Body Mass Index and Hemoglobin A1c Correlate with Clinical Needs After COVID-19 Vaccination in the Veterans Affairs System

<b>Background:</b> Throughout the course of the COVID-19 pandemic, clinicians recognized that individuals with metabolic syndrome, including elevated body mass index (BMI) and type 2 diabetes, have increased clinical care requirements and worsened outcomes during COVID-19 infection. With the availability of COVID-19 vaccines, it was unknown whether vaccination could mitigate the clinical outcomes among patients with metabolic syndrome. In this study, we sought to determine whether BMI and hemoglobin A1c are associated with a risk of breakthrough infection and increased clinical needs among patients who have been fully vaccinated against COVID-19. <b>Methods</b>: We conducted a retrospective cohort study of patients in the Veterans Affairs healthcare system who were vaccinated against COVID-19 between 1 December 2020 and 22 August 2021. We sampled a random subset of 549,344 patients from a total of over 1 million de-identified patients greater than age 18 who were vaccinated between 1 December 2020 and 22 August 2021, without a prior positive COVID-19 test in the VA healthcare system data warehouse. The primary study outcomes were breakthrough COVID-19 infections after vaccination and hospitalization due to breakthrough COVID-19 infections. <b>Results:</b> We identified 480,129 patients with available BMI and hemoglobin A1c data; of these, all had data available for the covariates of race, ethnicity, sex, and age, and 467,283 had data available for district as well. Adjusting for those covariates, Cox proportional hazards modeling for time from vaccination until breakthrough infection demonstrated that higher BMI (HR per unit 1.015, <i>p</i> < 0.001) and hemoglobin A1c were associated with an increased risk of infection (HR per unit 1.063, <i>p</i> < 0.001). The number of patients from this set who developed breakthrough infections within the study period was 8903 (9146 if those with missing district data were included). The average age of fully vaccinated patients with breakthrough COVID-19 infection within six months of full vaccination was 64.5. The average BMI was 31.2 ± 6.2 and the average A1c was 6.34 ± 1.5. Adjusting for the above covariates, multivariable logistic regression trends towards significance, with an increased risk of hospitalization due to breakthrough COVID-19 infection with increased BMI (HR per unit 1.010, <i>p</i> = 0.052), and was statistically significant for increased hemoglobin A1c (HR per unit 1.150, <i>p</i> < 0.010). <b>Conclusions:</b> This study identifies BMI and hemoglobin A1c as risk factors for breakthrough COVID-19 infection among fully vaccinated patients in the US veteran population.