ABSTRACT
BACKGROUND: The successful development of multiple COVID-19 vaccines has led to a global vaccination effort to reduce severe COVID-19 infection and mortality. However, the effectiveness of the COVID-19 vaccines wane over time leading to breakthrough infections where vaccinated individuals experience a COVID-19 infection. Here we estimate the risks of breakthrough infection and subsequent hospitalization in individuals with common comorbidities who had completed an initial vaccination series. METHODS: Our study population included vaccinated patients between January 1, 2021 to March 31, 2022 who are present in the Truveta patient population. Models were developed to describe 1) time from completing primary vaccination series till breakthrough infection; and 2) if a patient was hospitalized within 14â¯days of breakthrough infection. We adjusted for age, race, ethnicity, sex, and year-month of vaccination. RESULTS: Of 1,218,630 patients in the Truveta Platform who had completed an initial vaccination sequence between January 1, 2021 and March 31, 2022, 2.85, 3.42, 2.75, and 2.88 percent of patients with CKD, chronic lung disease, diabetes, or are in an immunocompromised state experienced breakthrough infection, respectively, compared to 1.46 percent of the population without any of these four comorbidities. We found an increased risk of breakthrough infection and subsequent hospitalization in individuals with any of the four comorbidities when compared to individuals without these four comorbidities. CONCLUSIONS: Vaccinated individuals with any of the studied comorbidities experienced an increased risk of breakthrough COVID-19 infection and subsequent hospitalizations compared to the people without any of the studied comorbidities. Individuals with immunocompromising conditions and chronic lung disease were most at risk of breakthrough infection, while people with CKD were most at risk of hospitalization following breakthrough infection. Patients with multiple comorbidities have an even greater risk of breakthrough infection or hospitalization compared to patients with none of the studied comorbidities. Individuals with common comorbidities should remain vigilant against infection even if vaccinated.