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 6 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 49.28% in the last 2 weeks and 136.4% 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 57.9% of isolates in the week ending May 21.
Something to look out for is the rise of infections in South Africa to 94,255 infections in the last 14 days ending 5/20/22, a 31% increase from the previous two weeks. This is 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 and now make up 92% 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 5/20/22, 0.77% of cases sequenced in the United States are BA.4 and 0.78% are BA.5. On May 12, the European CDC designated both BA.4 and BA.5 as variants of concern.
The Omicron variant will continue to mutate just like Delta. There are now 100 Omicron sub-variants that have been assigned Pango lineages, including 50 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 5/17/22 the UK Health Security Agency reports 2,049 sequences of the XE recombinant in the UK data.
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.
In the last 14 days in the United States, the number of infections has increased by 32,374 infections per day compared to the preceding 14-day period. Our infections per day have increased for the third 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 over the age of 64. SARS-CoV-2 is now in the top ten most common causes of death for children. Anyone over the age of 5 years can now get vaccinated in the United States at no cost. This should get done immediately.In Monterey County, as of 5/24/22, only 38.3% of 5-11 year-olds have received the first two doses of vaccine, while 80.3% of 12-17 year-olds have received two doses.
On 5/20/22, the United States had 98,665 documented new infections. There were also 244 deaths. In the United States the number of hospitalized patients had been increasing in many areas. Now there are 2,289 patients who are seriously or critically ill; that number was 1,724 two weeks ago. The number of critically ill patients has increased by 565 in the last 14 days, while at least 4,355 new deaths occurred (a decrease of 33 deaths per day from the previous 14 days). The number of critically ill patients has increased for the second time in nineteen 14-day periods. Patients are still dying each day (average 311/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 5/20/22, we have had 1,028,741 deaths and 84,935,202 SARS-CoV-2 infections in the United States. We have had 1,401,202 new infections in the last 14 days. We were adding an average of 700,601 infections every seven days. For the pandemic in the United States we are averaging one death for every 82.56 infections reported for each death or over 12,112 deaths for each one million infections. As of 5/20/22, 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 69,000 deaths. California and Texas have each had greater than 88,000 deaths with California having 91,322 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 5/20/22, in the United States, 25.38% of the population has had a documented SARS-CoV-2 infection. In the last 17 months, 22.73% 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 768,610 new deaths from SARS-CoV-2. For fourteen of those months, vaccines have been available to all adults. During these fourteen months, 457,644 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 5/20/22, California was ranked 37th in the USA in infection percentage at 23.90%. In California 20.06% of Californians were infected in the last 17 months. As of 5/20/22 forty-six states have had greater than 20% of their population infected. Rhode Island was at 36.53% (ranked #1), Alaska was at 34.10% (ranked #2), North Dakota was at 31.91% (ranked #3), Kentucky was at 30.09% (ranked #4), Tennessee was at 29.98% (ranked #5), Utah was at 29.42% (ranked #6), South Carolina was at 28.89% (ranked #7), Wisconsin jumped to 28.42% (ranked #8),West Virginia was at 28.41% (ranked #9), Florida jumped to 28.41% (ranked #10), Arizona was at 28.00% (ranked #12), Arkansas was at 28.73% (ranked #14) and Texas was at 23.75% (ranked #37) 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, and Arkansas have the ninth highest COVID-19 deaths per million in the world. Louisiana had the tenth, New York was at eleventh, and Florida and Rhode Island were tied at twelth. The United States as a whole ranks 16th in the world for deaths per million population (3,108 deaths per million). California ranks 39th in the USA (and 36th in the world). If we look at the death rates per million in South Korea (465), Iceland (443), Japan (240), and Israel (1,161), 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 1,851 per million, compared to 556 per million in Norway and 793 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|
|New Jersey||3,783||7th||9th tied|
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:
- Facility/Provider Name for Registration
- Provider Type (Hospital, Pharmacy, Etc)
- Shipping Address
- Contact Name(s)
- Contact Email(s)
- Contact Phone Number(s)
As for my immunocompromised patients: We provided this information by email to the Monterey County EMS Agency on 1/26/22 and will update you when or if we become an eligible provider and receive our first doses of Evusheld.
On 2/24/22, the FDA revised its dosing guidance for Evusheld, doubling the dosage of its two components, Tixagevimab and Cilgavimab, from 150 mg each to 300 mg each. They explain, “Based on the most recent information and data available, Evusheld may be less active against certain Omicron subvariants. The dosing regimen was revised because available data indicate that a higher dose of Evusheld may be more likely to prevent infection by the COVID-19 Omicron subvariants BA.1 and BA.1.1 than the originally authorized Evusheld dose.” Patients who have already received their first administration of Evusheld intramuscularly will need to contact their healthcare provider to get a second 150 mg injection of Tixagevimab and Cilgavimab. If you have not received Evusheld yet, the correct dose is 3 mL/300 mg of each monoclonal antibody injected intramuscularly. This large volume necessitates administration of the antibodies in the gluteus, with two separate injections.
Watching World Data
Over the next few months, we’ll be paying close attention to correlations between the SARS-CoV-2 data, the number of isolates identified in various countries and states, and the non-pharmaceutical interventions (like mask mandates and lockdowns) put in place by state and national governments. Data on infections, deaths, and percent of population infected was compiled from Worldometers. Data for this table for SARS-CoV-2 Isolates Currently Known in Location was compiled from GISAID and the CDC. It’s worth noting that GISAID provided more data than the CDC.
|Location||Total Infections as of 5/20/22||New Infections on 5/20/22||Total Deaths||New Deaths on 5/20/22||% of Pop.Infected||SARS-CoV-2 Isolates Currently Known in Location||National/ State Mask Mandate||Currently in Lockdown|
|World||526,381,589(9,885,575 new infections in 14 days).||760,754||6,298,738(24,190 new deaths in last 14 days)||1,395||6.75%||B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines) Mu/B.1.621 (Colombia)C.1.2 (South Africa 2% of isolates in July 2021)R1 (Japan)Omicron/B.1.1.529 + BA.1 + BA.2 + BA.3 (South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)Four new recombinants 12/31 to 3/22)BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)||No||No|
|USA||84,935,262(ranked #1) 1,401,202 new infections in the last 14 days.||98,665(ranked #2)||1,028,741(ranked #1)4,355 new deaths in the last 14 days.||244||25.38%||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)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan) Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)Recombinant Delta AY.119.2- Omicron BA.1.1 (Tennessee, USA 12/31/21)\BA.2BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)||No||No|
|Brazil||30,762,413(ranked #3) 218,405 new infections in the last 14 days.||10,187 (ranked #11)||665,595(ranked #2)||104||14.28%||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||43,134,332(ranked #2); 106,300 new infections in 2 weeks.||2,510||524,348(ranked #3)||25||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||22,238,706(ranked #6; was #6 thirty-four weeks ago; 124,672 new infections in 2 weeks.||6,338(ranked 16th in the world).||177,977 ranked #7 in world)||87||32.43%||B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)C.1.2 (South Africa)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)XD (AY.4/BA.1) recombinantXF (Delta/BA.1) recombinantXE (BA.1/BA.2) recombinantBA.2BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)||No||No|
|California, USA||9,446,122(ranked #13 in the world; 157,349 new infections in the last 14 days).||16,044||91,322 (ranked #20 in world)||47||23.90%||B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)||No||No|
|Mexico||5,752,441(ranked #20) 12,361 new infections in 14 days).||———||324,617(ranked #5)||——–||4.37%||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||3,921,633(ranked #29; 94,255 new infections in 14 days).||6,375||100,916 (ranked #18)||18||6.45%||B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India) C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)||No||No|
|Canada||3,787,378(ranked #31, was 26th eighteen weeks ago; 57,347 new infections in 14 days).||2,292||40,664(ranked #25)||37||10.02% .||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||6,005,101 (ranked #20; 5,558 new infections in 14 days).||315||116,255 (ranked #15)||13||15.89%||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||15,060,112(ranked #10, 19,874 new infections in 14 days).||————||98,918 (ranked #19)||———||17.50%||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||18,283,706(ranked #7), 51,635 new infections in 14 days).||5,089||378,168(ranked #4 in world)||96||12.51%||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||9,135,308(ranked #13; 51,635 new infections in 14 days).||———–||128,776 (ranked #14 in world)||——–||19.87%||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||6,099,111(ranked #18, 5,466 new infections in 14 days).||———–||139,833 (ranked #12 in the world)||———||11.75%||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||3,574,876(ranked #35, 8,850 new infections in 14 days).||694||213,086(ranked #6)||9||10.56%||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; —– new infections in 14 days)||250||156,513 (ranked #9)||3||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||7,229,582 5,151 new infections in last 14 days(ranked 16th; was 12th thirty-four weeks ago)||228||141,262 (ranked #11)||9||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||12,238,073(ranked 11th; 229,014 new infections in 14 days).||19,631||105,947 (ranked #17)||101||26.15%||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||29,315,478 (ranked #4; 425,339 new infections in the last 14 days).||24,332 (ranked #9)||147,780 (ranked #10)||65||44.72%||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||26,053,934(ranked #5; 764,344 new infections in 14 days.).||40,651 (ranked #5)||138,633 (ranked #13)||145||30.91%||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)GKA (AY.4/BA.1) recombinant||No||No|
|Hungary||1,914,697 (ranked #44; 11,497 new infections in 14 days).||———||46,446 (ranked #23)||——–||19.91%||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)||No||No|
|Romania||2,905,539(ranked #38; 7,281 new infections in 14 days).||484||65,644 (ranked#20)||4||15.29%||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||17,914,957 (ranked 8th) ; 450,175 new infections in 14 days).||25,108(ranked#8)||23,885 (ranked #39);||43||34.88%||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||5,009,301(ranked #22; 6,431new infections in 14 days),||——–||108,497 (ranked #16)||——–||11.58%||No||No|
|Vietnam||10,706,111(ranked #12; 35,541new infections in 14 days).||1,587||43,075 (ranked #24)||2||10.81%||No||No|
|Netherlands||8,075,194 (ranked #15; 17,494 new infections in 14 days).||1,048||22,306 (ranked #41)||5||46.93%||B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinant||No||No|
|Denmark||2,979,238 (ranked #37) 8,429 new infections in 14 days||———||6,312 (ranked #81)||———||51.09%||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|
|North Korea (DPRK)First listing)||2,241,618 (ranked#41)||263,380 (ranked#1)||85||2||8.62%|
What Our Team Is Reading This Week
- An early warning system for emerging SARS-CoV-2 variants (Nature Medicine) https://doi.org/10.1038/s41591-022-01836-w
- 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
- Take a look at SARS-CoV-2’s family tree. It’s full of surprises (NPR) https://www.npr.org/sections/goatsandsoda/2022/02/09/1047616658/take-a-look-at-sars-cov-2s-family-tree-its-full-of-surprises
- SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 35 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1050999/Technical-Briefing-35-28January2022.pdf
- Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants (Nature) https://www.nature.com/articles/s41586-022-04466-x_reference.pdf
- Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time (Preprint) https://www.medrxiv.org/content/10.1101/2022.01.14.22269235v1
- Syncytin, envelope protein of human endogenous retrovirus (HERV): no longer ‘fossil’ in human genome (Animal Cells and Systems) https://doi.org/10.1080/19768354.2021.2019109
- Host Chitinase 3-like-1 is a Universal Therapeutic Target for the Delta, Omicron and Other SARS-CoV-2 Viral Variants in COVID 19 (Preprint) https://www.biorxiv.org/content/10.1101/2022.01.21.477274v1
- COVID-19 reinfections among naturally infected and vaccinated individuals (Nature) https://www.nature.com/articles/s41598-022-05325-5
- Duration of Protection against Mild and Severe Disease by Covid-19 Vaccines (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2115481
- Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants (Preprint) https://www.medrxiv.org/content/10.1101/2022.01.25.22269794v1
- COVID-19 and the Common Cold—Preexisting Coronavirus Antibodies May Hinder SARS-CoV-2 Immunity (JAMA) https://jamanetwork.com/journals/jama/fullarticle/2788621?guestAccessKey=0bbad800-e651-496b-8046-d124bbc63a5a&term=01262022&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jama&utm_content=olf&utm_term=012622
- Viral dynamics and duration of PCR positivity of the SARS-CoV-2 Omicron variant https://dash.harvard.edu/handle/1/37370587
- Emergence in Southern France of a new SARS-CoV-2 variant of probably Cameroonian origin harbouring both substitutions N501Y and E484K in the spike protein (Preprint) https://doi.org/10.1101/2021.12.24.21268174
- A living WHO guideline on drugs for covid-19 (BMJ) https://doi.org/10.1136/bmj.m3379
- Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis (Science) https://doi.org/10.1126/science.abj8222
- Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection (Nature) https://www.nature.com/articles/s41590-021-01113-x
- An upper bound on one-to-one exposure to infectious human respiratory particles (PNAS) https://www.pnas.org/content/118/49/e2110117118
- Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies (Nature) https://doi.org/10.1038/d41586-021-03796-6
- Frequent Occurrence of SARS-CoV-2 Transmission among Non-close Contacts Exposed to COVID-19 Patients (Journal of Korean Medical Science) https://doi.org/10.3346/jkms.2021.36.e233
- Serial Screening for SARS-CoV-2 in Rectal Swabs of Symptomatic COVID-19 Patients (Journal of Korean Medical Science) https://doi.org/10.3346/jkms.2021.36.e301
- Saliva swabs are the preferred sample for Omicron detection (Preprint) https://doi.org/10.1101/2021.12.22.21268246
- SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing: Update on hospitalisation and vaccine effectiveness for Omicron VOC-21NOV-01 (B.1.1.529) 31 December 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1044481/Technical-Briefing-31-Dec-2021-Omicron_severity_update.pdf
- Characteristics and Clinical Outcomes of Children and Adolescents Aged <18 Years Hospitalized with COVID-19 — Six Hospitals, United States, July–August 2021 (MMWR) https://www.cdc.gov/mmwr/volumes/70/wr/mm705152a3.htm
- The SARS-CoV-2 variant, Omicron, shows rapid replication in human primary nasal epithelial cultures and efficiently uses the endosomal route of entry. (Preprint) https://drive.google.com/file/d/1vam2PVMWvfRBczqs_uZbnUixGja1QPZD/view
- Initial Assessment of SARS-CoV-2 Omicron Variant in Exhaled Breath Aerosol (Preprint) https://mfr.osf.io/render?url=https%3A%2F%2Fosf.io%2Fdscy3%2Fdownload
- Multisystem Involvement in Post-acute Sequelae of COVID-19 (PASC) (Annals of Neurology) https://doi.org/10.1002/ana.26286
- Taiwan rejects US CDC guidance on 5-day quarantine (Taiwan News) https://www.taiwannews.com.tw/en/news/4393548
- Risk assessment for SARS-CoV-2 variant: Omicron VOC-21NOV-01 (B.1.1.529) (UK Health Security Agency) https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1041896/15-december-2021-risk-assessment-for-SARS_Omicron_VOC-21NOV-01_B.1.1.529.pdf
- HKUMed finds Omicron SARS-CoV-2 can infect faster and better than Delta in human bronchus but with less severe infection in lung https://www.med.hku.hk/en/news/press/20211215-omicron-sars-cov-2-infection
- mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant (Preprint) https://www.medrxiv.org/content/10.1101/2021.12.14.21267755v1/
- “Breakthrough” COVID-19 Hospitalizations Among Fully Vaccinated Patients Occur Most Often among Older Adults and Involve People with Chronic Health Conditions (KFF) https://www.kff.org/coronavirus-covid-19/press-release/breakthrough-covid-19-hospitalizations-among-fully-vaccinated-patients-occur-most-often-among-older-adults-and-involve-people-with-chronic-health-conditions/
- Discovery Health, South Africa’s largest private health insurance administrator, releases at-scale, real-world analysis of Omicron outbreak based on 211 000 COVID-19 test results in South Africa, including collaboration with the South Africa https://www.discovery.co.za/corporate/news-room#/documents/press-release-dot-pdf-417948
- SARS-CoV-2 variants of concern and variants under investigation in England, Technical Briefing 31 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1040076/Technical_Briefing_31.pdf
- Minimal cross-over between mutations associated with Omicron variant of SARS-CoV-2 and CD8+ T cell epitopes identified in COVID-19 convalescent individuals (Preprint) https://www.biorxiv.org/content/10.1101/2021.12.06.471446v1
- COVID-19 vaccines dampen genomic diversity of SARS-CoV-2: Unvaccinated patients exhibit more antigenic mutational variance (Preprint) https://www.medrxiv.org/content/10.1101/2021.07.01.21259833v1
- SARS-CoV-2 B.1.1.529 variant (Omicron) evades neutralization by sera from vaccinated and convalescent individuals (Preprint) https://www.medrxiv.org/content/10.1101/2021.12.08.21267491v1
- Myocarditis after Covid-19 Vaccination in a Large Health Care Organization (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2110737
- Myocarditis after BNT162b2 mRNA Vaccine against Covid-19 in Israel (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2109730
- Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2116185
- Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial (Science) https://www.science.org/doi/10.1126/science.abm3425
- Dissecting the early COVID-19 cases in Wuhan (Science) https://www.science.org/doi/10.1126/science.abm4454
- Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis (The Lancet) https://doi.org/10.1016/S2666-5247(21)00267-6
- An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19 (Science) https://doi.org/10.1126/science.abl4784
- Pfizer’s Novel Covid-19 Oral Antiviral Treatment Candidate Reduced Risk Of Hospitalization Or Death By 89% In Interim Analysis Of Phase 2/3 Epic-Hr Study https://www.pfizer.com/news/press-release/press-release-detail/pfizers-novel-covid-19-oral-antiviral-treatment-candidate