In 2022, multiple new Omicron variants BA.1, BA.2, BA.4, and BA.5 assaulted the world’s population of humans and other animals. By the time multiple companies made and tested Omicron BA.1 vaccines, BA.1 was no longer the dominant variant; in fact, it was no longer present. On August 31, 2022, the FDA allowed rapid introduction of an Omicron BA.5 bivalent vaccine. In 2023 our problems are being caused by XBB recombinant variants and BA.5 sub-variants BQ.1 and BQ.1.1. The Omicron BA.5 bivalent vaccine has had no effect on the immune evading BQ variants or XBB recombinant variants. In December the first highly infectious recombinant variant, XBB, began spreading around the world. The XBB variant XBB.1.5, has rapidly spread across the country and the world. Another new variant, CH.1.1 (BA.184.108.40.206.220.127.116.11) caused 5.9% of infections in the world from December 25 to January 14, 2023 and, from December 26 to January 1, 19.5% of infections in the United Kingdom.
On January 13, the World Health Organization (WHO) updated its recommendations on mask wearing to specify that, given the global spread of COVID-19, masks should be worn “irrespective of the local epidemiological situation,” meaning that masks are now recommended for everyone, not just people in areas with high levels of transmission. Here are our 14-day moving average determinations for SARS-CoV-2 for the United States. 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.
XBB.1.5 Variant Continues to Dominate in the United States
During the week ending in 2/24/23, the CDC estimates that based on genomic surveillance, XBB.1.5 accounted for 85% of infections, followed by BQ.1.1 at 9.4%, BQ.1 at 2.6%, XBB at 1.2%, CH.1.1 at 0.9%, BN.1 at 0.4%, BA.5 at 0.1%, and BF.7 at 0.1%.
BQ.1.1 has five spike mutations that are different from BA.5. Four of these mutations allow escape from immunity from monoclonal antibodies, any prior infection (including Omicron BA.5), or any vaccine to include the bivalent Omicron BA.5 vaccine. Infections are still occurring in our clinic in patients that received the Omicron BA.5 bivalent vaccine. The XBB recombinant isolate XBB.1.5 has rapidly become the dominant infection in the USA. It took 28 days to become the cause of 40% of infections in the USA. As of 2/24/23, XBB.1.5 now causes over 85% of infections in the United States.
XBB.1.5 Proportion of Sequenced Isolates in the USA
BQ. 1 and BQ.1.1 Totaled Proportion of Sequenced Isolates in the USA
Percent of isolates identified as XBB.1.5 by Region
|Week ending in||1||2||3||4||5||6||7||8||9||10|
SARS-CoV-2 infections per day in the United States have decreased for the first time in 4 weeks. There is still widespread underreporting by states, a failure to capture all positive home tests, and a decreased PCR screening program in most states. Deaths per day in the United States have decreased by 234 deaths per day. Many states are not reporting deaths or infections in a timely manner. The number of infections per day is expected to increase in the next four weeks due to a lack of mask use in schools, businesses, and airports; a failure of adequate building ventilation; lack of social distancing; and low rates of bivalent booster uptake. XBB, an Omicron recombinant variant first identified in India, caused a major outbreak in Singapore. XBB is the first recombinant variant combining spike protein sequences from two other Omicron BA.2 variants, that has spread aggressively around the world. New mutations of XBB, specifically XBB.1.5 have rapidly crowded out other variants in the USA. Current vaccines, monoclonal antibodies and prior infections will not protect you from getting an XBB.1.5 infection. A more detailed description of XBB variant mutations and epidemiology can be found on page 17 of the UK Health Security Agency Technical Briefing from November 25.
For a more detailed picture of COVID variant evolution in the United States, we recommend checking out the dashboard put together by Raj Rajnarayanan, Assistant Dean of Research and Associate Professor at NYITCOM at Arkansas State University.
To understand the true impact of these variants, it’s helpful to examine their evolution. 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.
Past infections with a BA.1, BA.2 or BA.5 variants will not prevent infections with any of the newer variants. Monoclonal antibodies are no longer effective against newer BQ variants, XBB variants and other spike protein mutated variants. The last remaining monoclonal antibody, bebtelovimab, was removed from use by the FDA on 12/2/22. Paxlovid was only 89% effective in the original clinical trials against SARS-CoV-2. If resistance develops this winter to oral Paxlovid, we will have more Paxlovid failures and increased hospitalizations and deaths.
A Deeper Dive into U.S. COVID Data
On 2/24/23, the United States had 8,922 documented new infections. There were also 73 deaths. Thirty-nine states did not report their infections, and 38 states and the District of Columbia didn’t report their deaths. In the United States on 2/23/23 the number of hospitalized patients (27,966) has decreased (-4.76% compared to the previous 14 days) and was 29,299 on February 9th. On 2/23/23 there were 3,610 patients who were seriously or critically ill (a 0.06% increase); that number was 3,608 two weeks ago. The number of critically ill patients has increased by 2 in the last 14 days, while at least 4,462 new deaths occurred. Patients are still dying each day (average 319/day).
As of 2/24/23, we have had 1,144,441 deaths and 105,169,945 SARS-CoV-2 infections in the United States. We have had 409,500 new infections in the last 14 days. We are adding an average of 204,750 new infections every seven days. For the pandemic in the United States we are averaging one death for every 91.90 infections or over 10,882 deaths for each one million infections. As of 2/24/23, thirty-nine states have had greater than 500,000 total infections, and 38 states and Puerto Rico have had greater than 5,000 total deaths. Forty-six states have had greater than 2,000 deaths. Only Vermont has had less than a thousand deaths (910 deaths). Now 12 states have over 4,000 deaths per million population: Mississippi (4,476), Arizona (4,534), Alabama (4,261), West Virginia (4,428), New Mexico (4,302), Tennessee (4,263), Arkansas (4,295), Michigan (4,201), New Jersey (4,047), Kentucky (4,041), Louisiana (4,024) and the new addition, Florida (4,005). 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. Nine states have had greater than 40,000 deaths: Florida (86,012 deaths), Texas (93,604 deaths), New York (77,086 deaths), Pennsylvania (50,160 deaths), Georgia (42,332 deaths), Ohio (41,686 deaths), Illinois (41,338 deaths), Michigan (41,957), and California (100,562 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 (27 months), there were 877,340 new deaths from SARS-CoV-2. For twenty-three of those months, vaccines have been available to all adults. During these twenty-three months, 572,242 people have died of SARS-CoV-2 infections. Clearly, a vaccine-only approach is not working anywhere, especially not in the United States. In addition to getting more people vaccinated, most of the hospitalizations and deaths could have been prevented by proper masking (N95 or better), social distancing, and treatment with oral antiviral agents like Paxlovid. We recommend all of these precautions and treatments to every patient in our clinic, and we have only lost one patient to COVID in 3 years.
As of 2/24/23, California was ranked 32nd in the USA in infection percentage at 30.43%. In California, 26.46% of the people were infected in the last 22 months. As of 2/24/23, 33 states have had greater than 30% of their population infected. Fifty states, the District of Columbia and Puerto Rico have 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 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 showed 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. PAXLOVID™ one year later is widely available at major pharmaceutical chains and smaller independent drug stores throughout the USA. We have been able to obtain PAXLOVID™ for any patient desiring treatment. We have only had one drug failure and death from SARS-CoV-2 during 2022. That death occurred in an octogenarian male in the fourth quarter of 2022.
28, p740–746 (2021)with four 200 mg capsules orally twice a day for five dayfour 200 mg capsules orally twice a day for five daysIntravenous Drug Treatment for non-hospitalized SARS-CoV-2 Infected Patient
Watching World Data
Over the next few months, we’ll be paying close attention to correlations between the SARS-CoV-2 data, the number of isolates identified in various countries and states, and the non-pharmaceutical interventions (like mask mandates and lockdowns) put in place by state and national governments. Data on infections, deaths, and percent of population infected was compiled from Worldometers. Data for this table for SARS-CoV-2 Isolates Currently Known in Location was compiled from GISAID and the CDC. It’s worth noting that GISAID provided more data than the CDC.
|Location||Total Infections as of 2/24/23||New Infections on 2/24/23||Total Deaths||New Deaths on 2/24/23||% of Pop.Infected||SARS-CoV-2 Isolates Currently Known in Location||National/ State Mask Mandate||Currently in Lockdown|
|World||679,493,562(2,199,451 new infections in the last 14 days with an average of 157,111 infections per day).||117,709||6,797,242(16,487 new deaths in the last 14 days with an average of 1,178 deaths per day.)||677||8.71%||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)BF.7BJ.1XBB (new recombinant India)BQ.1BQ.1.1BS.1BN.1XBB.1XBB.1.5CH.1.1||No||No|
|USA||105,169,945(ranked #1) 409,500 new infections in the last 14 days with an average of 29,250 infections/day||8,922(ranked #6)|
39 states failed to report infections on 2/24/23.
|1,144,441(ranked #1) 4,462 new deaths reported in the last 14 days or an average of 319 deaths/ day.||73|
38 states failed to report deaths on 2/24/23.
|31.43%||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)BA.4.6 (USA 7/22)BF.7BJ.1XBB (new recombinant India)BQ.1BQ.1.1BN.1XBB.1XBB.1.5CH.1.1||No||No|
|Brazil||37,020,531(ranked #5) 90,192 new infections in the last 14 days.||11,587 (ranked#4)||698.928(ranked #2; 1,266 new deaths in the last 14 days)||94||17.19%||No||No|
|India||44,685,530(ranked #2).||–||530,764(ranked #3)||–||3.17%|
Unchanged in 10 weeks
|United Kingdom||24,341,615(ranked #9) 47,863 new infections in the last 2 weeks.||–||206,246 (ranked #7) 1,348 new deaths in the last 2 weeks||–||35.53%||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.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)||No||No|
|California, USA||12,025,682(ranked #13 in the world; 14,161 new infections in the last 14 days).||1,459||100,562 (ranked #20 in world; 217 new deaths in the last 14 days||11||30.43%||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)BQ.1BQ.1.1BN.1XBBXBB.1XBB.1.5CH.1.1||No||No|
|Mexico||7,443,151(ranked #19) 42,303 new infections in 14 days).||3,870 (ranked #10)||332,938(ranked #5) 78 new deaths in the last 14 days)||25||5.65%||No||No|
|South Africa||4,061,383(ranked #38; 4,172 new infections in the last 14 days).||298||102,595 (ranked #18) no new deaths reported in the last 28 days).||–||6.68%||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)||No||No|
|Canada||4,581,763(ranked #34) 20,801 new infections in 14 days).||–||51,061(ranked #24) 432 new deaths in the last 14 days.||–||11.93%||No||No|
|Russia||22,232,492 (ranked #10), 184,967 new infections in 14 days).||13,829 (ranked #2)||395,970(ranked #4)486 new deaths in 14 days||32||15.24%||No||No|
|Peru||4,485,033(ranked #35, 1,797 new infections in 14 days).||100||219,378(ranked #6) 149 new deaths in the last 14 days.||13||13.31%||No||No|
|Spain||13,762,280(ranked #12; 13,362 new infections in 14 days).||1,054 (ranked #17)||119,354 (ranked #15) 478 new deaths in 14 days.||28||29.45%||No||No|
|France||39,605,037 (ranked #3) 45,910 new infections in 14 days).||4,489 (ranked #10)||164,848 (ranked #10) 311 new deaths in 14 days.||44||60.39% a 0.08% increase in 14 days.||No||No|
|Germany||38,090,089(ranked #4; 350,619 new infections in 14 days.)||21,177 (ranked #1)||167,723 (ranked #9)960 new deaths in 14 days.||119||45.41%0.22% increase in 14 days||No||No|
|South Korea||30,469,702 (ranked #7; 144,219 new infections in 14 days).||10,845(ranked #7)||33,909 (ranked #32) 212 new deaths in 14 days.||22||59.36%0.29% increase in 14 days||No||No|
|Netherlands||8,591,721 (ranked #17; 5,349 new infections in 14 days).||–||22,992 (ranked #41)|
Unchanged in 4 weeks
|Taiwan||9,985,320(ranked #16); 211,693 new infections in 14 days||14,387 (ranked #4)||17,709 (ranked #56; 745 new deaths in the last 14 days)||37||41.79%|
0.87% of population has been infected in the last 14 days
|Japan||33,151,209(ranked #6)242,969 new infections in the last 14 days||15,193(ranked #2)||72,051(ranked #20)|
1,674 new deaths in the last 14 days for an average of 120 deaths per day.
0.20% of the population infected in the last 14 days.
|Australia||11,363,400(ranked #14) 33,058 new infections in 14 days.||2,961 (ranked #12)||19,357(ranked #49) 287 new deaths in 14 days.||17||43.59% |
0.13% of the population infected in last 14 days.
|Hong Kong||2,882,823(ranked# 41) 2,305 new infections in the last 14 days.||140||13,445 (ranked#60)33 new deaths in the last 14 days.||–||37.91%|
0.03% of the population infected in the last 14 days.
What Our Team Is Reading This Week
- SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 50, 10 February 2023 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1135877/variant-technical-briefing-50-10-february-2023.pdf
- Identification of a molnupiravir-associated mutational signature in SARS-CoV-2 sequencing databases (Preprint) https://doi.org/10.1101/2023.01.26.23284998
- COVID drug drives viral mutations — and now some want to halt its use https://www.nature.com/articles/d41586-023-00347-z#ref-CR1
- SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 49, 11 January 2023 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1128554/variant-technical-briefing-49-11-january-2023.pdf
- Long COVID: major findings, mechanisms and recommendations (Nature) https://www.nature.com/articles/s41579-022-00846-2
- Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation (Nature) https://doi.org/10.1038/s41586-021-04266-9
- Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants (Preprint) https://doi.org/10.1101/2022.12.27.521986
- SARS-CoV-2 infection and persistence in the human body and brain at autopsy (Nature) https://doi.org/10.1038/s41586-022-05542-y
- Lifting Universal Masking in Schools — Covid-19 Incidence among Students and Staff (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMoa2211029
- FDA Announces Bebtelovimab is Not Currently Authorized in Any US Region (FDA) https://www.fda.gov/drugs/drug-safety-and-availability/fda-announces-bebtelovimab-not-currently-authorized-any-us-region
- SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 48, 25 November 2022 (UK Health Security Agency) https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1120304/technical-briefing-48-25-november-2022-final.pdf
- Omicron sublineage BQ.1.1 resistance to monoclonal antibodies (The Lancet) https://doi.org/10.1016/S1473-3099(22)00733-2
- SARS-CoV-2 Infection and Increased Risk for Pediatric Stroke (Pediatric Neurology) https://www.pedneur.com/article/S0887-8994(22)00210-7/fulltext
- Single-cell multiomics revealed the dynamics of antigen presentation, immune response and T cell activation in the COVID-19 positive and recovered individuals https://doi.org/10.3389/fimmu.2022.1034159
- Novel treatment combining antiviral and neutralizing antibody-based therapies with monitoring of spike-specific antibody and viral load for immunocompromised patients with persistent COVID-19 infection (Experimental Hematology & Oncology) https://ehoonline.biomedcentral.com/articles/10.1186/s40164-022-00307-9
- Covid-19 is a leading cause of death in children and young people ages 0-19 years in the United States (Preprint) https://doi.org/10.1101/2022.05.23.22275458
- Post-COVID-19-associated morbidity in children, adolescents, and adults: A matched cohort study including more than 157,000 individuals with COVID-19 in Germany (PLOS Medicine) https://journals.plos.org/plosmedicine/article?id=10.1371%2Fjournal.pmed.1004122
- Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies (Acta Pharmacologica Sinica) https://doi.org/10.1038/s41401-022-00998-0
- Cognitive Deficits in Long Covid-19 (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMcibr2210069
- Brain 18F-FDG PET imaging in outpatients with post-COVID-19 conditions: findings and associations with clinical characteristics (European Journal of Nuclear Medicine and Molecular Imaging) https://doi.org/10.1007/s00259-022-06013-2
- Acute and postacute sequelae associated with SARS-CoV-2 reinfection (Nature) https://doi.org/10.1038/s41591-022-02051-3
- Associations between indoor relative humidity and global COVID-19 outcomes (Journal of the Royal Society) https://doi.org/10.1098/rsif.2021.0865
- Successful treatment of prolonged, severe COVID-19 lower respiratory tract disease in a B-cell ALL patient with an extended course of remdesivir and nirmatrelvir/ritonavir (Clinical Infectious Diseases) https://doi.org/10.1093/cid/ciac868
- Impact of SARS-CoV-2 ORF6 and its variant polymorphisms on host responses and viral pathogenesis (Preprint) https://doi.org/10.1101/2022.10.18.512708
- Anti-PF4 antibodies associated with disease severity in COVID-19 (PNAS) https://www.pnas.org/doi/10.1073/pnas.2213361119
- A multinational Delphi consensus to end the COVID-19 public health threat (Nature) https://doi.org/10.1038/s41586-022-05398-2
- Pfizer and BioNTech Announce Updated Clinical Data for Omicron BA.4/BA.5-Adapted Bivalent Booster Demonstrating Substantially Higher Immune Response in Adults Compared to the Original COVID-19 Vaccine https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-updated-clinical-data-omicron
- Paxlovid and Long Covid (Ground Truths, Eric Topol) https://erictopol.substack.com/p/paxlovid-and-long-covid?utm_source=substack&utm_medium=email
- Risk of Infection and Hospitalization Among Children and Adolescents in New York After Emergence of the SARS-CoV-2 Omicron Variant – Comment and Response (JAMA) https://jamanetwork.com/journals/jama/article-abstract/2797231
- Myocarditis (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMra2114478
- SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 47 (UK Health Security Agency) https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1115077/Technical-Briefing-47.pdf
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