A Retrospective Cross-Sectional Study of Severe Breakthrough SARS-CoV-2 Infection in the General Population Requiring Hospitalization Within a Single Health System

Background: Despite coronavirus disease 2019 (COVID-19) vaccination efforts, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in vaccinated individuals ("breakthrough SARS-CoV-2 infections") have emerged. Our understanding of breakthrough SARS-CoV-2 infections continues to evolve, and there is a paucity of information describing severe breakthrough SARS-CoV-2 infections. We conducted this study with the aim of describing breakthrough SARS-CoV-2 infections requiring hospitalization and exploring factors associated with severe breakthrough infection.

Methods: The study included patients within our health network who received at least one dose of a messenger RNA (mRNA) COVID-19 vaccine and required hospitalization due to breakthrough SARS-CoV-2 infection from January 1 to August 15, 2021. We performed a descriptive analysis of vaccinated patients requiring hospitalization. Multivariable logistic regression (LR) analysis was performed to explore factors associated with severe breakthrough infection.

Results: Out of 67,223 vaccinated individuals, 78 (0.12%) patients were hospitalized with breakthrough SARS-CoV-2 infection, of which 25 individuals (0.04% of those vaccinated, and 32% of all hospitalized) developed severe infection. The mean age of those with breakthrough infection was 72 years, the majority were White (60%), and dyspnea was the most common reason for hospital admission (53%), with bimodal peaks of hospitalization in January-February (40%) and July-August (34%). In LR analysis, male patients had 4.03 times the odds of developing severe SARS-CoV-2 infection than female patients (adjusted odds ratio (aOR): 4.03, 95% confidence interval (CI): 1.21 - 13.40), and an immunocompromising condition had 6.32 times the odds of developing severe COVID-19 disease (aOR: 6.32, 95% CI: 1.48 - 26.18).

Conclusions: The rate of severe breakthrough SARS-CoV-2 infection was very low, and male sex and immunocompromising conditions were associated with severe breakthrough infection. Clinicians and health systems should continue to campaign for COVID-19 vaccination aggressively.