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Virological characteristics of SARS-CoV-2 vaccine breakthrough infections in health care workers

Our take —

Vaccines are highly efficacious at preventing severe disease and reducing likelihood of infection, but breakthrough infections do occur. This study from the Netherlands was available as a preprint and thus has not yet been peer reviewed. When comparing primary infections occurring between April and December 2020 to breakthrough infections (infections after vaccination) that occurred between April and July 2021, it was found that Ct values were similar but that the probability of detection of infectious virus was lower among breakthrough infections. Comparing these two groups should be done cautiously as there are a number of reasons that could explain these differences in virological characteristics (changes in attitudes and behaviors at the hospital over time, different dominant variants, etc.). This study does not provide sufficient evidence of the comparability of these two groups. Further, given the dominance of the Delta variant which is known to be more virulent, in the latter time period when the breakthrough infections occurred, the effectiveness of the vaccine at reducing viral replication and infectiousness may have been greater had the Alpha variant remained the dominant variant in circulation.  

Study design


Study population and setting

Virological data (RT-PCR and Ct values) were compared between unvaccinated healthcare workers (HCWs) with primary infection (April-December 2020) and vaccinated HCWs with breakthrough infections (April-July 2021, n=161) at two tertiary care centers in the Netherlands. Virological characteristics were compared using the first RT-PCR positive sample. Positive samples underwent sequencing to determine the variant (Alpha, Beta, Gamma, or Delta) and were cultured to assess viability of the virus. Testing algorithms remained constant across the two periods, with symptomatic HCWs seeking testing and contact tracing performed in the event of a positive case.

Summary of Main Findings

Among the 161 breakthrough infections detected between April and July 2021, the majority (70.8%, n=114) were identified as the Delta variant (B.1.617.2). None of the infections required hospitalization and were described as mild. The mean age of HCWs experiencing a breakthrough infection was 25.5 years old. Ct values were significantly lower in symptomatic vs. asymptomatic breakthrough infections (23.2 vs. 26.7), indicating a higher viral load among symptomatic breakthrough infections vs. asymptomatic breakthrough infections. When comparing those with breakthrough infections and those with primary infections, Ct values were similar but the probability of infectious virus detection based on culture was lower among those with breakthrough infections.   

Study Strengths

The sequencing data for all cases is a strength, as was the availability of viral culture data.


The authors indicate that the two groups did not differ with respect to demographic characteristics, but a Table indicating symptom status, age, variant, and Ct-value are only provided for the breakthrough infections (April-July 2021), making it difficult for the reader to evaluate similarities and differences between the two groups. Comparison between the two groups is challenged because these two groups were infected in two different time periods (could have been changes in attitudes, behaviors, mandated NPIs) and predominantly by different variants, which could mean different virological characteristics regardless of whether a breakthrough or primary infection. Primary infection sequencing data appear to have been collected, but were not reported in the paper.

Value added

This study helps us better understand differences in transmission likelihood between those who are vaccinated with breakthrough infections and those who are unvaccinated with primary SARS-CoV-2 infections.

This review was posted on: 18 October 2021