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 14 consecutive weeks despite underreporting by states and the failure to capture positive home tests and a decreased screening program in most states. Deaths per day had been decelerating at a rapid rate in the United States but are now increased by 8 more deaths per day. The number of infections have increased as the Omicron BA.2.12.1, BA.2, BA.4, and BA.5 variants of SARS CoV-2 have spread across the nation. The CDC estimates that BA.2.12.1 accounted for 42% of isolates, BA.2 accounted for 5.7%, BA.5 accounted for 36.6%, BA.4 accounted for 15.7%, and B.1.1.529 accounted for 0% in the week ending June 25.

We frequently hear messaging from health officials and politicians that Omicron is “mild,” especially compared to the Delta variant, and as a result, many of our patients believe that they no longer need to wear their masks. This is a dangerous misconception. SARS-CoV-2 still remains a highly transmissible, airborne virus. The following graph, based on CDC data from April 2, 2022, shows that Omicron deaths in people over 65 are much higher than Delta deaths in the same age group. In fact, the peak of Omicron deaths in people over 65 years of age is 163% higher than the Delta peak. The death rate from Omicron is only lower than Delta in the populations between 12 and 64 years of age. Until we have more data on these newer mutants of SARS-CoV-2, we will not know the lethality of each variant. It may take months to measure objective differences in the death rates of new circulating variants. We recommend that all of our patients and family members continue to wear N95 masks in all enclosed spaces.

In patients treated with Paxlovid for five days who have persistent symptoms and continued positivity, we feel that clinicians should consider giving a second course of Paxlovid for five days. Boucau et al have demonstrated that in a study of seven patients with recurrent symptoms, “High viral loads (median 6.1 log10 copies/mL) were detected after rebound for a median of 17 days after initial diagnosis. Three had culturable virus for up to 16 days after initial diagnosis.” This was not due to resistance-associated mutations of the virus, suggesting that the course of therapy may be inadequate in this group of persistently infected patients. 

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.” On May 12, the European CDC designated both BA.4 and BA.5 as variants of concern. 

The Omicron variant has continued to mutate just like Delta. There are now 199 Omicron sub-variants (an increase of 42 in the last two weeks) that have been assigned Pango lineages, including 104 sub-lineages of BA.2 (an increase of 12 in two weeks), one sub-lineage of BA.3, nine sub-lineages of BA.4 (an increase of 6 in two weeks), and 15 sub-lineages of BA.5 (an increase of 10 in two weeks). The BF lineage (new two weeks ago), with BF.1 first detected in England, Denmark, Spain and Scotland now has 6 sublineages. The BE lineage (also new two weeks ago), with BE.1 first detected in South Africa, Austria and England, now has 3 new sublineages. There are also new lineages: BC.1 (Japan), BC.2 (Peru),BD.1 (UK), BG.1 (Peru), BG.2 (US, Denmark, Canada), BG.3 (Peru), BG.4 (Israel). 

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. 

Unless people continue to wear masks and 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 7/3/22, only 0.6% of 0-4 year-olds and 43.2% of 5-11 year-olds have received the first two doses of vaccine, while 78.7% of 12-17 year-olds have received two doses. On June 17, The FDA authorized both the Pfizer and Moderna vaccines for use in children ages 6 months to four years. We believe children under 5 should be vaccinated as soon as possible. 

On 7/1/22, the United States had 102,788 documented new infections. There were also 283 deaths. Twenty-one states did not report their infections, and 27 states didn’t report their deaths. In the United States the number of hospitalized patients had been increasing in many areas. Now there are 3,400 patients who are seriously or critically ill; that number was 3,006 two weeks ago. The number of critically ill patients has increased by 394 in the last 14 days, while at least 5,106 new deaths occurred (an increase of 8 deaths per day from the previous 14 days). The number of critically ill patients has increased for the fifth time in twenty-two 14-day periods. Patients are still dying each day (average 358/day). Omicron BA.2, BA.2.12.1, BA.4, and BA.5 variants causing infections should continue to increase and critically ill patients may continue to increase. Deaths, which usually lag two to four weeks behind exponential increase in infections, are increasing now. Past infections with a BA.1 or BA.2 variant will not prevent infections with BA.2.12.1, BA.4, or BA.5. 

As of 7/1/22, we have had 1,043,281 deaths and 89,507,083 SARS-CoV-2 infections in the United States. We have had 1,538,264 new infections in the last 14 days. We are adding an average of 769,312 infections every seven days. For the pandemic in the United States we are averaging one death for every 86.2 infections or over 11,656 deaths for each one million infections. As of 7/1/22, thirty-eight 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 70,000 deaths. California and Texas have each had greater than 89,000 deaths with California having 92,621 deaths (20th most deaths in the world). 

As of 7/1/22, in the United States, 26.72% of the population has had a documented SARS-CoV-2 infection. In the last 18 months, 23.97% 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 18 months, there were 783,150 new deaths from SARS-CoV-2. For fifteen of those months, vaccines have been available to all adults. During these fifteen months, 472,184 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 7/1/22, California was ranked 35th in the USA in infection percentage at 25.69%. In California, 21.72% of people were infected in the last 18 months. As of 7/1/22, 36 states have had greater than 25% of their population infected. 

Worldwide, average deaths per day are 1,470 for the last 14 days. The United States has 24.35% (358 per day) of all deaths per day in the world over the last two weeks. Worldwide infections per day were 712,693. The United States accounts for 15.42% of those infections (or 109,902 infections per day). 

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

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

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

FDA Approved 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. 

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 7/1/22	New Infections on 7/1/22	Total Deaths	New Deaths on 7/1/22	% of Pop.Infected	SARS-CoV-2 Isolates Currently Known in Location	National/ State Mask Mandate	Currently in Lockdown
World	553,598,056(9,977,707 new infections in 14 days).	825,008	6,359,972(20,585 new deaths in last 14 days)	1,503	7.10%	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	89,507,083(ranked #1) 1,538,264 new infections in the last 14 days.	102,788(ranked #2) 21 states failed to report infections.	1,043,281(ranked #1) 5,016 new deaths in the last 14 days.	283 27 states failed to report deaths.	26.72%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan)         Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)Recombinant Delta AY.119.2- Omicron BA.1.1 (Tennessee, USA 12/31/21)\BA.2BA.2.12.1 (United States)BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India)	No	No
Brazil	32,434,063(ranked #3) 760,688 new infections in the last 14 days.	75,612 (ranked #5)	671,700(ranked #2; 2,732 new deaths in 14 days)	234	15.04%	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	43,488,519(ranked #2); 204,726 new infections in 2 weeks.	17,237	525,168(ranked #3)	29	3.09%	B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)APTK India VOI 32421Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Iota/B.1.526 (USA-NYC) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2.75 (India)	No	No
United Kingdom	22,741,065(ranked #6) 268,562 new infections in 2 weeks.	20,720	180,417 (ranked #7) 880 new deaths in 2 weeks	87	33.15%	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)BA.2.75 (India)	No	No
California, USA	10,154,345(ranked #12 in the world;  262,248 new infections in the last 14 days).	23,524	92,620 (ranked #20 in world) 439 new deaths in the last 14 days	60	25.69%	B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa)BA.5 (South Africa)	No	No
Mexico	6,034,602(ranked #20) 182,006 new infections in 14 days).	24,537(ranked #9)	325,716(ranked #5)	47	4.58%	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	3,994,223(ranked #31; 9,577 new infections in 14 days).	380	101,804 (ranked #18)	16	6.56%	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	3,946,087(ranked #32) 35,876 new infections in 14 days).	–	42,010(ranked #25)	–	10.27% .	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	6,015,634 (ranked #21; 4,715 new infections in 14 days).	643	116,429 (ranked #15)	5	15.92%	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	15,123,331(ranked #10, 37,582 new infections in 14 days).	————	99,032 (ranked #19)	———	17.51%	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	18,433,394(ranked #8), 41,597 new infections in 14 days).	3,155	381,165(ranked #4 in world)	53	12.62%	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	9,367,172(ranked #14; 53,619 new infections in 14 days).	———–	129,070 (ranked #14)	——–	20.35%	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	6,175,181(ranked #18, 43,424 new infections in 14 days).	–	140,070 (ranked #14)	–	11.88%	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	3,629,796(ranked #38, 33,432 new infections in 14 days).	4,706	235,526(ranked #6)	29	10.71%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)	No	No
Iran	7,238,589(ranked 17th; 4,066 new infections in last 14 days)	463	141,390(ranked #11)	1	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	12,818,184(ranked 11th;   254,785 new infections in 14 days).	28,048(ranked #8)	108,111 (ranked #17)	89	27.39%	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	31,208,925 (ranked #4; 1,129,467 new infections in the last 14 days).	125,066 (ranked #1)	149,585 (ranked #10)	52	47.60%	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	28,392,629(ranked #5; 1,268,170 new infections in 14 days.).	98,669 (ranked #3)	141,292 (ranked #12)	103	33.67%	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
South Korea	18,368,857 (ranked #9 105,214 new infections in 14 days).	9,516(ranked #17)	24,555 (ranked #39)	8	35.76%	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	10,747,397 (ranked #12; 10,989 new infections in 14 days).	927	43,087 (ranked #24)	–	10.84%	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	8,190,255 (ranked #15; 67,997 new infections in 14 days).	6,083	22,380 (ranked #41)	2	47.58%	B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinant	No	No
Denmark	3,016,049 (ranked #39) 19,336  new infections in 14 days	1,455	6,471 (ranked #81)	2	51.70%	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)	4,744,430 (ranked #24; 163,010 new infections in 14 days)	4,570	73	–	18.24%	Omicron/B.1.1.529 South Africa November 2021)	No	No
Taiwan	3,803,029(ranked #38) 612,283 new infections in 14 days	35,780 (ranked #6)	6,772 (ranked #79)	121	15.91%	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
Japan	9,329,520(ranked #14) 221,197 new infections in the last 14 days	23,523(ranked #10)	31,281(ranked #31)	15	7.42%	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)	No	No

What Our Team Is Reading This Week

• Characterization of virologic rebound following nirmatrelvir-ritonavir treatment for COVID-19 (Clinical Infectious Diseases) https://doi.org/10.1093/cid/ciac512 
• Potential Autoimmunity Resulting from Molecular Mimicry between SARS-CoV-2 Spike and Human Proteins (Preprint) https://doi.org/10.1101/2021.08.10.455737 
• COVID-19 positive patients at higher risk of developing neurodegenerative disorders, new study shows (Medical Express) https://medicalxpress.com/news/2022-06-covid-positive-patients-higher-neurodegenerative.html 
• Evidence of previous SARS-CoV-2 infection in seronegative patients with long COVID (eBioMedicine) https://doi.org/10.1016/j.ebiom.2022.104129 
• SARS-CoV-2 infection induces inflammatory bone loss in golden Syrian hamsters (Nature Communications) https://doi.org/10.1038/s41467-022-30195-w 
• Persistent 129Xe MRI Pulmonary and CT Vascular Abnormalities in Symptomatic Individuals with Post-Acute COVID-19 Syndrome (Radiology) https://doi.org/10.1148/radiol.220492 
• ACE2-independent infection of T lymphocytes by SARS-CoV-2 (Signal Transduction and Targeted Therapy) https://doi.org/10.1038/s41392-022-00919-x 
• Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae (Preprint) https://doi.org/10.1101/2022.06.14.22276401 
• SARS-CoV-2 is detected in the gastrointestinal tract of asymptomatic endoscopy patients but is unlikely to pose a significant risk to healthcare personnel (Gastro Hep Adv) https://doi.org/10.1016/j.gastha.2022.06.002 
• Long COVID symptoms in SARS-CoV-2-positive children aged 0–14 years and matched controls in Denmark (LongCOVIDKidsDK): a national, cross-sectional study (Child & Adolescent Health) https://doi.org/10.1016/S2352-4642(22)00154-7 
• Age and sex-specific risks of myocarditis and pericarditis following Covid-19 messenger RNA vaccines (Nature Communications) https://doi.org/10.1038/s41467-022-31401-5 
• COVID-19 positive patients at higher risk of developing neurodegenerative disorders, new study shows https://medicalxpress.com/news/2022-06-covid-positive-patients-higher-neurodegenerative.html 
• Posttranslational modifications optimize the ability of SARS-CoV-2 spike for effective interaction with host cell receptors (Biophysics and Computational Biology) https://doi.org/10.1073/pnas.2119761119 
• Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2 (The Lancet) https://doi.org/10.1016/S0140-6736(22)00941-2 
• Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum (Cell) https://doi.org/10.1016/j.cell.2022.06.005 
• Immunomodulatory treatment in postural tachycardia syndrome: A case series (European Journal of Neurology) https://doi.org/10.1111/ene.14711 
• Long COVID-19 Liver Manifestation in Children (JPGN) https://journals.lww.com/jpgn/abstract/9900/long_covid_19_liver_manifestation_in_children.84.aspx 
• Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C (Nature Communications) https://doi.org/10.1038/s41467-022-30649-1 
• C.D.C. Dismisses Airborne Transmission of Monkeypox. Some Experts Disagree. (NY Times) https://www.nytimes.com/2022/06/10/health/monkeypox-airborne.html 
• Omicron BA.1 breakthrough infection drives cross-variant neutralization and memory B cell formation against conserved epitopes (Science Immunology) https://doi.org/10.1126/sciimmunol.abq2427 
• SARS-CoV-2 Infection and Persistence Throughout the Human Body and Brain (National Institutes of Health) https://videocast.nih.gov/watch=45296?jwsource=twi 
• Long COVID is associated with extensive in-vivo neuroinflammation on [18F]DPA-714 PET (Preprint) https://doi.org/10.1101/2022.06.02.22275916 
• Unexpected worsening of progressive multifocal leucoencephalopathy following COVID-19 pneumonia (Journal of Neurovirology) https://doi.org/10.1007%2Fs13365-021-00980-2 
• Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5 (Preprint) https://doi.org/10.1101/2022.05.26.493539 
• During the Omicron Wave, Death Rates Soared for Older People (NY Times with CDC data) https://www.nytimes.com/2022/05/31/health/omicron-deaths-age-65-elderly.html 
• PD-1 blockade counteracts post–COVID-19 immune abnormalities and stimulates the anti–SARS-CoV-2 immune response (JCI Insight) https://insight.jci.org/articles/view/146701
• Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance (Nature Reviews Clinical Oncology) https://doi.org/10.1038/s41571-019-0218-0 
• Herpesvirus infections and post-COVID-19 manifestations: a pilot observational study (Observational Research) https://doi.org/10.1007/s00296-022-05146-9 
• 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