What should define a SARS-CoV-2 “breakthrough” infection?
John S. Schieffelin, Elizabeth B. Norton, Jay K. Kolls
Abstract
Recently, there have been several reports of SARS-CoV-2 "breakthrough" infections that have occurred in recipients of the FDA-approved SARS-CoV-2 vaccines (1). These reports have the potential to undermine public confidence in the efficacy of these vaccines. Moreover, the use of the term "breakthrough" infections implies that the virus broke through a protective barrier provided by the vaccine. But is this what happened in these cases? In most cases, the answer is no, and this answer lies in the fundamental understanding of the mucosal immune system throughout the respiratory tract: the upper respiratory tract and the lower respiratory tract. The current vaccines prevent COVID-19, by definition a lower respiratory tract illness, in greater than 90% of recipients (2-5). Recent studies of fully vaccinated individuals monitored by routine nasal testing have shown marked reductions, but not a complete absence, of SARS-CoV-2-positive tests (6-9). We believe it is a mistake to think that these vaccines will prevent nasal (upper airway) infection. This inference is based on the current routes of immunization.