Three-Year Follow-Up of COVID-19 Cases in District of Constance, Germany. A Prospective, Controlled Cohort Study (FSC19-KN)

<b>Background and Objectives</b>: Long-term sequalae of viral diseases, especially after infections with SARS-CoV-2 (COVID-19), can induce multi-organ involvement, as around 65 million people worldwide report persistent symptoms that go far beyond the acute course. Studies indicate that early virus variants pose a higher risk of developing post-COVID-19 conditions. The primary aim of this study was to investigate the possible long-term effects based on the hospitalization rates and associated clinical events in patients infected with SARS-CoV-2 over an observational period of three years after the initial infection. Secondarily, an investigation of health-related quality of life and functional status was performed. <b>Methods and Materials</b>: The study presented was designed as a prospective, controlled cohort study to follow up on COVID-19 cases in the district of Konstanz, Germany (FSC19-KN). The positive group included subjects who had a primary infection with SARS-CoV-2 between March and December 2020. The control group included subjects who did not have a SARS-CoV-2 infection, as evidenced by a negative antibody test. As the primary endpoint, hospitalization rates and respective related admission diagnosis during the observational period of three years from January 2021 until July 2024 were analyzed. The health-related quality of life and functional outcomes were measured by the SF-36 questionnaire and Post-COVID-19 Functional Status (PCFS) as the secondary endpoint. <b>Results</b>: During the three years of observation after inclusion in the study, the hospitalization rate did not differ significantly between the two groups of initially infected and non-infected subjects (cumulative events, verum group 57 to control group 45, OR 1.24, CI 0.83; 1.85, <i>p</i> = 0.30). However, the health-related quality of life, measured by SF-36 sub scores of the SARS-CoV-2-positive subjects, achieved significantly lower results, except for the dimension 'energy and fatigue', in which subjects of the verum group still achieved significantly lower scores. <b>Conclusions</b>: Mild COVID-19 cases have no significant impact on hospitalization rates during an observational period of three years after initial infection. Yet, SARS-CoV-2-positive subjects reported a reduced health-related quality of life and functional outcomes. Ultimately, only the sub score quality 'energy and fatigue' still registered significant differences between both cohorts at the end of the three-year observational period.