Risk of reinfection and disease after SARS-CoV-2 primary infection. Meta-analysis

Introduction: A precise estimate of the frequency and severity of SARS-CoV-2 reinfections would be critical to optimize restriction and vaccination policies for the hundreds of millions previously infected subjects. We performed a meta-analysis to evaluate the risk of reinfection and COVID-19 following primary infection. Methods: We searched MedLine, Scopus and preprint repositories for cohort studies evaluating the onset of new infections among baseline SARS-CoV-2-positive subjects. Random-effect meta-analyses of proportions were stratified by gender, exposure risk, vaccination status, viral strain, time between episodes, and reinfection definition. Results: Ninety-one studies, enrolling 15,034,624 subjects, were included. Overall, 158,478 reinfections were recorded, corresponding to a pooled rate of 0.97% (95% CI: 0.71%–1.27%), with no substantial differences by definition criteria, exposure risk or gender. Reinfection rates were still 0.66% after ≥12 months from first infection, and the risk was substantially lower among vaccinated subjects (0.32% vs. 0.74% for unvaccinated individuals). During the first 3 months of Omicron wave, the reinfection rates reached 3.31%. Overall rates of severe/lethal COVID-19 were very low (2–7 per 10,000 subjects according to definition criteria) and were not affected by strain predominance. Conclusions: A strong natural immunity follows the primary infection and may last for more than one year, suggesting that the risk and health care needs of recovered subjects might be limited. Although the reinfection rates considerably increased during the Omicron wave, the risk of a secondary severe or lethal disease remained very low. The risk–benefit profile of multiple vaccine doses for this subset of population needs to be carefully evaluated.