Response to: Factors Associated With COVID-19 Breakthrough Infections: Correspondence.

Abstract

Reply: Thank you for your correspondence regarding “Factors associated with COVID-19 breakthrough infections in large Midwestern healthcare system: implications for vulnerable healthcare personnel.”1,2 The primary objective of the article was to identify factors associated with COVID-19 breakthrough infections among health care personnel (HCP) working in one health care system in the United States Midwestern region who were fully vaccinated with either the Pfizer-BioNTech or Moderna mRNA vaccines. As the article states (and you acknowledge), HCP who were younger, working in COVID-19–designated clinical units, and received the Pfizer-BioNTech primary series vaccine were most at risk of COVID-19 breakthrough infection within our sample. Separately, prior COVID-19 infection status was identified as an effect modifier. Specifically, among the identified at-risk groups, those with a prior COVID-19 infection had reduced odds of COVID-19 breakthrough infection when compared with those with no prior COVID-19 infection, indicating supplemental immunity is protective. As stated in the Methods section, COVID-19 infections in this study are most likely represented by symptomatic cases that resulted in a SARS-CoV-2 polymerase chain reaction (PCR) test being performed. It is very possible that our study results would look different among asymptomatic infection cases. Although we agree that asymptomatic infections continue to be a cause for concern and, further, that medical history, immune system quality, postvaccination preventative behavior, and local outbreak scenario can contribute to COVID-19 breakthrough infection risk, our study did not measure these factors, so we cannot speak on their role in breakthrough infection risk. Given that this study included HCP in the United States Midwestern region whose COVID-19 infection status—before and after their primary series vaccination—was defined by the presence or absence of a positive SARS-CoV-2 PCR result and whose primary series vaccination was one of the two available FDA-approved mRNA vaccines, I will state that the conclusions of this article may not generalize to the following groups you mentioned in your correspondence: Individuals or HCP living in Southeast Asia Individuals or HCP who did not receive two doses of either the Pfizer-BioNTech or Moderna mRNA vaccines as their primary series vaccination Individuals or HCP who did not have a positive SARS-CoV-2 PCR result indicating an active COVID-19 infection, symptomatic or asymptomatic Nonetheless, we will argue that the main takeaway of this article applies regardless, specifically that supplemental immunity in the form of a booster vaccine could provide additional protection from COVID-19 breakthrough infection for vulnerable HCP. This takeaway does not disavow the role of medical history, immune system, and prevention behaviors as they relate to risk of COVID-19 breakthrough infection, but our current data simply did not contain any information that would make it appropriate for us to draw conclusions on these factors in this article. Anne Rivelli, MPH, MAVeronica Fitzpatrick, DrPH Advocate Aurora Health Advocate Aurora Research Institute Downers Grove, ILKenneth Copeland, PhD Advocate Aurora Health ACL Laboratories Downers Grove, ILJon Richards, MD, PhD Advocate Aurora Health Downers Grove, IL