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COVID-19 Vaccine Breakthrough Infections Reported to CDC — United States, January 1–April 30, 2021

Our take —

Some fully vaccinated individuals are expected to develop breakthrough SARS-CoV-2 infection, despite high vaccine efficacy. This report describes SARS-CoV-2 vaccine breakthrough infections in the United States through April 2021. At the time of this study, less than one third of the US population had been fully vaccinated, and new case rates exceeded 350,000 per week. Breakthrough infections represented only a small proportion of SARS-CoV-2 cases; only 0.01% (10,262 of 101 million) of fully vaccinated individuals tested positive for SARS-CoV-2 during the study period, supporting the very high efficacy data from clinical trials. Breakthrough cases were not more frequent based on age, sex, or infection with a variant of concern. In contrast with clinical trial data, a small number of deaths (n=160) were seen among older individuals with vaccine breakthrough infection; this is likely because the population observed in this study was much larger (millions vs. thousands). This report demonstrates that COVID-19 vaccines are highly effective for preventing SARS-CoV-2 infection, even in areas with a largely unvaccinated population, widespread community transmission, and a high variant prevalence.

Study design

Retrospective Cohort

Study population and setting

Vaccines for COVID-19 are extremely effective in preventing SARS-CoV-2 infection. However, it is expected that some individuals will still become infected post-vaccination, especially in regions where community transmission remains high. This report describes SARS-CoV-2 vaccine breakthrough infections in the United States as monitored through April 30, 2021. Cases were voluntarily reported to the CDC by local health departments in 46 US states and territories. Breakthrough infection was defined as a positive test for SARS-CoV-2 (either RNA or antigen) >14 days after completion of all recommended vaccine doses. A subset of RNA-positive samples was used for genomic sequencing to identify breakthrough infections caused by variants of concern.

Summary of Main Findings

Of the 10,262 reported SARS-CoV-2 vaccine breakthrough infections, 63% (n=6,446) occurred in women, with a median patient age of 58 years (IQR: 40-74 years). These data were consistent with the distribution of sex and age in the population of vaccinated individuals at the time of the study. One quarter of breakthrough infections were classified as asymptomatic (n=2,725 [27%]). However, cases were also identified among hospitalized patients (n=995 [10%]), although many (n=289 [29%]) had been hospitalized for reasons unrelated to COVID-19 disease. Breakthrough infections were also identified in 160 (2%) patients who died (median age, 82 years), although some deaths (n=28 [18%]) were attributed to other causes. Genomic sequences were obtained for 555 (5%) breakthrough cases, 356 (64%) of which were caused by variants of concern (B.1.1.7, B.1.429, B.1.427, P.1, and B.1.351). These results are consistent with the proportion of all US cases attributed to variants of concern (70%) between March 28 and April 10, 2021.

Study Strengths

This study includes a review of SARS-CoV-2 vaccine breakthrough infections reported in the United States through April 2021.


Sampling was completed via voluntary, passive reporting; data may not have been complete or adequately representative. Breakthrough cases may have included those where exposure took place prior to the 14-day cutoff, but symptoms developed, and testing took place after the 14-day cutoff. Vaccinated individuals are far less likely to experience symptomatic or severe illness, leading to lower rates of SARS-CoV-2 testing for this group vs. the unvaccinated population; the number of reported breakthrough cases was likely substantially undercounted as a result. Sequencing data were generated for only a small subset of breakthrough cases and may not be representative. Results were not stratified according to vaccine type, which may confound results because the Johnson & Johnson vaccine reaches maximum levels of effectiveness later than the Pfizer and Moderna vaccines.

Value added

This study describes SARS-CoV-2 vaccine breakthrough infections in the United States in early 2021. At the close of the study period, 101 million people in the United States had been fully vaccinated, and community transmission was still high (355,000 cases reported between April 24–30). The study therefore represents a measure of population level vaccine effectiveness in the United States at a time when ongoing risk of SARS-CoV-2 infection remained high.

This review was posted on: 13 June 2021