MAJOR ARTICLE 622 • CID 2022:74 (15 February) • Leidi et al Clinical Infectious Diseases Received 31 March 2021; editorial decision 20 May 2021; published online 27 May 2021. a A. L., F. K., I. G., and S. S. contributed equally to this work. Correspondence: A. Leidi, General Internal Medicine, Department of Medicine, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland (Antonio.Leidi@ hcuge.ch). Clinical Infectious Diseases ® 2022;74(4):622–9 © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. DOI: 10.1093/cid/ciab495 Risk of Reinfection Afer Seroconversion to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): A Population-based Propensity-score Matched Cohort Study Antonio Leidi, 1,a, Flora Koegler, 1,a Roxane Dumont, 2 Richard Dubos, 2 María-Eugenia Zaballa, 2 Giovanni Piumatti, 2,3 Matteo Coen, 1 Amandine Berner, 1 Pauline Darbellay Farhoumand, 1 Pauline Vetter, 4 Nicolas Vuilleumier, 5 Laurent Kaiser, 4 Delphine Courvoisier, 6 Andrew S. Azman, 2,7 Idris Guessous, 2,a and Silvia Stringhini 2,a ; for the SEROCoV-POP study group 1 Division of General Internal Medicine, Geneva University Hospitals, Geneva, Switzerland; 2 Division of Primary Care Medicine, Geneva University Hospitals, Geneva, Switzerland; 3 Institute of Public Health, Faculty of BioMedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland; 4 Geneva Center for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland; 5 Division of Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland; 6 General Directorate of Health, Geneva, Switzerland; and 7 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA Background. Serological assays detecting anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies are being widely deployed in studies and clinical practice. However, the duration and efectiveness of the protection conferred by the immune response remains to be assessed in population-based samples. To estimate the incidence of newly acquired SARS-CoV-2 in- fections in seropositive individuals as compared to seronegative controls, we conducted a retrospective longitudinal matched study. Methods. A seroprevalence survey including a representative sample of the population was conducted in Geneva, Switzerland, between April and June 2020, immediately afer the frst pandemic wave. Seropositive participants were matched one-to-two to se- ronegative controls, using a propensity-score including age, gender, immunodefciency, body mass index (BMI), smoking status, and education level. Each individual was linked to a state-registry of SARS-CoV-2 infections. Our primary outcome was confrmed infections occurring from serological status assessment to the end of the second pandemic wave (January 2021). Results. Among 8344 serosurvey participants, 498 seropositive individuals were selected and matched with 996 seronegative controls. Afer a mean follow-up of 35.6 (standard deviation [SD] 3.2) weeks, 7 out of 498 (1.4%) seropositive subjects had a positive SARS-CoV-2 test, of whom 5 (1.0%) were classifed as reinfections. In contrast, the infection rate was higher in seronegative indi- viduals (15.5%, 154/996) during a similar follow-up period (mean 34.7 [SD 3.2] weeks), corresponding to a 94% (95% confdence interval [CI]: 86%– 98%, P < .001) reduction in the hazard of having a positive SARS-CoV-2 test for seropositives. Conclusions. Seroconversion afer SARS-CoV-2 infection confers protection against reinfection lasting at least 8 months. Tese fndings could help global health authorities establishing priority for vaccine allocation. Keywords: antibody; COVID-19; protection; reinfection; SARS-CoV-2. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces seroconversion detectable in up to 99% of in- dividuals 2–4 weeks following infection with the magnitude of antibody response being influenced by the severity of the di- sease, timing for testing and the diagnostic performance of im- munoassay [1, 2]. Markers of cellular and humoral immunity have been shown to last at least 6–8 months after infection [3, 4]. However, the extent to which and how long these markers are related to protection against future infections need to be better defined. Because of limited testing availability in the early phases of the pandemic and because of asymptomatic infections, seroprevalence surveys gave the best estimate of the infection’s burden in early phases of pandemic, with rates of seroposi- tivity <10% after the first wave in Switzerland and in the United States [5, 6]. Although over 154 million virologically confirmed SARS-CoV-2 infections have been registered worldwide to date (May 2021), reports of reinfection are scarce and often limited to mild cases [7], suggesting that SARS-CoV-2 infection elicits protective immunity [8]. Few recent studies among healthcare workers [9–11], care homes [12], national registries [13–15], and laboratory de-identified data sets [16] reported low inci- dence of reinfection among seropositive or previously infected participants. However, generalization of their conclusions to the general population is limited by sampling bias (eg, selection of healthy young participants), lack of control for confounding fac- tors (eg, no adjustment for comorbidities), or low incidence of infections during the period of observation. To date, no longitu- dinal assessment of reinfection upon positive serological status Downloaded from https://academic.oup.com/cid/article/74/4/622/6287116 by guest on 24 June 2022