The excitement is concerned about emerging variants and whether the vaccines will hold against them and thats. The topic of this weeks – healthcare, triage Music before we get started talking about vaccine efficacy against the coven 19 variants – lets lay some groundwork the primary way these viruses mutate is by changing regions of the spike protein used by the virus to bind to and enter human Cells, these changes either cause tighter binding of the receptor which increases transmissibility or they change one of the sites where antibodies bind. Additionally, some variants suppress human inflammatory reactions, allowing them to create more copies before the bodys able to mount a response. The cdc has identified a number of variants of concern labeled by greek letters. We have the alpha variant which emerged from the uk and currently accounts for 2.4 percent of u.s cases. This strain is notable for increased transmissibility and potentially more severe disease. Next is the beta variant, which also has been detected in the united states and is also notable for increased transmissibility as well as potentially reduce susceptibility to antibodies in vitro, but it does not account for many us cases, at least at the time the script was written. Then we have the gamma variant, which was prominent in brazil, appears to be less susceptible to antibodies in vitro and currently accounts for 1.3 percent of us cases and finally, the delta variant, which has garnered major attention in the media. At present, this variant accounts for over 80 percent of us cases and is also notable for increased transmissibility and potentially reduce susceptibility to antibodies in vitro the body of high quality.

Evidence for efficacy of specific vaccines against specific variants is sparse. Part of the issue is that the outcome were most interested in severe coveted cases is rare. Trying to get statistically significant evidence by randomized controlled trial for specific variants requires humongous sample sizes, which, even if possible, will be hard to justify, given the undoubtable benefit of vaccines. The data we do have suggests that the pfizer vaccine has good efficacy against all the major variants. Although some evidence suggests that neutralizing antibody activity may be lower for the beta and delta variants, but thats in vitro data lets. Look at how this plays out in vivo. A prospective cohort study of over 23 000 uk healthcare workers found that the pfizer vaccine was about 85 percent effective at preventing all covet during a period when the prevalence of the alpha variant in the uk was greater than 50 a case control study conducted during qatars. Third wave of covid reported 90 efficacy of the pfizer vaccine against the alpha strain and 75 efficacy against the beta strain, notably. However, there were no severe coveted cases with either of these variants in the vaccinated group. Finally, another case control study from the uk similarly found that the pfizer vaccine had 93 efficacy against the alpha strain and 88 efficacy against the delta strain. There are limited data on modernist efficacy for variants, but its presumed to be similar to pfizers, given their shared mechanism. So whats, behind this difference between the in vitro antibody data and the in vivo observational data, the antibody data is derived by taking vaccinated animals or humans and assessing the ability of their serum to neutralize covid long time.

Viewers at the show know how we feel about surrogate outcomes. The level of neutralizing antibodies is far from a perfect correlate, and the level of antibody necessary to prevent severe covet is fairly low to make the issue more complicated as weve covered in previous episodes. Much of the immunity that develops against covet comes from the t cell response, which isnt measured in many studies and has been shown to have much less variation. Moving on to the other vaccines, a recent preprint suggested that in individuals who had received the j and j vaccine neutralizing antibody activity against variants, including delta, was low. One of the authors of that study did declare some conflicts of interest. Having received research grants from and serving on advisory boards for places like pfizer, contrary to that study, johnson and johnson released preliminary data from an in vitro study that suggested a strong antibody response to the delta variant, but keep in mind that this is from a subset Of only eight participants looking to the in vivo data, the original johnson and johnson study showed up to 85 efficacy overall in preventing severe covid. That study was performed in south africa and brazil, while variants of concern like beta were prominent and found no difference in efficacy. For these looking at the delta variant, preliminary data released in early august from a clinical trial in south africa suggest that the j j vaccine showed up to 71 efficacy against hospitalization from the delta variant, so thats good news too.

Finally, the astrazeneca vaccine in a post hoc analysis of the original astrazeneca randomized controlled trial. The efficacy of this vaccine against the alpha variant compared to placebo was 70, not statistically different from the overall efficacy. A separate, randomized, controlled trial showed no significant benefit against mild to moderate infections with the beta variant, but this study had many limitations, including a small sample size, a young population at low risk for symptomatic covid and lack of severe infections. Another case control study found 74.5 efficacy for the alpha variant and 67 efficacy for the delta variant after 2, but not 1 doses keep in mind. Most of these studies are observational, while they control for some factors. They cant account for individual patient behaviors, its not unreasonable to think that individuals who have avoided covid vaccines may have underlying medical or social reasons not to additionally, groups that were more likely to be exposed to covid were more likely to be vaccinated early in rollouts, which May skew the data, but even then theres no evidence to suggest that any of the vaccines struggle to prevent severe covet infections from variants still there are contingency plans if this changes, including modernas new booster vaccine, which reportedly has increased neutralizing activity against certain variants. On a final note, there have been a few headlines about the delta plus variant, but its still under investigation and as of the shooting of this video isnt accounting for a large number of delta cases.

Well, continue to monitor the situation and keep you all posted with any updates. In the meantime, please continue to get vaccinated as ed young recently detailed in the atlantic. Unvaccinated people are highly susceptible to the variants and the longer that remains true. The less likely our current vaccines will be able to hold the line hey and a special shout out to elliot rappaport the summer healthcare triage intern, who did the heavy lifting for this episode? Hey? Did you like this video? You might enjoy this other video on how effective is alcoholics, anonymous, wed appreciate it if youd like the video and subscribe down below and consider going to patreon.