{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:34:11Z","timestamp":1792622051130,"version":"4.5.0"},"reference-count":39,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>Limited randomized clinical trial data exist on the safety of simultaneous administration of COVID-19 and influenza vaccines.<\/jats:p><\/jats:sec>Objective<\/jats:title>To compare the reactogenicity, safety, and changes in health-related quality of life (HRQOL) after simultaneous vs sequential receipt of messenger RNA (mRNA) COVID-19 vaccine and quadrivalent inactivated influenza vaccine (IIV4).<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This randomized, placebo-controlled clinical trial was conducted between October 8, 2021, and June 14, 2023, at 3 US sites. Participants were nonpregnant persons aged 5 years or older with the intention of receiving both influenza and mRNA COVID-19 vaccines.<\/jats:p><\/jats:sec>Interventions<\/jats:title>Intramuscular administration in opposite arms of either IIV4 or saline placebo simultaneously with mRNA COVID-19 vaccine at visit 1. Those who received placebo at visit 1 received IIV4 and those who received IIV4 at visit 1 received placebo 1 to 2 weeks later at visit 2.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary composite reactogenicity outcome was the proportion of participants with fever, chills, myalgia, and\/or arthralgia of moderate or greater severity within 7 days after vaccination visits 1 and\/or 2, using a 10% noninferiority margin. Secondary outcomes were solicited reactogenicity events and unsolicited adverse events (AEs) for 7 days after each visit separately and HRQOL after visit 1, assessed by the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index. Serious AEs (SAEs) and AEs of special interest (AESIs) were assessed for 121 days. Outcomes were compared between groups.<\/jats:p><\/jats:sec>Results<\/jats:title>A total of 335 persons (mean [SD] age, 33.4 [15.1] years) were randomized (169 to the simultaneous group and 166 to the sequential group); 211 (63.0%) were female, and 255 (76.1%) received bivalent BNT162b2 mRNA COVID-19 vaccine. The proportion with the primary composite reactogenicity outcome in the simultaneous group (25.6% [n\u2009=\u200943]) was noninferior to the proportion in the sequential group (31.3% [n\u2009=\u200952]) (site-adjusted difference, \u20135.6 percentage points [pp]; 95% CI, \u221215.2 to 4.0 pp). Respective proportions in each group were similar after each visit separately (visit 1, 40 [23.8%] vs 47 [28.3%]; visit 2, 5 [3.0%] vs 9 [5.4%]). No significant group differences in participants with AEs (21 [12.4%] vs 16 [9.6%]), SAEs (1 [0.6%] vs 1 [0.6%]), and AESIs (19 [11.2%] vs 9 [5.4%]) were observed in the simultaneous vs sequential groups, respectively. Among participants with severe reactogenicity, the mean (SD) EQ-5D-5L Index score decreased from 0.92 (0.08) to 0.92 (0.09) prevaccination to 0.81 (0.09) to 0.82 (0.12) postvaccination.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this randomized clinical trial assessing simultaneous vs sequential administration of mRNA COVID-19 and IIV4 vaccines, reactogenicity was comparable in both groups. These findings support the option of simultaneous administration of these vaccines.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ClinicalTrials.gov Identifier: NCT05028361<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2024.43166","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T16:00:56Z","timestamp":1730908856000},"page":"e2443166","source":"Crossref","is-referenced-by-count":22,"title":["Safety of Simultaneous vs Sequential mRNA COVID-19 and Inactivated Influenza Vaccines"],"prefix":"10.1001","volume":"7","author":[{"given":"Emmanuel B.","family":"Walter","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina"},{"name":"Duke Human Vaccine Institute, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth P.","family":"Schlaudecker","sequence":"additional","affiliation":[{"name":"Division of 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