Effect of 2 Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults A Randomized Clinical Trial
Effect of 2 Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults A Randomized Clinical Trial
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DOI：
10.1001/jama.2021.8565
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发表时间：
2021-05-26
影响因子：
120.7
通讯作者：
Yang, Xiaoming
中科院分区：
文献类型：
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作者：
Al Kaabi, Nawal;Zhang, Yuntao;Yang, Xiaoming
本研究对一项正在进行的随机试验进行了中期分析，旨在评估两种冠状病毒灭活疫苗在预防健康成人出现症状性COVID-19和免疫后不良事件方面的有效性。重要性尽管已开发出针对COVID-19的有效疫苗，但仍需要额外的疫苗。目的评价2种新型冠状病毒灭活疫苗的免疫效果和不良反应。设计、设置和参与者对一项正在阿拉伯联合酋长国和巴林进行的随机、双盲、III期试验进行预先规定的中期分析，该试验在18岁及以上的成年人中进行，没有已知的COVID-19病史。研究入组于2020年7月16日开始。用于疗效和不良事件中期分析的数据集分别于2020年12月20日和2020年12月31日锁定。参与者被随机分配接受由SARS-CoV-2 WIV04（5 μ g/剂; n = 13 459）和HB 02（4 μ g/剂; n = 13 465）菌株开发的2种灭活疫苗中的1种或仅氢氧化铝（明矾）对照（n = 13 458）;他们接受2次肌肉注射，间隔21天。主要结局和指标主要结局是在随机分组时没有SARS-CoV-2感染病毒学证据的参与者中，在第二次疫苗接种后14天对实验室确认的症状性COVID-19的有效性。次要结局是对严重COVID-19的疗效。在接受至少1剂的参与者中收集不良事件和反应的发生率。结果在40382名参与者中，随机接受至少1剂2种疫苗或仅明矾对照（平均年龄36.1岁; 32 261人[84.4%]，38 206人（94.6%）接受了2次给药，在第2次给药后第14天后至少提供了1次随访措施，入组时逆转录-聚合酶链反应试验结果为阴性的患者纳入主要疗效分析。在中位（范围）77（1 - 121）天的随访期间，WIV04组中有26名参与者被确定为有症状的COVID-19（12.1 [95% CI，8.3 - 17.8]/1000人-年），HB 02组21例（9.8 [95% CI，6.4 - 15.0]/1000人-年），仅明矾组为95（44.7 [95%CI，36.6 - 54.6]/1000人-年），与仅使用明矾相比，疫苗有效性为72.8% WIV 04为78.1%（95% CI，58.1%-82.4%），HB 02为78.1%（95% CI，64.8%-86.3%）（两者P <0.001）。两例严重的COVID-19病例发生在仅使用明矾的组中，而疫苗组中没有发生。3组中41.7%至46.5%的受试者在每次注射后7天发生不良反应;严重不良事件罕见，3组相似（WIV 04：64 [0.5%]; HB 02：59 [0.4%];仅铝：78 [0.6%]）。结论和相关性在这项预先设定的随机临床试验中期分析中，用两种灭活SARS-CoV-2疫苗中的任何一种治疗成人显著降低了症状性COVID-19的风险，严重不良事件罕见。问题2种灭活SARS-CoV-2疫苗预防症状性COVID-19的有效性如何？这项预先设定的随机临床试验中期分析包括40382名参与者，他们接受了至少1剂由SARS-CoV-2WIV04开发的2剂灭活疫苗系列。（5 μ g/剂）或HB 02（4 μ g/剂）菌株或仅氢氧化铝对照，主要终点为第二次注射后至少14天出现症状性COVID-19。与仅氢氧化铝对照相比，WIV 04组和HB 02组中两种疫苗的有效性分别为72.8%和78.1%;两种比较均具有统计学显著性。两种灭活SARS-CoV-2疫苗与仅氢氧化铝对照相比，对症状性COVID-19表现出有效性。
This interim analysis of an ongoing randomized trial evaluates the efficacy of 2 inactivated coronavirus vaccines for preventing symptomatic COVID-19 in healthy adults and adverse events after immunization.Importance Although effective vaccines against COVID-19 have been developed, additional vaccines are still needed. Objective To evaluate the efficacy and adverse events of 2 inactivated COVID-19 vaccines. Design, Setting, and Participants Prespecified interim analysis of an ongoing randomized, double-blind, phase 3 trial in the United Arab Emirates and Bahrain among adults 18 years and older without known history of COVID-19. Study enrollment began on July 16, 2020. Data sets used for the interim analysis of efficacy and adverse events were locked on December 20, 2020, and December 31, 2020, respectively. Interventions Participants were randomized to receive 1 of 2 inactivated vaccines developed from SARS-CoV-2 WIV04 (5 mu g/dose; n = 13 459) and HB02 (4 mu g/dose; n = 13 465) strains or an aluminum hydroxide (alum)-only control (n = 13 458); they received 2 intramuscular injections 21 days apart. Main Outcomes and Measures The primary outcome was efficacy against laboratory-confirmed symptomatic COVID-19 14 days following a second vaccine dose among participants who had no virologic evidence of SARS-CoV-2 infection at randomization. The secondary outcome was efficacy against severe COVID-19. Incidence of adverse events and reactions was collected among participants who received at least 1 dose. Results Among 40 382 participants randomized to receive at least 1 dose of the 2 vaccines or alum-only control (mean age, 36.1 years; 32 261 [84.4%] men), 38 206 (94.6%) who received 2 doses, contributed at least 1 follow-up measure after day 14 following the second dose, and had negative reverse transcriptase-polymerase chain reaction test results at enrollment were included in the primary efficacy analysis. During a median (range) follow-up duration of 77 (1-121) days, symptomatic COVID-19 was identified in 26 participants in the WIV04 group (12.1 [95% CI, 8.3-17.8] per 1000 person-years), 21 in the HB02 group (9.8 [95% CI, 6.4-15.0] per 1000 person-years), and 95 in the alum-only group (44.7 [95% CI, 36.6-54.6] per 1000 person-years), resulting in a vaccine efficacy, compared with alum-only, of 72.8% (95% CI, 58.1%-82.4%) for WIV04 and 78.1% (95% CI, 64.8%-86.3%) for HB02 (P < .001 for both). Two severe cases of COVID-19 occurred in the alum-only group and none occurred in the vaccine groups. Adverse reactions 7 days after each injection occurred in 41.7% to 46.5% of participants in the 3 groups; serious adverse events were rare and similar in the 3 groups (WIV04: 64 [0.5%]; HB02: 59 [0.4%]; alum-only: 78 [0.6%]). Conclusions and Relevance In this prespecified interim analysis of a randomized clinical trial, treatment of adults with either of 2 inactivated SARS-CoV-2 vaccines significantly reduced the risk of symptomatic COVID-19, and serious adverse events were rare. Data collection for final analysis is pending.Question What is the efficacy of 2 inactivated SARS-CoV-2 vaccines for prevention of symptomatic COVID-19? Findings This prespecified interim analysis of a randomized clinical trial included 40 382 participants who received at least 1 dose of a 2-dose inactivated vaccine series developed from either SARS-CoV-2 WIV04 (5 mu g/dose) or HB02 (4 mu g/dose) strains or an aluminum hydroxide-only control, with a primary end point of the incidence of symptomatic COVID-19 at least 14 days after the second injection. The efficacy for the 2 vaccines, compared with an aluminum hydroxide-only control, was 72.8% in the WIV04 group and 78.1% in the HB02 group; both comparisons were statistically significant. Meaning Two inactivated SARS-CoV-2 vaccines demonstrated efficacy against symptomatic COVID-19 compared with an aluminum hydroxide-only control.