Would you prefer a Covid-19 vaccine that you knew would only protect you against the most mild form of Covid-19, or one that would prevent its serious complications?

Of course you would want to protected against the worst case.

But that’s not how the companies testing three of the leading coronavirus vaccine candidates, Moderna, Pfizer and Astra Zeneca are approaching the problem.

According to the protocols for their studies, released in September, a vaccine could meet the companies’ benchmark for success if it lowered the risk of mild Covid-19, but was not shown to reduce moderate or severe forms of the disease, or the risk of hospitalization, admissions to the intensive care unit or death.

Moderna and AstraZeneca will involve about 30,000 participants each and Pfizer 44,000 participants. Half the participants will receive two doses of vaccines separated by three or four weeks, and the other half will receive saltwater placebo shots. The final determination of efficacy will occur after 150 to 160 participants develop Covid-19.

The trials will only be meaningful if allowed to run long enough to achieve the objective and all the companies will look at the accumulating data during the trial.

This of course means that, given the endpoint of vaccine efficacy, even a mild case of Covid-19 – including an asymptomatic case – would qualify towards the endpoint of the trial and thus be a finding that only cloud the results.

As not only severe cases are counted towards the 150 Covid-19 case goal this means that the trial would conclude and we will still not know if a vaccine against mild Covid-19 would protect against severe disease.   The reason is that the vaccine may not work equally well in frail and other at-risk populations. Healthy adults, who could form a majority of trial participants, might be less likely to get mild Covid-19, but adults over 65 – particularly those with significant frailty – might still get sick.  (This is the case with influenza vaccines, which reduce the risk of mild disease in healthy adults.)

Moderna and Pfizer also acknowledge that their vaccines appear to induce side effects that are similar to the symptoms of mild Covid-19 which makes the trial data difficult to interpret.  (Pfizer already reported that more than half of the vaccinated participants experienced headache, muscle pain and chills.)

The other problem is that, even if the studies are allowed to run past their interim analyses, stopping a trial of 30,000 or 44,000 people after just 150 or so Covid-19 cases may make statistical sense, but it defies common sense. Giving a vaccine to hundreds of millions of healthy people based on such limited data requires a real leap of faith.

None of this is to say that these vaccines can’t reduce the risk of serious Covid-19 but unless the trials are allowed to run long enough to address that question, we won’t know the answer.