From Regeneron Pharmaceuticals, Tarrytown, NY (M.P.O., E.F.-N., B.J.M., F.I., K.-C.C., N. Sarkar, P.H., I.H., J.D.D., K.C.T., D.R., A.M., A.T.H., J.D.H., Y.K., L.A.P., A.B., C.A.K., B.K., A.T.D., N. Stahl, L.L., N.B., G.H., G.D.Y., D.M.W.); the Departments of Medicine and Microbiology, University of Pennsylvania, Philadelphia (K.J.B.); the Departments of Global Health and Epidemiology and the Division of Allergy and Infectious Diseases, University of Washington, and the Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center - both in Seattle (R.V.B.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston (D.H.B.); the Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill (M.S.C., C.B.H.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD (D.R.B., M.A.M.); Clinical Trials of Florida (J.K.) and Medical Research of Westchester (R.P.-P.) - both in Miami; and the Catalina Research Institute, Montclair, CA (R.M.).
N Engl J Med. 2021 Sep 23;385(13):1184-1195. doi: 10.1056/NEJMoa2109682. Epub 2021 Aug 4.
REGEN-COV (previously known as REGN-COV2), a combination of the monoclonal antibodies casirivimab and imdevimab, has been shown to markedly reduce the risk of hospitalization or death among high-risk persons with coronavirus disease 2019 (Covid-19). Whether subcutaneous REGEN-COV prevents severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent Covid-19 in persons at high risk for infection because of household exposure to a person with SARS-CoV-2 infection is unknown.
We randomly assigned, in a 1:1 ratio, participants (≥12 years of age) who were enrolled within 96 hours after a household contact received a diagnosis of SARS-CoV-2 infection to receive a total dose of 1200 mg of REGEN-COV or matching placebo administered by means of subcutaneous injection. At the time of randomization, participants were stratified according to the results of the local diagnostic assay for SARS-CoV-2 and according to age. The primary efficacy end point was the development of symptomatic SARS-CoV-2 infection through day 28 in participants who did not have SARS-CoV-2 infection (as measured by reverse-transcriptase-quantitative polymerase-chain-reaction assay) or previous immunity (seronegativity).
Symptomatic SARS-CoV-2 infection developed in 11 of 753 participants in the REGEN-COV group (1.5%) and in 59 of 752 participants in the placebo group (7.8%) (relative risk reduction [1 minus the relative risk], 81.4%; P<0.001). In weeks 2 to 4, a total of 2 of 753 participants in the REGEN-COV group (0.3%) and 27 of 752 participants in the placebo group (3.6%) had symptomatic SARS-CoV-2 infection (relative risk reduction, 92.6%). REGEN-COV also prevented symptomatic and asymptomatic infections overall (relative risk reduction, 66.4%). Among symptomatic infected participants, the median time to resolution of symptoms was 2 weeks shorter with REGEN-COV than with placebo (1.2 weeks and 3.2 weeks, respectively), and the duration of a high viral load (>10 copies per milliliter) was shorter (0.4 weeks and 1.3 weeks, respectively). No dose-limiting toxic effects of REGEN-COV were noted.
Subcutaneous REGEN-COV prevented symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in previously uninfected household contacts of infected persons. Among the participants who became infected, REGEN-COV reduced the duration of symptomatic disease and the duration of a high viral load. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04452318.).
REGEN-COV（以前称为 REGN-COV2）是两种单克隆抗体 casirivimab 和 imdevimab 的组合，已被证明可显著降低患有 2019 年冠状病毒病（COVID-19）的高危人群住院或死亡的风险。皮下注射 REGEN-COV 是否能预防因家庭接触感染 SARS-CoV-2 的人而感染严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）并随后发生 COVID-19，尚不清楚。
我们采用 1:1 的比例，随机分配参与者（年龄≥12 岁），这些参与者在家庭接触者被诊断出 SARS-CoV-2 感染后 96 小时内入组，接受 1200mg 总量的 REGEN-COV 或匹配的安慰剂，通过皮下注射给药。在随机分组时，根据当地 SARS-CoV-2 诊断检测的结果以及年龄对参与者进行分层。主要疗效终点是未感染 SARS-CoV-2（通过逆转录-定量聚合酶链反应检测）或无既往免疫（血清阴性）的参与者在第 28 天内发生有症状的 SARS-CoV-2 感染。
REGEN-COV 组 753 名参与者中有 11 名（1.5%）和安慰剂组 752 名参与者中有 59 名（7.8%）发生有症状的 SARS-CoV-2 感染（相对风险降低[1-相对风险]，81.4%；P<0.001）。在第 2 周到第 4 周，REGEN-COV 组 753 名参与者中有 2 名（0.3%）和安慰剂组 752 名参与者中有 27 名（3.6%）出现有症状的 SARS-CoV-2 感染（相对风险降低，92.6%）。REGEN-COV 还预防了有症状和无症状感染（相对风险降低，66.4%）。在有症状的感染参与者中，REGEN-COV 组症状缓解的中位时间比安慰剂组短 2 周（分别为 1.2 周和 3.2 周），高病毒载量（>10 拷贝/毫升）的持续时间也较短（分别为 0.4 周和 1.3 周）。未观察到 REGEN-COV 的剂量限制毒性作用。
皮下注射 REGEN-COV 可预防未感染的感染者家庭接触者发生有症状的 COVID-19 和无症状的 SARS-CoV-2 感染。在感染的参与者中，REGEN-COV 降低了有症状疾病的持续时间和高病毒载量的持续时间。（由 Regeneron 制药公司等资助；ClinicalTrials.gov 编号，NCT04452318）。
