ABSTRACT
Background: Cases of reinfection with SARS-CoV-2 are reported in increasing numbers. Since the required molecular proof of reinfection is challenging to obtain, we aimed to provide serological evidence of reinfection in a cohort of potential reinfection cases.Methods: The study comprises 38 RT-PCR confirmed reinfection cases, with a COVID-19 symptom-free interval of at least 8 weeks (range 57-133 days) since their first RT-PCR confirmed episode. Specific disease symptoms were retrieved from 22 cases by contact tracing and compared between the two disease episodes. The oropharyngeal specimens from 13 cases enabled adequate genomic sequence comparisons. Seventeen cases provided a serum specimen, of which 12 within 7 days after onset of symptoms. Antibody determinations included SARS-CoV-2-specific total Ig, IgM, IgG, avidity, and virus neutralization. Antibody data were compared to that of a control group of primary cases (n=86) in relation to time since onset of disease symptoms.Findings: Reinfection cases generally experienced fewer or milder symptoms. Five of 8 cases which passed genomic comparison between both disease episodes showed reinfection with a different lineage. From 12 reinfection cases that provided a serum sample within 7 days after onset of symptoms, 11/12 (92%) and 12/12 (100%) showed high levels of specific total Ig and IgG antibodies, respectively, compared to 1/23 (4%) and 2/23 (9%) within the control group. Virus neutralizing antibodies were detected in 9/12 (75%) reinfection cases, 5 of which were above a titer of 30. Serological discrimination diminished after 7 days, except for IgG avidity; all 17 reinfection cases had antibodies of higher avidity when compared to control cases.Interpretation: IgG concentration and avidity can be used as an additional diagnostic marker to confirm reinfection with SARS-Cov-2. Reinfection cases that show a rapid and effective secondary immune response are expected to clear the infection more effectively, thereby reducing contagiousness and clinical severity. Understanding this reinfection response is also important for breakthrough infections following vaccination.Funding Statement: This work was supported by the National Institute for Public Health and the Environment, The Netherlands.Declaration of Interests: None of the authors have an association that poses a conflict of interest.Ethics Approval Statement: Approved by the Medical-Ethical Review Committee of the University Medical Center Utrecht.