Background: In August 2022, the FDA authorized the use of bivalent COVID-19 vaccines (Moderna and Pfizer) which contain components of both the original COVID-19 vaccine and omicron subvariants (BA.4 and BA.5). The safety and potential risks associated with bivalent COVID-19 vaccines were unknown. The Department of Veterans Affairs (VA) monitored the safety through rapid cycle analysis surveillance efforts and conducted a retrospective cohort study evaluating the risk of potential adverse events following bivalent COVID-19 vaccines in Veteran patients.
Objectives: To evaluate the risk of pre-specified adverse events in patients who received bivalent COVID-19 vaccines.
Methods: Patients who were vaccinated with bivalent COVID-19 and/or influenza vaccines from September 1, 2022 to January 10, 2023 were identified based on the CPT codes and CVX codes in the VA Corporate Data Warehouse (CDW). The study cohort aged 18 or older was restricted to consistent VA users defined as at least one clinic visit every 6 months within one year prior to vaccination. Patients were classified into 5 groups: influenza only (FLU), Pfizer only (BPF), Moderna only (BMD), influenza + Pfizer (FBPF), and influenza + Moderna (FBMD) vaccinees. Selected adverse events of interest included acute myocardial infarction (AMI), pulmonary embolism (PE), and venous thromboembolism (VTE) identified using ICD-10 codes. The risk period was 21 days following vaccination. Demographics and comorbid conditions were included in the multinomial logistic model to estimate the propensity score. Cox regression model with an inverse probability treatment weighting was employed.
Results: Approximately, 1.2 million patients were vaccinated with either influenza or bivalent COVID-19 vaccines (714K FLU, 106K BPF, 97K BMD, 148K FBPF, and 144K FBMD). Overall, about 91% were male, 66% were >= 65 years, 65% were White, 19% were Black. The risks (HR and 95% CI) for AMI were 1.38 (0.57-3.35) for BMD vs BPF; 0.96 (0.50-1.87) for BMD vs FLU; 0.70 (0.37-1.32) for BPF and FLU; 0.73 (0.39-1.40) for FBMD vs FBPF. The risks (HR and 95% CI) for PE were 0.48 (0.16-1.47) for BMD vs BPF; 0.37 (0.15-0.92) for BMD vs FLU; 0.77 (0.38-1.56) for BPF vs FLU; 0.75 (0.37-1.53) for FBMD vs FBPF. The risks (HR and 95% CI) for VTE were 0.80 (0.43-1.51) for BMD vs BPF; 0.81 (0.49-1.34) for BMD vs FLU; 1.01 (0.65-1.58) for BPF vs FLU; 0.75 (0.46-1.22) for FBMD vs FBPF.
Conclusions: No difference were found in AMI, PE, and VTE between BMD and BPF and FBMD and FBPF. There were no significant differences in AMI, and VTE between BMD or BPF and FLU. There was no difference between BPF and FLU for PE. However, there was less risk of PE for BMD compared to FLU and further investigation is needed.
