COVID Vigilance

How Public Health messaging should prepare for potholes

In my last post I mentioned that it would take a significant pothole to derail our communal trip down the COVID exit ramp. Now that mitigation strategies are being abandoned around the country and vaccinations have stalled, I would say that the virus is largely in charge of what happens next. Yes, sooner or later we will have more ready access to oral therapeutics which should make the disease less disruptive, but the virus has shocked us numerous times over the past two years and there is no reason to think it won’t again. For an excellent detailed, lay level discussion of some of the possible mutational changes in SARS-Cov2 which could have very significant effects on the trajectory of the pandemic I would recommend reading William Hazeltine’s recent article in Forbes, https://www.forbes.com/sites/williamhaseltine/2022/02/17/do-not-underestimate-the-consequences-of-sars-cov-2-escape-the-omicron-example/?sh=331423ad3e1e

Hazeltine is one of our senior virologists, biotech innovators and respected scientists. He was someone who cautioned against the consensus among many virologists at the start of the pandemic that the SARS-Cov2 was an RNA virus with a proofreading system and would not be expected to mutate quickly. I won’t attempt to summarize his arguments here, but just say they are a realistic and sobering look at possible bad outcomes that should be considered and planned for. Back in the early days of the HIV pandemic I frequently thought what a position we would be facing if that virus just happened to be a respiratory pathogen with its then 100% mortality. When you look at other well known Corona viruses like MERS and SARS1, with much higher lethality but lesser transmissibility, and then reflect on how dramatically and rapidly this current virus has changed it’s infectiousness, antibody escape potential, mechanism of cellular entry and disease severity, you have to be concerned. “We didn’t see Alpha, Delta or Omicron coming”, doesn’t sound like a sentence we want to eventually include Pi.

A preprint out this week from Yamasoba et al. in Japan provides some further information on the BA.2 variant of Omicron, which if you have been reading these posts you will recognize as one of the potential potholes on the off ramp. Several media outlets have presented a somewhat grim interpretation of these findings which seem a bit out of proportion. The Japanese scientist’s epidemiological models, with input data from countries where BA.2 has risen rapidly, show it is about 1.4 times as transmissible as Omicron. No surprises there. Animal and cellular experiments they report on show an increased ability to enter human cells and increased toxicity for both human cells and hamsters, with increased lung toxicity in the animals. What I find most interesting is that BA.2’s sensitivity to neutralization by antibodies from people with prior Omicron infection is only about 2 fold less. Considering the significant mutational distance between the two that is a lucky break, and is not likely to be very significant clinically or on a population level. One the biggest potential risks now is the emergence of a variant with a high level of ability to evade pre-existing vaccine or Omicron immunity, and right now data is suggesting it won’t be BA.2. An enormous percentage of the world’s population, both vaccinated and unvaccinated, is going to be infected by Omicron before it has run out of steam, and it’s good to see data suggesting that most of those people are, at least temporarily, immune from reinfection with BA.2. Bill Gates, who I suppose qualifies as a vaccine supporter since he has donated hundreds of millions to that effort, recently observed that Omicron has been much more efficient in delivering COVID immunity to the third world than we have. Since Omicron is spreading rapidly in India and other countries which don’t have high levels of vaccine uptake, how come we are not seeing images of vast fields of funeral pyres? The likely answer has nothing to do with this variant being marginally less lethal, rather it is that most people in the world have already been infected with an earlier version of SARS2, and have some long lasting protection from severe disease, just like vaccinated people. On the issue of Omicron immunity, there is some experimental evidence that the protection generated is rather narrowly directed at Omicron, and may not be as broadly protective against some of the other variants. That would translate into a recommendation that if someone had Omicron, without prior infection with an earlier variant or vaccination, then a dose of vaccine now would be a good idea. As far as experimental data suggesting it might be more severe in hamsters, I’m glad nobody issued me a wheel at birth. Beyond that lucky break, I think by now we would have strong indications from places like Denmark, where BA.2 is dominant, of coffin shortages if this virus was importantly more severe.

So is the current rush around the country to remove non-pharmacological mitigation orders misguided, when I’m making the case for the serious need to anticipate the possibility of new and enhanced COVID variants? It may be a bit premature in some locals where Omicron arrived later and disease transmission is still very high, especially if their hospitals are near capacity. But overall I feel this is a wise move for several reasons. Pandemic fatigue is a real phenomena which can’t be ignored. The vast majority of people have decided they are taking off their masks and congregating, with or without the permission of Public Health authorities and government. The Super Bowl images of thousands of unmasked attendees when LA. County still had a mask mandate in effect sent a very clear message. If the populace sees very low disease levels and Public Health authorities do not make appropriate reductions in mitigation orders that will only exacerbate the level of mistrust and disdain. I have no idea whether this is the true slow end of the pandemic morphing into a seasonal endemic virus, or whether COVID has more surprises in store. Either way, it is important that Public Health and government use this opportunity to enhance their credibility by responding adroitly to both the rapid change in disease levels and public acceptance of restrictions. It does seem like a very good time to blare out the following message. “We are doing much better right now. Take off your masks if you feel comfortable, and have fun with your friends and family. Thanks to all of you who helped to keep everyone safer. We all know things can change and we are keeping a close eye on the virus. If it rears it’s ugly head again we will let you know to start doing all the things, like masks and social distancing, which we know beyond a shadow of a doubt, have helped to save many lives.”