A recent randomized clinical trial published in JAMA Network Open has provided further evidence supporting the safety of administering mRNA COVID-19 vaccines and quadrivalent inactivated influenza vaccines (IIV4) simultaneously. The study, which compared simultaneous versus sequential administration, found that the safety profile, including reactogenicity, was similar between the two methods.
The trial addressed a crucial question given the CDC's recommendation for simultaneous vaccination against influenza and COVID-19. Researchers sought to provide robust evidence supporting this recommendation, which can streamline vaccine delivery and improve public health outcomes.
Study Design and Patient Population
The study enrolled participants aged 5 years and older who were either receiving their primary 2-dose COVID-19 vaccine series or a booster vaccine and intended to receive both COVID-19 and influenza vaccines. Key exclusion criteria included pregnancy or planned pregnancy within the next 3 months, and immunosuppressed individuals. Participants provided blood samples to determine their SARS-CoV-2 serostatus.
On the first visit, all participants received an mRNA COVID-19 vaccine intramuscularly. They were then randomized in a 1:1 ratio to receive either the FDA-approved IIV4 or a saline placebo vaccine. During the second visit, those who initially received the IIV4 vaccine received the placebo, and vice versa.
Key Findings: Safety and Reactogenicity
The primary outcome assessed was reactogenicity. The proportion of participants in the sequential group (31.3%) experiencing reactogenicity was noninferior to the simultaneous group (25.6%), with a site-adjusted difference of -5.6 percentage points (95% CI, -15.2 to 4.0 pp).
Over the 121-day assessment period, there were no significant differences in the proportion of participants experiencing serious adverse events (SAEs) between the simultaneous (0.6%) and sequential (0.6%) groups (difference, -0.01 pp [95% CI, -1.66 to -1.64 pp]). Similarly, there was no significant difference in adverse events of special interest (AESIs) between the simultaneous (11.2%) and sequential (5.4%) groups (difference, 5.8 pp [95% CI, -0.1 to 11.7 pp]).
Implications for Vaccination Strategies
These findings reinforce the safety of administering COVID-19 and influenza vaccines simultaneously, aligning with CDC recommendations. This approach simplifies vaccine administration, potentially increasing vaccination rates and reducing the burden of both influenza and COVID-19, which have been associated with significant hospitalizations and deaths.
