In some places in the United States like New York and Massachusetts, COVID case numbers are going down. In Santa Clara county, we see that wastewater SARS-CoV-2 levels in the Palo Alto area are decreasing but are still at a similar level to 2 weeks ago. Sunnyvale and Gilroy wastewater viral levels have plateaued for now and will need to be followed. Even though many places have peaked for Omicron case numbers, we still need to be cautious and protect ourselves until there is a significantly lower community prevalence of COVID. Community positivity levels for SARS-CoV-2 should be significantly lower in about a month from now. That should make many activities safer especially for vaccinated and boosted people.
Three new studies (UKHSA, Kaiser Southern California, CDC VISION study) show that getting a 3rd shot booster with an mRNA vaccine protects 90% against hospitalization from Omicron infections within the first 3 months after the booster. Omicron has immune evasion so it can dodge our neutralizing antibodies which is our initial line of defense after vaccination so some people will get breakthrough Omicron infections. But, our memory B cells and T cells then kick in to protect us against severe disease and hospitalization.
Studies from Israel this week show that mRNA vaccination reduces Long COVID symptoms in pre-Omicron times. Another report from Israel shows that giving a 4th dose of the Pfizer vaccine does not appear to significantly increase protection against Omicron breakthrough infection.
In a fascinating tweet thread, Dr. Akiko Iwasaki of Yale explained a newly published article on how a mild COVID infection of the lungs can cause Long COVID of the brain. She states that similar neuropathology is seen in "chemo brain" for cancer patients and brain fog symptoms in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).
The U.S. is reporting 756,358 new coronavirus cases, down 17% when compared to the same day last week.
This and other data continues to indicate that the Omicron wave has peaked at the national level, although the situation varies across the country. Most of the drops have been seen in states along the U.S. East Coast, but cases are now also declining on the West Coast.
The number of Americans hospitalized with COVID-19 rose to 157,986 (+1,285), the highest since the pandemic began.
2,446 new deaths were reported, pushing the seven-day average to 1,992, the highest since September 29. This means that, every 44 seconds, one American dies of COVID-19.
US Daily Cases peaked at 933,249 and are now starting to descend:
Reassuring independent replication of booster VE data:
UK 3 shot booster, < 10 weeks, 88% against Omicron hospitalization
Kaiser 3 shot booster, < 3 months 89% against Omicron hospitalization
CDC VISION study 3 shot booster, 90% against Omicron hospitalization
1/21/22 CDC: Effectiveness of a Third Dose of mRNA Vaccines Against COVID-19 Emergency Department and Hospitalizations During Periods of Delta and Omicron Variant Predominance — VISION Network study https://buff.ly/35bHWOO
During both Delta and Omicron-predominant periods, receipt of a third vaccine dose was highly effective at preventing COVID-19–associated:
Emergency dept and urgent care visits (94% for Delta and 82% for Omicron)
Hospitalizations (94% for Delta and 90% for Omicron).
1/21/22 Kaiser So Cal: BNT162b2 (Pfizer–BioNTech) mRNA COVID-19 vaccine against Omicron-related hospital and emergency department admission in a large US health system https://buff.ly/3rBTiTG
90% durable protection (>3 months) with Pfizer booster against Omicron for hospital admissions
As expected, not as high protection (VE waning) against Omicron infection for ER visits for booster (yet better than 2-shots)
1/14/22 UKHSA: SARS-CoV-2 variants of concern and variants under investigation in England, Technical briefing 34, 14 January 2022 https://buff.ly/3Al4tnK
1/21/22 NIH: COVID-19 vaccination does not reduce chances of conception, study suggests https://buff.ly/3AoN0uz
In couples in which the male partner had tested positive for COVID infection within 60 days of a given cycle were 18% less likely to conceive in that cycle.
This short-term decline in male fertility could potentially be avoided by vaccination.
The researchers concluded:
Vaccination against COVID-19 had no harmful association with fertility.
Vaccination against COVID-19 also could help avert the risks that SARS-CoV-2 infection poses for maternal and fetal health.
1/20/22 Science: Cannabidiol (CBD) inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses https://buff.ly/3tGcBho
In human lung cells, CBD and its metabolite 7-OH-CBD inhibits SARS-CoV-2 replication in human lung epithelial cells.
Combining CBD with THC (1:1) significantly suppressed CBD efficacy consistent with competitive inhibition by THC.
CBD’s ability to block SARS-CoV-2 appears to be mediated in part by activation of the IRE1α RNase and interferon pathways.
In mice, CBD treatment significantly inhibited viral replication in lungs and nasal turbinates in a dose-dependent manner.
In humans, a survey of 1,212 U.S. patients taking prescribed CBD 100 had positive COVID-19 tests at much lower rates than control groups with similar medical backgrounds who did not take CBD.
1/20/22 National Post: Departing Hong Kong residents fly their pets out of city on private jets https://buff.ly/3nKq2c6
With Hong Kong’s zero-COVID regime leading to soaring cargo rates and flight cancellations, people are grouping together to use private jets at a cost of about HK$200,000 (US$25,665) for each owner with their pet.
1/20/22 Science: SARS-CoV-2 Omicron variant: Antibody evasion and cryo-EM structure of spike protein–ACE2 complex https://buff.ly/3nMnJp3
Cryo-EM structural analysis of the Omicron variant spike protein in complex with human ACE2 reveals new salt bridges and hydrogen bonds formed by mutated residues R493, S496 and R498 in the RBD with ACE2.
Cryo-EM structure of the Omicron spike protein-ACE2 complex
Omicron evades humoral (antibody) immunity because of antigenic drift. Therefore, vaccinated people can get an Omicron infection.
However, Memory B cells and T cells can work against Omicron but their response is a bit delayed so people get the infection, but do not end up with severe (hospitalizations) disease.
Nature Reviews: B cell memory: building two walls of protection against pathogens https://buff.ly/2stP0mr
Long-lived plasma cells in the bone marrow secrete highly selected, highly specific antibodies (depicted in red) that form a first ‘wall’ (bottom) against reinfection by homologous pathogens.
Variant pathogens can find holes in this wall; however, having escaped the antibodies from the long-lived plasma cells, the variant pathogens encounter a second wall (top) formed by memory
B cells that were less highly selected and therefore maintain a broader range of antigen affinities and specificities.
The memory B cells are activated by the variant pathogen to differentiate into long-lived plasma cells or to re-enter the germinal centers (GCs) to replenish the memory B cell pool.
1/20/22 NEJM: Immunogenicity and Reactogenicity of Vaccine Boosters after Ad26.COV2.S (J&J vaccine) Priming https://buff.ly/3KtPDQj
S-specific binding antibodies, levels of neutralizing antibodies, S-specific T-cell responses, and reactogenicity were measured.
The increase in spike antibodies, neutralizing antibodies and Interferon-gamma was significantly larger with a second dose of mRNA vaccines (Moderna or Pfizer) than with the homologous J&J booster.
Moderna (mRNA-1273) booster after the original J&J vaccination was the most immunogenic and was associated with higher reactogenicity than the Pfizer (BNT162b2) and J&J (Ad26.COV2.S) boosters.
FACTOR change (Log scale) differences between boosters after initial J&J:
Breakthrough infections with Omicron induce potent neutralizing antibody responses.
Number of exposures (infection or vaccination) correlate with potency and breadth of antibodies.
Three-dose vaccination improves neutralization of the SARS-CoV-2 Omicron variant.
1/20/22 AHA: Longitudinal Assessment of Cardiac Outcomes of Multisystem Inflammatory Syndrome in Children (MIS-C) Associated With COVID‐19 Infections https://buff.ly/3nIj5IN
Recovery of cardiac function for MIS-C is fairly rapid within the first week, with complete normalization by 3 months.
1/20/22 Nature: The pandemic’s true death toll: millions more than official counts https://buff.ly/3qKg5xm
Global excess deaths are estimated at double or even quadruple what is reported especially in low and middle income countries.
1/20/22 Nature: How does Omicron spread so fast? A high viral load isn’t the answer https://buff.ly/33BB9gQ
Data on viral levels point to immune evasion as a cause of the variant’s transmissibility.
There is more variability in viral load in individuals infected with Omicron than in people infected with Delta.
Story of all of the hoops she needed to go through to find a Paxlovid prescription and a doctor to prescribe it.
1/19/22 Health Day: Nearly Half of Americans Gained Weight in Pandemic's First Year https://buff.ly/3tM2NCk
1/19/22 The Hill, by Bruce Farber MD: CDC guidelines for antivirals give the unvaccinated the lion's sharehttps://buff.ly/3GQJfRi
Paradoxically, unvaccinated patients refuse vaccines but are willing to accept monoclonal antibody treatments which carry many more side effects than the vaccines.
Breakthrough cases routinely occur among the vaccinated and boosted. 25% of our current COVID-19 hospitalizations have been in vaccinated patients, with a small percent having been boosted as well.
The use and administration of these therapies — funded by the federal government without cost to the end user — are governed by the CDC and state prioritizations. Although immunosuppressed patients are appropriately atop the list, most unvaccinated patients will be granted the next highest level of priority.
For example, a 35-year-old unvaccinated former smoker with asthma gains priority over a 66-year-old vaccinated cancer patient. Similarly, an unvaccinated 25-year-old smoker with depression takes precedence over a 64-year-old vaccinated patient with chronic pulmonary disease.
“The decision to refuse vaccination is a matter of personal choice, but with choice comes consequence.
“Without personal consequences, refusing vaccination becomes an easier decision. Denying the unvaccinated priority to remedial treatments and therapies needs to be reevaluated.
1/20/22 The Atlantic, Ed Yong: It’s a Terrible Idea to Deny Medical Care to Unvaccinated People https://t.co/Qo9dqvuPwV
Omicron is pushing hospitals to their limit, but the medical system still has an ethical responsibility to all patients—no matter the choices they make.
Unvaccinated Americans are disproportionately poor—and within the lowest income brackets, people who want or would consider a vaccine outnumber those who would never get one but logistics make it difficult for them to get vaccinated.
“We’ve irrigated many of our rural communities with more misinformation than investments in health care, education, and economic well-being,”
Giving monoclonal antibodies preferentially to unvaccinated people is more likely to keep someone out of the hospital.
1/19/22 The Hill: At least 20 percent of Americans have been infected with COVID-19, data show https://buff.ly/3Kq7MyF
66,400,000 Americans have been infected although the total number could be much higher because of asymptomatic cases.
>850,000 COVID deaths in the U.S. so far.
63% of Americans are vaccinated with 2 doses, although that figure significantly varies by locality — from about 48% in Alabama and Wyoming to 87% in Washington, D.C.
1/19/22 Reuters: EU regulator finds mRNA COVID-19 vaccines safe during pregnancyhttps://buff.ly/3KtqK7m
65,000 pregnancies did not show any sign of higher risk of complications, miscarriages, preterm births or side-effects on the unborn babies from mRNA shots, the European Medicines Agency said.
Omicron has impaired cell-fusion, inability to use TMPRSS2, and more dependency on the endosomal pathway for cell entry.
Omicron appears to have gained significant evasion from neutralizing antibodies while maintaining sensitivity to antiviral drugs (Paxlovid) targeting the polymerase.
Omicron has shifted cellular tropism away from TMPRSS2 expressing cells that are enriched in cells found in the lower respiratory and GI tracts.
Omicron has less tropism and less infectivity for the lungs and the gastrointestinal tract.
Paxlovid maintains plasma concentrations many-fold times higher than the amount required to prevent Omicron from replicating in cells, so the pharmacokinetics are in the right range.
1/18/22 AP: Hong Kong to kill 2,000 animals after hamsters get COVID-19 https://buff.ly/3FOErKw
“We cannot exclude the possibility that the shopkeeper was in fact actually infected from the hamsters.”
1/17/22 Nature: The UGT2A1/UGT2A2 locus is associated with COVID-19-related loss of smell or tastehttps://buff.ly/3ruWikE
Genome-wide association study (GWAS) of COVID-19-related loss of smell or taste in 47,298 23andMe research participants.
UGT2A1 and UGT2A2 genes are expressed in the olfactory epithelium and play a role in metabolizing odorants. They turn off stimulation of the olfactory bulb once the odorant is no longer present.
These genes show a genetic link to the biological mechanisms underlying COVID-19-related loss of smell or taste.
1/17/22 Bloomberg: Top Carmaker Shutdowns Hint More to Come in Covid-Zero Chinahttps://buff.ly/3GC0Pbr
Toyota and VW factories have been shut down to prevent the spread of COVID.
VW also makes the Audi Q3.
The COVID-Zero policy has a global impact given the role China plays in the global auto supply chain.
1/17/22 Times of Israel: Israeli trial, world’s first, finds 4th dose of Pfizer vaccine ‘not good enough’ against Omicronhttps://buff.ly/3tFH9zJ
1/17/22 Nature: Post-acute neurological consequences of COVID-19: an unequal burden https://buff.ly/3FErlzJ
Long COVID neurological consequences particularly burden marginalized communities.
In the United States, members of the Black, Indigenous and Latino communities are 2x to 3x more likely to be infected, hospitalized or die from COVID-19.
Health equity and healthcare insurance coverage is important to eliminate barriers to neurological services.
MedRxiV: Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain https://buff.ly/3tBpZU0
Mild COVID lung infection may cause Long COVID of the brain via:
Prolonged elevated cytokines (CCL11 especially),
Reactive microglia causing impaired neurogenesis in the hippocampus which can cause memory loss
Loss of oligodendrocytes and reduced myelinated axon density in subcortical white matter within 7 days of infection.
1/17/22 MedRxiV (Israel): Vaccination status and reported incidence of post-acute COVID-19 (PASC) symptoms in Israel: a cross-sectional study of patients tested between March 2020 and November 2021 https://buff.ly/3Id2hRT
Long COVID, pre-Omicron
951 infected (67% were vaccinated) and 2437 uninfected
People vaccinated with 2 doses of Pfizer who had a breakthrough infection reported much fewer Long COVID symptoms than unvaccinated people.
In fact, vaccinated people with breakthrough COVID infections reported Long COVID (PASC) symptoms such as fatigue, headache, etc with the same frequency as uninfected people. Vaccination brought these symptoms back to baseline.
In addition to reducing the risk of acute illness, COVID-19 vaccination may have a protective effect against long COVID.
France’s parliament approved a law excluding unvaccinated people from all restaurants, sports arenas and other venues, to protect hospitals amid record infections driven by highly contagious Omicron.
1/17/22 AP: COVID deaths and cases are rising again at US nursing homeshttps://buff.ly/3nzBZkR
Omicron has caused COVID cases to rise again at US nursing homes leading to new restrictions on family visits and a renewed push to get more residents and staff members vaccinated and boosted.
Despite the rising numbers, the situation is not as dire as it was in December 2020.
Experts credit the high vaccination rates now among nursing home residents:
Nursing home residents’ vaccinations: 87% 2 doses, 63% are boosted.
Nursing home staff vaccinations: 83% 2 doses, only 29% are boosted.
1/16/22 Descent of cases seen in NY, MA, NJ, PR, IL, MD
