COVID-19 Vaccine Breakthrough Infections: Microbial Minutes

June 10, 2021

What is a breakthrough infection? Why is COVID-19 vaccine breakthrough occurring and how does its frequency compare to that of other viruses and vaccines?

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Amidst encouraging real world data about the effectiveness of COVID-19 vaccines, and the CDC’s announcement last month that fully vaccinated individuals can engage in indoor and outdoor activities without a mask, reports of fully vaccinated people becoming infected with SARS-CoV-2 have raised questions about the frequency and cause of breakthrough infection. Why are some people who are fully vaccinated still testing positive for the virus? 
In this Microbial Minutes, we take a look at preliminary research evaluating trends in case characteristics and sequence data from breakthrough SARS-CoV-2 infections.

How frequently is COVID-19 vaccine breakthrough occurring?

COVID-19 Vaccine Breakthrough Infections Reported to CDC — United States, January 1–April 30, 2021. MMWR Morb Mortal Wkly Rep 2021;70:792–793.

Why is COVID-19 vaccine breakthrough occurring?

McEwen A.E. et al. Variants of concern are overrepresented among post-vaccination breakthrough infections of SARS-CoV-2 in Washington State. MedRxiv. May 25, 2021.

Kustin T. et al. Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2 mRNA vaccinated individuals. MedRxiv. April 16, 2021.

Venkatakrishnan A.J. et al. Antigenic minimalism of SARS-CoV-2 is linked to surges in COVID-19 community transmission and vaccine breakthrough infections. MedRxiv. May 31, 2021.

Take-Away Points

  • Unless a vaccine is 100% effective at preventing infection, a small percentage of breakthrough cases are expected and not overly concerning.
  • At this time, the frequency of COVID-19 vaccine breakthrough is very low (~ 0.01%), which means COVID-19 vaccines are highly effective at preventing COVID-19, particularly when it comes to severe disease.
  • There are a number of reasons that breakthrough infections may occur, including a weak or ineffective immune response to vaccination, decreased immunity over time and/or evolution of the virus. 
  • Evidence suggests that certain virus mutations may be enriched in breakthrough SARS-CoV-2 infections. 
  • Deletions in the “NTD-antigenic supersite” are of particular interest and require further investigation.

Author: Ashley Hagen, M.S.

Ashley Hagen, M.S.
Ashley Hagen, M.S. is the Scientific and Digital Editor for the American Society for Microbiology and host of ASM's Microbial Minutes.