Background: Reinfection by SARS-CoV-2 is a rare but possible event. We evaluated the prevalence of reinfections in the Province of Modena and performed an overview of systematic reviews to summarize the current knowledge. Methods: We applied big data analysis and retrospectively analysed the results of oro- or naso-pharyngeal swab results tested for molecular research of viral RNA of SARS-CoV-2 between 1 January 2021 and 30 June 2021 at a single center. We selected individuals with samples sequence of positive, negative and then positive results. Between first and second positive result we considered a time interval of 90 days to be sure of a reinfection. We also performed a search for and evaluation of systematic reviews reporting SARS-CoV-2 reinfection rates. Main information was collected and the methodological quality of each review was assessed, according to A Measurement Tool to Assess systematic Reviews (AMSTAR). Results: Initial positive results were revealed in more than 35,000 (20%) subjects; most (28%) were aged 30–49 years old. Reinfection was reported in 1,258 (3.5%); most (33%) were aged 30–49 years old. Reinfection rates according to vaccinated or non-vaccinated subjects were 0.6% vs 1.1% (p < 0.0001). Nine systematic reviews were identified and confirmed that SARS-CoV-2 reinfection rate is a rare event. AMSTAR revealed very low-moderate levels of quality among selected systematic reviews. Conclusions: There is a real, albeit rare risk of SARS-CoV-2 reinfection. Big data analysis enabled accurate estimates of the reinfection rates. Nevertheless, a standardized approach to identify and report reinfection cases should be developed. [ABSTRACT FROM AUTHOR]