The specific antibodies induced by SARS-CoV-2 infection may provide protection against a subsequent infection. However, the efficacy and duration of protection provided by naturally acquired immunity against subsequent SARS-CoV-2 infection remain controversial. We systematically searched for the literature describing COVID-19 reinfection published before 07 February 2022. The outcomes were the pooled incidence rate ratio (IRR) for estimating the risk of subsequent infection. The Newcastle–Ottawa Scale (NOS) was used to assess the quality of the included studies. Statistical analyses were conducted using the R programming language 4.0.2. We identified 19 eligible studies including more than 3.5 million individuals without the history of COVID-19 vaccination. The efficacy of naturally acquired antibodies against reinfection was estimated at 84% (pooled IRR = 0.16, 95% CI: 0.14-0.18), with higher efficacy against symptomatic COVID-19 cases (pooled IRR = 0.09, 95% CI = 0.07-0.12) than asymptomatic infection (pooled IRR = 0.28, 95% CI = 0.14-0.54). In the subgroup analyses, the pooled IRRs of COVID-19 infection in health care workers (HCWs) and the general population were 0.22 (95% CI = 0.16-0.31) and 0.14 (95% CI = 0.12-0.17), respectively, with a significant difference ( P = 0.02), and those in older (over 60 years) and younger (under 60 years) populations were 0.26 (95% CI = 0.15–0.48) and 0.16 (95% CI =  0.14-0.19), respectively. The risk of subsequent infection in the seropositive population appeared to increase slowly over time. In conclusion, naturally acquired antibodies against SARS-CoV-2 can significantly reduce the risk of subsequent infection, with a protection efficacy of 84%. Registration number: CRD42021286222

The live-attenuated influenza virus vector-based intranasal vaccine (dNS1-RBD, Pneucolin®) is the world’s first COVID-19 mucosal vaccine to enter human trials, and has been issued for emergency use authorization in China. Here, we report safety and efficacy data from a multi-centre randomized, double-blind, placebo-controlled phase 3 clinical trial of Pneucolin® (two doses, 14 days apart) in adults (18 years and older) during the Omicron circulation. The result showed a favorable safety profile, with no difference in the incidence of adverse reactions between the vaccine and placebo groups. In the per-protocol set, for symptomatic COVID-19, the efficacies among total population, naïve participants, particiants with inactivated vacciantion history were 32.6% (95%CI 8.2 to 50.5), 55.2% (95%CI 13.8 to 76.7), 38.2% (95%CI -49.2 to 74.4) , and for symptomatic COVID-19 with three or more of the suspected symptoms, the efficacies were 42.3% (95%CI 15.7 to 60.5), 66.7% (95%CI 8.3 to 87.9) and 63.1% (95%CI -15.8 to 88.3) for the above mentioned 3 cohorts. An efficacy of 100.0% (95%CI -9.2 to 100.0) against hospitalized COVID-19 was observed in the whole enrolled population. We conclude that Pneucolin® is well-tolerated and can be an antibody-independent broad-spectrum effective tool to combat SARS-CoV-2 variants, as primary immunization or heterologous booster.

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