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Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine breakthrough infections: a multi-center cohort study

Our take —

This study from Singapore, available as a preprint and thus not yet peer reviewed, found that patients who were fully vaccinated with an mRNA vaccine had lower risk of severe outcomes after SARS-CoV-2 infection with the variant of concern B.1.617.2 (Delta). The study also seems to suggest that vaccinated patients clear viral load at a faster rate compared to unvaccinated infected patients.

Study design

Retrospective Cohort

Study population and setting

Between April 1 and June 14, 2021, 218 patients hospitalized with the Delta variant were identified across the 5 study sites in Singapore, of whom 130 were unvaccinated, and 71 were fully (2 dose) mRNA vaccinated patients and included in the analyses. Those were not fully vaccinated or who did not receive an mRNA vaccine (n=17) were excluded from the study.  A subset of 69 fully vaccinated and 45 unvaccinated patients further had serologic data on record.

Summary of Main Findings

Those in the vaccine-breakthrough group tended to be older (56 years vs. 39.5 years) than the unvaccinated group.  Fully vaccinated breakthrough patients in the study had fewer symptoms (28% asymptomatic vaccinated vs. 9% asymptomatic unvaccinated) and better clinical outcomes (fewer cases with pneumonia, need for oxygen and ICU admissions).  Those who were vaccinated had similar peak Delta SARS-CoV-2 viral load but cleared virus at a faster rate compared to unvaccinated patients. In the subset of patients with serologic data, vaccinated breakthrough cases had earlier, more robust boosting of anti-spike SARS-CoV-2 protein antibodies than unvaccinated patients.

Study Strengths

This study is based on real-world evidence of viral kinetics in mRNA vaccine-breakthrough and unvaccinated patients after a SARS-CoV-2 Delta infection. 

Limitations

Although the manuscript states Singapore has a system where all identified COVID-19 cases, regardless of symptom status, are admitted to the hospital for evaluation, it is not clear where these cases are identified in the context of the study (e.g., whether they are representative of the Singapore population with the Delta variant infection or whether there are specific subgroups that tend to test more and end up in the hospital, especially in the asymptomatic cases).  It is also not clear how they accounted for immunocompromised patients, especially in the vaccine-breakthrough group.  As such, the viral kinetics mapped by the study may not be representative of all cases, especially undetected cases that may be more likely asymptomatic. Also, PCR ct values were used as a surrogate marker of viral load. Since only the viral kinetics of mRNA vaccines were examined, these findings cannot be generalized to other COVID-19 vaccine types.  It is also not clear whether there were differences in viral kinetics of Moderna versus Pfizer vaccine breakthrough cases or in older versus younger adults since the subgroup analyses were not shared.

Value added

This study suggests that mRNA vaccinated patients with breakthrough COVID-19 infection from the Delta variant had similar viral loads to unvaccinated patients at time of diagnosis but cleared the virus more quickly than unvaccinated cases.

This review was posted on: 4 October 2021