COVID news 8/19/22
Hi all,
The BA.5 wave here in the US is now starting to decline by about 15 to 20%. So, what should we expect next? No one can say for sure, but it may be either BA.2.75 or BA.4.6 that wins out as the next variant causing a wave of COVID infection. Some countries in Oceania and Asia (India, Singapore, Australia) are seeing a rise in BA.2.75 (aka Centaurus). But, in Europe, the Middle East and North America, BA.4.6 is starting to compete. A new variant may show up, but for now we will just have to wait and see and be glad that cases are starting to go down. Each country has a different "immunity wall" depending on which variants have caused infection waves there, which vaccines and boosters people have gotten or not gotten, so we may see variation in waves around the world going forward.
Regarding the fall booster, the UK has approved Moderna's bivalent vaccine that has both mRNA from the original virus and mRNA from BA.1 (Omicron). My understanding is that there are some human studies, in addition to animal studies, to support this vaccine's use. In the US, Pfizer is making a new bivalent vaccine with mRNA from the original virus plus mRNA from BA.5. Early animal studies show that this may provide more broad neutralizing antibodies to the other Omicron subvariants. But there is controversy with the BA.5 bivalent vaccine, as the FDA has said that they will approve the Pfizer bivalent (original virus + BA.5) with only animal study data and without human clinical trials. Proponents say adding the mRNA to BA.5 is similar to how we change the flu vaccine components each year by trying to match circulating variants. Others think that it is not wise to give this vaccine until it has been tested in humans. Levels of neutralizing antibodies made by humans could be different from those made by mice. The US has had a bad track record for getting older adults over age 50 to get the 4th dose booster vaccine even though the fourth dose has been proven in many studies to reduce severe COVID and death for that age group. I am concerned that the lack of human studies will make people even less likely to get the new fall bivalent booster. I guess we will find out soon since the new bivalent vaccine should start to roll out in September. In any case, it is a guessing game as to which new variant we will have in the future and I agree with Drs. Iwasaki and Topol that nasal vaccine boosters and pan-coronavirus vaccines may be our way out of the pandemic.
A very large study in the Lancet this week compared 1.28 Million people who had COVID in the last 2 years to 1.28 Million controls who did not get COVID and the results on neurologic and psychiatric sequelae are concerning. For people over age 65, having a COVID infection in the last 2 years increased both dementia and psychotic disorders. For people ages 18 to 65, brain fog was noted more commonly in patients who had COVID in the last 2 years. Children under age 18 who had COVID had double the risk for new seizures and triple the risk for psychosis although the psychosis risk was rare.
Even if there are only a few percent more people getting dementia, psychotic disorders or brain fog, this could really stress our health care and social systems. The above neurologic and psychiatric risks were noted for both Delta and Omicron variants. "Living with COVID" , which has been touted as our new normal, may not be the best idea.
Two days ago, Dr. Walensky called for a reorganization of the US CDC aimed at changing the agency's culture and trying to restore public trust. Goals include better communication and timeliness with messaging. As it stands now, funding is very siloed at the CDC and each disease has a different budget. The hope is to make funding for urgent disease issues more flexible going forward.
Finally, two old drugs have been found to possibly reduce severe COVID- the 100 year old BCG tuberculosis vaccine in unvaccinated adult Type I diabetics, and in a separate study, Metformin. The small BCG study (n = 144) found that giving multiple doses of BCG given over 1 to 2 years was 92% effective in unvaccinated adult Type I diabetics in preventing COVID and those who did get COVID in the BCG group had less severe symptoms. We will need more studies to see if these effects are reproducible, but it's nice to see some positive news. By the way, the Metformin study also showed that Ivermectin and Fluvoxamine do not prevent severe COVID disease or death.
Have a good weekend,
Ruth Ann Crystal MD
Twitter: https://twitter.com/CatchTheBaby
Other medical news:
8/16/22 Reuters: U.S. FDA approves sale of over-the-counter hearing aids https://buff.ly/3AvW2YE
8/16/22 Human Monkeypox without Viral Prodrome or Sexual Exposure, Stanford, California, USA, 2022 https://buff.ly/3dv4Y7n
Man in his 20s with monkeypox on his hands, torso and back. No recent sexual contact, no genital lesions or inguinal lymphadenopathy, and no viral prodrome.
His primary risk factor was close, nonsexual contact (dancing) with numerous unknown persons at a crowded outdoor event.
The lack of both sexual exposure and anogenital involvement indicates that mode of transmission may be associated with clinical symptoms; fomites (hotel bedding and sheets, high-touch areas in public settings) may be alternative modes of transmission.
US Monkeypox cases:
COVID News:
World
United States
US cases: https://www.nytimes.com/interactive/2021/us/covid-cases.html
Cases have fallen by 20% or more this month in more than a dozen states.
In California, daily case counts were nearly twice as high a month ago as they are today.
VARIANTS:
US Variant proportions: https://covid.cdc.gov/covid-data-tracker/#variant-proportions
World Variant proportions (reported every 2 weeks): COVID-19 Data Explorer - Our World in Data
Reference: 8/1/22 BioRxiV: Antigenic characterization of the SARS-CoV-2 Omicron subvariant BA.2.75 https://buff.ly/3wfdXQC
WASTEWATER:
US Wastewater: https://covid.cdc.gov/covid-data-tracker/#wastewater-surveillance
Bay Area Wastewater: https://soe-wbe-pilot.wl.r.appspot.com/charts
(“Silicon Valley” = San Mateo area)
8/19/22 The Hill: White House: Updated boosters for adults, teens expected in a few weeks https://buff.ly/3QUsf0N
New bivalent vaccine (original virus mRNA + BA.5 mRNA) should be available in early to mid-September per Dr. Ashish Jha.
Every American over the age of 12 will be eligible.
8/18/22 NY Times: The Abysmal Covid Vaccination Rate for Toddlers Speaks Volumes https://buff.ly/3AGEMA1
Only 5% of eligible children under 5 have received the first dose of the vaccine series.
Only 30% of those ages 5 to 11 are fully vaccinated and those vaccines have been available since fall 2021.
Several European countries are not recommending vaccination against Covid in young children because they believe they are not at high enough risk of disease.
Although most young children will not get very sick with COVID, some will get severe disease, MIS-C or Long COVID and they can transmit COVID to other family members who may get very sick.
8/18/22 JAMA: Awareness of SARS-CoV-2 Omicron Variant Infection Among Adults With Recent COVID-19 Seropositivity https://buff.ly/3c6uGyO
N = 210, Los Angeles
Over half of people positive for COVID-19 (56%) during Omicron surge were unaware of infection in this study.
Only 10% of those infected had experienced symptoms, which they believed to be a common cold or another type of infection.
This makes sense because in the past we knew that 40% of people were asymptomatic with COVID infections.
8/17/22 Lancet: Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: an analysis of 2-year retrospective cohort studies including 1,284,437 COVID patients https://buff.ly/3c0vhls
2-year retrospective cohort studies of people with COVID-19:
Increased incidence of mood and anxiety disorders was transient, with similar frequency as with other respiratory infections.
In contrast, the increased risk of psychotic disorder, cognitive deficit, dementia, and epilepsy or seizures persisted throughout.
Neurological and psychiatric outcomes were similar during Delta and Omicron waves.
8/17/22 FT referring to the above study: Covid significantly increases the risk of developing dementia, psychosis and brain fog 2 years after infection. https://buff.ly/3AuON35
EMR records of 1.25 million people who had COVID compared to 1.25 million controls.
Age 65+: Dementia (4.5% vs 3.3%), Psychosis (0.85% vs 0.6%)
Age 18 to 65: Brain fog (6.4% vs. 5.5%)
Children (under 18):
Seizures (2.6% vs. 1.3%)
Psychosis (rare): was noted to be 3x higher in kids who had COVID.
8/17/22 WSJ: What, Exactly, Is ‘Paxlovid Mouth,’ and How Do You Get Rid of It? https://buff.ly/3QxHdKF
Paxlovid mouth happens in 5.6% of people and is a bad taste that can linger for as long as you take the drug. The foul taste has been described as sun-baked trash-bag liquid, a mouthful of dirty pennies and rotten soymilk.
Drinking chocolate milk or eating a spoonful of peanut butter to coat the mouth before taking each dose can help. Cinnamon gum is also effective.
8/17/22 NEJM: Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19 https://buff.ly/3SXqOk2
In this double blind placebo-controlled clinical trial of Metformin, Ivermectin, and Fluvoxamine for early outpatient treatment of SARS-CoV-2 infection, none of the three drugs had a significant effect on the composite primary end point of hypoxemia, emergency department visit, hospitalization, or death.
A possible benefit for the prevention of the more severe components of the primary end point (emergency department visit, hospitalization, or death) was shown for Metformin,
However, this finding was a prespecified secondary end point and thus cannot be considered to be definitive pending the results of other trials.
8/17/22 CNN: CDC announces sweeping reorganization, aimed at changing the agency's culture and restoring public trust https://buff.ly/3QsbBpA
"My goal is a new, public health action-oriented culture at CDC that emphasizes accountability, collaboration, communication, and timeliness." Dr. Walensky
The hope is to also make funding urgent issues more flexible and share public health info more readily.
8/16/22 Science: Blood abnormalities found in people with Long Covid https://buff.ly/3JZ1w0O
Review of study from last week from Mount Sinai and Yale implicates Long COVID causes low cortisol, battle-weary immune cells (exhausted T cells), and reawakened viruses (EBV, VZV).
To Putrino’s surprise, “It was quite challenging to find people who were fully recovered from COVID.” Many post–COVID-19 volunteers described themselves as healthy but then admitted, for example, that their once-normal gym workouts were too exhausting to resume.
Preprint from last week: Distinguishing features of Long COVID identified through immune profiling https://buff.ly/3zKYAAp
20 to 30% of LC patients in the study had “exhausted” T cells that can be recognized by certain markers they express.
Such cells surge in the ongoing presence of pathogens—suggesting “the bodies of people with Long Covid are actively fighting something,” Putrino says.
8/18/22 NPR: What's behind the FDA's controversial strategy for evaluating new COVID boosters https://buff.ly/3QBa8gS
For the first time, the FDA will base its decision whether to authorize new boosters on studies involving mice instead of humans.
The new bivalent booster will contain mRNA for the original virus and for the BA.4/BA.5 Omicron subvariants.
Some scientists say we know enough about the mRNA vaccines to start treating them more like flu shots that change each year to match circulating strains.
8/16/22 Tweet thread by Megan Ranney MD MPH on which fall booster may be better
UK Moderna booster = original virus + BA.1 mRNA
US Pfizer booster = original virus + BA.4/5 mRNA
UK just approved the Moderna bivalent vaccine (original virus mRNA + Omicron BA.1 mRNA) https://buff.ly/3Ppcrlx
BA1 bivalent vaccine MAY increase antibodies against BA4/5 (the most common strains today) but by a lower amount (by 3x) than it increases BA1 antibodies.
In the US, we're betting on a Pfizer booster specific to the currently dominant strains of Omicron (BA4/BA5) rather than to BA1.
Preliminary (animal & human) data suggests that the US was right in taking this bet: we're seeing higher titers of antibodies against both old and new variants with this strategy. https://buff.ly/3QLfcPp
8/16/22 Cell: Multiple BCG vaccinations for prevention of COVID-19 and other infections in Type 1 diabetes https://buff.ly/3QnH8ch
BCG (Bacillus Calmette-Guerin) tuberculosis vaccine may guard against COVID and other infections by broadly bolstering the immune system.
A small (n = 144) randomized, placebo controlled trial in unvaccinated adults with Type 1 diabetes showed that BCG was protective against COVID infection.
BCG was 92% effective in this population (1% of BCG patients versus 12.5% of placebo patients got COVID.)
Those who got COVID in the BCG treated group had less severe symptoms.
Findings also suggest BCG protection against additional infectious diseases.
Efficacy takes 1-2 years to manifest, but the protection may last decades.
8/16/22 JAMA (Switzerland): Risk of SARS-CoV-2 Acquisition in Health Care Workers (HCW) According to Cumulative Patient Exposure and Preferred Mask Type https://buff.ly/3SNLICa
HCWs using respirator masks only (FFP4 or N95/KN95 types) were 40% less likely to get COVID than those who used only surgical or both mask types.
8/16/22 CDC: Rapid Increase in Suspected SARS-CoV-2 Reinfections, Clark County, Nevada https://buff.ly/3w9nqZT
SARS-CoV-2 reinfections were uncommon (2.7%) before Dec. 2021 in Clark County.
After Omicron and its subvariants arrived, COVID reinfections increased to about 11% of infections, especially in certain demographic groups.
8/15/22 Some Light on Long Covid by Eric Topol MD https://buff.ly/3vXdGlm
Review of last week's many articles on Long COVID prevalence, mechanisms and biomarkers, and potential treatments.
8/14/22 Tweet thread by Eric Topol MD re: the next variant.
Will it be BA.4.6 or BA.2.75?
While BA.2.75 is becoming dominant in India and is out-competing BA.5, we're now seeing signs it can also compete with BA.4.6 in Australia.
BA.4.6 (Aeterna):
Spike mutation R346T may be key
BA.4.6: More immune evasion than BA.5, some cross-immunity w/ BA.5 breakthrough infections, not resistant to Bebtelovimab, but Evusheld may not protect as well.
BA.2.75 (Centaurus):
Spike: 9 amino acid residues differ from BA.2
BA.2.75 has less immune evasion than BA.5 in 2 reports https://buff.ly/3QzO3PF and https://buff.ly/3QKPavy
Similar pathogenicity as BA.5 in experimental model: https://buff.ly/3dmbMUU
Unlike BA.4.6, BA.2.75 is more evasive to BA.5 breakthrough infections
Growth advantage tied to enhanced ACE2 binding
Bebtelovimab and Evusheld predicted to still be effective
No significant increase in hospitalizations in India.
Summary: It looks like we'd be better off with BA.4.6 with its homology to BA.5 and a BA.5 booster in the works.
Mike Honey: @Mike_Honey_
For Australia (16 July to 2 Aug), BA.2.75 "Centaurus" is showing a growth advantage of 11% per day against B.4.6 "Aeterna", with a recent crossover to dominance.