COVID-19 Weekly Briefing for Monday, February 21, 2022.
COVID-19 (C19) Weekly Briefing for 2/21/22, in Summary:
Vaccine update including data on fourth shots and new mRNA preparations tuned to Omicron and Delta; the relative protectiveness of prior infections; update on protection from hybrid immunity (infection plus vaccination); vaccination during pregnancy is safe and effective; common infectious diseases are down due to pandemic mitigation measures (like masking); the US passes 1M excess deaths since the pandemic began; what are the odds of infection from attending a party?; was there a ‘long influenza’ which followed the Spanish Flu pandemic of 1918?; and perhaps a cure for HIV disease.
1452 - 1456 The real-world efficacy of a fourth dose of mRNA vaccine against Omicron infection is not fully understood yet but new data suggest that while a fourth shot does restore antibody levels to those seen shortly after the third shot, it does not offer significant protection against infection (30% for Pfizer, 11% for Moderna). Critically, those with breakthrough infections had high viral titers, indicating a high potential for transmissibility even among fully vaccinated people.
How about the new Omicron-specific vaccines? Both Pfizer and Moderna are now testing their new mRNA vaccines tuned to the Omicron spike protein. Early data show the new vaccines are not providing significantly better protection compared to the original vaccines when used as a booster.
In this small study on macaques, neutralizing antibodies, expansion of memory B-cells, and protection against infection vs. Omicron were comparable between the original and new Omicron-specific vaccines when each was used as a third (booster) shot.
The size of the dose counts
In mice, Omicron-specific mRNA vaccination was protective against Omicron but significantly less so against other (prior) variants.
It was more protective when compared to a low dose 2-shot regimen of the original vaccine but not when compared against 2 shots using a high dose. We saw a similar distribution of outcomes when comparing the (low dose) Pfizer vaccine against the (high dose) Moderna one with Moderna inducing higher antibody titers and more durable protection against infections.
Overall, when used as a booster, Omicron-tuned vaccine provided slightly better antibody response and marginally better protection against Omicron compared to boosting with the original vaccine.
Omicron, Delta, mixed, and hybrid vaccines
Also, in mice, a hybrid vaccine that targets all the spike mutations found on both Omicron and Delta was protective against Omicron but not Delta or any other prior variant. But a bivalent vaccine consisting of a half dose of the Omicron-tuned vaccine plus a half-dose of the Delta-tuned vaccine elicited protection against Omicron and all other variants, as did the Delta-tuned vaccine alone, given as a full-dose.
1457. A 2-shot vaccination regimen in pregnant women protects newborns from C19: completion of 2 shots early in pregnancy = 32% protection; late in pregnancy = 80% protection; overall protection = 61%. My note: does this mean that pregnant women should wait until their third trimester to get vaccinated? I don’t think so…. The risks to mom and fetus are high during pregnancy and getting 2 shots in the first trimester means a third shot will be possible at the end of pregnancy or soon after delivery when, as we know, immunity can continue to be transmitted to the newborn via breast milk.
https://www.cdc.gov/mmwr/volumes/71/wr/mm7107e3.htm?s_cid=mm7107e3_w
Vaccine Update Summary
Fourth shots probably make sense for immunocompromised patients but not for everyone. Providers should feel free to schedule 4th doses at their discretion based on this understanding.
Newly updated mRNA vaccines tuned to new variants will likely not be game-changers. Variant-specific vaccines do not seem like the right strategy to end the pandemic. We should be looking to pan HCOV vaccines going forward.
Immunity from prior C19 infection(s)
1458. The effectiveness of previous infection in preventing reinfection, controlled for vaccination, was estimated to be 90% against Alpha, 85% against Beta, 92% against Delta, and 56% against Omicron:
https://www.nejm.org/doi/full/10.1056/NEJMc2200133
1459. Among 150K patients who had recovered from C19, 83K received subsequent vaccination during the 270-day study period. Reinfection occurred in 354 of the vaccinated patients (2.5 cases per 100K/day) and in 2,168 of 66K unvaccinated patients (10 cases per 100K/day). Vaccine effectiveness was estimated at 82% among patients aged 16 to 64 and 60% among those 65 and older. No significant difference in vaccine effectiveness was found after two doses compared to one dose in this convalescent population. My note: Why is a second dose of Pfizer vaccine not more protective than one dose among those with prior infections? It is being given too soon (3 weeks after the first dose). From the standpoint of strategic immunization, we should treat an infection the same way we do a single shot of mRNA vaccine. That is, we should give the first vaccine dose about 4-6 weeks after infection and the second vaccine dose 4-5 months later (as we currently do with a third shot).
https://www.nejm.org/doi/full/10.1056/NEJMoa2119497
1460. In a high-powered study from Israel, rates of infectious respiratory and GI diseases went way up after C19 mitigation measures were lifted. We can probably expect the same here with more people getting colds, flu, and other infections.
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2788557
1461 - 1462. There have been more than 1M excess deaths in the US during the pandemic according to the CDC, of which > 900K were attributed to C19.
https://covid.cdc.gov/covid-data-tracker/#trends_totaldeaths
Here is a look at excess deaths, state by state:
Keep in mind that California has a population of a little over 40M while Texas has about 30M and Florida about 22M. Excess deaths in those latter states are occurring at a much higher rate, undoubtedly reflecting lower compliance with anti-pendemic risk mitigation measures. Additionally, Florida has the highest percentage of winter time residents who do not claim the state as their primary residence and, per their Governor, does not include the deaths of those without primary residency in Florida among their C19 mortality or excess mortality data.
1463. The Great Bob Wachter, head of UCSF Department of Medicine, pens an amazing piece for the Washington Post in which he explains his own process for calculating the risks and odds of C19 associated with attending a party, unmasked, in Florida, while also visiting his mother (in her 80’s). Why is it amazing? One of the smartest and most trustworthy people in medicine begins his calculation with the following:
“Odds that someone at the party was infected: about 1 in 50. This was a back-of-the-envelope calculation that began with Florida’s test-positivity rate, 17 percent, which I adjusted downward because the guests were mostly asymptomatic vaccinated professionals from blue states who had undergone rapid tests that day.”
Ahem. First of all, as we know, 17% is an extremely high positivity rate. It means that nearly one in 5 PCR tests being performed in Florida are coming back positive. We also know that the testing window has shifted to the right so many people who are getting tested on days 1 or 2 of symptoms or shortly after exposure before onset of symptoms, are having false negative results.
Secondly, he states that his personal comfort level with attending a party unmasked would start when the case rate was about 1-2/100K. But the party he attended was in Miami which had, at that time, the highest case rate in the state (52/100K). We also know that comparatively few people are pursuing PCR testing–positive results from which constitute the sole source of Florida’s published daily case numbers. A conservative estimate of the real case rate is at least four times that high, making the adjusted case rate closer to > 200/100K (or about 100 x riskier than Dr. Wachter’s stated comfort level).
Thankfully, he brings up long-covid (LC) as a reasonable concern. But estimates his odds of LC at 5% and links to an article from nature which in turn links to a paper from the UK that estimates the rate of LC at 7-18%. Leaving aside that this is the lowest estimate I have seen of the rate of progression to LC, 7-18% is nevertheless significantly higher than the 5% figure he uses.
He points out that “The host asked his guests to be vaccinated and boosted and to take a rapid test immediately beforehand. My assumption was that most did, raising the level of safety.” Really? That seems rather like wishful thinking to me when attending a party full of people one has not seen in decades. There appears to have been no verification whatsoever of either the guests’ vaccination status’ or RAT results. Is it reasonable to estimate high compliance in today’s America? In Florida? I was left wondering, too, how many of those who did perform a home RAT did so correctly (using a combined throat and nose swab) within a few hours of the party?
We should also keep in mind, as reported above, that data are showing high levels of breakthrough infections and high viral titers among vaccinatated people infected with Omicron. Is it reasonable to downgrade the risk of transmission because people were asked to be vaccinated?
Finally, he estimates the odds of contracting C19 from a close conversation with an infected person at 1 in 10. So the odds of transmission from an unmasked, close conversation with someone infected is just 10%? With the Omicron variant estimated to be more infectious than measles? He acknowdedges that this was “hard data to find” but then sites as his source the recent Danish study (1407) included in the 1/31/22 Weekly Briefing which estimated the transmission of Omicron within households at 31%. How he used that study’s data to extraplate the risk of unmasked face-to-face conversations at a party, and arrive at an estimated 10% odds of infection is, to me, quite unfathomable.
In the end, Dr. Wachter’s approach amounts to an intuitive, personal decision, based not on a careful analysis of risk and odds, but on irrational assumptions and data that were either poorly representative, or diminished to create a bias in favor of allowing him to do something that he very much wanted to do–socialize unmasked indoors with old friends.
I understand, of course. I visited my mom, too, just before the Omicron wave. And I was best man at my closest friend’s wedding (15 people, outdoors, all boosted except one youngster) the following weekend. I can accept someone making the choice he made in a country where (tragically) everyone seems to be left having to analyze risk and create personal health strategy for themselves. Dr. Wachter has every right, amidst the chaos of American public health messaging, to be looser with his behavior than I am with mine (although it makes me wince when I think of him doing so while staying with his 86YO mother). What is amazing about the article, to me, is instead the level of self-justification (self-deception?) involved in his calculations. At least one person (that he knows about) “tested positive a few days later, possibly from the gathering.” I’m glad it wasn’t Bob Wachter or his mom. But it could very easily have been…
My take: I like the metric of comfort that he proposed at the outset of his article: A community prevalence of 1-2 cases/100K population = acceptable risk for a special event like a party with old friends that you really want to attend. That’s about where things stood when we decided to hold our office holiday party outdoors, with HEPA units, among approximately 20 people, all of whom had had 3 shots and had tested negative using RATs within a few hours of attending (all of which was verified by Christina).
When case numbers are low, it is reasonable to drop one or two layers of protection for special occasions. But it is also important to understand that statistically, risk and odds change with repeated behavior. At a given community prevalence, there might be a 10% chance of contracting Scov2 infection by attending a gathering among unmasked participants. But those odds go up with the second such event and if risky behavior becomes a weekly or daily occurrence, the likelihood of infection becomes extremely high.
https://www.washingtonpost.com/outlook/2022/02/18/covid-odds-unmasking-indoor-gathering/
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Covid Adjacent
1464 - 1468. In an earlier briefing, I discussed chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and post-polio syndrome as long-term sequelae of viral infections. Epstein-Barr virus (EBV) and poliovirus are both known to produce chronic post-infectious, neurologically-based illnesses among a high percentage of those infected. As reported in an earlier Weekly Briefing (January 24, 2022; 1396-1398), there are now compelling evidence that activation of EBV may trigger MS and we also saw how oligoclonal bands in the CSF of patients with MS look remarkably similar to those seen in patients with long-covid (LC).
Here, we learn that the ‘Spanish flu’ pandemic of 1918 may very well have resulted in a post-viral illness with some neurological features that overlapped with LC. Referred to as ‘encephalitis lethargica (EL)’ or ‘sleepy sickness,’ chronic fatigue as well as CNS symptoms which amounted to a Parkinson’s-like syndrome were noted among many thousands of patients previously infected with Spanish flu or its descendants along the H1N1 lineage of influenza over the next decade to create a ‘parallel epidemic.’
Was EL a kind of ‘long influenza’? Do novel viruses routinely trigger autoimmune processes or infect the CNS (and other organ tissues) to cause chronic or delayed-onset illnesses that feature fatigue or somnolence as one of the chief symptoms? The neurological tails of subsequent flu pandemics, in 1957 and 1968, were also followed by rises in cases of encephalitis and chronic neurologically-based illness. And it has been established that viruses such as influenza can infect the brain. It is common, after every flu season, to see increases in the rates of strokes and heart attacks. Flu can cause encephalitis in children too (albeit rarely) and those who survive can be left with long-term brain injury.
Polio, Mono, and Flu are not the only infectious diseases with long-term effects. Chronic illness following measles and hepatitis are well documented—including progressive neurological disorders like subacute sclerosing panencephalitis and chronic liver disease, respectively. Lyme Disease routinely gives way to CFS/ME. And the long-term or delayed-onset sequellae of new diseases like C19 will likely take time to sort out. It took decades for researchers to demonstrate that EBV is a trigger for MS. This is the chief case against excluding LC and the likely possibility of delayed-onset health problems from pandemic strategy which has shifted almost completely away from prevention of infections.
Non Covid
1469. The third person to be cured of HIV disease makes the news. A mixed race woman was treated using a transplant with umbilical cord blood. She stopped antiretroviral therapy 37 months after the transplant and, more than 14 months later, still shows no signs of HIV on blood tests. Two other people have been cleared of HIV after receiving bone-marrow transplant. Transplanting cord blood, instead of bone marrow, allowed doctors to use a partially matched donor while giving her immune system a boost with blood from a close relative. This approach could offer the promise of treatment to more HIV-positive people, regardless of their race or ethnicity. Wow.