Now We Know: Covid-19 Vaccines Prevent Asymptomatic Infection, Too

The CDC has now confirmed what we have hoped for: the mRNA vaccines made by Pfizer and Moderna are highly effective at preventing SARS-CoV-2 infection in real world conditions. It was known previously from clinical trials that these vaccines were effective at preventing symptomatic disease. What was not known was whether they prevented asymptomatic infection.

Here is how the CDC reached this conclusion. Beginning in mid-December 2020, 3,950 people employed in frontline health care professions (e.g. physicians, nurses, and first responders) in eight US locations were tested each week for 13 weeks to determine if they were infected with the novel coronavirus. Prior to the start of the study, 62.8% of the participants had received two mRNA vaccine doses, and an additional 12.1% had received at least one dose. The balance of the study group (25%) had not received any.

Of vaccinated people in the study, 62.7% received Pfizer-BioNTech vaccine while 29.6%  received the Moderna vaccine. (A very small number received the Johnson & Johnson vaccine.) During the 13 week study, some individuals within each group became infected.  However, by the time the study concluded on March 13, 2021, the population that received both doses had yielded just 0.04 infections/1,000 person days, while the population that received one dose had 0.19 infections/1,000 person days and the unvaccinated population exhibited 1.38 infections/1,000 person days.From these data, the CDC estimated that having two doses of an mRNA vaccine offers 90% protection against infection. Even one dose is quite effective, reducing infection rates by approximately 80%.

An important caveat is that the relatively small number of infections observed during the study period means that there is considerable uncertainty surrounding these estimates. The CDC report expresses this lack of precision in terms of a confidence interval. For two doses, we can be quite confident that the true effectiveness is between 68% and 97%. For one dose, we can be confident that the vaccine effectiveness is between 59% and 90%. Even if the true values are at the lower ends of these ranges, the finding is still very good news. Prevention against infection means that as vaccine rollout increases, we may expect a dramatic decline in cases, not just hospitalizations and deaths.

One limitation of the study is its poor demographic representation. Particularly, a large majority of participants were white (86.3%) and non-hispanic (82.9%). This is not representative of the country over all. There is no reason to believe that other demographics were excluded from the study: these are just the people who chose to participate given the opportunity. But, strictly speaking, statistical generalization to the larger population is questionable. That said, the authors of the study did a sensitivity analysis to look at effects of sex, age, ethnicity, and occupation. The effects of these covariates were found to be minimal.

Another issue is that variants of concern, which have arisen recently, were not widely circulating at the time of this study. There is mounting evidence that the immune response a person develops as a result of vaccination is not as effective at fighting some of these variants. According to nextstrain.org, the variant most prevalent in North America right now, sometimes referred to as B.1.1.7, still only accounts for about 25% of the SRS-CoV-2 genomes sequenced. Fortunately, a preprint from a study in the United Kingdom found broad evidence for protective immunity at a time when B.1.1.7 was quite prevalent there.

All this discussion of the different vaccines and variants leads to the related issue of “vaccine choice.” As vaccines have become more widely available, some people are discussing the pros and cons of the different options. The CDC study was not able to determine whether there is any difference between the two mRNA vaccines in terms of effectiveness. For most people in the US, the best vaccine to get is the one you can get first.

Despite the success of these vaccines, wearing a face mask and physical distancing are still important behaviors to adopt until cases go down more. The 10% of people for whom infection is not blocked may still be able to transmit the virus and there are groups, such as children, who will not be widely vaccinated for a considerable time still to come. We want to prevent these groups of people from maintaining the virus in the population to the greatest extent possible, and that may be hard to do.