Background

Understanding the level and characteristics of protection from past SARS-CoV-2 infection against subsequent re-infection, symptomatic COVID-19 disease, and severe disease is essential for predicting future potential disease burden, for designing policies that restrict travel or access to venues where there is a high risk of transmission, and for informing choices about when to receive vaccine doses. We aimed to systematically synthesise studies to estimate protection from past infection by variant, and where data allow, by time since infection.

Methods

In this systematic review and meta-analysis, we identified, reviewed, and extracted from the scientific literature retrospective and prospective cohort studies and test-negative case-control studies published from inception up to Sept 31, 2022, that estimated the reduction in risk of COVID-19 among individuals with a past SARS-CoV-2 infection in comparison to those without a previous infection. We meta-analysed the effectiveness of past infection by outcome (infection, symptomatic disease, and severe disease), variant, and time since infection. We ran a Bayesian meta-regression to estimate the pooled estimates of protection. Risk-of-bias assessment was evaluated using the National Institutes of Health quality-assessment tools. The systematic review was PRISMA compliant and was registered with PROSPERO (number CRD42022303850).

Findings

We identified a total of 65 studies from 19 different countries. Our meta-analyses showed that protection from past infection and any symptomatic disease was high for ancestral, alpha, beta, and delta variants, but was substantially lower for the omicron BA.1 variant. Pooled effectiveness against re-infection by the omicron BA.1 variant was 45·3% (95% uncertainty interval [UI] 17·3–76·1) and 44·0% (26·5–65·0) against omicron BA.1 symptomatic disease. Mean pooled effectiveness was greater than 78% against severe disease (hospitalisation and death) for all variants, including omicron BA.1. Protection from re-infection from ancestral, alpha, and delta variants declined over time but remained at 78·6% (49·8–93·6) at 40 weeks. Protection against re-infection by the omicron BA.1 variant declined more rapidly and was estimated at 36·1% (24·4–51·3) at 40 weeks. On the other hand, protection against severe disease remained high for all variants, with 90·2% (69·7–97·5) for ancestral, alpha, and delta variants, and 88·9% (84·7–90·9) for omicron BA.1 at 40 weeks.

Interpretation

Protection from past infection against re-infection from pre-omicron variants was very high and remained high even after 40 weeks. Protection was substantially lower for the omicron BA.1 variant and declined more rapidly over time than protection against previous variants. Protection from severe disease was high for all variants. The immunity conferred by past infection should be weighed alongside protection from vaccination when assessing future disease burden from COVID-19, providing guidance on when individuals should be vaccinated, and designing policies that mandate vaccination for workers or restrict access, on the basis of immune status, to settings where the risk of transmission is high, such as travel and high-occupancy indoor settings.

Funding

Bill & Melinda Gates Foundation, J Stanton, T Gillespie, and J and E Nordstrom.

中文翻译：

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过去 SARS-CoV-2 感染对再次感染的保护：系统评价和荟萃分析

背景

了解对过去 SARS-CoV-2 感染的保护水平和特征，以及针对随后的再次感染、有症状的 COVID-19 疾病和严重疾病的保护水平和特征，对于预测未来潜在的疾病负担、设计限制旅行或进入某些场所的政策至关重要。传播风险很高，并且需要告知选择何时接种疫苗剂量。我们的目的是系统地综合研究，以估计变体对过去感染的保护作用，并在数据允许的情况下，按感染后的时间进行计算。

方法

在这项系统回顾和荟萃分析中，我们从科学文献中识别、回顾和提取了从开始到 2022 年 9 月 31 日发表的回顾性和前瞻性队列研究以及测试阴性病例对照研究，这些研究估计了以下风险的降低：与以前没有感染过的人相比，过去感染过 SARS-CoV-2 的个体中的 COVID-19。我们按结果（感染、有症状疾病和严重疾病）、变异和感染后时间对过去感染的有效性进行了荟萃分析。我们运行贝叶斯元回归来估计保护的汇总估计值。使用美国国立卫生研究院质量评估工具评估偏倚风险。系统评价符合 PRISMA 标准，并已在 PROSPERO 注册（编号 CRD42022303850）。

发现

我们总共确定了来自 19 个不同国家的 65 项研究。我们的荟萃分析表明，祖先、α、β 和 δ 变体对过去感染和任何有症状疾病的保护作用较高，但 omicron BA.1 变体的保护作用要低得多。针对 omicron BA.1 变体再次感染的汇总有效性为 45·3%（95% 不确定区间 [UI] 17·3–76·1）和 44·0% (26·5–65·0)。 BA.1 有症状的疾病。所有变体（包括 omicron BA.1）针对严重疾病（住院和死亡）的平均汇总有效性均大于 78%。随着时间的推移，对祖先、α 和 δ 变体再次感染的保护作用逐渐下降，但在 40 周时仍保持在 78·6% (49·8–93·6)。omicron BA.1 变体对再次感染的保护作用下降得更快，估计在 40 周时为 36·1% (24·4–51·3)。另一方面，所有变体对严重疾病的保护仍然很高，祖先、α 和 δ 变体的保护率为 90·2% (69·7–97·5)，88·9% (84·7–90·5)。 9) 40 周时的 omicron BA.1。

解释

对过去感染和前微米变体再次感染的保护非常高，并且即使在 40 周后仍然保持高水平。omicron BA.1 变体的保护作用明显较低，并且随着时间的推移，其下降速度比对之前变体的保护作用更快。所有变体对严重疾病的保护作用都很高。在评估 COVID-19 未来的疾病负担、就个人何时应接种疫苗提供指导以及根据免疫状况设计强制工人接种疫苗或限制接种的政策时，应权衡过去感染所赋予的免疫力与疫苗接种的保护，到传播风险高的环境，例如旅行和高占用率的室内环境。

资金

比尔及梅琳达·盖茨基金会、J·斯坦顿、T·吉莱斯皮、J 和 E·诺德斯特龙。