COVID news 7/1/22
COVID news 7/1/22
Hi all,
BA.4 and especially BA.5 is spreading fairly quickly around the world as we see cases rise in Australia, Europe, Israel, Indonesia, Brazil and the United States. BA.4 and BA.5 together make up about 52% of new cases in the United States now. Test positivity rate in the U.S. now is high at 16%. We have only seen test positivity rates this high two other times during the entire pandemic- the first weeks of the pandemic in 2020 and the beginning of January 2022 with Omicron (BA.1).
BA.5 is causing increased cases, but it is also causing increases in hospitalizations for COVID. John Burn-Murdoch discusses BA.5 in an excellent tweet thread discussing that even if there is a lower percentage of cases hospitalized than with earlier variants, when a low percentage is multiplied by an extremely large number of cases, hospitals may fill. Each country has a different immune profile related to vaccinations and prior infections so numbers may look different when comparing South Africa to Portugal for example. Unfortunately Long COVID cases are continuing to climb and as of May, about 2% of people in the UK have Long COVID symptoms that limit their daily activities. As Burn-Murdoch says, "Considered alongside other stats — take the unemployment rate at 3.8% — 2% is a huge number. The kind of number that can have a huge impact on the number of people who are able to work, or on the number of additional people needing healthcare from an already stretched system."
Eric Topol MD also reviews BA.5 in his article "The BA.5 story". He talks about BA.5 being the most immune evasive SARS-CoV-2 variant to date making it more transmissible even when people are vaccinated. Boosters can help prevent severe disease and 4th shots show a 99% reduction in risk of death, but unfortunately only about 1 in 4 eligible people over age 50 have gotten the 4th dose booster.
Vaccines save lives and it is estimated that in the first year of COVID vaccinations, about 20 million lives were saved worldwide because of vaccination. The FDA announced yesterday that it has asked Moderna and Pfizer to make bivalent boosters for the fall and winter containing the original virus plus a BA.4/5 component. Instead of chasing individual mutations and the latest variant-du-jour, we should focus efforts into making nasal vaccine boosters that can increase IgA in the nose and throat to prevent transmission. In vaccinated people who have been infected with COVID, scientists have discovered antibodies that can stop all of the variants. With this knowledge, we have targets to make a pan-coronavirus vaccine that can stop all future variants if the science is funded.
Antiviral drugs Paxlovid and Molnupiravir:
Eighty-one year old Dr. Fauci got COVID last week and took Paxlovid. He had rebound COVID after stopping Paxlovid which caused worse symptoms than his first bout, so he took a second course of Paxlovid. Paxlovid was originally tested when the Delta variant was common. We may need to adjust the length of Paxlovid treatment in some people with Omicron infections because this variant is so different. This week, a group reported 11 naturally occurring mutations of the SARS-CoV-2 protease Mpro. In the future, one of these Mpro mutations may cause the virus to become resistant to Paxlovid.
Molnupiravir has a different mechanism of action than Paxlovid. It is inferior in that it does not work very well to stop disease progression and Molnupiravir is mutagenic which can be problematic. Dr. Michael Lin of Stanford and others are concerned that Molnupiravir has little or no clinical benefit but it could cause new mutations which lead to new SARS-CoV-2 variants. As he says, "Omicron evolved into many variants because it underwent bursts of rapid mutagenesis 4x faster than the usual rate, likely in chronic infections. Molnupiravir increases mutagenesis rates several-fold, so gets you the same result without a chronic infection." Maybe it is time for the FDA to reevaluate Molnupiravir's risks and benefits.
Have a happy and safe 4th of July weekend,
Ruth Ann Crystal MD
Twitter: https://twitter.com/CatchTheBaby
Non-COVID great news!
Sanofi caps out-of-pocket Insulin cost at $35 for uninsured U.S. patients https://buff.ly/3a6XDtq
Between this and @mcuban's new company http://CostPlusDrugs.com which provides generics at much cheaper prices, this is wonderful news for anyone who needs medications.
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COVID News:
World
United States
US cases
6/28/22 CDC variant percentages updated every Tuesday: https://covid.cdc.gov/covid-data-tracker/#variant-proportions
BA.5 is now 36.6% + BA.4 is 15.7% = BA.4/5 is 52.3% this week in the U.S.
Wastewater: https://covid.cdc.gov/covid-data-tracker/#wastewater-surveillance
7/1/22 US test positivity rates around about 16% now
7/1/22 England’s Hospitalizations are increasing because of BA.4/5 and are about 12 days from the BA.2 peak if BA.4/5 continues to grow at a similar rate per John Roberts
6/30/22 Dr Michael Lin’s thread on why Molnupiravir can lead to new virus mutations
With Molnupiravir (MOV) not all the mutated viruses are dying. That makes 5% of Molnupiravir patients stealth incubators of SARSCoV2 variants.
12/24/21 Washington Post by Dr. Michael Lin: A new drug to treat covid could create a breeding ground for mutant viruses https://buff.ly/32gFA05
NEW 6/30/22 MedRxiV: COVID-19 rebound after Paxlovid and Molnupiravir during January-June 2022 https://buff.ly/3yc2pxA
COVID-19 rebound occurred both after Paxlovid and Molnupiravir, especially in patients with underlying medical conditions.
Our results call for continuous surveillance of COVID-19 rebound after Paxlovid and Molnupiravir treatments.
Studies are necessary to determine the mechanisms underlying COVID-19 rebounds and to test dosing and duration regimes that might prevent such rebounds in vulnerable patients.
6/30/22 BA.2.75
6/30/22 STAT News: FDA recommends vaccine makers update Covid-19 shots to target Omicron BA.4/BA.5 for fall https://buff.ly/3yas3D5
The original vaccines protect against hospitalization and death, but have less efficacy against symptomatic infection with Omicron's evolution.
6/30/22 FDA Recommends Inclusion of Omicron BA.4/5 Component for COVID-19 Vaccine Booster Doses https://buff.ly/3AnaT85
6/30/22
Articles to which Dr. Topol is referring:
A broad and potent neutralization epitope in SARS-related coronaviruses | Proceedings of the National Academy of Sciences https://buff.ly/3nr7hds
IMM-BCP-01, a patient-derived anti-SARS-CoV-2 antibody cocktail, is active across variants of concern including Omicron BA.1 and BA.2 https://buff.ly/3OXlsT1
6/30/22 BioRxiV: Naturally occurring mutations of SARS-CoV-2 main protease confer drug resistance to nirmatrelvir https://buff.ly/3OSDcPI
Paxlovid is an FDA-approved oral COVID-19 antiviral that contains the Mpro inhibitor nirmatrelvir and the metabolic booster ritonavir.
Eleven naturally occurring mutations of Mpro were discovered which have the potential to cause drug resistance to Paxlovid in the future.
6/30/22 NEJM: Immunogenicity and Safety of Beta-Adjuvanted Recombinant Booster Vaccine https://buff.ly/3QZWLr7
Third dose booster with the MVB.1.351 (Beta variant adjuvanted recombinant protein) vaccine elicited higher neutralizing antibody titers than the other vaccines against the Original strain and against the Beta, Delta, and Omicron BA.1 variants.
A new vaccine (MVB.1.351) directed against the Beta variant has a stronger immune response vs Omicron than mRNAs w/ ancestral spike
6/30/22 NEJM: Pfizer BNT162b2 Vaccine Effectiveness against Omicron in Children 5 to 11 Years of Age https://buff.ly/3yxT2d7
Real world results in 5 to 11 year olds in Israel given 2 doses of Pfizer 10 mcg dose vaccine.
95,000 kids vaccinated with matched controls
VE 51% against any Omicron COVID infection
VE 48% against symptomatic Omicron COVID infection
VE was higher in younger children (5 or 6 years of age) than in older children (10 or 11 years of age).
VE in early studies was 91% against Delta. This is consistent with lower VE against Omicron seen in adults.
6/30/22 Nature: First reported case of a person getting COVID from a cat https://buff.ly/3uhHBns
Vet in Thailand got COVID from a cat who sneezed in her face.
6/30/22 Lancet: Augmented neutralization resistance of emerging omicron subvariants BA.2.12.1, BA.4, and BA.5 https://buff.ly/3a2PtCa
New BA.4/5 data on monoclonal antibody resistance and vaccination antibody evasion.
Sotrovimab: effectively neutralizes BA.1 but markedly reduced neutralization of BA.2, BA.2.12.1, and BA.4/BA.5.
Cilgavimab showed substantial activity against all Omicron subvariants except BA.1 but required high concentrations for efficient neutralization of BA.4/BA.5.
Bebtelovimab neutralized all subvariants with similarly high efficacy as with BA.1 and BA.2.
Triple vaccinated Pfizer BioNTech (3 doses):
BA.1 and BA.2 evaded neutralization antibodies from vaccination
4.3x lower neutralization for BA.1
4.2x lower neutralization for BA.2
6.1x lower neutralization for BA.2.12.1compared with B.1
8.1x lower neutralization for BA.4/5 compared with B.1
A similar tendency was seen in people triple vaccinated with BNT162b2 with subsequent BA.1 or BA.2 breakthrough infection
6/30/22 6/30/33 BMJ: Long distance airborne transmission of SARS-CoV-2: rapid systematic review https://buff.ly/3nALz6B
Review of 18 different outbreaks looking at transmission of SARS-CoV-2.
Long distance airborne transmission of SARS-CoV-2 can occur in indoor settings such as restaurants, workplaces, and venues for choirs.
Insufficient air filtration and replacement probably contributed to transmission.
6/30/22 Lancet: Associations of BMI with COVID-19 vaccine uptake, vaccine effectiveness, and risk of severe COVID-19 outcomes after vaccination in England: a large (9 million person) population-based cohort study https://buff.ly/3ORlZGf
A high BMI has been associated with a reduced immune response to vaccination against influenza.
For SARS-CoV-2, obesity did not impact vaccine effectiveness but being underweight had slightly lower vaccine effectiveness (VE) and had the lowest vaccine uptake for all ages.
In the vaccinated cohort, there were increased risks of severe COVID-19 outcomes for people with underweight or obesity compared with the vaccinated population with a healthy weight.
These results suggest the need for targeted efforts to increase uptake in people with low BMI (<18·5 kg/m2), in whom uptake is lower and vaccine effectiveness seems to be reduced.
3rd dose booster helped decrease hospitalizations and deaths in all groups.
6/28/22 MedPage Today: Kidney Failure May Drive COVID Deaths in People With Sickle Cell Trait https://buff.ly/3QXTTL8
COVID-19 patients with sickle cell trait (SCT) were prone to poor outcomes that appeared to be driven in part by kidney dysfunction.
The presence of either sickle cell anemia or another SCT-related condition was linked with more than 93-times higher odds of severe COVID-19 illness.
6/29/22 ABC: 81 year old Dr. Fauci says he's taking 2nd course of Paxlovid after experiencing rebound after the antiviral treatment https://buff.ly/3OC23HD
When Dr. Fauci had a recurrence of symptoms, they were more severe.
6/28/22
6/28/22 The BA.5 story by Eric Topol MD https://buff.ly/3bnYar0
BA.5 is genetically very different from the other virus strains.
BA.4 and BA.5 are the most immune-evasive variants with low levels of neutralizing antibody responses seen in multiple studies.
The rise of BA.4 and BA.5 is noted around the world and it has happened very quickly (Australia, Europe, Brazil, US). Some places like Portugal with increasing hospitalizations.
Both Moderna and Pfizer/BioNTech have a bivalent (ancestral + Omicron BA.1) booster.
Caused higher BA.1 neutralizing antibodies (vs the original vaccine), both vaccine programs showed that neutralizing antibodies were only 1/3 as high vs BA.4/5.
And, the virus keeps changing so should we keep making new boosters against new variants or should we focus on a variant-proof pan sarbecovirus or Beta-coronaviruses vaccine.
Boosters: 99% reduction in mortality for 4-shots vs 86% for 3 shots.
But only 1 in 4 Americans age 50+ have had a fourth shot!
Side note: Millions of these shots will soon expire, a profound waste, which should be made available to all people, age <50, who seek added protection.
BA.5 is taking off around the world and is outcompeting BA.2.12.1 and BA.4 around the world shown in these charts from @Mike_Honey_ https://buff.ly/3a0YpIl
Indonesia
Italy
France
6/28/22 Nature Immunology: The humoral response and antibodies against SARS-CoV-2 infection https://buff.ly/3Ac4VGJ
6/26/22 Tweet thread by John Burn-Murdoch on the BA.5 wave
Summary
BA.5 is causing both infections and hospitalisations to climb. It will do this everywhere, just a matter of time.
Even if there is a lower percentage of cases that are hospitalized, when that is multiplied by an extremely large number of cases, hospitals will fill.
Rates of severe disease are kept low by widespread immunity from vaccination and prior infection.
But rates of Long Covid continue to climb, with significant societal impacts.
Hospitalizations increasing with BA.4/5:
What appear to be declining overall numbers in Spain, or a slowing of growth in the US, are actually just the BA.5 rise being partially masked by the BA.2 decline
Hospitalizations:
Exactly how high each country’s BA.5 wave will grow is likely to vary considerably because of each country’s immunity profile from vaccination and prior infection waves.
Long COVID: As of the start of May (latest data), roughly 3% of the UK population said they had ongoing symptoms that could not be explained by another cause, and for two-thirds of them (2% of UK population), those symptoms mean their daily activities are now either somewhat or severely limited.
Considered alongside other stats — take the unemployment rate at 3.8% — 2% is a huge number.
The kind of number that can have a huge impact on the number of people who are able to work, or on the number of additional people needing healthcare from an already stretched system.
6/26/22 Economist: How many lives have been saved by covid-19 vaccines? https://buff.ly/3u1F6Wf
In the first year of COVID vaccinations, about 20 Million lives were saved because of the vaccines.
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