OBJECTIVES: Patients with multiple comorbid conditions are at increased risk of COVID-19 infection. Vaccines have been proven to be highly effective against COVID-19, however their effectiveness in patients with multiple comorbid conditions might be curtailed due to compromised immune function, increased viral replication, and induced immunosenescence, subsequently leading to breakthrough infections (BIs). This study assessed the association of multiple comorbid conditions with COVID-19 BIs in fully vaccinated adults.

METHODS: Using Optum Research Database, a large administrative claims database, adult enrollees with complete vaccination status were identified between December 1, 2020 and May 31, 2021. COVID-19 BIs was defined using ICD-10 diagnosis codes for COVID-19 ≥14 days of completing vaccination. Patients with multiple comorbid conditions were identified using ICD-10 diagnosis codes, and categorized into 0, 1, 2, 3+ groups. Logistic regression models were used to estimate the association between COVID-19 BIs and multiple comorbid conditions, separately, and categories of comorbid conditions adjusting for patient demographics.

RESULTS: The study included 1,520,838 fully vaccinated adults. Mean age was 47.6 years (±14.5) with 53.1% of females, and most patients resided in Midwest (34%) and Southern regions (33.7%). About 1.1% of patients reported COVID-19 BIs. Patients with HIV/Immunodeficiency (1.59%), asthma (1.56%) and stroke (1.4%) were more likely to have BIs. Compared to patients with no comorbid conditions, patients with 1, 2 and 3+ comorbid conditions were significantly associated with 1.3 (95% confidence interval (CI): 1.25-1.36), 1.5 (95% CI: 1.42-1.59) and 2.26 (95% CI: 2.13-2.41) times increased odds of COVID-19 BIs after adjusted for patient demographics and lifestyle factors.

CONCLUSIONS: The study provides real-world evidence of role of multiple comorbidities in increased risk of COVID-19 BIs among fully vaccinated individuals. As new SARS-CoV variants emerge, continued detection, prevention, and management efforts of comorbid conditions is important to sustain high effectiveness of COVID-19 vaccinations and reduce BIs.