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Although laboratory data show that antibody responses to COVID-19 immunization give superior neutralization of certain circulating variations to spontaneous infection, few real-world epidemiological studies demonstrate the advantage of vaccination for previously infected individuals. This paper summarizes the outcomes of a case–control study conducted in Romania between March 2020 and October 2021 on patients previously infected with SARS-CoV-2. A case–control study was implemented after identification of 62 breakthrough cases. These cases were matched by age and gender to a 1:1 ratio with a control group of unvaccinated patients with SARS-CoV-2 reinfection status. There were no significant differences in the severity of cases and mortality between the study groups. However, unvaccinated patients had a shorter protection from natural immunity than patients with full vaccination status (58 days versus 89 days). The unvaccinated cases with SARS-CoV-2 reinfection were also statistically more likely to have a longer hospital admission duration (12.4 days versus 9.8 days), and required more non-invasive oxygen supplementation during their stay than breakthrough cases (37.1% versus 19.4%). Individuals with prior SARS-CoV-2 infection who were not vaccinated are not at a higher risk of severe COVID-19 infection or mortality compared to those who were completely vaccinated with the mRNA vaccine Comirnaty® Pfizer/BioNTech BNT162b2 and acquired a breakthrough infection within 2–3 months of the previous infection with a Beta or Delta SARS-CoV-2 variant. Although our findings are consistent with natural immunity offering similar short-term protection to a second dose of mRNA vaccine, all eligible individuals should be provided with immunization to lower their risk of infection, even if they have already been infected with SARS-CoV-2.

Clinical Characteristics and Outcomes of COVID-19 Hospitalized Patients: A Comparison between Complete mRNA Vaccination Profile and Natural Immunity