SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN).
SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN).
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DOI：
10.1016/s0140-6736(21)00675-9
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发表时间：
2021-04-17
期刊：
影响因子：
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通讯作者：
SIREN Study Group
中科院分区：
文献类型：
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作者：
Hall VJ;Foulkes S;Charlett A;Atti A;Monk EJM;Simmons R;Wellington E;Cole MJ;Saei A;Oguti B;Munro K;Wallace S;Kirwan PD;Shrotri M;Vusirikala A;Rokadiya S;Kall M;Zambon M;Ramsay M;Brooks T;Brown CS;Chand MA;Hopkins S;SIREN Study Group
迫切需要进一步了解从COVID-19中康复的个体是否可以免受未来SARS-CoV-2感染。我们的目的是研究抗SARS-CoV-2抗体是否与有症状和无症状再感染风险降低相关。进行了一项大型、多中心、前瞻性队列研究，参与者来自英格兰所有地区的公立医院。所有在医院工作的卫生保健工作者、辅助人员和行政人员，只要能继续参与12个月的随访，都有资格参加SARS-CoV-2免疫和再感染评估研究。如果参与者在入组后没有进行PCR检测，在2020年12月31日之后入组，或者没有足够的PCR和抗体数据进行队列分配，则将其排除在外。参与者定期参加SARS-CoV-2 PCR和抗体检测（每2-4周），并每2周完成一次症状和暴露问卷。在招募时，参与者被分配到阳性队列（抗体阳性，或既往阳性PCR或抗体检测）或阴性队列（抗体阴性，既往无阳性PCR或抗体检测）。主要结果是阳性队列中的再感染或阴性队列中的原发性感染，通过PCR检测确定。根据病例定义（确认、很可能或可能）和疾病状态（取决于证据等级），对潜在的再感染进行临床审查和分类。阴性队列中的原发性感染定义为首次阳性PCR检测，当与阳性PCR检测无关时，排除血清转化。使用泊松分布的比例风险脆弱模型估计发病率比（IRR），以比较两个队列的感染率。从2020年6月18日至2020年12月31日，共有30625名参与者入组研究。51名参与者退出研究，4913名被排除，25661名参与者（抗体和PCR检测相关数据）被纳入分析。数据于2021年2月5日从所有来源提取，包括截至2021年1月11日的数据。在8278名参与者的基线阳性队列中检测到155例感染，共提供了2047113人-天的随访。相比之下，在17383名参与者的阴性队列中，有1704例新的PCR阳性感染，共进行了2971436人-天的随访。在2020年6月至2021年1月期间，阳性队列的发病密度为每10万人日7.6例再感染，而阴性队列为每10万人日57.3例原发感染。与PCR证实的原发性感染相比，所有再感染的校正IRR为0·159（95% CI 0·13-0·19）。初次感染与再感染的中位间隔时间超过200天。先前的SARS-CoV-2感染史与84%的感染风险降低相关，在初次感染后7个月观察到中位保护作用。该时间段是最小可能影响，因为未包括血清转化。这项研究表明，先前感染SARS-CoV-2可诱导大多数个体对未来感染的有效免疫力。联合王国政府卫生和社会保健部、英格兰公共卫生、国家卫生研究所，苏格兰、威尔士和北方爱尔兰政府提供捐助。
Increased understanding of whether individuals who have recovered from COVID-19 are protected from future SARS-CoV-2 infection is an urgent requirement. We aimed to investigate whether antibodies against SARS-CoV-2 were associated with a decreased risk of symptomatic and asymptomatic reinfection. A large, multicentre, prospective cohort study was done, with participants recruited from publicly funded hospitals in all regions of England. All health-care workers, support staff, and administrative staff working at hospitals who could remain engaged in follow-up for 12 months were eligible to join The SARS-CoV-2 Immunity and Reinfection Evaluation study. Participants were excluded if they had no PCR tests after enrolment, enrolled after Dec 31, 2020, or had insufficient PCR and antibody data for cohort assignment. Participants attended regular SARS-CoV-2 PCR and antibody testing (every 2–4 weeks) and completed questionnaires every 2 weeks on symptoms and exposures. At enrolment, participants were assigned to either the positive cohort (antibody positive, or previous positive PCR or antibody test) or negative cohort (antibody negative, no previous positive PCR or antibody test). The primary outcome was a reinfection in the positive cohort or a primary infection in the negative cohort, determined by PCR tests. Potential reinfections were clinically reviewed and classified according to case definitions (confirmed, probable, or possible) and symptom-status, depending on the hierarchy of evidence. Primary infections in the negative cohort were defined as a first positive PCR test and seroconversions were excluded when not associated with a positive PCR test. A proportional hazards frailty model using a Poisson distribution was used to estimate incidence rate ratios (IRR) to compare infection rates in the two cohorts. From June 18, 2020, to Dec 31, 2020, 30 625 participants were enrolled into the study. 51 participants withdrew from the study, 4913 were excluded, and 25 661 participants (with linked data on antibody and PCR testing) were included in the analysis. Data were extracted from all sources on Feb 5, 2021, and include data up to and including Jan 11, 2021. 155 infections were detected in the baseline positive cohort of 8278 participants, collectively contributing 2 047 113 person-days of follow-up. This compares with 1704 new PCR positive infections in the negative cohort of 17 383 participants, contributing 2 971 436 person-days of follow-up. The incidence density was 7·6 reinfections per 100 000 person-days in the positive cohort, compared with 57·3 primary infections per 100 000 person-days in the negative cohort, between June, 2020, and January, 2021. The adjusted IRR was 0·159 for all reinfections (95% CI 0·13–0·19) compared with PCR-confirmed primary infections. The median interval between primary infection and reinfection was more than 200 days. A previous history of SARS-CoV-2 infection was associated with an 84% lower risk of infection, with median protective effect observed 7 months following primary infection. This time period is the minimum probable effect because seroconversions were not included. This study shows that previous infection with SARS-CoV-2 induces effective immunity to future infections in most individuals. Department of Health and Social Care of the UK Government, Public Health England, The National Institute for Health Research, with contributions from the Scottish, Welsh and Northern Irish governments.