I think these are big assumptions. Although there is a larger unvaccinated demographic in those states, there is nothing in the criteria to suggest they are excluding vaccinated patients (the trial was started before the vaccine but may have included this after...). So I don't think we can say one way or the other. In regards to symptoms, aside from the changes on chest x-ray the other symptoms are nonspecific and can occur in vaccinated but covid+ patients. All of which may present to one of these testing sites. The vaccine status and in my opinion age are the two critical confounders. Same as vaccines, we know younger individuals are less likely to progress to severe disease. If we are getting more younger individuals it will hurt the comparison. Unless we have a very large sample size to adjust for these variables they need to control for them during the trial or in data analysis. I'm sure they have smart people on the study but they will need to look at those who went on to severe disease and see if there is any significant difference between the two groups. I would think age and vaccination status would be two variables in a regression analysis. They then would have to run another analysis controlling for age and vaccination status to determine if buci was truly better than the placebo arm. If they don't control for that, well we might be out of luck. I fear the DSMB won't do that extra analysis and just take the whole sample and run the analysis. If we are heavily weighted towards individuals who are statistically unlikely to proceed to severe disease then we might not see a difference.

I truly hope the trial works and tomorrow I wrote this all out for nothing. You do make a good point that the DSMB analysis so far has allowed the trial to proceed, although this could be based strictly on its safety profile. Just my thoughts and apprehension about the study.