

The Omicron variant will continue to mutate just like Delta. There are now 92 Omicron sub-variants that have been assigned Pango lineages, including 43 sub-lineages of BA.2.

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 5/8/22 the UK Health Security Agency reports 1,880 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. 

Omicron variants have mutations which decrease the effectiveness of current vaccines and monoclonal antibodies. The effectiveness of the new Pfizer drug, PAXLOVID^TM, should not be compromised by any of the current mutations in Omicron or Delta variants. Pfizer completed their filing with the FDA on 11/15/21. The FDA approved PAXLOVID^TM on December 22 , 2021.The FDA approved Merck’s drug Molnupiravir on December 23, 2021. On 12/23/21 CVS announced by fax it was selected by the Government to distribute oral PAXLOVID^TM and Molnupiravir. On 12/27/21, another fax from CVS listed which CVS pharmacies in California would have these drugs. Monterey County covers 3,771 square miles with a population of 434,061. Three CVS pharmacies in Monterey, Salinas, and Soledad are the only listed pharmacies in our county. I have now been able to obtain PAXLOVID^TM 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 PAXLOVID^TM 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.

On 5/06/22, the United States had 77,116 documented new infections. There were also 291 deaths. In the United States the number of hospitalized patients had been decreasing in many areas. Now there are 1,724  patients who are seriously or critically ill; that number was 1,512 two weeks ago. The number of critically ill patients has increased by 212 in the last 14 days, while at least 6,232 new deaths occurred (a decrease of 19 deaths per day from the previous 14 days). The number of critically ill patients has increased for the first time in nineteen 14-day periods. Patients are still dying each day (average 445/day). Omicron BA.2  variants causing infections should continue to increase and critically ill patients may continue to increase. Deaths usually lag two to four weeks behind exponential increase in infections so we will have to see how lethal BA.2.12.1 infections are in a month. Infections with a BA.1, and BA.2 will not prevent infections with BA.2.12.1. There have already been reports out of Israel of patients infected with BA.1 being later reinfected with BA.2. 

As of 5/06/22, we have had 1,024,386 deaths and 83,534,060 SARS-CoV-2 infections in the United States. We have had 905,971 new infections in the last 14 days. We were adding an average of 452,985 infections every seven days. For the pandemic in the United States we are averaging one death for every 81.5 infections reported for each death or over 12,263 deaths for each one million infections. As of 5/06/22, thirty-seven states have had greater than 500,000 total infections, and 36 states have had greater than 5,000 total deaths. Seventeen states (Virginia, Missouri, North Carolina, Indiana, Tennessee, Massachusetts, Ohio, Michigan, Georgia, Illinois, New Jersey, Pennsylvania, Florida, Texas, New York, Arizona and California) have had greater than 20,000 deaths. Four states (Florida, Texas, New York, and California) have had greater than 68,000 deaths. California and Texas have each had greater than 85,000 deaths with California having 90,804 deaths (20th most deaths in the world). 

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 5/06/22, in the United States, 24.96% of the population has had a documented SARS-CoV-2 infection. In the last 17 months, 22.27% 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 17 months, there were 764,255 new deaths from SARS-CoV-2. For fourteen of those months, vaccines have been available to all adults. During these fourteen months, 453,289 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 5/06/22, California was ranked 37th in infection percentage at 23.50%. In California 19.66% of Californians were infected in the last 17 months. As of 5/06/22 forty-five states have had greater than 20% of their population infected. Rhode Island was at 35,48% (ranked #1), Alaska was at 33.67% (ranked #2), North Dakota was at 31.72% (ranked #3), Kentucky was at 29.81% (ranked #4), Tennessee was at 29.78% (ranked #5), Utah was at 29.17% (ranked #6), South Carolina was at 28.69% (ranked #7), West Virginia was at 28.06% (ranked #8), Florida jumped to 27.97% (ranked #9). Wisconsin jumped to 27.87% (ranked #10), Arizona was at 27.82% (ranked #11), Arkansas was at 27.73% (ranked #12) and Texas was at 23.59% (ranked #36) 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 have the eighth highest death rates, New Jersey, Arkansas, West Virginia and Tennessee have the ninth highest COVID-19 deaths per million in the world. Louisiana had the tenth, New York was at eleventh,  Florida and Rhode Island were tied at twelth. The United States as a whole ranks 16th in the world for deaths per million population (3,095 deaths per million). California ranks 40th in the USA (and 36th in the world). If we look at the death rates per million in South Korea (452), Iceland (345), Japan (286), and Israel (1,152), 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 1,839 per million, compared to 47 per million in Norway and 747 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 population	Rank in USA	Ranked within World
Mississippi	4,185	1st	8th tied
New Jersey	3,770	7th	9th tied
Louisiana	3,716	8th	10th
New York	3,544	13th	11th
Alabama	3,998	3rd	8th tied
Arizona	4,148	2nd	8th tied
Rhode Island	3,559	20th	12th
Arkansas	3,780	6th	9th tied
Florida	3,449	19th	12th
California	2,298	40th	36th
USA	3,095		16th
Peru	6,296		1st
Bosnia-Herzegovina	4,862		3rd
Hungary	4,812		4th
Montenegro	4,325		6th
Bulgaria	5,395		2nd
Czechia	3,742		9th
Brazil	3,084		16th
Georgia	4,229		7th
Sweden	1,839		57th
Israel	1,152		84th
Canada	1,036		91st
Finland	747		111th
Norway	547		125th
Japan	286		149th
Iceland	345		142nd
South Korea	452		129th

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

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

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

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

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

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

As for my immunocompromised patients: We provided this information by email to the Monterey County EMS Agency on 1/26/22 and will update you when or if we become an eligible provider and receive our first doses of Evusheld. On 2/24/22, the FDA revised its dosing guidance for Evusheld, doubling the dosage of its two components, Tixagevimab and Cilgavimab, from 150 mg each to 300 mg each. They explain, “Based on the most recent information and data available, Evusheld may be less active against certain Omicron subvariants. The dosing regimen was revised because available data indicate that a higher dose of Evusheld may be more likely to prevent infection by the COVID-19 Omicron subvariants BA.1 and BA.1.1 than the originally authorized Evusheld dose.” Patients who have already received their first administration of Evusheld intramuscularly will need to contact their healthcare provider to get a second 150 mg injection of Tixagevimab and Cilgavimab. If you have not received Evusheld yet, the correct dose is 3 mL/300 mg of each monoclonal antibody injected intramuscularly. This large volume necessitates administration of the antibodies in the gluteus, with two separate injections.

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):

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 5/8/22:

Map of Omicron sequenced transmissions:

Delta cases sequenced as of 5/8/22: 

Map of Delta sequenced transmissions:

GKA (AY.4/BA.1) cases sequenced as of 5/8/22:

B.1.640 cases sequenced as of 5/8/22:

Watching World Data

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

Location	Total Infections as of 5/06/22	New Infections on 5/06/22	Total Deaths	New Deaths on 5/06/22	% of Pop.Infected	SARS-CoV-2 Isolates Currently Known in Location	National/ State Mask Mandate	Currently in Lockdown
World	516,495,714(7,985,986 new infections in 14 days).	514,703	6,274,548(34,384 new deaths in last 14 days)	2,006	6.62%	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)	No	No
USA	83,534,060(ranked #1) 905,971 new infections in the last 14 days.	77,116(ranked #2)	1,024,386(ranked #1)6,232 new deaths in the last 14 days.	291	24.96%	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)	No	No
Brazil	30,543,908(ranked #3) 497,143 new infections in the last 14 days.	19,725 (ranked #9)	664,143(ranked #2)	178	14.18%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
India	43,018,032(ranked #2); 44,151 new infections in 2 weeks.	4,195	524,024(ranked #3)	22	3.06%	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)	No	No
United Kingdom	22,114,034(ranked #6; was #6 thirty-two weeks ago; 180,828 new infections in 2 weeks.	6,551(ranked 15th in the world).	176,212(ranked #7 in world)	228	32.26%	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) recombinant	No	No
California, USA	9,288,773(ranked #13 in the world;  44,240 new infections in the last 14 days).	39,514	90.804 (ranked #20 in world)	55	23.50%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Mexico	5,740,080(ranked #20) 8,445 new infections in 14 days).	———	324,350(ranked #5)	——–	4.36%	B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
South Africa	3,827,378(ranked #30; 71,869 new infections in 14 days).	9,253	100,505 (ranked #18)	34	6.30%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)       C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)	No	No
Canada	3,787,378(ranked #27, was 26th sixteen weeks ago; 95,613 new infections in 14 days).	8,557	37,977(ranked #26)	42	9.29% .	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)	No	No
Poland	5,999,513(ranked #19; 43,262 new infections in 14 days).	607	116,124 (ranked #15)	26	15.88%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3	No	No
Turkey	15,040,238(ranked #10, 26,622 new infections in 14 days).	1,743	98,826 (ranked #19)	7	17.48%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)	No	No
Russia	18,216,719(ranked #7), 96,857 new infections in 14 days).	5,541	376,696(ranked #4 in world)	136	12.47%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)R1 (Japan) B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Argentina	9,083,673(ranked #13; 22,650 new infections in 14 days).	———–	128,194 (ranked #14 in world)	——–	19.76%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gama/P.1 (Brazil)Delta/B.1.617.2 (India)Lambda/C.37 (Peru)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Colombia	6,093,645(ranked #18, 2,842 new infections in 14 days).	———–	139,809 (ranked #12 in the world)	———	11.74%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Epsilon/B.1.427 + B.1.429 (USA)*Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Peru	3,569,026(ranked #35, 9,683 new infections in 14 days).	334	212,913(ranked #6)	7	10.55%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Indonesia	6,097,986(ranked #18; 54,720 new infections in 14 days)	245	156,357 (ranked #9)	17	2.16%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Eta/B.1.525 (Nigeria/UK)Theta/P.3 (Philippines) Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Iran	7,224,431 9,527 new infections in last 14 days(ranked 16th; was 12th  thirty-two weeks ago)	375	141,157 (ranked #11)	12	8.40%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Spain	12,009,059(ranked 11th;   381,572  new infections in 14 days).	18,526	104,869 (ranked #17)	67	25.66%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)	No	No
France	28,890,139 (ranked #4; 725,733 new infections in the last 14 days).	40,224 (ranked #4)	146,608 (ranked #10)	110	44.08%	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) recombinant	No	No
Germany	25,289,590(ranked #5; 1,279,822 new infections in 14 days.).	86,026 (ranked #1)	136,812 (ranked #13)	336	30.00%	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)GKA (AY.4/BA.1) recombinant	No	No
Hungary	1,903,200 (ranked #43; 12,237new infections in 14 days).	———	46,266 (ranked #23)	——–	19.79%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No
Romania	2,898,258(ranked #38; 11,000 new infections in 14 days).	730	65,554 (ranked#20)	9	15.25%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No
South Korea	17,464,782 (ranked 8th) ; 709,727 new infections in 14 days).	26,714(ranked#7)	23,206 (ranked #39);	48	34.01%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No
Ukraine	5,002,870(ranked #22; 20,621 new infections in 14 days),	——–	108,411 (ranked #16)	——–	11.56%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No
Vietnam	10,670,570(ranked #12; 126,246 new infections in 14 days).	3,819	43,051 (ranked #24)	6	10.78%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)	No	No
Netherlands	8,057,700 (ranked #14; 22,097 new infections in 14 days).	1,303	22,270 (ranked #41)	1	46.83%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinant	No	No
Denmark	2,970,809, (ranked #37) 12,283  new infections in 14 days	807	6,266 (ranked #81)	8	50.95%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinant	No	No

What Our Team Is Reading This Week

• SARS-CoV-2 Omicron Variant is as Deadly as Previous Waves After Adjusting for Vaccinations, Demographics, and Comorbidities (Preprint) https://doi.org/10.21203/rs.3.rs-1601788/v1 
• Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1 (Preprint) https://www.medrxiv.org/content/10.1101/2022.04.25.22274187v1 

• COVID-19 Associated Hepatitis in Children (CAH-C) during the second wave of SARS-CoV-2 infections in Central India: Is it a complication or transient phenomenon. (Preprint) https://doi.org/10.1101/2021.07.23.21260716 
• Liver and Gastrointestinal Involvement in Patients With COVID-19: A Retrospective Study https://www.cureus.com/articles/90062-liver-and-gastrointestinal-involvement-in-patients-with-covid-19-a-retrospective-study 
• Cortical Grey Matter Volume Loss links to Neurological Sequelae in post COVID-19 “Long Haulers” (Preprint) https://doi.org/10.21203/rs.3.rs-1582065/v1 
• Virological characteristics of the SARS-CoV-2 Omicron BA.2 spike (Cell) https://doi.org/10.1016/j.cell.2022.04.035 
• Continued Emergence and Evolution of Omicron in South Africa: New BA.4 and BA.5 lineages https://www.krisp.org.za/manuscripts/MEDRXIV-2022-274406v1-deOliveira.pdf 
• Molecular consequences of SARS-CoV-2 liver tropism (Nature Metabolism) https://doi.org/10.1038/s42255-022-00552-6 
• China CDC shares latest COVID-19 data (GISAID) https://www.gisaid.org/resources/gisaid-in-the-news/china-shares-latest-11-apr-2022/#c920 
• Persistent COVID-19 symptoms in a community study of 606,434 people in England (Nature) https://www.nature.com/articles/s41467-022-29521-z 
• Brain Inflammation and Intracellular α-Synuclein Aggregates in Macaques after SARS-CoV-2 Infection (Viruses) https://www.mdpi.com/1999-4915/14/4/776 
• Antibody Resistance of SARS-CoV-2 Omicron BA.1, BA.1.1, BA.2 and BA.3 Sub-lineages (Preprint) https://www.biorxiv.org/content/10.1101/2022.04.07.487489v1 
• Infectious viral load in unvaccinated and vaccinated individuals infected with ancestral, Delta or Omicron SARS-CoV-2 (Nature Medicine) https://www.nature.com/articles/s41591-022-01816-0 
• Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain (Preprint) https://www.biorxiv.org/content/10.1101/2022.01.07.475453v1 
• Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study (BMJ) https://www.bmj.com/content/377/bmj-2021-069590 
• SARS-CoV-2 Infection Induces Ferroptosis of Sinoatrial Node Pacemaker Cells (Circulation Research) https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.121.320518 
• SARS-CoV-2 variants of concern and variants under investigation in England (UK Health Security Agency) https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1063424/Tech-Briefing-39-25March2022_FINAL.pdf 
• Neutralization of Omicron BA.1, BA.2, and BA.3 SARS-CoV-2 by 3 doses of BNT162b2 vaccine (Preprint) https://doi.org/10.1101/2022.03.24.485633 
• COVID-19-Associated Encephalitis: Two Case Reports https://www.cureus.com/articles/86903-covid-19-associated-encephalitis-two-case-reports 
• First evidence that an emerging mammalian alphacoronavirus is able to infect an avian species (Transboundary and Emerging Diseases) https://doi.org/10.1111/tbed.14535 
• SARS-CoV-2 co-infection with influenza viruses, respiratory syncytial virus, or adenoviruses (The Lancet) https://doi.org/10.1016/S0140-6736(22)00383-X 
• Evidence for SARS-CoV-2 Delta and Omicron co-infections and recombination (Preprint) https://www.medrxiv.org/content/10.1101/2022.03.09.22272113v1
• Culture and identification of a “Deltamicron” SARS-CoV-2 in a three cases cluster in southern France (Preprint) https://www.medrxiv.org/content/10.1101/2022.03.03.22271812v1.full 
• Mandatory masking in schools reduced COVID-19 cases during Delta surge (NIH press release) https://www.nih.gov/news-events/news-releases/mandatory-masking-schools-reduced-covid-19-cases-during-delta-surge 
• School Masking Policies and Secondary SARS-CoV-2 Transmission (Pediatrics) https://publications.aap.org/pediatrics/article/doi/10.1542/peds.2022-056687/185379/School-Masking-Policies-and-Secondary-SARS-CoV-2 
• Transmission of SARS-CoV-2 delta variant (AY.127) from pet hamsters to humans, leading to onward human-to-human transmission: a case study (The Lancet) https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00326-9/fulltext 
• COVID-19 Variant Dashboard – USA by Raj Rajnarayanan https://public.tableau.com/app/profile/raj.rajnarayanan/viz/USAVariantDB/VariantDashboard 
• SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 38 (UK Health Security Agency) https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1060337/Technical-Briefing-38-11March2022.pdf 
• SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 37 (UK Health Security Agency) https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1057359/Technical-Briefing-37-25February2022.pdf 
• Engineered extracellular vesicles antagonize SARS-CoV-2 infection by inhibiting mTOR signaling (Biomaterials and Biosystems) https://www.sciencedirect.com/science/article/pii/S2666534422000046?via%3Dihub 
• Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study (Preprint) https://doi.org/10.21203/rs.3.rs-1385593/v1 
• Dynamics of the Delta and Omicron variants of SARS-CoV-2 in the United States: the battle of supremacy in the presence of vaccination, mask usage and antiviral treatment (Preprint) https://doi.org/10.21203/rs.3.rs-1420446/v1 
• Virological characteristics of SARS-CoV-2 BA.2 variant (Preprint) https://www.biorxiv.org/content/10.1101/2022.02.14.480335v1 
• Transmission of SARS-CoV-2 Omicron VOC subvariants BA.1 and BA.2: Evidence from Danish Households (Preprint) https://www.medrxiv.org/content/10.1101/2022.01.28.22270044v1
• Waning 2-Dose and 3-Dose Effectiveness of mRNA Vaccines Against COVID-19–Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominance — VISION Network, 10 States, August 2021–January 2022 (MMWR) https://www.cdc.gov/mmwr/volumes/71/wr/mm7107e2.htm?s_cid=mm7107e2_e&ACSTrackingID=USCDC_921-DM75599&ACSTrackingLabel=MMWR%20Early%20Release%20-%20Vol.%2071%2C%20February%2011%2C%202022&deliveryName=USCDC_921-DM75599 
• SARS-CoV-2 B.1.1.529 (Omicron) Variant Transmission Within Households — Four U.S. Jurisdictions, November 2021–February 2022 (MMWR) https://www.cdc.gov/mmwr/volumes/71/wr/mm7109e1.htm?s_cid=mm7109e1_w 
• Pediatric Emergency Department Visits Before and During the COVID-19 Pandemic — United States, January 2019–January 2022 (MMWR) https://www.cdc.gov/mmwr/volumes/71/wr/mm7108e1.htm?s_cid=mm7108e1_w#F2_down 
• Birth Of The Omicron Family: BA.1, BA.2, BA.3. Each As Different As Alpha Is From Delta. (Forbes) https://www.forbes.com/sites/williamhaseltine/2022/01/26/birth-of-the-omicron-family-ba1-ba2-ba3-each-as-different-as-alpha-is-from-delta/?sh=403de4ee3da9