Settling in for the Viral Season
New Data on the Booster shots
Now that the two most frightening times of the year are behind us, Halloween and Election Day, we have a lot of new scientific data, and as usual a lot of uncounted votes. The question of how effective the new boosters are likely to be is in the process of being answered by a number of hot-off the presses preprints. There is new data addressing not only the question of how effective are the bivalent boosters against BA.5, but much more importantly, the first look at their performance against the newer variants, which are rapidly displacing BA.5 as the major circulating viral strains. My first reaction to the plan to produce a bivalent booster targeting BA.5, was, “Good luck with that, BA.5 will likely be history by the time you have that scaled up in production and into people’s arms; and if BA.5 is replaced, it will likely be by a new variant which can at least partially elude immunity to BA.5.” Below is this week’s NowCast data from CDC showing just how rapidly BA.5 is being replaced by the new variants. Two weeks ago BA.5 was 53% of viral sequences across the country, today it is 29.7% and on the way out, with BQ.1 And BQ.1.1 leading the charge.
This is a good juncture to review the ways scientists and epidemiologists gauge the performance of a vaccine. The first is by measuring the neutralizing antibody (NAB) levels it produces in vaccinated individuals. The other, and more important issue in the real world of people, is how effective it is in preventing infection, and reducing the severity of disease. Obviously the real world data takes much longer to accrue, so as far as the brand new BQ.1, BQ.1.1, BF.7 etc. variants are concerned, we are just getting information on the new booster’s ability to create NABs against them. The results are not very good at all— as predicted by the high degree of immune evasion to panels of monoclonal antibodies observed as soon as the variants were recognized. These are the experiments which can be done immediately when new concerning variants appear. As noted in these pages previously, the initial batch of preprints showed basically the same NAB response against BA.5 for the new bivalent booster as the original Wuhan formulation. Several new preprints using different experimental methods have now shown a little better performance for the new boosters. (See Eric Topol’s “Ground Truths” of Nov. 4 for a summary—he seems a bit more impressed by this than I am). This comparison is fairly academic at this point, with BA.5 evaporating faster than my breath in the Telluride night air. (It’s Greta Thunberg cold here at 4 degrees in early November). In any event-you don’t have a choice of which booster to take.
Below is a link to a BioRxiv preprint by Kurhade, et al. demonstrating that in fact these newer variants are highly resistant to the serum of people vaccinated with the new bivalent boosters. The new boosters do slightly better than the original vaccine against BA.5, but perhaps not in a clinically meaningful way. Whereas NAB titers against the original Wuhan virus are in the 1500 to 3600 range for the old verses new boosters; against the new variants unfortunately both vaccines lead to NAB titers consistently below 100, and for BQ.1.1 and XBB, barely above the limit of positive detection. In my opinion what all this means is that even post- boosting now, we will remain highly susceptible to infection. Many fewer will be going to the hospital, but that cheery assessment doesn’t extend to the elderly, those with serious co-morbidities, and the immunocompromised.
Kurhade C, …. Shi P-Y. Low neutralization of SARS-CoV-2 Omicron BA.2.75.2, BQ.1.1, and XBB.1 by 4 doses of parental mRNA vaccine or a BA.5-bivalent booster. October 31, 2022. BioRxiv
Most of us have had COVID, the shrinking pool of Novids would be enormously smaller if nucleocapsid antibody tests, which confirm prior infection, were widely done. How important is it to avoid repeat infection? Beyond the inconvenience of a flu-like illness making you miserable, and perhaps keeping you isolated (if you bothered to test) there is the real concern for cumulative damage and Long COVID symptoms. This week Nature Medicine published the very large epidemiology study from the Veterans Administration looking at the question of risk associated with reinfections. (A preprint version of this was available previously)
Acute and postacute sequelae associated with SARS-CoV-2 reinfection 10 Nov. 2022
https://www.nature.com/articles/s41591-022-02051-3
It may seem like common sense that repeated episodes of what can be a very serious disease might have a cumulative negative impact, but it’s revealing to see this confirmed and quantified in this huge cohort. The increased risk from repeated infections is seen in every category of organ complications and increased hospitalization and mortality both acutely, and continuing for up to six months. Of course, this is a highly specific older group and the findings are not generalizable to the entire population. Two other points in their findings stand out. The median time from first to second infection was 191 days, and from second to third infection was 154 days. The other unfortunate finding, which I suppose really shouldn’t be a surprise at this point, was that the negative impact of re-infection was completely independent on vaccination status. The older age group is getting reinfected quickly with this virus, despite both natural and vaccine conferred immunity. That doesn’t imply that both forms of immunity aren’t helpful—simply that they are only partially protective and rapidly waning. We witnessed first hand the terrible toll this virus took on infection naive elderly persons during the first spring wave
In addition to the CDC study I discussed last week (Connecting the Dots), there is this NEJM correspondence of November 9th looking at the NAB and vaccine effectiveness in Israeli Health care workers following a fourth dose of Pfizer vaccine. This study looked only at people with no prior history of infection during the Omicron BA.1 and BA.2 wave (so no assessment of hybrid immunity). These researchers found NAB’s post this second boost peaked at 4 weeks, and returned to baseline pre-boost levels by 13 weeks. The following is a quote from their text regarding the booster’s efficacy in preventing clinical disease.
Time-specific vaccine effectiveness (which, in our analysis, compared infection rates among participants who had not yet been infected since vaccination) waned with time, decreasing from 52% (95% CI, 45 to 58) during the first 5 weeks after vaccination to −2% (95% CI, −27 to 17) at 15 to 26 weeks.
This is further evidence that, given the current vaccines, the idea of a yearly COVID shot having much, if any value, seems unlikely. This is true both from the perspective of preventing infection, and for preventing severe disease, which as we have seen from multiple studies fades dramatically after 3-4 months. We could speculate that both protections will be less in the face of the new more immune evasive variants. One bright spot in this Israeli study of over 10,000 people is that they were “unable to assess the effectiveness (of a fourth dose) against severe outcomes of infection owing to the absence of such outcomes in the study cohort”. The combination of built up immunity and less virulent variants (compared to Wuhan and Delta) must be having a positive effect.
That’s it for today’s infectious disease update. Enjoy your Thanksgiving Holiday. Remember to always pass the salt and pepper together, and not the BQ.1. Hit the like button at the top if so inclined, and use the other buttons to pass this along to your circle of influence.