COVID-19

SARS-CoV-2 Update

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

SARS-CoV-2 infections per day in the United States have decreased for the second time in four weeks; however, there is still widespread underreporting by states, a failure to capture positive home tests, and a decreased PCR screening program in most states. Deaths per day in the United States have decreased by 14 deaths per day. The number of infections per day has decreased by 19,313.  The CDC estimates that BA.5 accounted for 83.1%, BA.4.6 accounted for 11.9%, BF.7 accounted for 2.3%, BA.4 accounted for 1.4%, BA.2.12.1 accounted for 0.0% of isolates, BA.2 accounted for 0.0%, BA.1.1 accounted for 0.0%, and B.1.1.529 accounted for 0% in the week ending September 10. The rise in BA.4.6 cases is especially concerning because the September 9 UK Security Agency Technical Briefing says that, “Pseudoviral neutralisation assays performed on BA.4.6 show that titres are reduced 2-fold, compared to neutralisation of BA.4 or BA.5 using sera from triple dosed recipients of the Pfizer BNT162b2 vaccine.” The same briefing also states that BA.4.6 has a growth advantage relative to BA.5. 

CDC

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. 

NY Times

The Omicron variant has continued to mutate just like Delta. The list of variants was not updated in the last four weeks, but as of six weeks ago, there are now 276 Omicron sub-variants that have been assigned Pango lineages, including 123 sub-lineages of BA.2, one sub-lineage of BA.3, 15 sub-lineages of BA.4, and 45 sub-lineages of BA.5. The BF lineage (new fourteen weeks ago) now has 21 sublineages.. The BE lineage (also new fourteen weeks ago), with BE.1 first detected in South Africa, Austria and England, now has 7 sublineages. There are also new lineages from fourteen weeks ago: BC.1 (Japan), BC.2 (Peru), BD.1 (UK), BG.1 (Peru), BG.2 (US, Denmark, Canada), BG.3 (Peru), BG.4 (Israel). In the last six weeks, the BG lineage has expanded to include BG.5 (USA) and BG.6 (Peru). Lastly, two new sublineages were added in the past six weeks: BH.1 (India) and BK.1 (USA and Canada). 

In Monterey County, as of 9/24/22, 1.1% of 0-4 year-olds and 39.9% of 5-11 year-olds have received the first two doses of vaccine, while 73.1% of 12-17 year-olds have received two doses. Only 53.6% of Monterey County residents have received a third dose of the vaccine. 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. All Monterey County residents should get up to date on COVID-19 vaccinations as soon as possible. 

Monterey County Health Department

On 9/23/22, the United States had 33,238 documented new infections. There were also 259 deaths. Twenty-six states did not report their infections, and 30 states didn’t report their deaths. In the United States the number of hospitalized patients has decreased slightly in many areas and was 30,273 on September 24, a decrease of 6,417 hospitalizations compared to the previous 14 days. On 9/14/22 there are 3,176 patients who are seriously or critically ill; that number was 3,829 two weeks ago. The number of critically ill patients has decreased by 653 in the last 14 days, while at least 5,228 new deaths occurred. The number of critically ill patients has decreased for the fourth time in twenty-eight 14-day periods. Patients are still dying each day (average 375/day). Omicron BA.4, BA.4.6 and BA.5 variants are still causing infections. Past infections with a BA.1 or BA.2 variant will not prevent infections with BA.4, BA.4.6 or BA.5. Evusheld may not prevent BA.4.6 infections.

As of 9/23/22, we have had 1,081,566 deaths and 97,880,451 SARS-CoV-2 infections in the United States. We have had 854,450 new infections in the last 14 days. We are adding an average of 427,225 new infections every seven days. For the pandemic in the United States we are averaging one death for every 90.48 infections or over 11,050 deaths for each one million infections. As of 9/23/22, thirty-eight states have had greater than 500,000 total infections, and 38 states have had greater than 5,000 total deaths. Forty-six states have had greater than 2,000 deaths, and 43 states have greater than 2,000 deaths per million population. Vermont, at 1,152 deaths per million, and Hawaii, 1,186 deaths per million, are the states with the lowest death rates. Six states have over 4,000 deaths per million population: Mississippi (4,327), Arizona (4,304), Alabama (4,160), West Virginia (4,119), New Mexico (4,079) and Tennessee (4,057). Eighteen states (Alabama, 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 have had greater than 70,000 deaths: Florida (81,139 deaths), Texas (91,159 deaths), New York (72,058 deaths), and  California (95,970 deaths, 20th most deaths in the world). 

On 11/20/20, there were 260,331 (cumulative) deaths in the US from SARS-CoV-2. Since 11/20/20 (22 months), there were 820,435 new deaths from SARS-CoV-2. For eighteen of those months, vaccines have been available to all adults. During these eighteen months, 509,469 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 9/23/22, California was ranked 32nd in the USA in infection percentage at 28.40%. In California, 24.43% of people were infected in the last 19 months. As of 9/23/22, 43 states have had greater than 25% of their population infected. No state has less than 20% of their population infected. Below are the variant proportions for Region 9, which includes California, Nevada, and Arizona. 

CDC

Worldwide, average deaths per day are 1,737 for the last 14 days, which is a 340 deaths-per-day decrease over the previous 14 days. The United States accounts for 21.58% (375 per day) of all deaths per day in the world over the last two weeks. Worldwide infections per day were 474,827. The United States accounts for 12.854% of those infections (or 61,032 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 Intravenous Monoclonal Antibody Treatment for Non-Hospitalized SARS-CoV-2 Patients 

Bebtelovimab is a monoclonal antibody treatment for mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options approved or authorized by FDA are not accessible or clinically appropriate. The authorized dose of bebtelovimab is 175 mg, given as an intravenous injection over at least 30 seconds. The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for this drug on 2/11/22. Bebtelovimab is a human antibody that demonstrates neutralization against the Omicron variants and is available in every state and many hospitals and some clinics. If you are planning on using a monoclonal antibody to treat a SARS-CoV-2 infection, currently only bebtelovimab has activity against all Omicron variants, including BA.4.6. Researchers at Columbia University recently reported that “The loss of activity of tixagevimab and cilgavimab [components of Evusheld] against BA.4.6 leaves us with bebtelovimab as the only therapeutic mAb that has retained potent activity against all circulating forms of SARS-CoV-2.” For this reason, we no longer recommend Evusheld for immunocompromised patients with Omicron infections. 

An examination of the three variants that Wang et al identified as capable of immune escape in patients who receive the two monoclonal antibodies that are contained in Evusheld reveals that all three variants have a mutation in the spike protein at position 346. The changes substitute an uncharged amino acid— threonine (T), serine (S), or isoleucine (I)—for a positively-charged amino acid, arginine. This just goes to show that a single point mutation in the spike protein can render a monoclonal antibody treatment ineffective. Policy makers should keep in mind that the only way to prevent new drug-resistant variants like BA.4.6 from emerging is to prevent transmission of SARS-CoV-2 in the first place, using non-pharmaceutical interventions. The lack of use of N95 masks, with impending winter and influenza outbreaks, on top of COVID-19, is not wise public health and infectious disease policy. If we don’t make effective use of the non-pharmaceutical interventions available to us (masks, ventilation, social distancing), then the pharmaceutical interventions we have will all eventually be useless. 

Two virologists collaborated on Twitter to create the figure below, which Professor Johnson titled “Convergent Evolution on Steroids.”  It shows the key mutations present in many of the currently-circulating Omicron subvariants and demonstrates that mutation at site 346 is becoming more and more common. This means that even if prevalence of BA.4.6 wanes, we are still likely to have drug resistance issues with other newer variants. 

From Professor Marc Johnson, molecular virologist @SolidEvidence on Twitter and Daniele Focosi, M.D., Ph.D. @dfocosi on Twitter

Watching World Data

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

LocationTotal Infections as of 9/23/22New Infections on 9/23/22Total DeathsNew Deaths on 9/23/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World619,585,969(6,647,575  new infections in 14 days).410,5586,538,850(24,324 new deaths in last 14 days)1,3127.94%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.2.12.1 (USA)BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)  NoNo
USA97,880,451(ranked #1) 854,450 new infections in the last 14 days.
33,238(ranked #5)
26 states failed to report infections on 9/23/22.
1,081,566(ranked #1) 5,228 new deaths reported in the last 14 days. 259
30 states failed to report deaths on 9/23/22.
29.57%
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 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)NoNo
Brazil34,666,387(ranked #4) 129,467 new infections in the last 14 days. 6,861685,816(ranked #2; 950 new deaths in 14 days)9116.05%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)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)NoNo
India 44,563,337(ranked #2); 73,054 new infections in 2 weeks.4,912
528,487(ranked #3) 348 new deaths in 2 weeks.383.16%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.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India)NoNo
United Kingdom
23,621,952(ranked #7) 67,433 new infections in 2 weeks.189,919 (ranked #7) 893  new deaths in 2 weeks34.39%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.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)NoNo
California, USA11,228,790(ranked #14 in the world; 100,708 new infections in the last 14 days).1,61995,970 (ranked #20 in world)
616 new deaths in the last 14 days
1328.40%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 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)NoNo
Mexico7,080,152(ranked #18) 27,224 new infections in 14 days).4,147330,017(ranked #5)312 new deaths in 14 days)685.36%NoNo
South Africa4,017,163(ranked #37; 3,113 new infections in 14 days).152102,169 (ranked #18) 40 new deaths in 14 days)6.58%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.4 (South Africa 11/21)BA.5 (South Africa 11/21)NoNo
Canada4,233,468(ranked #33) 35,767 new infections in 14 days).2,47744,992(ranked #24)
618new deaths in the last 14 days
3611.60% NoNo
Poland6,268,049 (ranked #21; 61,157 new infections in 14 days). 4,438117,431 (ranked #15)1916.60%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3 NoNo
Russia20,694,894(ranked #10), 734,599 new infections in 14 days).53,335 (ranked #2)386,551(ranked #4)1,386 new deaths in 14 days10414,16%NoNo
Peru4,140,129(ranked #34, 16,694 new infections in 14 days). 1,150216,446(ranked #6)1712.17%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Iran7,546,276(ranked #17; 8,495 new infections in last 14 days)421144,367(ranked #12)8.73%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)


NoNo
Spain13,393,196(ranked #12;   34,671 new infections in 14 days).-(ranked #18)113,845(ranked #16)676 new deaths in 14 days28.61%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
France35,050,133 (ranked #3; 367,940 new infections in the last 14 days).38,464 (ranked #6)154,854 (ranked #10)
386  new deaths in 14 days
3053.44%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinantNoNo
Germany32,905,086(ranked #5; 452,824 new infections in 14 days.).50,800 (ranked #3)149,368 (ranked #11)
1,139  new deaths in 14 days
9339.22%
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
South Korea24,535,940 (ranked #6 601,906 new infections in 14 days).39,972(ranked #8)28,009 (ranked #37) 
628 new deaths in 14 days
5947.80%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Vietnam11,467,619 (ranked #13; 32,147 new infections in 14 days).1,92843,146 (ranked #26)11.58%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)NoNo
Netherlands8,413,532 (ranked #16; 16,553 new infections in 14 days).1,75622,633 (ranked #41)148.98%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
Denmark3,097,088 (ranked #40) 7,517 new infections in 14 days6407,021 (ranked #79)53.22%53.07%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo




Taiwan6,132,744(ranked #22)
518,546 new infections in 14 days
42,420 (ranked #4)10,702 (ranked #63)
5925.67%
2.17% of population has been infected in the last 14 days
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Japan20,840,785(ranked #9)
958,392 new infections in the last 14 days
61,478(ranked #1)44,071(ranked #25)
1,970 new deaths in the last 14 days
12016.59%
0.76% of population has been infected in the last 14 days
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)BA.2*BA.5*NoNo

What Our Team Is Reading This Week

COVID-19

SARS-CoV-2 Update

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

SARS-CoV-2 infections per day in the United States have decreased for the second time in four weeks; however, there is still widespread underreporting by states, a failure to capture positive home tests, and a decreased PCR screening program in most states. Deaths per day in the United States have decreased by 14 deaths per day. The number of infections per day has decreased by 19,313.  The CDC estimates that BA.2.12.1 accounted for 0.1% of isolates, BA.2 accounted for 1.0%, BA.5 accounted for 87.5%, BA.4 accounted for 2.2%, BA.4.6 accounted for 9.2%, and B.1.1.529 accounted for 0% in the week ending September 10. The rise in BA.4.6 cases is especially concerning because the September 9 UK Security Agency Technical Briefing says that, “Pseudoviral neutralisation assays performed on BA.4.6 show that titres are reduced 2-fold, compared to neutralisation of BA.4 or BA.5 using sera from triple dosed recipients of the Pfizer BNT162b2 vaccine.” The same briefing also states that BA.4.6 has a growth advantage relative to BA.5. 

CDC

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. 

NY Times

The Omicron variant has continued to mutate just like Delta. The list of variants was not updated in the last two weeks, but as of four weeks ago, there are now 276 Omicron sub-variants that have been assigned Pango lineages, including 123 sub-lineages of BA.2, one sub-lineage of BA.3, 15 sub-lineages of BA.4, and 45 sub-lineages of BA.5. The BF lineage (new twelve weeks ago) now has 21 sublineages.. The BE lineage (also new twelve weeks ago), with BE.1 first detected in South Africa, Austria and England, now has 7 sublineages.. There are also new lineages from twelve weeks ago: BC.1 (Japan), BC.2 (Peru), BD.1 (UK), BG.1 (Peru), BG.2 (US, Denmark, Canada), BG.3 (Peru), BG.4 (Israel). In the last four weeks, the BG lineage has expanded to include BG.5 (USA) and BG.6 (Peru). Lastly, two new sublineages were added in the past four weeks: BH.1 (India) and BK.1 (USA and Canada). 

In Monterey County, as of 9/11/22, 0.6% of 0-4 year-olds and 39.7% of 5-11 year-olds have received the first two doses of vaccine, while 73.0% of 12-17 year-olds have received two doses. Only 53.4% of Monterey County residents have received a third dose of the vaccine. 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. All Monterey County residents should get up to date on COVID-19 vaccinations as soon as possible. 

Monterey County Health Department

On 9/09/22, the United States had 50,822 documented new infections. There were also 317 deaths. Twenty-six states did not report their infections, and 29 states didn’t report their deaths. In the United States the number of hospitalized patients has decreased slightly in many areas and was 36,690 on September 6, a decrease of 1,949 hospitalizations compared to the previous 14 days. On 9/09/22 there are 3,829 patients who are seriously or critically ill; that number was 3,992 two weeks ago. The number of critically ill patients has decreased by 153 in the last 14 days, while at least 6,495 new deaths occurred. The number of critically ill patients has decreased for the third time in twenty-seven 14-day periods. Patients are still dying each day (average 464/day). Omicron BA.4, BA.4.6 (a new USA variant) and BA.5 variants causing infections should continue to increase and critically ill patients may increase. Deaths usually lag two to four weeks behind exponential increase in infections. Past infections with a BA.1 or BA.2 variant will not prevent infections with BA.4, BA.4.6 or BA.5. Evusheld may not prevent BA.4.6 infections.

As of 9/09/22, we have had 1,075,338 deaths and 97,026,001 SARS-CoV-2 infections in the United States. We have had 1,055,994 new infections in the last 14 days. We are adding an average of 527,997 new infections every seven days. For the pandemic in the United States we are averaging one death for every 90.23 infections or over 11,083 deaths for each one million infections. As of 9/09/22, thirty-eight states have had greater than 500,000 total infections, and 37 states have had greater than 5,000 total deaths. Forty-six states have had greater than 2,000 deaths, and 46 states have greater than 2,000 deaths per million population. Vermont, at 1,146 deaths per million, and Hawaii, 1,169 deaths per million, are the states with the lowest death rates. Five states have over 4,000 deaths per million population: Mississippi (4,308), Arizona (4,281), Alabama (4,134), West Virginia (4,088), New Mexico (4,046( and Tennessee (4,032). Eighteen states (Alabama, 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 have had greater than 70,000 deaths: Florida (80,384 deaths), Texas (90,860 deaths), New York (71,730 deaths), and  California (95,354 deaths, 20th most deaths in the world). 

On 11/20/20, there were 260,331 (cumulative) deaths in the US from SARS-CoV-2. Since 11/20/20 (22 months), there were 815,207 new deaths from SARS-CoV-2. For eighteen of those months, vaccines have been available to all adults. During these eighteen months, 504,241 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 9/09/22, California was ranked 32nd in the USA in infection percentage at 28.16%. In California, 24.19% of people were infected in the last 19 months. As of 9/09/22, 42 states have had greater than 25% of their population infected. No state has less than 20% of their population infected. 

Worldwide, average deaths per day are 2,077 for the last 14 days, which is a 322 deaths-per-day decrease over the previous 14 days. The United States accounts for 15.95% (464 per day) of all deaths per day in the world over the last two weeks. Worldwide infections per day were 584,902. The United States accounts for 12.899% of those infections (or 75,428 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 Intravenous Monoclonal Antibody Treatment for Non-Hospitalized SARS-CoV-2 Patients 

Bebtelovimab is a monoclonal antibody treatment for mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options approved or authorized by FDA are not accessible or clinically appropriate. The authorized dose of bebtelovimab is 175 mg, given as an intravenous injection over at least 30 seconds. The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for this drug on 2/11/22. Bebtelovimab is a human antibody that demonstrates neutralization against the Omicron variants and is available in every state and many hospitals and some clinics. If you are planning on using a monoclonal antibody to treat a SARS-CoV-2 infection, currently only bebtelovimab has activity against all Omicron variants, including BA.4.6. Researchers at Columbia University recently reported that “The loss of activity of tixagevimab and cilgavimab [components of Evusheld] against BA.4.6 leaves us with bebtelovimab as the only therapeutic mAb that has retained potent activity against all circulating forms of SARS-CoV-2.” For this reason, we no longer recommend Evusheld for immunocompromised patients with Omicron infections. 

An examination of the three variants that Wang et al identified as capable of immune escape in patients who receive the two monoclonal antibodies that are contained in Evusheld reveals that all three variants have a mutation in the spike protein at position 346. The changes substitute an uncharged amino acid— threonine (T), serine (S), or isoleucine (I)—for a positively-charged amino acid, arginine. This just goes to show that a single point mutation in the spike protein can render a monoclonal antibody treatment ineffective. Policy makers should keep in mind that the only way to prevent new drug-resistant variants like BA.4.6 from emerging is to prevent transmission of SARS-CoV-2 in the first place, using non-pharmaceutical interventions. The lack of use of N95 masks, with impending winter and influenza outbreaks, on top of COVID-19, is not wise public health and infectious disease policy. If we don’t make effective use of the non-pharmaceutical interventions available to us (masks, ventilation, social distancing), then the pharmaceutical interventions we have will all eventually be useless. 

Watching World Data

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

LocationTotal Infections as of 9/09/22New Infections on 9/09/22Total DeathsNew Deaths on 9/09/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World612,988,394(8,188,628  new infections in 14 days).492,2846,514,526(29,079 new deaths in last 14 days)1,7167.86%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.2.12.1 (USA)BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)  NoNo
USA97,026,001(ranked #1) 1,055,994 new infections in the last 14 days.
50,822(ranked #4)
26 states failed to report infections on 9096/22.
1,076,338(ranked #1) 6,495  new deaths reported in the last 14 days. 317
29 states failed to report deaths on 9/09/22.
26.72%*
*Not updated for 10 weeks by Worldometer.
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 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)NoNo
Brazil34,536.920(ranked #4) 195,011 new infections in the last 14 days. 14,005 (ranked #9)684,866(ranked #2; 1,402 new deaths in 14 days)8216.01%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)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)NoNo
India 44,490,283(ranked #2); 101,587 new infections in 2 weeks.9,938 (ranked #11)
528,139(ranked #3) 631 new deaths in 2 weeks.363.16%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.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India)NoNo
United Kingdom
23,554,519(ranked #7) 61,644 new infections in 2 weeks.189,026 (ranked #7) 1,265 new deaths in 2 weeks34.30%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.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)NoNo
California, USA11,128,082(ranked #14 in the world; 75,216 new infections in the last 14 days).2,19195,354 (ranked #20 in world)
395 new deaths in the last 14 days
1428.16%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 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)NoNo
Mexico7,052,928(ranked #18) 51,338 new infections in 14 days).2,973329,705(ranked #5)426 new deaths in 14 days)305.34%NoNo
South Africa4,014,050(ranked #36; 3,418 new infections in 14 days).329102,129 (ranked #18) 45 new deaths in 14 days)6.58%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.4 (South Africa 11/21)BA.5 (South Africa 11/21)NoNo
Canada4,197,701(ranked #33) 39,219 new infections in 14 days).2,62644,374(ranked #24)
550 new deaths in the last 14 days
3410.93% NoNo
Poland6,206,982 (ranked #21; 44,320 new infections in 14 days). 4,553117,233 (ranked #15)1416.44%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3 NoNo
Russia19,960,295(ranked #9), 648,322 new infections in 14 days).52,106 (ranked #4)385,165(ranked #4)1,255 new deaths in 14 days9613.68%NoNo
Peru4,123,435(ranked #34, 28,783 new infections in 14 days). 2,399216,045(ranked #6)4212.24%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Iran7,537,781(ranked #17; 16,788 new infections in last 14 days)700144,135(ranked #12)278.76%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)


NoNo
Spain13,367,647(ranked #12;   34,671 new infections in 14 days).2,975(ranked #18)113,130 (ranked #16)676 new deaths in 14 days6928.61%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
France34,682,193 (ranked #3; 235,339 new infections in the last 14 days).19,087 (ranked #7)154,468 (ranked #10)
621 new deaths in 14 days
3152.88%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinantNoNo
Germany32,452,250(ranked #5; 410,902 new infections in 14 days.).30,166 (ranked #6)148,229 (ranked #11)
1,125 new deaths in 14 days
8238.68%
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
South Korea23,933,949 (ranked #6 1,130,964 new infections in 14 days).69,389(ranked #2)27,381 (ranked #37) 
968 new deaths in 14 days
6846.62%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Vietnam11,435,472 (ranked #13; 36,072 new infections in 14 days).1,21943,126 (ranked #25)11.55%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Netherlands8,396,979 (ranked #15; 15,970 new infections in 14 days).1,21922,613 (ranked #41)148.78%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)GKA (AY.4/BA.1) recombinantNoNo
Denmark3,097,088 (ranked #40) 7,970 new infections in 14 days6146,968 (ranked #79)353.07%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo




Taiwan5,614,198(ranked #22)
445,249 new infections in 14 days
34,231 (ranked #5)10,225 (ranked #64)
5523.50%
1.89% of population has been infected in the last 14 days
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Japan19,882,393(ranked #10)
1,918,596 new infections in the last 14 days
112,404(ranked #1)42,101(ranked #26)
3,904 new deaths in the last 14 days
26115.83%
1.52% of population has been infected in the last 14 days
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)BA.2*BA.5*NoNo

What Our Team Is Reading This Week

COVID-19

SARS-CoV-2 Update

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

SARS-CoV-2 infections per day in the United States have decreased for the first time in two weeks; however, there is still widespread underreporting by states, a failure to capture positive home tests, and a decreased PCR screening program in most states. Deaths per day in the United States have decreased by 31 deaths per day. The number of infections have decreased by 19,061 infections per day.  The CDC estimates that BA.2.12.1 accounted for 0.2% of isolates, BA.2 accounted for 0%, BA.5 accounted for 88.7%, BA.4 accounted for 3.6%, BA.4.6 accounted for 7.5%, and B.1.1.529 accounted for 0% in the week ending August 27.

CDC

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.

NY Times

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. 

The Omicron variant has continued to mutate just like Delta. There are now 276 Omicron sub-variants (an increase of 46 in the last two weeks) that have been assigned Pango lineages, including 123 sub-lineages of BA.2 (an increase of 7 in two weeks), one sub-lineage of BA.3, 15 sub-lineages of BA.4 (an increase of one in two weeks), and 45 sub-lineages of BA.5 (an increase of 21 in two weeks). The BF lineage (new ten weeks ago) now has 21 sublineages, an increase of 10 in two weeks. The BE lineage (also new ten weeks ago), with BE.1 first detected in South Africa, Austria and England, now has 7 sublineages, an increase of 3 in two weeks. There are also new lineages from ten weeks ago: BC.1 (Japan), BC.2 (Peru),BD.1 (UK), BG.1 (Peru), BG.2 (US, Denmark, Canada), BG.3 (Peru), BG.4 (Israel). In the last two weeks, the BG lineage has expanded to include BG.5 (USA) and BG.6 (Peru). Lastly, two new sublineages were added in the past two weeks: BH.1 (India) and BK.1 (USA and Canada). 

In Monterey County, as of 8/28/22, 0.5% of 0-4 year-olds and 39.4% of 5-11 year-olds have received the first two doses of vaccine, while 72.9% of 12-17 year-olds have received two doses. Only 53.4% of Monterey County residents have received a third dose of the vaccine. 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. We would anticipate, with the start of school on August 5 and the low vaccination rates in our county, that we’ll have a marked increase in the number of infected patients. All Monterey County residents should get up to date on COVID-19 vaccinations as soon as possible. 

Monterey County Health Department

On 8/26/22, the United States had 63,798 documented new infections. There were also 312 deaths. Twenty-four states did not report their infections, and 28 states didn’t report their deaths. In the United States the number of hospitalized patients has decreased slightly in many areas and was 38,630 on August 27, a decrease of 9% compared to the previous 14 days. Now there are 3,992 patients who are seriously or critically ill; that number was 4,490 two weeks ago. The number of critically ill patients has decreased by 498 in the last 14 days, while at least 6,692 new deaths occurred. The number of critically ill patients has decreased for the second time in twenty-six 14-day periods. Patients are still dying each day (average 478/day). Omicron BA.4, BA.4.6 (a new USA variant) and BA.5 variants causing infections should continue to increase and critically ill patients may increase. Deaths usually lag two to four weeks behind exponential increase in infections. Past infections with a BA.1 or BA.2 variant will not prevent infections with BA.4, BA.4.6 or BA.5. 

As of 8/26/22, we have had 1,068,843 deaths and 95,970,007 SARS-CoV-2 infections in the United States. We have had 1,326,375 new infections in the last 14 days. We are adding an average of 663,188 infections every seven days. For the pandemic in the United States we are averaging one death for every 89.78 infections or over 11,137 deaths for each one million infections. As of 8/26/22, thirty-eight states have had greater than 500,000 total infections, and 37 states have had greater than 5,000 total deaths. Forty-six states have had greater than 2,000 deaths, and 42 states have greater than 2,000 deaths per million population. Vermont, at 1,153 deaths per million, and Hawaii, 1,133 deaths per million, are the states with the lowest death rates. Eighteen states (Alabama, 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 have had greater than 70,000 deaths: Florida (79,568 deaths), Texas (90,539 deaths), New York (71,422 deaths), and  California (94,959 deaths, 20th most deaths in the world). 

On 11/20/20, there were 260,331 (cumulative) deaths in the US from SARS-CoV-2. Since 11/20/20 (21 months), there were 808,712 new deaths from SARS-CoV-2. For seventeen of those months, vaccines have been available to all adults. During these seventeen months, 497,746 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 8/26/22, California was ranked 32nd in the USA in infection percentage at 27.97%. In California, 24.0% of people were infected in the last 19 months. As of 8/26/22, 41 states have had greater than 25% of their population infected. No state has less than 20% of their population infected. 

Worldwide, average deaths per day are 2,399 for the last 14 days, which is a 55 deaths-per-day decrease over the previous 14 days. The United States accounts for 19.92% (478 per day) of all deaths per day in the world over the last two weeks. Worldwide infections per day were 774,366. The United States accounts for 12.23% of those infections (or 94,741 infections per day). 

Watching World Data

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

LocationTotal Infections as of 8/26/22New Infections on 8/26/22Total DeathsNew Deaths on 8/26/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World604,789,766(10,841,118 new infections in 14 days).689,1946,485,447(33,589 new deaths in last 14 days)1,9277.75%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.2.12.1 (USA)BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)  NoNo
USA95,970,007(ranked #1) 1,326,375 new infections in the last 14 days.
63,798(ranked #3)
24 states failed to report infections on 8/26/22.
1,068,843(ranked #1) 6,692  new deaths reported in the last 14 days. 312
30 states failed to report deaths on 8/26/22.
26.72%*
*Not updated for 8 weeks by Worldometer.
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 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)NoNo
Brazil34,368,909(ranked #4) 220,778 new infections in the last 14 days. 18,270 (ranked #8)683,464(ranked #2; 2,147 new deaths in 14 days)13615.92%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)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)NoNo
India 44,398,696(ranked #2); 159,324 new infections in 2 weeks.9,520 (ranked #12)
527,597(ranked #3) 631 new deaths in 2 weeks.413.15%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.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India)NoNo
United Kingdom
23,492,875(ranked #6) 72,049 new infections in 2 weeks.187,761 (ranked #7) 1,674 new deaths in 2 weeks34.22%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)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.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)NoNo
California, USA11,052,866(ranked #14 in the world;  156,070 new infections in the last 14 days).11,37494,959 (ranked #20 in world)
640 new deaths in the last 14 days
5527.97%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 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)NoNo
Mexico7,001,590(ranked #18) 7,728 new infections in 14 days).7,281(ranked #16)329,289(ranked #5)693 new deaths in 214 days)645.31%B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
South Africa4,010,632(ranked #36; 2,607 new infections in 14 days).247102,084 (ranked #18) 6.58%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.4 (South Africa 11/21)BA.5 (South Africa 11/21)NoNo
Canada4,158,491(ranked #33) 48,560 new infections in 14 days).3,27043,797(ranked #24)3910.81% B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
Poland6,162,662 (ranked #21; 48,822 new infections in 14 days). 3,847117,007 (ranked #15)4016.32%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3 NoNo
Russia19,311,973(ranked #9), 487,691 new infections in 14 days).46,452 (ranked #4)383,910(ranked #4)899 new deaths in 14 days8113.22%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)R1 (Japan) B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Peru4,094,652(ranked #34, 80,821 new infections in 14 days). 3,286215,566(ranked #6)4212.05%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Iran7,520,993(ranked #17; 55,414 new infections in last 14 days)2,019143,647(ranked #12)358.71%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)


NoNo
Spain13,332,976(ranked #12;   38,737 new infections in 14 days).3,064(ranked #26)112,454 (ranked #16)787 new deaths in 14 days7028.49%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
France34,446,854 (ranked #3; 254,935 new infections in the last 14 days).18,116 153,857 (ranked #10)
793 new deaths in 14 days
5152.52%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinantNoNo
Germany32,041,348(ranked #5; 506,005 new infections in 14 days.).33,226 (ranked #5)147,104 (ranked #11)
1,406 new deaths in 14 days
10137.98%
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
South Korea22,802,985 (ranked #7 1,691,145 new infections in 14 days).101,064(ranked #2)26,413 (ranked #37) 8144.39%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Vietnam11,399,400 (ranked #13; 36,860 new infections in 14 days).3,19543,110 (ranked #25)11.48%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Netherlands8,381,009 (ranked #16; 18.445 new infections in 14 days).1,15622,594 (ranked #41)248.68%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
Denmark3,089,118 (ranked #40) 12,476 new infections in 14 days6806,893 (ranked #79)552.93%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) recombinantNoNo




Taiwan5,168,949(ranked #23)
322,462 new infections in 14 days
26,713 (ranked #6)9,773 (ranked #65)
4521.61%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Japan17,983,797(ranked #10)
2,897,493 new infections in the last 14 days
227,139(ranked #1)38,197(ranked #27)
3,660 new deaths in the last 14 days
31014.31%
2.31% of population has been infected in the last 14 days
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)BA.2*BA.5*NoNo

What Our Team Is Reading This Week

COVID-19

SARS-CoV-2 Update

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

SARS-CoV-2 infections per day in the United States have decreased for the first time in two weeks; however, there is still widespread underreporting by states, a failure to capture positive home tests, and a decreased PCR screening program in most states. Deaths per day had been decelerating at a rapid rate in the United States but are now increased by 57 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 0.8% of isolates, BA.2 accounted for 0%, BA.5 accounted for 88.8%, BA.4 accounted for 5.3%, BA.4.6 accounted for 5.1%, and B.1.1.529 accounted for 0% in the week ending August 13.

CDC

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. 

NY Times

The Omicron variant has continued to mutate just like Delta. There are now 230 Omicron sub-variants (an unexplained decrease of 9 in the last two weeks) that have been assigned Pango lineages, including 116 sub-lineages of BA.2 (no increase in two weeks), one sub-lineage of BA.3, 14 sub-lineages of BA.4 (no increase in two weeks), and 24 sub-lineages of BA.5 (no increase in two weeks). The BF lineage (new eight weeks ago) now has 11 sublineages, no increase in two weeks. The BE lineage (also new eight weeks ago), with BE.1 first detected in South Africa, Austria and England, still has 4 sublineages. There are also new lineages from eight weeks ago: BC.1 (Japan), BC.2 (Peru),BD.1 (UK), BG.1 (Peru), BG.2 (US, Denmark, Canada), BG.3 (Peru), BG.4 (Israel). 

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. 

In Monterey County, as of 8/14/22, 0.3% of 0-4 year-olds and 38.9% of 5-11 year-olds have received the first two doses of vaccine, while 72.8% of 12-17 year-olds have received two doses. Only 53.3% of Monterey County residents have received a third dose of the vaccine. 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. We would anticipate, with the start of school on August 5 and the low vaccination rates in our county, that we’ll have a marked increase in the number of infected patients. All Monterey County residents should get up to date on COVID-19 vaccinations as soon as possible. 

Monterey County Public Health

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. 

Watching World Data

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

LocationTotal Infections as of 8/12/22New Infections on 8/12/22Total DeathsNew Deaths on 8/12/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World593,948,648(13,178,472 new infections in 14 days).792,5726,451,858(34,360 new deaths in last 14 days)2,2417.61%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.2.12.1 (USA)BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)NoNo
USA94,643,632(ranked #1) 1,589,448 new infections in the last 14 days.
85,116(ranked #3)
22 states failed to report infections on 8/12/22.
1,062,151(ranked #1) 7,131  new deaths reported in the last 14 days. 335
28 states failed to report deaths on 8/12/22..
26.72%*
*Not updated for 6 weeks by Worldometer.
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 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)NoNo
Brazil34,148,131(ranked #3) 352,939 new infections in the last 14 days. 23,552 (ranked #7)681,317(ranked #2; 2,942 new deaths in 14 days)29215.82%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)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)NoNo
India 44,239.372(ranked #2); 239,234 new infections in 2 weeks.15,815 (ranked#11)
526,966(ranked #3) 654 new deaths in 2 weeks.683.14%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.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India)NoNo
United Kingdom*
*No reported data for 8/12/22
23,420,826(ranked #6) 116,347 new infections in 2 weeks.186,087 (ranked #7) 2,134 new deaths in 2 weeks34.12%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.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)NoNo
California, USA10,896,796(ranked #14 in the world;  198618 new infections in the last 14 days).13,30694,319 (ranked #20 in world)
615 new deaths in the last 14 days
5027.57%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 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)NoNo
Mexico6,903,862(ranked #18) 192,015 new infections in 14 days).13,313(ranked #12)328,596(ranked #5)1,071 new deaths in 214 days)715.23%B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
South Africa4,007,925(ranked #33; 3,370 new infections in 14 days).313101,982 (ranked #18) Not updated in last 2 weeks.6.58%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.4 (South Africa 11/21)BA.5 (South Africa 11/21)NoNo
Canada4,109,931(ranked #33) 87,572 new infections in 14 days).3,60343,583(ranked #24)3710.69% B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
Poland6,113,840 (ranked #21; 48,508 new infections in 14 days). 4,223116,751 (ranked #15)1416.19%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3 NoNo
Russia18,824,282(ranked #9), 247,309 new infections in 14 days).27,810383,011(ranked #4 in world)5712.88%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)R1 (Japan) B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Peru4,013,831(ranked #34, 118,345 new infections in 14 days). 10,882214,890(ranked #6)7211.82%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Iran7,465,579(ranked #17; 88,785 new infections in last 14 days)6,404142,806(ranked #12)548.65%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)


NoNo
Spain13,294,139(ranked #12;   67,560 new infections in 14 days).4,528(ranked #22)111,667 (ranked #16)11028.41%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
France34,191,919 (ranked #3; 405,153 new infections in the last 14 days).22,638 (ranked #9)153,064 (ranked #10)
1,101 new deaths in 14 days
7452.13%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinantNoNo
Germany31,535,343(ranked #5; 682,031 new infections in 14 days.).45,859 (ranked #4)145,698 (ranked #11)
1,726 new deaths in 14 days
13737.38%
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
South Korea21,111,840 (ranked #8 1,491,323 new infections in 14 days).128,671(ranked #2)25,499 (ranked #37) 5841.10%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Vietnam11,362,540 (ranked #13; 586,056 new infections in 14 days).2,19243,096 (ranked #25)111.45%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Netherlands8,362,564 (ranked #16; 31,241 new infections in 14 days).1,88222,542 (ranked #41)448.57%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
Denmark3,076,642 (ranked #40) 16,658 new infections in 14 days1,3236,792 (ranked #80)1252.72%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo




Taiwan4,846,477(ranked #24)
300,841 new infections in 14 days
21,965 (ranked #10)9,373 (ranked #67)
3120.27%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Japan15,086,304(ranked #11)
2,908,192 new infections in the last 14 days
224,929(ranked #1)34,537(ranked #30)
2,251 new deaths in the last 14 days
21412.00%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)BA.2*BA.5*NoNo

What Our Team Is Reading This Week

COVID-19

SARS-CoV-2 Update

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

SARS-CoV-2 infections per day have been increasing in the United States for 16 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 65 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 5.0% of isolates, BA.2 accounted for 0.3%, BA.5 accounted for 89.1%, BA.4 accounted for 12.9%, and B.1.1.529 accounted for 0% in the week ending July 23.

CDC

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. 

NY Times

The Omicron variant has continued to mutate just like Delta. There are now 239 Omicron sub-variants (an increase of 28 in the last two weeks) that have been assigned Pango lineages, including 116 sub-lineages of BA.2 (an increase of 4 in two weeks), one sub-lineage of BA.3, 14 sub-lineages of BA.4 (an increase of 3 in two weeks), and 24 sub-lineages of BA.5 (an increase of 7 in two weeks). The BF lineage (new six weeks ago) now has 11 sublineages, an increase of 5 in two weeks. The BE lineage (also new six weeks ago), with BE.1 first detected in South Africa, Austria and England, still has 4 sublineages. There are also new lineages from six weeks ago: BC.1 (Japan), BC.2 (Peru), BD.1 (UK), BG.1 (Peru), BG.2 (US, Denmark, Canada), BG.3 (Peru), BG.4 (Israel).

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, those who 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 7/31/22, 0.1% of 0-4 year-olds and 38.6% of 5-11 year-olds have received the first two doses of vaccine, while 72.6% of 12-17 year-olds have received two doses. Only 53.2% of Monterey County residents have received a third dose of the vaccine. 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. We would anticipate, with the start of school on August 5 and the low vaccination rates in our county, that we’ll have a marked increase in the number of infected patients. All Monterey County residents should get up to date on COVID-19 vaccinations as soon as possible. 

Monterey County Health Department
Monterey County Health Department

On 7/29/22, the United States had 99,061 documented new infections. There were also 286 deaths. Twenty-two states did not report their infections, and 28 states didn’t report their deaths. In the United States the number of hospitalized patients has been increasing in many areas and was 44,207 on July 29, an increase of 9% compared to the previous 14 days. Now there are 4,723 patients who are seriously or critically ill; that number was 4,180 two weeks ago. The number of critically ill patients has increased by 543 in the last 14 days, while at least 6,327 new deaths occurred (an increase of 65 deaths per day from the previous 14 days). The number of critically ill patients has increased for the seventh time in twenty-four 14-day periods. Patients are still dying each day (average 387/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 7/29/22, we have had 1,055,020 deaths and 93,054,184 SARS-CoV-2 infections in the United States. We have had 1,883,613 new infections in the last 14 days. We are adding an average of 941,807 infections every seven days. For the pandemic in the United States we are averaging one death for every 88.20 infections or over 11,338 deaths for each one million infections. As of 7/29/22, thirty-eight states have had greater than 500,000 total infections, and 37 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 93,704 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 18 months preceding 7/1/22, 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 794,889 new deaths from SARS-CoV-2. For fifteen of those months, vaccines have been available to all adults. During these fifteen months, 483,923 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 7/29/22, California was ranked 32th in the USA in infection percentage at 27.07%. In California, 23.1% of people were infected in the last 18 months. As of 7/29/22, 38 states have had greater than 25% of their population infected. 

Worldwide, average deaths per day are 2,263 for the last 14 days, which is a 417 deaths-per-day increase over the previous 14 days. The United States accounts for 19.97% (452 per day) of all deaths per day in the world over the last two weeks. Worldwide infections per day were 1,030,492. The United States accounts for 13.06% of those infections (or 134,544 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.

LocationTotal Infections as of 7/29/22New Infections on 7/29/22Total DeathsNew Deaths on 7/29/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World580,770,176(14,426,888 new infections in 14 days).905,4056,417,498(31,678 new deaths in last 14 days)2,8087.45%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)NoNo
USA93,054,184(ranked #1) 1,883,613 new infections in the last 14 days.
99,081(ranked #4)
22 states failed to report infections.
1,055,020(ranked #1) 6,327 new deaths in the last 14 days. 28628 states failed to report deaths.26.72%*
*Not updated for four weeks by Worldometers
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)NoNo
Brazil33,795,192(ranked #3) 545,075 new infections in the last 14 days. 42,816 (ranked #8)678,375(ranked #2; 3,230 new deaths in 14 days)22815.66%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
India 44,000,138(ranked #2); 270,067 new infections in 2 weeks.20,408
526,312(ranked #3)543.12%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)NoNo
United Kingdom*
*No reported data for 7/29/22
23,304,479(ranked #6) 229,119 new infections in 2 weeks.183,953 (ranked #7) 
2,373 new deaths in 2 weeks
33.95%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)NoNo
California, USA10,698,178(ranked #14 in the world;  317,309 new infections in the last 14 days).18,71593,704 (ranked #20 in world)
687 new deaths in the last 14 days
5127.07%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)NoNo
Mexico6,711,847(ranked #18) 337,971 new infections in 14 days).24,893(ranked #9)327,525(ranked #5)1135.09%B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
South Africa4,004,555(ranked #33; 4,704 new infections in 14 days).354101,982 (ranked #18)56.58%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)NoNo
Canada4,012,359(ranked #32) 4,896 new infections in 14 days).43,583(ranked #24)10.44% .B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
Poland6,065,332 (ranked #21; 35,385 new infections in 14 days). 3,391116,556 (ranked #15)916.06%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3 NoNo
Russia18,576,973(ranked #9), 96,039 new infections in 14 days).11,422382,352(ranked #4 in world)3912.71%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)R1 (Japan) B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Peru3,895,486(ranked #37, 181,125 new infections in 14 days). 6,467214,195(ranked #6)4111.48%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Iran7,376,794(ranked 17th; 106,771 new infections in last 14 days)7,849141,891(ranked #12)548.55%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)


NoNo
Spain13,226,579(ranked 11th;   136,103 new infections in 14 days).7,783(ranked #18)110,719 (ranked #16)10928.26%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
France33,786,766 (ranked #4; 967,865 new infections in the last 14 days).45,515 (ranked #6)151,983 (ranked #10)
1,407 new deaths in 14 days
8951.52%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinantNoNo
Germany30,853,312(ranked #5; 1,170,323 new infections in 14 days.).66,003 (ranked #4)143,972 (ranked #11)
1,437 new deaths in 14 days
11736.58%
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) recombinantNoNo
South Korea19,620,517 (ranked #9 940,375 new infections in 14 days).85,275(ranked #3)24,999 (ranked #38) 3538.20%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Vietnam10,776,484 (ranked #13; 17,339 new infections in 14 days).1,80343,093 (ranked #25)110.86%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Netherlands8,331,315 (ranked #18; 57,081 new infections in 14 days).3,23822,492 (ranked #41)448.40%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
Denmark3,059,984 (ranked #39) 20,125 new infections in 14 days1,0376,639 (ranked #81)1152.44%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo




Taiwan4,545,636(ranked #29)
330,436 new infections in 14 days
23,289 (ranked #10)8,833 (ranked #69)
916 new deaths in 14 days
5719.01%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)NoNo
Japan12,118,112(ranked #12)
2,117,392 new infections in the last 14 days
230,055(ranked #1)32,286(ranked #30)1169.64%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo

What Our Team Is Reading This Week

COVID-19

SARS-CoV-2 Update

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

SARS-CoV-2 infections 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 29 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 17.3% of isolates, BA.2 accounted for 1.4%, BA.5 accounted for 65.0%, BA.4 accounted for 16.3%, and B.1.1.529 accounted for 0% in the week ending June 25.

CDC

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.

NY Times

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. 

The Omicron variant has continued to mutate just like Delta. There are now 211 Omicron sub-variants (an increase of 12 in the last two weeks) that have been assigned Pango lineages, including 112 sub-lineages of BA.2 (an increase of 8 in two weeks), one sub-lineage of BA.3, 11 sub-lineages of BA.4 (an increase of 2 in two weeks), and 17 sub-lineages of BA.5 (an increase of 2 in two weeks). The BF lineage (new four weeks ago), with BF.1 first detected in England, Denmark, Spain and Scotland still has 6 sublineages. The BE lineage (also new four weeks ago), with BE.1 first detected in South Africa, Austria and England, now has 4 sublineages (one new in the past two weeks). There are also new lineages from four weeks ago: BC.1 (Japan), BC.2 (Peru),BD.1 (UK), BG.1 (Peru), BG.2 (US, Denmark, Canada), BG.3 (Peru), BG.4 (Israel). 

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, those who 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 7/17/22, 0.0% of 0-4 year-olds and 38.3% of 5-11 year-olds have received the first two doses of vaccine, while 72.4% of 12-17 year-olds have received two doses. Only 53% of Monterey County residents have received a third dose of the vaccine. 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. We would anticipate, with the start of school on August 5 and the low vaccination rates in our county, that we’ll have a marked increase in the number of infected patients. All Monterey County residents should get up to date on COVID-19 vaccinations as soon as possible. 

Monterey County Health Department
Monterey County Health Department

On 7/15/22, the United States had 94,037 documented new infections. There were also 207 deaths. Twenty-one states did not report their infections, and 28 states didn’t report their deaths. In the United States the number of hospitalized patients has been increasing in many areas and was 40,650 on July 15, an increase of 20% compared to the previous 14 days. Now there are 4,180 patients who are seriously or critically ill; that number was 3,400 two weeks ago. The number of critically ill patients has increased by 780 in the last 14 days, while at least 5,412 new deaths occurred (an increase of 29 deaths per day from the previous 14 days). The number of critically ill patients has increased for the sixth time in twenty-three 14-day periods. Patients are still dying each day (average 387/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 7/15/22, we have had 1,048,693 deaths and 91,170,571 SARS-CoV-2 infections in the United States. We have had 1,663,488 new infections in the last 14 days. We are adding an average of 831,744 infections every seven days. For the pandemic in the United States we are averaging one death for every 86.94 infections or over 11,503 deaths for each one million infections. As of 7/15/22, thirty-eight states have had greater than 500,000 total infections, and 37 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 93,017 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 788,562 new deaths from SARS-CoV-2. For fifteen of those months, vaccines have been available to all adults. During these fifteen months, 477,596 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 7/15/22, California was ranked 32th in the USA in infection percentage at 26.27%. In California, 22.3% of people were infected in the last 18 months. As of 7/15/22, 38 states have had greater than 25% of their population infected. 

Worldwide, average deaths per day are 1,846 for the last 14 days. The United States has 20.96% (387 per day) of all deaths per day in the world over the last two weeks. Worldwide infections per day were 910,374. The United States accounts for 13.05% of those infections (or 118,821 infections per day). 

Watching World Data

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

LocationTotal Infections as of 7/15/22New Infections on 7/15/22Total DeathsNew Deaths on 7/15/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World566,343,288(12,745,232 new infections in 14 days).903,2726,385,820(25,848 new deaths in last 14 days)1,7377.26%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)NoNo
USA91,170,571(ranked #1) 1,663,488 new infections in the last 14 days.
94,037(ranked #4)
21 states failed to report infections.
1,048,693(ranked #1) 5,412 new deaths in the last 14 days. 207
27 states failed to report deaths.
26.72%*
*Not updated
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)NoNo
Brazil33,250,117(ranked #3) 816,054 new infections in the last 14 days. 107,959 (ranked #4)675,145(ranked #2; 3,145 new deaths in 14 days)29915.42%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
India 43,730,071(ranked #2); 241,552 new infections in 2 weeks.20,044
525,660(ranked #3)563.10%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)NoNo
United Kingdom*
*No reported data for 7/14/22- 7/16/22
23,075,360(ranked #6) 334,295 new infections in 2 weeks.181,580 (ranked #7) 33.63%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)NoNo
California, USA10,380,889(ranked #12 in the world;  226,544 new infections in the last 14 days).8,69493,017 (ranked #20 in world)
397 new deaths in the last 14 days
1626.27%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)NoNo
Mexico6,373,876(ranked #18) 339,174 new infections in 14 days).34,885(ranked #9)326,335(ranked #5)744.84%B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
South Africa3,999,751(ranked #33; 5,528 new infections in 14 days).406101,918 (ranked #18)36.57%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)NoNo
Canada4,007,463(ranked #32) 61,376 new infections in 14 days).1,88143,555(ranked #24)5110.43% .B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
Poland6,029,947 (ranked #21; 14,313 new infections in 14 days). 1,974116,470 (ranked #15)215.96%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3 NoNo
Russia18,480,934(ranked #9), 47,540 new infections in 14 days).4,457381,794(ranked #4 in world)4012.65%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)R1 (Japan) B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Argentina9,426,171(ranked #14; 58,999 new infections in 14 days).———–140,365 (ranked #14)——–20.47%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gama/P.1 (Brazil)Delta/B.1.617.2 (India)Lambda/C.37 (Peru)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Colombia6,223,497(ranked #19, 48,316 new infections in 14 days).3,523140,365 (ranked #13)2611.97%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Epsilon/B.1.427 + B.1.429 (USA)*Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Peru3,714,361(ranked #38, 84,565 new infections in 14 days). 10,610235,526(ranked #6)1510.95%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Iran7,270,023(ranked 17th; 31,434 new infections in last 14 days)4,772141,477(ranked #11)138.43%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)


NoNo
Spain13,090,476(ranked 11th;   272,292 new infections in 14 days).19,211(ranked #12)109,348 (ranked #17)13427.97%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
France32,818,901 (ranked #4; 1,609,976 new infections in the last 14 days).119,684 (ranked #1)150,576 (ranked #10)10850.05%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinantNoNo
Germany29,692,989(ranked #5; 1,300,360 new infections in 14 days.).123,046 (ranked #2)142,535 (ranked #11)13435.21%
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
South Korea18,680,142 (ranked #9 310,285 new infections in 14 days).38,864(ranked #8)24,712 (ranked #38) 1636.37%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Vietnam10,759,145 (ranked #12; 11,748 new infections in 14 days).95643,090 (ranked #26)10.85%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Netherlands8,274,234 (ranked #16; 83,979 new infections in 14 days).6,52722,422 (ranked #41)548.07%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
Denmark3,039,859 (ranked #39) 23,810  new infections in 14 days1,5676,551 (ranked #81)852.10%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo




North Korea (DPRK)4,770,400 (ranked #24; 25,670 new infections in 14 days)5007418.34%Omicron/B.1.1.529 South Africa November 2021)NoNo
Taiwan4,215,200(ranked #30)
412,171 new infections in 14 days
25,310 (ranked #10)7,917 (ranked #73)11417.63%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Japan10,000,720(ranked #13)
671,200 new infections in the last 14 days
97,339(ranked #5)31,528(ranked #34)347.95%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)NoNo

What Our Team Is Reading This Week

COVID-19

SARS-CoV-2 Update

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

SARS-CoV-2 infections 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.

CDC

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. 

NY Times

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. 

Monterey County Health Department

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.

LocationTotal Infections as of 7/1/22New Infections on 7/1/22Total DeathsNew Deaths on 7/1/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World553,598,056(9,977,707 new infections in 14 days).825,0086,359,972(20,585 new deaths in last 14 days)1,5037.10%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)NoNo
USA89,507,083(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)NoNo
Brazil32,434,063(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)23415.04%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)NoNo
India 43,488,519(ranked #2); 204,726 new infections in 2 weeks.17,237525,168(ranked #3)293.09%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)NoNo
United Kingdom22,741,065(ranked #6) 268,562 new infections in 2 weeks.20,720180,417 (ranked #7) 880 new deaths in 2 weeks8733.15%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)NoNo
California, USA10,154,345(ranked #12 in the world;  262,248 new infections in the last 14 days).23,52492,620 (ranked #20 in world)
439 new deaths in the last 14 days
6025.69%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)NoNo
Mexico6,034,602(ranked #20) 182,006 new infections in 14 days).24,537(ranked #9)325,716(ranked #5)474.58%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)NoNo
South Africa3,994,223(ranked #31; 9,577 new infections in 14 days).380101,804 (ranked #18)166.56%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)NoNo
Canada3,946,087(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)NoNo
Poland6,015,634 (ranked #21; 4,715 new infections in 14 days). 643116,429 (ranked #15)515.92%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 NoNo
Turkey15,123,331(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)NoNo
Russia18,433,394(ranked #8), 41,597 new infections in 14 days).3,155381,165(ranked #4 in world)5312.62%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)NoNo
Argentina9,367,172(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)NoNo
Colombia6,175,181(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)NoNo
Peru3,629,796(ranked #38, 33,432 new infections in 14 days). 4,706235,526(ranked #6)2910.71%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)NoNo
Iran7,238,589(ranked 17th; 4,066 new infections in last 14 days)463141,390(ranked #11)18.40%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)


NoNo
Spain12,818,184(ranked 11th;   254,785 new infections in 14 days).28,048(ranked #8)108,111 (ranked #17)8927.39%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)NoNo
France31,208,925 (ranked #4; 1,129,467 new infections in the last 14 days).125,066 (ranked #1)149,585 (ranked #10)5247.60%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) recombinantNoNo
Germany28,392,629(ranked #5; 1,268,170 new infections in 14 days.).98,669 (ranked #3)141,292 (ranked #12)10333.67%
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) recombinantNoNo
South Korea18,368,857 (ranked #9 105,214 new infections in 14 days).9,516(ranked #17)24,555 (ranked #39) 835.76%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)NoNo
Vietnam10,747,397 (ranked #12; 10,989 new infections in 14 days).92743,087 (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)NoNo
Netherlands8,190,255 (ranked #15; 67,997 new infections in 14 days).6,08322,380 (ranked #41)247.58%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) recombinantNoNo
Denmark3,016,049 (ranked #39) 19,336  new infections in 14 days1,4556,471 (ranked #81)251.70%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) recombinantNoNo




North Korea (DPRK)4,744,430 (ranked #24; 163,010 new infections in 14 days)4,570 7318.24%Omicron/B.1.1.529 South Africa November 2021)NoNo
Taiwan3,803,029(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)NoNo
Japan9,329,520(ranked #14)
221,197 new infections in the last 14 days
23,523(ranked #10)31,281(ranked #31)157.42%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo

What Our Team Is Reading This Week

COVID-19

SARS-CoV-2 Update

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

SARS-CoV-2 infections per day have been increasing in the United States for 8 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 19 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 64.2% of isolates, BA.2 accounted for 14.2%, BA.5 accounted for 13.3%, BA.4 accounted for 8.3%, and B.1.1.529 accounted for 0% in the week ending June 11.

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. 

NY Times

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. 

European Centre for Disease Prevention and Control

The Omicron variant will continue to mutate just like Delta. There are now 157 Omicron sub-variants (an increase of 57 in the last two weeks) that have been assigned Pango lineages, including 92 sub-lineages of BA.2 (an increase of 42 in two weeks), one sub-lineage of BA.3, three sub-lineages of BA.4, and five sub-lineages of BA.5. There are also two new lineages: BF.1, detected in England, Denmark, Spain and Scotland, and BE.1, detected in South Africa, Austria and England. Curiously, the UK Health Security Agency, which usually releases updates every two weeks, has not released a new Technical Briefing on SARS-CoV-2 variants since May 20. 

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. 

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 6/19/22, only 38.9% of 5-11 year-olds have received the first two doses of vaccine, while 80.8% 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. 

Monterey County Health Department

On 6/17/22, the United States had 81,733 documented new infections. There were also 200 deaths. Twenty-one states did not report their infections, and 32 states didn’t report their deaths. In the United States the number of hospitalized patients had been increasing in many areas. Now there are 3.006 patients who are seriously or critically ill; that number was 2,683 two weeks ago. The number of critically ill patients has increased by 323 in the last 14 days, while at least 4,896 new deaths occurred (an increase of 19 deaths per day from the previous 14 days). The number of critically ill patients has increased for the fourth time in twenty-one 14-day periods. Patients are still dying each day (average 350/day). Omicron BA.2, BA.4, 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 6/17/22, we have had 1,038,265 deaths and 87,968,819 SARS-CoV-2 infections in the United States. We have had 1,518,216 new infections in the last 14 days. We were adding an average of 759,108 infections every seven days. For the pandemic in the United States we are averaging one death for every 84.72 infections or over 11,803 deaths for each one million infections. As of 6/17/22, 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 92,181 deaths (20th most deaths in the world). 

As of 6/17/22, in the United States, 26.27% of the population has had a documented SARS-CoV-2 infection. In the last 18 months, 23.52% 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 778,134 new deaths from SARS-CoV-2. For fifteen of those months, vaccines have been available to all adults. During these fifteen months, 467,168 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 6/17/22, California was ranked 35th in the USA in infection percentage at 25.03%. In California, 21.06% of people were infected in the last 18 months. As of 6/17/22, 35 states have had greater than 25% of their population infected. 

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.

LocationTotal Infections as of 6/17/22New Infections on 6/17/22Total DeathsNew Deaths on 6/17/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World543,620,349(8,989,675 new infections in 14 days).497,2656,339,387(20,374 new deaths in last 14 days)1,0916.97%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)NoNo
USA87,968,819(ranked #1) 1,518,216 new infections in the last 14 days.
81,733(ranked #1)
21 states failed to report infections.
1,038,265(ranked #1) 4,896 new deaths in the last 14 days. 200
32 states failed to report deaths.
26.27%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)NoNo
Brazil31,673,375(ranked #3) 535,896 new infections in the last 14 days. 28,672 (ranked #6)668,968(ranked #2; 1,949 new deaths in 14 days)7614.69%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
India43,283,793(ranked #2); 101,921 new infections in 2 weeks.13,216524,840(ranked #3)3.07%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)APTK India VOI 32421Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Iota/B.1.526 (USA-NYC) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
United Kingdom22,472,503(ranked #6) 166,610 new infections in 2 weeks.12,054179,537 (ranked #7)6532.76%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)*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)NoNo
California, USA9,892,097(ranked #13 in the world;  233,150 new infections in the last 14 days).14,60392,181 (ranked #20 in world)4525.03%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)NoNo
Mexico5,852,596(ranked #21) 70,191 new infections in 14 days).9,406325,340(ranked #5)694.48%B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
South Africa3,984,646(ranked #30; 19,224 new infections in 14 days).971105,589 (ranked #18)56.55%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)NoNo
Canada3,910,211(ranked #32) 30,111 new infections in 14 days).78241,723(ranked #25)610.18% .B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
Poland6,010,919 (ranked #20; 2,724 new infections in 14 days). 48116,390 (ranked #15)15.91%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3 NoNo
Turkey15,085,742(ranked #10, 12,995 new infections in 14 days).————98,996 (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)NoNo
Russia18,391,797(ranked #7), 47,833 new infections in 14 days).3,373380,333(ranked #4 in world)6312.59%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)R1 (Japan) B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Argentina9,313,453(ranked #13; 82,880 new infections in 14 days).———–128,984 (ranked #14)——–20.24%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gama/P.1 (Brazil)Delta/B.1.617.2 (India)Lambda/C.37 (Peru)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Colombia6,131,657(ranked #18, 26,642 new infections in 14 days).139,908 (ranked #13)11.80%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Epsilon/B.1.427 + B.1.429 (USA)*Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Peru3,596,374(ranked #35, 12,974 new infections in 14 days). 1,400213,374(ranked #6)1310.61%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Iran7,234,523(ranked 17th; 1,909 new infections in last 14 days)156141,361(ranked #11)18.40%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)


NoNo
Spain12,563,399(ranked 11th;   160,154 new infections in 14 days).16,090107,482 (ranked #17)8126.85%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
France30,079,458 (ranked #4; 483,566 new infections in the last 14 days).50,605 (ranked #3)149,039 (ranked #10)4345.88%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinantNoNo
Germany27,124,459(ranked #5; 613,531 new infections in 14 days.).28,471 (ranked #7)140,292 (ranked #12)32.17%
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
South Korea18,263,643 (ranked #8 121,808 new infections in 14 days).7,186(ranked #17)21,416 (ranked #39) 935.56%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)NoNo
Vietnam10,736,408 (ranked #12; 12,735 new infections in 14 days).72343,083 (ranked #24)10.83%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)NoNo
Netherlands8,122,258 (ranked #15; 32,021 new infections in 14 days).3,85522,343 (ranked #41)147.19%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
Denmark2,996,713 (ranked #39) 10,405 new infections in 14 days9956,421 (ranked #81)51.38%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo




North Korea (DPRK)4,581,420 (ranked #24; 663,840 new infections in 14 days)23,160 (ranked #8)7317.62%Omicron/B.1.1.529 South Africa November 2021)NoNo
Taiwan3,190,746(ranked #38)55,220 (ranked #2)4,868 (ranked #89)154 (ranked #2)13.34%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Japan9,108,323(ranked #14)15,802(ranked #10)30,980(ranked #31)177.24%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo

What Our Team Is Reading This Week

COVID-19

SARS-CoV-2 Update

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

SARS-CoV-2 infections per day have been increasing in the United States for 8 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 8.14% in the last 2 weeks and 57.42% from 4 weeks ago and 144.54% from 6 weeks ago. Deaths per day had been decelerating at a rapid rate in the United States but are now increased by 20 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 59.1% of isolates, BA.2 accounted for 34.7%, and B.1.1.529 (which includes cases of BA.4 and BA.5) accounted for 6.1% in the week ending May 28.

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. 

NY Times

Something to look out for is the rise of infections in South Africa to 94,255 infections in the 14 day period ending 5/20/22, and 43,789 cases in the 14 days ending 6/3/22. 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. 

European Centre for Disease Prevention and Control

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. 

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

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

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.

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 5/24/22, only 38.5% of 5-11 year-olds have received the first two doses of vaccine, while 80.5% of 12-17 year-olds have received two doses.

Monterey County Health Department

On 6/3/22, the United States had 103,221 documented new infections. There were also 316 deaths. In the United States the number of hospitalized patients had been increasing in many areas. Now there are 2,683 patients who are seriously or critically ill; that number was 2,289 two weeks ago. The number of critically ill patients has increased by 394 in the last 14 days, while at least 4,628 new deaths occurred (an increase of 20 deaths per day from the previous 14 days). The number of critically ill patients has increased for the third time in twenty 14-day periods. Patients are still dying each day (average 331/day). Omicron BA.2, BA.4, 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 6/3/22, we have had 1,033,369 deaths and 86,450,603 SARS-CoV-2 infections in the United States. We have had 1,515,341 new infections in the last 14 days. We were adding an average of 757,671 infections every seven days. For the pandemic in the United States we are averaging one death for every 83.66 infections or over 11,953 deaths for each one million infections. As of 6/3/22, 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 91,750 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 6/3/22, in the United States, 25.82% of the population has had a documented SARS-CoV-2 infection. In the last 17 months, 23.07% 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 773,238 new deaths from SARS-CoV-2. For fourteen of those months, vaccines have been available to all adults. During these fourteen months, 462,272 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 6/3/22, California was ranked 39th in the USA in infection percentage at 24.45%. In California 20.61% of Californians were infected in the last 17 months. As of 6/3/22 forty-six states have had greater than 20% of their population infected

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.

LocationTotal Infections as of 6/3/22New Infections on 6/3/22Total DeathsNew Deaths on 6/3/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World534,630,674(8,249,085 new infections in 14 days).520,9676,318,913(20,175 new deaths in last 14 days)1,1626.85%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)NoNo
USA86,450,603(ranked #1) 1,515,341 new infections in the last 14 days.103,221(ranked #1)1,033,369(ranked #1) 4,628 new deaths in the last 14 days. 31625.82%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)NoNo
Brazil31,137,479(ranked #3) 375,066 new infections in the last 14 days. 36,189 (ranked #5)667,019(ranked #2)4114.45%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
India43,171,872(ranked #2); 37,542 new infections in 2 weeks.2,273524,651(ranked #3)3.07%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)APTK India VOI 32421Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Iota/B.1.526 (USA-NYC) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
United Kingdom22,305,893(ranked #6) 67,187 new infections in 2 weeks.178,749 ranked #7 in world)32.53%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)NoNo
California, USA9,658,947(ranked #13 in the world;  211,825 new infections in the last 14 days).15,59291,750 (ranked #20 in world)2924.45%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)NoNo
Mexico5,782,405(ranked #20) 29,964 new infections in 14 days).3,778324,966(ranked #5)154.39%B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
South Africa3,965,422(ranked #29; 43,789 new infections in 14 days).2,028101,285 (ranked #18)356.52%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)NoNo
Canada3,880,100(ranked #32) 92,722 new infections in 14 days).1,43641,235(ranked #25)1010.11% .B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
Poland6,008,295 (ranked #20; 3,194 new infections in 14 days). 236116,336 (ranked #15)415.90%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3 NoNo
Turkey15,072,747(ranked #10, 12,635 new infections in 14 days).————98,965 (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)NoNo
Russia18,343,964(ranked #7), 60,259 new infections in 14 days).4,188379,363(ranked #4 in world)7812.55%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)R1 (Japan) B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Argentina9,230,573(ranked #13; 95,365 new infections in 14 days).———–128,889f (ranked #14 in world)——–20.07%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gama/P.1 (Brazil)Delta/B.1.617.2 (India)Lambda/C.37 (Peru)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Colombia6,109,015(ranked #18, 9,984 new infections in 14 days).304139,697 (ranked #12 in the world)111.76%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Epsilon/B.1.427 + B.1.429 (USA)*Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Peru3,583,403(ranked #35, 8,527 new infections in 14 days). 799213,228(ranked #6)110.58%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Iran7,232,614(ranked 16th; 4,032 new infections in last 14 days)171141,321(ranked #11)38.40%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)


NoNo
Spain12,403,245(ranked 11th;   165,172 new infections in 14 days).4,329106,797 (ranked #17)10226.50%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
France29,595,892 (ranked #4; 280,414 new infections in the last 14 days).25,130 (ranked #7)148,464 (ranked #10)3645.14%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinantNoNo
Germany26,510,828(ranked #5; 456,894 new infections in 14 days.).41,297 (ranked #4)139,697 (ranked #13)8131.44%
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
Romania2,910,081(ranked #39; 4,542 new infections in 14 days).40465,689 (ranked #20)315.32%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
South Korea18,141,835 (ranked #8 226,878 new infections in 14 days).12,522(ranked #10)24,229 (ranked #39) 1735.32%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Ukraine5,011,433(ranked #22; 2,132 new infections in 14 days),——–108,538 (ranked #16)——–11.59%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Vietnam10,723,673(ranked #12; 17,562 new infections in 14 days).1,03943,080 (ranked #24)10.83%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)NoNo
Netherlands8,090,237 (ranked #15; 15,043 new infections in 14 days).1,46122,325 (ranked #41)47.01%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)GKA (AY.4/BA.1) recombinantNoNo
Denmark2,986,308 (ranked #38) 7,080 new infections in 14 days4936,376 (ranked #81)451.09%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) recombinantNoNo




North Korea (DPRK)3,917,580 (ranked #41; 1,675,961 new infections in 14 days)82,160 (ranked #2)15.07%

What Our Team Is Reading This Week

COVID-19

SARS-CoV-2 Update

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

SARS-CoV-2 infections 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. 

European Centre for Disease Prevention and Control

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.

Monterey County Health Department

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 populationRank in USARanked within World
Mississippi4,1881st8th tied
New Jersey  3,7837th9th tied
Louisiana3,7248th10th 
New York 3,56013th11th 
Alabama4,0073rd8th tied
Arizona4,1572nd8th tied
Rhode Island  3,362 20th12th
Arkansas3,7886th9th tied
Florida3,46119th12th 
California2,31139th36th
USA3,10816th
Peru6,2981st
Bosnia-Herzegovina  4,8683rd
Hungary4,8314th
Montenegro4,3286th
Bulgaria5,4142nd
Czechia3,7479th
Brazil3,09016th
Georgia4,2297th
Sweden1,85156th
Israel1,16185th
Canada1,06092nd
Finland793109th
Norway556126th
Japan240149th
Iceland443132nd
South Korea465130th

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.

LocationTotal Infections as of 5/20/22New Infections on 5/20/22Total DeathsNew Deaths on 5/20/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World526,381,589(9,885,575 new infections in 14 days).760,7546,298,738(24,190  new deaths in last 14 days)1,3956.75%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)NoNo
USA84,935,262(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. 24425.38%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)NoNo
Brazil30,762,413(ranked #3) 218,405 new infections in the last 14 days. 10,187 (ranked #11)665,595(ranked #2)10414.28%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)NoNo
India43,134,332(ranked #2); 106,300 new infections in 2 weeks.2,510524,348(ranked #3)253.06%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)APTK India VOI 32421Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Iota/B.1.526 (USA-NYC) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
United Kingdom22,238,706(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)8732.43%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)NoNo
California, USA9,446,122(ranked #13 in the world;  157,349 new infections in the last 14 days).16,04491,322 (ranked #20 in world)4723.90%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)NoNo
Mexico5,752,441(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)NoNo
South Africa3,921,633(ranked #29; 94,255 new infections in 14 days).6,375100,916 (ranked #18)186.45%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)NoNo
Canada3,787,378(ranked #31, was 26th eighteen weeks ago; 57,347 new infections in 14 days).2,29240,664(ranked #25)3710.02% .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)NoNo
Poland6,005,101 (ranked #20; 5,558 new infections in 14 days). 315116,255 (ranked #15)1315.89%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 NoNo
Turkey15,060,112(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)NoNo
Russia18,283,706(ranked #7), 51,635 new infections in 14 days).5,089378,168(ranked #4 in world)9612.51%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)NoNo
Argentina9,135,308(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)NoNo
Colombia6,099,111(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)NoNo
Peru3,574,876(ranked #35, 8,850 new infections in 14 days). 694213,086(ranked #6)910.56%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)NoNo
Indonesia6,097,986(ranked #18; —– new infections in 14 days)250156,513 (ranked #9)32.16%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)
NoNo
Iran7,229,582 5,151 new infections in last 14 days(ranked 16th; was 12th  thirty-four weeks ago)228141,262 (ranked #11)98.40%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)


NoNo
Spain12,238,073(ranked 11th;   229,014  new infections in 14 days).19,631105,947 (ranked #17)10126.15%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)NoNo
France29,315,478 (ranked #4; 425,339 new infections in the last 14 days).24,332 (ranked #9)147,780 (ranked #10)6544.72%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) recombinantNoNo
Germany26,053,934(ranked #5; 764,344 new infections in 14 days.).40,651 (ranked #5)138,633 (ranked #13)14530.91%
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) recombinantNoNo
Hungary1,914,697 (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)NoNo
Romania2,905,539(ranked #38; 7,281 new infections in 14 days).48465,644 (ranked#20)415.29%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)NoNo
South Korea17,914,957 (ranked 8th) ; 450,175 new infections in 14 days).25,108(ranked#8)23,885 (ranked #39); 4334.88%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)NoNo
Ukraine5,009,301(ranked #22; 6,431new infections in 14 days),——–108,497 (ranked #16)——–11.58%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)NoNo
Vietnam10,706,111(ranked #12; 35,541new infections in 14 days).1,58743,075 (ranked #24)210.81%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Netherlands8,075,194 (ranked #15; 17,494 new infections in 14 days).1,04822,306 (ranked #41)546.93%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) recombinantNoNo
Denmark2,979,238 (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) recombinantNoNo




North Korea (DPRK)First listing)2,241,618 (ranked#41)263,380 (ranked#1)8528.62%

What Our Team Is Reading This Week