Welcome to Science with Shrike! Today we’re going to continue discussing recent updates with COVID and the Inspector General’s report on funding for the Wuhan Institute of Virology. There will be multiple interpretations going around because this is academic politics at the highest levels.
Summary of NIH Funding to EcoHealth/WIV
The Wuhan Institute of Virology (WIV) was funded via the USAID program and indirectly by the NIH through EcoHealth. The “indirect funding” was via a subaward. In a subaward, the organization funded by the NIH subcontracts a specific part of the work to another organization. The subcontract information is included at the time of the grant, along with details on who is going to do the work, budget and the agreement between both organizations should the award be funded.
These projects aimed to identify new coronaviruses that could jump into humans from animals. It is unclear if gain of function research was 1) performed at WIV and 2) money from the NIH used for that research. If you’re curious about the challenges in teasing that apart, Shrike previously covered that.
Science has an overview of the Inspector General’s report, and more on the backstory.
In 2020, the NIH grant to EcoHealth, which included WIV as a subaward, was terminated. After termination, there was a large outcry, and the grant was reinstated, and then suspended again. NIH set some interesting conditions on reinstating the grant, including (bullet points quote Science, emphasis mine):
"‘The EcoHealth Alliance must provide a sample of the pandemic coronavirus that WIV used to determine its genetic sequence.
The group must arrange for an outside inspection of WIV and its records "with specific attention to addressing the question of whether WIV staff had SARS-CoV-2 in their possession prior to December 2019," Lauer wrote.
The nonprofit must explain purported restrictions at WIV including "diminished cell-phone traffic in October 2019, and the evidence that there may have been roadblocks surrounding the facility from October 14-19, 2019."
The nonprofit must "provide the NIH with WIV's responses to the 2018 Department of State cables regarding safety concerns."‘
After this request, EcoHealth and NIH continued to argue back and forth about the grants and what information they needed to provide. If you’re curious about the legal/paperwork end of NIH grants, you can read the requests from NIH and EcoHealth’s responses.
The tl;dr of the back and forth is the following:
NIH faults EcoHealth for having sloppy subaward contracts
WIV refused to provide lab books and access
NIH believes tighter subaward contracts/processes can be fixed, but defiance cannot
As a result, the recommendation is to ban WIV from future NIH funding, but EcoHealth still has a chance to get funding. This concurs with the IG report. The IG audit found some unallowed expenditures, but the most exciting thing they could find in those unallowed funds worth reporting was a $5 beer and a conference trip. EcoHealth is taking a victory lap since they escaped the ban hammer.
Learning points from this: 1) for scientists, make sure your grants people are competent because the subcontract language gets scrutinized when things blow up, 2) NIH tried to get the lab books and was rebuffed, 3) none of the WuHaN bIoWeApOn! people seem to have noticed or cared about the failure to get the lab books.
On one hand, the lab books must be assumed to be compromised, and politics don’t require facts or reasonable doubt in the first place. On the other hand, this means foreign organizations can thumb their nose at any and all NIH regulations. Shrike expects some of the enhanced requirements imposed on EcoHealth may get imposed on others with subawards to China and other countries, but it is unlikely NIH will devote the needed resources to checking themselves and helping the recipient organizations get this information from foreign countries.
Congress could push harder if they wanted to—instead of just banning funding to WIV for 2023, they could ban all funds to China until the lab books get produced, and the people who failed to produce them get fired. This would hurt research in the short term—there are good scientists in China doing good work who are collaborating with US scientists—but it would be a test of how much Chinese research depends on US funding initiatives. If China is comfortable doing without the funding, they can fund their own researchers.
This is also a reminder that anyone fear-mongering over lab origins of SARS-CoV2, Chinese responsibility, and/or NIH coverups who does not mention NIH efforts to investigate is just manipulating your emotions for their gain. In many ways, the fear-mongering has become part of the Show to keep you emotionally invested and manipulable.
Origin and Initial Spread of SARS-CoV2
Also out last July is an examination of the early spread of SARS-CoV2 in the Hunan meat market. The authors believe SARS-CoV2 jumped from animals into humans twice, based on two distinct early genomes, and this likely happened in the Hunan meat market. Along with a lot of statistical arguments, they note Raccoon Dogs (Nyctereutes procyonoides), Hog Badgers (Arctonyx albogularis) and Red Foxes (Vulpes vulpes) for sale. More, these mammals can both be infected by SARS-CoV2, and were sold near the earliest reported cases’ locations in the meat market.
Shrike thinks this is about as circumstantial as the evidence supporting the lab leak hypothesis, but it is important to consider other ideas and hypotheses about the SARS-CoV2 origins. Aside from being able to find SARS-CoV2 in an intermediate host (2 transmission events from distinct viral lineages raises a lot of questions), codon optimization would be the other way to test this hypothesis. If the virus passed long enough in the intermediate host (if two distinct lineages jumped into humans, this is a reasonable assumption), it should be more codon optimized for Raccoon Dogs or another proposed intermediate host.
Multiple transmission events seem unlikely to Shrike, but there is evidence for multiple transmission events in the related lethal coronavirus MERS. This one jumps regularly from camels into humans, but does not spread well between humans.
Overall, this discussion remains ongoing, and from a scientific standpoint, it is important to rigorously test your own hypotheses. If they prove false, it is time to update them.
Bivalent vaccines
As the virus continues to evolve, so do the vaccines aimed at countering them. Leaving aside the public propaganda and policy that rightfully deserves your scorn, let’s look at the evolution of the virus and the vaccines.
The major variants that reached public attention are the Wuhan/alpha strain, delta, omicron, and then omicron BA.4/BA.5. Calling these variants, strains or substrains is something of a misnomer for the public. This conveys the idea that all of these viruses are the same and just a little bit different. These variants have distinct immune profiles and have distinct transmission and severity profiles. For example, the Wuhan strain is deadlier, but not spread as well as omicron. Shrike is convinced if the viruses in a different taxonomic group (eg mammals or birds), these would be recognized as separate ‘species.’
On one hand, this is a quirk of how different fields assign species. The definition of a species is whatever the experts in the field say it is. At the species level, virologists do it by % nucleic acid similarity, while mammologists use multiple criteria. On the other hand, Shrike thinks it is important to help people mentally distinguish the viruses. If they’re all “SARS-CoV2” (or “COVID”), the bias is to assume they’re the same. This bias hits scientists, policy makers and the public. Leaving aside the unusual naming changes for SARS-CoV2 variants (virus strains are named by their location of identification/outbreak, so it is correctly the Wuhan strain of SARS-CoV2, not alpha. Then with the Greek naming system, the WHO skipped xi for omicron), it is important to consider each of these as distinct viruses.
That this has been a challenge is reflected in the various statements regarding vaccines and transmission, and the outrage generated by these statements. The vaccine and all subsequent boosters prior to the “bivalent” vaccine targeted the Wuhan SARS-CoV2. The approval was based on the 10x reduction in severe disease (hospitalizations) observed in the clinical trial. Transmission was not measured, in part because that’s hard. After approval and widespread deployment, it became apparent that the vaccine reduced transmission of the Wuhan strain. By the time these data had percolated to the policy messaging system, delta had emerged as the dominant strain. Shrike believes this was accelerated by the vaccine rollout. However, the vaccines had reduced efficacy in blocking transmission of delta, and by omicron the vaccine did not help against transmission at all. Notably, prior infection with the Wuhan strain also did not prevent infection with omicron, which is why many people have had COVID multiple times now.
The policy messaging system lagged these events by ~3-6 months or so. Thus, the policy messaging ‘the vaccine prevents transmission of SARS-CoV2’ was going out once that statement was no longer true (and when it was true, policy messaging was ‘we don’t know yet’). Is this because bureaucracies are inefficient, or for nefarious reasons? Shrike will leave that for the reader to decide.
The boosters were not intended to solve the ‘virus is mutating’ issue. They were intended to help boost waning antibody titers, especially for older people. Durability of immunity varies by pathogen (and by age!), so this often needs to be figured out empirically. However, by the time the boosters were widely available, it was directed against a pathogen that was declining and being outcompeted by the newer models. Hence Shrike sees value in the initial vaccine (especially for the elderly and other at-risk), but not in the later booster shots.
Note on vaccinating children: Initial data showed the vaccine cut deaths 10x in child populations infected with the Wuhan strain, too. However, testing ‘does it reduce hospitalizations/deaths’ in children is hard because the hospitalization rate is low in children (=huge numbers needed for clinical trial). Also, by the time they wanted to do more trials aimed at children, the virus had escaped. This is due to the time lag of bureaucratic efficiency vs how fast the virus evolves in a new host (ie humans). So while there was an initial benefit at the population level, for most people vaccinating your kids against SARS-CoV2 did not (and still does not) make sense to Shrike. Your choice to vaccinate should be a decision between you and your physician.
The bivalent vaccine released in late 2022 is an attempt to solve this issue. This is the first vaccine directed against both omicron and the Wuhan strains of SARS-CoV2. In theory this would be helpful if one is at risk (immunocompromised, high risk for respiratory pathogens, expecting to become pregnant, or 50+) AND has not yet had omicron. Shrike expects it will remain helpful until the virus escapes it. In this case, one would need to distinguish between viral strains for COVID cases. As a rough measure, when cases start peaking in the general population, it’s a sign that the virus escaped immune control again. Alternatively, if you hear about people who had omicron getting COVID again, it’s also a sign that the virus may have mutated (waning immunity is the other option). If omicron infection does not protect, it is unlikely that the vaccine based on omicron will protect.
In general, escape is expected once or twice a year now. This, combined with waning immunity, means an annual shot would be needed to maintain immunity. In theory, the mRNA platform makes this is doable from a technical standpoint. It also means the valency (ie number of targets the vaccine goes after) could increase. Note that other vaccines are already polyvalent, such as the anti-human papillomavirus vaccine, and the anti-pneumococcal vaccine. That means adding targets is not breaking new ground. Multi-targets for mRNA vaccines have also be tried in cancer, so it’s not even new for mRNA vaccines.
All that said, the cost/benefit analysis of an annual booster for circulating strains for the population remains to be seen. Shrike would be surprised if it turned out to be worthwhile for most under 50 or 60. However, Shrike expects enough concern about SARS-CoV2 to remain to leave some degree of demand, even without any additional policy messaging or mandates.