What Is a Breakthrough Infection?

07 February, 2024

Q: What do we know about breakthrough SARS-CoV-2 infections in vaccinated individuals?

A: “Breakthrough infection” refers to a SARS-CoV-2 infection that occurs after completion of a recommended COVID-19 vaccine series. Breakthrough infections can occur for a variety of reasons, including:

  • Primary vaccine failure: When an individual does not mount an adequate immune response to the primary series of a recommended COVID-19 vaccine. An example of this would be an immunocompromised patient whose immune system does not develop high levels of antibody after receiving two doses of an mRNA COVID-19 vaccine.
  • Secondary vaccine failure: When an individual’s initial immune response to a vaccine, which may have been robust, diminishes over time (see “What Is Waning Immunity?”), making them more vulnerable to infection. An example of this would be an individual who becomes sick with COVID-19 caused by a virus that matches the antigens in COVID-19 vaccines, 14 months after completing a recommended COVID-19 vaccine series.
  • Immune escape: When changes in the SARS-CoV-2 virus over time (i.e., emergence of novel variants) allow the virus to escape vaccine-induced immune responses. An example of this would be infection due to an Omicron variant in an individual who was fully vaccinated against the ancestral strain of SARS-CoV-2 and did not receive a bivalent (Omicron-specific) booster.

Our knowledge of SARS-CoV-2 breakthrough infections after vaccination is still evolving. Importantly, breakthrough infections appear to occur at a lower incidence compared with infections in unvaccinated individuals, even with the development of novel variants such as Omicron. Additionally, existing evidence suggests that breakthrough infections are less likely to cause severe illness compared to primary infections in unvaccinated individuals. Therefore, the occurrence of breakthrough infections does not diminish the critical importance of vaccination against COVID-19. However, the risk of breakthrough infections appears to be higher for circulating variants of concern compared to the ancestral SARS-CoV-2 strain.

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