Rate and Risk Factors for Severe/Critical Disease Among Fully Vaccinated Persons with Breakthrough SARS-CoV-2 Infection in a High-risk National Population

Abstract

Background

Breakthrough SARS-CoV-2 infections after vaccination have been reported. Outcomes among persons with breakthrough infection are poorly understood.

Methods

We identified all Veterans with a confirmed SARS-CoV-2 infection >14 days after the second dose of an mRNA vaccine between December 15, 2020 and June 30, 2021, and propensity-score matched unvaccinated controls with SARS-CoV-2 infection. Primary outcome was severe/critical disease, defined as admission to an intensive care unit, mechanical ventilation, or death within 28 days of diagnosis or during index hospitalization.

Results

Among 502,780 vaccinated and 599,974 unvaccinated persons, there were 2,332 (0.5%) breakthrough infections in the vaccinated group and 40,540 (6.8%) infections in the unvaccinated group over a follow up period of 69,083 person-days in each group. Among these groups, we identified 1,728 vaccinated persons with breakthrough infection (cases) and 1,728 propensity-score matched unvaccinated controls with infection. Among the former, 95 (5.5%) persons met the criteria for severe/critical disease, while 200 (11.6%) persons met the criteria among the latter group. Incidence rate for severe/critical disease per 1,000 person-days (95% CI) was 0.55 (0.45-0.68) among the former and 1.22 (1.07-1.41) among the latter group (P<0.0001). Risk was higher (HR, 95% CI) with increasing age (per 10-year increase 1.25; 1.11-1.41), and those with >4 comorbidities (2.85; 1.49-5.43), while being vaccinated was associated with strong protection against severe/critical disease (HR 0.41; 0.32-0.52).

Conclusion

Rate of severe/critical disease is higher among older persons and those with >4 comorbidities, but lower among fully vaccinated persons with breakthrough infection compared with unvaccinated controls who develop infection.