key: cord-0836293-kac6jvb2
authors: Flacco, M. E.; Soldato, G.; Acuti Martellucci, C.; Di Martino, G.; Carota, R.; Caponetti, A.; Manzoli, L.
title: Risk of SARS-CoV-2 reinfection 18 months after primary infection: population-level observational study.
date: 2022-02-19
journal: nan
DOI: 10.1101/2022.02.19.22271221
sha: f0232775dfb90ad41db6ad67fe0d169ff595f981
doc_id: 836293
cord_uid: kac6jvb2

Current data suggest that SARS-CoV-2 reinfections are rare, but uncertainties remain on the duration of the natural immunity, its protection against Omicron variant, finally the impact of vaccination to reduce reinfection rates. In this retrospective cohort analysis of the entire population of an Italian Region, we followed 1,293,941 subjects from the beginning of the pandemic to the current scenario of Omicron predominance (up to mid-January 2022). After an average of 334 days, we recorded 260 reinfections among 84,907 previously infected subjects (overall rate: 0.31%), two hospitalizations (2.4 x100,000), and one death. Importantly, the incidence of reinfection did not vary substantially over time: after 18-22 months from the primary infection, the reinfection rate was still 0.32%, suggesting that protection conferred by natural immunity may last beyond 12 months. The risk of reinfection was significantly higher among the unvaccinated subjects, and during the Omicron wave.

A number of field studies reported low rates of SARS-CoV-2 reinfections after a primary episode 1, 2 .

Uncertainties remain, however, on the duration of natural immunity, its protection against BA.1/B.1. 1.529 (Omicron) variant, and the impact of vaccination to decrease reinfection rates. We performed a retrospective cohort study on the entire population of an Italian region in order to estimate the incidence of SARS-CoV-2 reinfections and diseases according to vaccination status, predominant viral strain, and time after primary infection.

We included all residents in the Abruzzo Region, Italy with ≥1 positive nasopharyngeal swab detected by the regional accredited laboratories, from pandemic start (March 2, 2020) up to November 30, 2021. On January 14, 2022 (to allow ≥45 days of follow-up), we extracted all data of the official vaccination, COVID-19, demographic, hospital and co-pay exemption datasets of the National Healthcare System, merging individual information through encrypted fiscal code 3 . 

From the start of the pandemic, a total of 152,986 infections were detected among the 1,293,941 residents in the Abruzzo Region. After the exclusions of the subjects with a follow-up <45 days, or lacking negative intermediate swabs, a total of 84,907 subjects with a primary infection were included in the analysis. The average time after the primary infection was 334 days; 2829 subjects had a follow-up longer than 18 months (Table 1) . All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in Overall, the incidence of reinfection was 0.31% (n=260). Two subjects were hospitalized due to COVID-19 (2.4x100,000), and one died (a 73-year old female, with major cardiovascular disease and diabetes). Table 2 , the reinfection rate was significantly higher among females, younger subjects, and unvaccinated individuals (0.50% vs. 0.25% among those who received ≥2 vaccine doses). Moreover, a markedly higher rate of reinfections was recorded during the first 17 days of the Omicron wave (n=144/84,791; 8.5 per day) than during the 317 days of the pre-Omicron period (n=116/84,907; 0.4 per day). In contrast, the incidence of reinfection did not vary substantially by baseline comorbidities and over time: after 18 or more months from the primary infection (up to 22 months), the reinfection rate was still 0.32%. The multivariable analysis (Cox proportional hazards model adjusted for all the recorded variables, included a priori) confirmed univariate results ( Table 2) . When the analysis was stratified by circulating variant, the effectiveness of ≥2 vaccine doses was substantially higher in pre-Omicron (adjusted hazard ratio -HR vs. unvaccinated: 0.20; 95% Confidence Interval: 0.12-0.33) than Omicron wave (HR: 0.57; 0.36-0.90).

This study confirms and expands previous findings reporting a low risk of SARS-CoV-2 reinfection, and a very low risk of severe or lethal COVID-19 for those who recovered from a primary infection 2,6 , suggesting that the protection conferred by the natural immunity lasts beyond 12 months. Although the marked increase of the reinfection rates during the Omicron wave is concerning, the risk of a secondary severe disease or death remained close to zero. Therefore, despite the vaccines were able to significantly reduce the likelihood of reinfection in both pre-Omicron and Omicron waves, the risk-benefit profile of multiple vaccine doses for this population should be carefully evaluated.

All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in All rights reserved. No reuse allowed without permission.

perpetuity.

preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in 

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