ARTICLES| VOLUME 397, ISSUE 10280, P1204-1212, MARCH 27, 2021

Assessment of protection against reinfection with SARS-CoV-2 among 4 million PCR-tested individuals in Denmark in 2020: a population-level observational study

Christian Holm Hansen, Daniela Michlmayr, Sophie Madeleine Gubbels, et al.

Lancet 2021; 397: 1204-1212

DOI:https://doi.org/10.1016/S0140-6736(21)00575-4

Summary

Background 背景

The degree to which infection with SARS-CoV-2 confers protection towards subsequent reinfection is not well described. In 2020, as part of Denmark's extensive, free-of-charge PCR-testing strategy, approximately 4 million individuals (69% of the population) underwent 10·6 million tests. Using these national PCR-test data from 2020, we estimated protection towards repeat infection with SARS-CoV-2.

SARS-CoV-2感染对于后续的再次感染究竟在多大程度上起到保护作用尚不清楚。2020年，作为丹麦全民免费PCR检测策略的一部分，约有400万人（69%的人口）接受了1060万次检测。根据2020年全国PCR检测数据，我们对于SARS-CoV-2再次感染的保护作用进行了评估。

Methods 方法

In this population-level observational study, we collected individual-level data on patients who had been tested in Denmark in 2020 from the Danish Microbiology Database and analysed infection rates during the second surge of the COVID-19 epidemic, from Sept 1 to Dec 31, 2020, by comparison of infection rates between individuals with positive and negative PCR tests during the first surge (March to May, 2020). For the main analysis, we excluded people who tested positive for the first time between the two surges and those who died before the second surge. We did an alternative cohort analysis, in which we compared infection rates throughout the year between those with and without a previous confirmed infection at least 3 months earlier, irrespective of date. We also investigated whether differences were found by age group, sex, and time since infection in the alternative cohort analysis. We calculated rate ratios (RRs) adjusted for potential confounders and estimated protection against repeat infection as 1 – RR.

在这项基于人口的观察性研究中，我们收集了2020年丹麦微生物数据库中接受检测的患者个人资料，并通过比较第一波疫情期间（2020年3月至5月）PCR阳性与阴性者的感染率，在2020年9月1日至12月31日COVID-19第二波疫情中的感染率进行了分析。作为主要分析，我们排除了两次疫情之间首次检测阳性的人群，以及第二波疫情前死亡的人群。我们还进行了另一项队列分析，比较了伴有或不伴有既往明确感染者（至少3个月前，无论日期如何）全年期间的感染率。我们还在另一队列研究中分析了不同年龄组、性别以及距离感染时间是否存在差异。我们对于可能的混杂因素进行校正后计算率比值(RRs)，将再次感染保护作用表示为1-RR。

Findings 结果

During the first surge (ie, before June, 2020), 533 381 people were tested, of whom 11 727 (2·20%) were PCR positive, and 525 339 were eligible for follow-up in the second surge, of whom 11 068 (2·11%) had tested positive during the first surge. Among eligible PCR-positive individuals from the first surge of the epidemic, 72 (0·65% [95% CI 0·51–0·82]) tested positive again during the second surge compared with 16 819 (3·27% [3·22–3·32]) of 514 271 who tested negative during the first surge (adjusted RR 0·195 [95% CI 0·155–0·246]). Protection against repeat infection was 80·5% (95% CI 75·4–84·5). The alternative cohort analysis gave similar estimates (adjusted RR 0·212 [0·179–0·251], estimated protection 78·8% [74·9–82·1]). In the alternative cohort analysis, among those aged 65 years and older, observed protection against repeat infection was 47·1% (95% CI 24·7–62·8). We found no difference in estimated protection against repeat infection by sex (male 78·4% [72·1–83·2] vs female 79·1% [73·9–83·3]) or evidence of waning protection over time (3–6 months of follow-up 79·3% [74·4–83·3] vs ≥7 months of follow-up 77·7% [70·9–82·9]).

在第一波疫情 (即2020年6月前)，共有533 381人接受检测，其中11 727人 (2·20%) PCR阳性，525 339人在第二波疫情期间接受随访，其中11 068人 (2·11%)在第一次疫情期间检测阳性。在第一波疫情期间PCR检测阳性的人群中，72人 (0·65% [95% CI 0·51–0·82]) 在第二波疫情期间检测再次阳性，在第一波疫情期间检测阴性的514 271人中，16 819人 (3·27% [3·22–3·32]) 在第二波疫情期间检测呈阳性 (校正 RR 0·195 [95% CI 0·155–0·246])。再次感染的保护作用为 80·5% (95% CI 75·4–84·5)。队列分析也显示相似结果 (校正 RR 0·212 [0·179–0·251], 估计保护作用 78·8% [74·9–82·1])。另一项队列分析显示，65岁及以上的老年人中，再次感染的保护作用为 47·1% (95% CI 24·7–62·8)。我们发现再次感染的保护作用与性别无关 (男性 78·4% [72·1–83·2] vs 女性 79·1% [73·9–83·3])，也与时间无关 (3–6个月随访 79·3% [74·4–83·3] vs ≥7个月随访 77·7% [70·9–82·9])。

Interpretation 结论

Our findings could inform decisions on which groups should be vaccinated and advocate for vaccination of previously infected individuals because natural protection, especially among older people, cannot be relied on.

我们的研究结果对于何种人群应当接受疫苗接种决策提供信息，提示即往感染者应当接受疫苗接种，因为天然保护是不可靠的，尤其对于老年人而言。

Funding

None.