Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina.
Duke Human Vaccine Institute, Durham, North Carolina.
JAMA Netw Open. 2024 Nov 4;7(11):e2443166. doi: 10.1001/jamanetworkopen.2024.43166.
Limited randomized clinical trial data exist on the safety of simultaneous administration of COVID-19 and influenza vaccines.
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).
DESIGN, SETTING, AND PARTICIPANTS: 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.
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.
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.
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 = 43]) was noninferior to the proportion in the sequential group (31.3% [n = 52]) (site-adjusted difference, -5.6 percentage points [pp]; 95% CI, -15.2 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.
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.
ClinicalTrials.gov Identifier: NCT05028361.
关于同时接种 COVID-19 和流感疫苗的安全性，仅有有限的随机临床试验数据。
比较信使 RNA（mRNA）COVID-19 疫苗和四价灭活流感疫苗（IIV4）同时接种与序贯接种后，在发热性疾病、安全性和健康相关生活质量（HRQOL）变化方面的差异。
设计、地点和参与者：这是一项在美国 3 个地点进行的随机、安慰剂对照临床试验，于 2021 年 10 月 8 日至 2023 年 6 月 14 日进行。参与者为有接种流感和 mRNA COVID-19 疫苗意愿的 5 岁及以上的非妊娠人群。
在第 1 次就诊时，在不同手臂肌肉内同时接种 IIV4 或生理盐水安慰剂，以及 mRNA COVID-19 疫苗。第 1 次就诊时接受安慰剂的参与者，在第 1 次就诊后 1 至 2 周时接受 IIV4；第 1 次就诊时接受 IIV4 的参与者，在第 2 次就诊时接受安慰剂。
主要复合发热性疾病结局是在第 1 次和第 2 次就诊后 7 天内，评估接种疫苗后参与者中出现中度或更严重发热、寒战、肌痛和/或关节痛的比例，使用 10%的非劣效性边界。次要结局是分别在每次就诊后 7 天内评估的发热性疾病和不良反应（AE），以及在第 1 次就诊后评估的健康相关生活质量，采用欧洲五维健康量表 5 维 5 级（EQ-5D-5L）指数进行评估。严重 AEs（SAEs）和特别关注的 AEs（AESIs）在 121 天内进行评估。对各组间的结局进行比较。
共 335 名参与者（平均[标准差]年龄，33.4[15.1]岁）被随机分配（同时组 169 名，序贯组 166 名）；211 名（63.0%）为女性，255 名（76.1%）接种了二价 BNT162b2 mRNA COVID-19 疫苗。同时组中出现主要复合发热性疾病结局的比例（25.6%[43 名]）与序贯组相似（31.3%[52 名]）（位置调整差异，-5.6 个百分点[pp]；95%CI，-15.2 至 4.0 pp）。每组在每次就诊后的比例也相似（就诊 1 时，40[23.8%] vs 47[28.3%]；就诊 2 时，5[3.0%] vs 9[5.4%]）。在同时组和序贯组中，AE（21[12.4%] vs 16[9.6%]）、SAE（1[0.6%] vs 1[0.6%]）和 AESIs（19[11.2%] vs 9[5.4%]）的发生率无显著差异。在有严重发热性疾病的参与者中，EQ-5D-5L 指数评分从接种前的 0.92（0.08）降至 0.92（0.09），再降至接种后的 0.81（0.09）至 0.82（0.12）。
在这项评估 mRNA COVID-19 和 IIV4 疫苗同时接种与序贯接种的随机临床试验中，两组的发热性疾病发生率相似。这些发现支持同时接种这些疫苗的选择。
ClinicalTrials.gov 标识符：NCT05028361。
