Are We Listening To Nature?
What is the intersection of sea lions and chickens telling us?
Recognizing that most folks have a limited attention span and bandwidth for all things COVID, I’m going to quickly touch on a few points that should still be of interest. Last week I opined on my personal recommendations for further boosters, and now the Washington Post is quoting anonymous FDA officials as stating that the FDA will authorize another round of bivalent boosters for people over 65, and those of younger age with significant immune compromise—if it has been at least 4 months since their last booster, OR COVID infection. Nice to see the acknowledgement of the virtual equivalence of natural immunity and booster vaccination in the Omicron era finally work its way into FDA calculus. The CDC will supposedly quickly follow suit in the next few weeks. 46% of people over age 65 took the fall bivalent booster, but with pandemic amnesia rapidly becoming the norm, I think it’s anybody’s guess what sort of demand there will be beyond the immune-compromised.
In January the CDC reported that there was a signal from the Vaccine Safety Datalink system of a possible increase in ischemic stroke in people over age 65 within 21 days of taking the Pfizer bivalent booster. This increased risk signal was not seen in multiple other vaccine monitoring programs in the US or in Europe. I doubt that this had much if any impact on the booster uptake, since the vast majority of individuals who planned on taking it had long ago done so. Now in a Letter to the Editor of the March 29th, NEJM, a group from France is reporting on a head to head safety comparison of the original Wuhan RNA booster and the bivalent BA.4/.5. (Both were available at the same time for a period in France). There was no difference in the observed rates of stroke, myocardial infarction, or pulmonary embolism in this extremely large cohort.
Stroke, Myocardial Infarction, and Pulmonary Embolism After Bivalent COVID Booster. DOI: 10.1056/NEJMc2302134
The bivalent boosters are as safe as the original RNA vaccine formulation. Whether they worked any better is open to discussion, and of more than academic interest; since the information gained may help inform COVID vaccination strategies going forward. In early 2022, David Ho’s group in New York was one of the first to publish data comparing neutralizing antibody (NAB) titers from the mono and bivalent boosters against BA.4/.5 and earlier Omicron lineage viruses. They found no significant differences, but only a trend toward mildly higher NABs from the bivalent. Other scientists, using live virus assays, subsequently found somewhat better results for the bivalent boosters. We know that the immune response matures over time, even up to six months. David Ho’s group has now compared the NAB responses of people boosted with the two types of vaccine 3 months after vaccination, and also compared them to a group with BA.5 breakthrough infection after primary vaccination. As expected, in both mono and bivalent booster groups, there was a decrease in NABs by 50% two months after peak levels, and no significant difference between the two groups with respect to any of the Omicron viruses tested. The group with BA.5 breakthrough infection did have significantly higher NABs compared to both booster groups and no significant drop in NABs over 3 months. Did both booster shot’s inclusion of RNA from the now extinct Wuhan virus lead to further imprinting of the immune system, and a less vigorous and more rapidly waning response than natural infection? I suspect so. It’s a short paper referenced below if you want to have a look at responses to the now virtually extinct early Omicron crew, and the more recent COVID flavors like BQ.1.1 and XBB.1.5. which they also tested this time.
SARS-CoV-2 neutralising antibodies after bivalent versus monovalent booster
Qian Wang, et al.
Published:March 29, 2023DOI:https://doi.org/10.1016/S1473-3099(23)00181-0
This is the last COVID item, if I may interrupt your yawning. Therapeutics for severe COVID have been extremely limited. The demise of the monoclonal antibody treatments was a major set back, molnupiravir was a very marginal drug at best, and Paxlovid remains severely under-utilized mainly due to multiple drug interactions. The anti-virals predictably had little effect on the disease once it had progressed to the stage of advanced respiratory failure and the need for mechanical ventilation. Early on in the Pandemic, immune suppressive treatments like steroids and Interleukin 6 inhibitors proved of value, but mortality remains high for these patients. This week the FDA approved a new drug vilobelimab, a monoclonal antibody blocking a critical step in the complement inflammatory cascade. (C5a inhibitor and receptor blocker). The data from a trial treating the sickest of the sick COVID patients on ventilators or ECMO (extra corporeal oxygenation) showed a significant reduction in mortality when this new drug was added on to current treatments. The probability of death for people in this state remains high, in the 30% range, even with the vilobelimab, but it is an incremental improvement.
Somewhere off on the horizon is a very dark cloud called Highly Pathogenic Influenza A H5N1, which is on a killing spree of incredible magnitude, of creatures both feathered and hairy. We should be focused this virus as it experiments with an ever widening circle of mammals, but so far only an occasional human. Currently the WHO considers H5N1 of only moderate concern, since it has not demonstrated the ability to spread from human to human, or even convincingly within other mammalian species. Back on February 10th, I discussed the episode in Spain, where it certainly seemed at least plausible that this Avian Influenza had spread rapidly through a mink farm with mink-to-mink transmission. A group of environmental scientists from Peru has now reported a massive sea lion mortality event on their southern coast with over 3000 animals dead. The sea lions had veterinary evidence of both pulmonary and neurological disease. Necropsies of selected animals showed evidence of both upper airway infection and pneumonia, as well as focal brain inflammation consistent with encephalitis. The death events were spread over a fairly large area of the coast, but on one island over 1000 dead animals were counted. An unclear number of animals were tested and were positive for H5N1. Two possible explanations exist. The sea lions may have all individually contracted the virus from infected seabirds that they live in proximity to, or the virus may be spreading among the mammals. Given the number of sea lions involved and the prior suspicious mink event, I would say the safest approach is to assume the worst, and proceed from there with an increase in surveillance and experimentation to try and answer key questions. H5N1 is passing through gigantic numbers of avians and now mammals, and with every replication it is fine tuning its potential to cause airborne infection of humans. If the WHO is waiting for the virus to demonstrate that it can cause contagion from human-to-human before considering this a more dangerous pathogen, then we just might find ourselves holding a bag with no cat, and a barn with a dead horse.
Mass Mortality of Marine Mammals Associated to Highly Pathogenic Influenza Virus H5N1 in South America (Images from this preprint)
https://www.biorxiv.org/content/10.1101/2023.02.08.527769v2.full.pd
Beyond stating the obvious fact that we seem to have learned surprisingly little when it comes to societal response from the COVID Pandemic—are there any concrete steps that seem logical and might even be possible? For starters I think we should be very concerned to answer the question of whether this current zoodemic version of H5N1 has already acquired the ability to spread between mammals—and if so, then by what mechanism. Experiments to answer this should be ongoing now. This is not gain of function research, but rather simply taking a natural virus which is running rampant all over the globe and subjecting it to some well designed animal experiments. As to the risk of exposing laboratory personnel, luckily the virus is not very contagious to humans YET; and millions of people are exposed to it on a daily basis with little or no protection.
One last thing about H5N1. I am going completely outside any realm of expertise here, and would be happy to have anyone with knowledge in this area instruct me. It strikes me as odd that when H5N1 is discovered in any poultry farm, whether it’s a backyard coup or a gigantic industrial operation with half a million birds, that the government comes in and kills every bird in the house. We are talking about over 50 million culled poultry in the US alone. I certainly understand that it is critical to prevent the spread of disease to birds not yet affected. But it stands to reason that the virus will not have 100% mortality, and the chickens who survive will be selected to have some significant natural immunity. Would it not be possible, at least in some instances, to quarantine the infected flock? Are we not interfering on a massive scale with the evolutionary ability of domestic birds to develop resistance to the virus, and thus insuring that strains of domestic fowl remain forever susceptible? Humans interfering with nature, that’s a real stretch!
I’m expecting a lot of likes this week from chickens and ducks—maybe some hate mail from veterinarians and animal husbandry experts. Enjoy the extended weekend and celebrate with your friends and family. Try and pass “Clear and Present Thinking” to at least one new friend or associate. As a side endeavor I am collecting lists of forbidden words from colleges and corporations around the country, with the goal of publishing at least one chapter here using only these words.