AUTHOR=Hu Wei-Hua , Cai Huan-Le , Yan Huan-Chang , Wang Han , Sun Hui-Min , Wei Yong-Yue , Hao Yuan-Tao 

TITLE=Protective effectiveness of previous infection against subsequent SARS-Cov-2 infection: systematic review and meta-analysis

JOURNAL=Frontiers in Public Health

VOLUME=12

YEAR=2024

URL=https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2024.1353415

DOI=10.3389/fpubh.2024.1353415

ISSN=2296-2565

ABSTRACT=<sec id="sec1"><title>Background</title><p>The protective effectiveness provided by naturally acquired immunity against SARS-CoV-2 reinfection remain controversial.</p></sec><sec id="sec2"><title>Objective</title><p>To systematically evaluate the protective effect of natural immunity against subsequent SARS-CoV-2 infection with different variants.</p></sec><sec id="sec3"><title>Methods</title><p>We searched for related studies published in seven databases before March 5, 2023. Eligible studies included in the analysis reported the risk of subsequent infection for groups with or without a prior SARS-CoV-2 infection. The primary outcome was the overall pooled incidence rate ratio (<italic>IRR</italic>) of SARS-CoV-2 reinfection/infection between the two groups. We also focused on the protective effectiveness of natural immunity against reinfection/infection with different SARS-CoV-2 variants. We used a random-effects model to pool the data, and obtained the bias-adjusted results using the trim-and-fill method. Meta-regression and subgroup analyses were conducted to explore the sources of heterogeneity. Sensitivity analysis was performed by excluding included studies one by one to evaluate the stability of the results.</p></sec><sec id="sec4"><title>Results</title><p>We identified 40 eligible articles including more than 20 million individuals without the history of SARS-CoV-2 vaccination. The bias-adjusted efficacy of naturally acquired antibodies against reinfection was estimated at 65% (pooled <italic>IRR</italic> = 0.35, 95% CI = 0.26–0.47), with higher efficacy against symptomatic COVID-19 cases (pooled <italic>IRR</italic> = 0.15, 95% CI = 0.08–0.26) than asymptomatic infection (pooled <italic>IRR</italic> = 0.40, 95% CI = 0.29–0.54). Meta-regression revealed that SARS-CoV-2 variant was a statistically significant effect modifier, which explaining 46.40% of the variation in <italic>IRR</italic>s. For different SARS-CoV-2 variant, the pooled <italic>IRRs</italic> for the Alpha (pooled <italic>IRR</italic> = 0.11, 95% CI = 0.06–0.19), Delta (pooled <italic>IRR</italic> = 0.19, 95% CI = 0.15–0.24) and Omicron (pooled <italic>IRR</italic> = 0.61, 95% CI = 0.42–0.87) variant were higher and higher. In other subgroup analyses, the pooled <italic>IRR</italic>s of SARS-CoV-2 infection were statistically various in different countries, publication year and the inclusion end time of population, with a significant difference (<italic>p</italic> = 0.02, <italic>p</italic> &lt; 0.010 and <italic>p</italic> &lt; 0.010), respectively. The risk of subsequent infection in the seropositive population appeared to increase slowly over time. Despite the heterogeneity in included studies, sensitivity analyses showed stable results.</p></sec><sec id="sec5"><title>Conclusion</title><p>Previous SARS-CoV-2 infection provides protection against pre-omicron reinfection, but less against omicron. Ongoing viral mutation requires attention and prevention strategies, such as vaccine catch-up, in conjunction with multiple factors.</p></sec>