Hubris in the Face of Catastrophe

Who is watching the hen house? ‘

As hard as this may be to believe, we learned this week that virologists at Boston University created an enhanced COVID virus. They apparently wanted to demonstrate that there are determinants of how pathogenic (lethal) the virus is which reside outside the Spike protein. I thought this was already fairly well understood and accepted. The original Wuhan virus was very lethal (100%) for chimeric mice with a human ACE2 receptor. Omicron is far more contagious due to mutations in its Spike, which allow it latch onto cells more avidly, and to avoid prior immunity to Wuhan vaccine or infection—but it is famously much less lethal. These scientists took the original Wuhan virus, deleted its Spike, and grafted onto it the Omicron Spike; and voila, they created a hybrid virus that retains the infectivity and immune escape of Omicron, but has nearly the lethality of Wuhan, killing 80% of infected mice. Essentially they created an Omicron virus that is capable of massively replicating in lung cells, an ability the natural Omicron lacks. That they would dare to do this in the first place is bad enough, but they apparently did it without the specific permission or knowledge of the NIAID/NIH who supplied the grant funds. In damage control mode, a spokesman for BU issued a statement that this is not gain of function research, and that the virus they created was less lethal than original Wuhan. Talk about a “Post Truth World”. This is a chimeric hybrid virus. While they are saying “calm down this Wuhan version we made is 20% less lethal”—they are of course avoiding the other side of the coin; which is that they took a virus far more lethal than Omicron and gave it the ability to spread at the Omicron level. BU appears to be hoping for a co-operative media, and a gullible public, without the scientific background necessary to identify the obvious lie. A spokesperson for NIAID/NIH issued a statement that there will be “serious discussions” with the researchers. Here is a quote from the NIH press release (see Helen Bramswell’s piece in STAT). Boston University researchers’ testing of lab-made version of Covid virus draws government scrutiny

Erbelding (NIH spokesperson) said, had NIAID known of the BU group’s plans to develop a chimeric virus, it probably would have conducted its own review to see if the matter should be referred to the HHS committee.

“What we would have wanted to do is to talk about exactly what they planned to do in advance, and if it met what the P3CO framework defines as enhanced pathogen of pandemic potential, ePPP, we could have put a package forward for review by the committee that’s convened by HHS, the office of the assistant secretary for preparedness and response. That’s what the framework lays out and that’s what we would have done,” she said.

So far I haven’t seen much of anything from the scientific community (outside BU) rushing to defend this work—beyond the predictable, “Rest assured that we are always very careful”. My prediction is the NIH will quickly realize that they can’t allow the perception that rogue scientists are using government money to conduct dangerous research under the radar and beyond NIH control, so they may change the tone of their initial messaging. Of course all reasonable, intelligent, non-racist people accept that something like this could never have happened in a Chinese lab concentrating in Corona virus research—a lab with a lower safety level rating than the lab at BU. Here is the link to the BU preprint by M. Saeed et al.

Role of spike in the pathogenic and antigenic behavior of SARS-CoV-2 BA.1 Omicron https://doi.org/10.1101/2022.10.13.512134;

Now that we have had a view of human directed Corona virus manipulation, we are going to look at the natural course of viral evolution. There is an explosion of new Omicron lineage mutants that have surfaced around the world in the last month or so. Their appearance was covered in several media reports last week; but I think they deserve a closer look, and an attempt at clearer explanation, because there is a good chance that some of them will quickly dominate the next stage of the Pandemic. COVID has accelerated its evolution into a web of variants, rapidly diverging from the BA.4/.5 strain and other Omicrons. Although they are diverging and quickly becoming distinct across the entire genome, when it comes to the the critical area of the Spike protein, which grabs hold of the humane ACE2 receptor, these variants are zeroing in on a number of critical mutations which allow them to evade the antibodies from vaccination or prior infection. This is referred to as “convergent evolution”. Earlier variants like Alpha, Beta, Gamma, and Delta hit on a few of these mutations in the RBD (receptor binding domain), but the current crop of new COVID strains are concentrating more of these mutations in unique combinations, and pushing the boundaries of antibody escape to new levels. This is the direct result of immune pressure placed upon the virus by the antibody landscape created through prior vaccination and Omicron infections. It’s both fascinating, and unnerving to watch. This likely has happened in the past, when totally novel viral pathogens initially invaded the human population—we just never had the scientific tools necessary on such a massive scale to watch it unfold in real time.

Several of these Omicron variants have suddenly expanded rapidly as a percentage of total COVID sequences around the world. Their designated names are more mind numbing alpha-numeric code. Last week the CDC began to break several of them out separately from the dominant BA.5 in their NowCast data. The significant variants in the US are BQ.1 and BQ.1.1. These new variants’ rate of doubling is extremely fast, and implies a very significant growth advantage over BA.5, which is beginning to slip in predominance. Within a month they grew from 1% of US sequences to over 10% nationally, and over 20% in certain areas like New York City. Another of the most concerning variants is XBB. This virus is showing up around the globe and has suddenly taken over as the dominant strain in Singapore, which boasts a 92% complete vaccination rate. Coincident with the arrival of XBB, the reinfection rate among new cases jumped from 4% to 17%. At this stage of the pandemic that strongly suggests an impressive ability to circumvent prior immunity, which essentially everyone has. COVID went through an early phase of a becoming more contagious (viral fitness advantage) by developing either a stronger attachment to the ACE2 cellular receptor, or by reaching higher viral densities in the upper airway, thus facilitating its spread. Omicron may have maxed out that avenue, and currently increased viral fitness seems to be determined primarily by immune escape.

A recent preprint out of China looks at the convergent evolution of these new COVID strains. I’m not going to go into great detail about the alphabet soup of variants but will reference the link below. If your virology and scrabble skills are high, have at it—perhaps some of you will be able to explain areas of the research that are above my pay grade. Key findings of their study show that breakthrough BA.2 or BA.5 Omicron infections, in previously vaccinated or infected people, primarily drive the memory B cell production of cross-reactive antibodies to BA.5. These are antibodies that were previously initiated by the original Wuhan vaccine (or infection). If you are wondering how original Wuhan vaccine would be creating antibodies that recognize BA.5, the answer is a phenomena known as “immune maturation”. Our immune systems initially produce antibodies specific to the antigen introduced, but over time the antibodies are tinkered with, varied, and expanded to recognize similar but different shapes. The breath of NEW antibodies created by the breakthrough Omicron infections are apparently limited, and many of them are non-neutralizing antibodies. That suggests to me that boosting with the new bivalent vaccine may have very limited advantage over boosting with the original Wuhan vaccine. Then again if people at risk of serious disease don’t take the new boosters, there will be exactly zero gain in immunity.

https://doi.org/10.1101/2022.09.15.507787 Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution. Yunlong Cao, et al.

This same paper shows that the new and improved Omicrons are demonstrating very high levels of escape from the antibodies found in people with prior history of vaccination, or with histories of vaccination followed by an Omicron breakthrough infection. The most immune evasive of all is XBB, which is barely inhibited by serum from people with even hybrid immunity. BQ.1 and BQ.1.1 are also in this group of elite antibody escape artists. We need to accept that the “whack a mole” approach to variant vaccine boosters may come up short, not just because of prior immune imprinting, but due to the arrival of brand new variants even before the bivalent boosters are widely taken. Myself and many others predicted this, and if it turns out to be the case, it will represent a terrible miscalculation and waste of resources. A great deal depends on the outcome as the government, with their partners Pfizer and Moderna, are clearly planning a course to yearly “updated” RNA boosters.

We may not be destined to vaccinate our way out of the Pandemic, and it’s clear that COVID is not close to being through with us. For a solid discussion of how the government has failed to learn important lessons, and implement critical changes that could improve our response to both the latter half of this episode, and the next Pandemic, I recommend an article in the NYT by Emanuel Ezekiel et al, This is an excellent review of many ways we can bolster our preparedness.

We Advised Biden on the Pandemic. Much Work Remains to Face the Next Crisis. https://www.nytimes.com/2022/10/19/opinion/covid-pandemic-failures.html?smid=nytcore-ios-share&referringSource=articleShare

Thanks for getting through the viral evolution information today; my editor thinks it is a bit dry, tedious and depressing, but then again I don’t pay her, so what can I reasonably expect. I appreciate all the referrals of this page to your friends and colleagues.