Quantification of multiple isotypes of anti-SARS-CoV-2 antibodies in kidney transplant recipients

ABSTRACT

Purpose: Solid organ transplant recipients are at increased risk of severe outcomes with infection by SARS-CoV-2, the etiologic agent of COVID-19. Antibodies directed against the virus are thought to offer protection and monoclonal antibodies directed against the virus have been used therapeutically. However, a thorough characterization of anti-SARS-CoV2 immune globulin isotypes in organ transplant recipients has not been reported. Methods: Using a semi-quantitative Luminex-based multiplex assay, we determined antibody levels from 48 SARS-CoV-2 PCR+ hospitalized kidney transplant recipients. We measured total IgG, IgM, IgA and IgG subtypes of antibodies directed against 5 distinct viral epitopes including the nucleocapsid protein as well as multiple regions of the spike protein including the receptor binding domain. Results: We identified multiple patterns of antibody responses. Specifically, 5 subjects were seronegative and 29 subjects had IgM, IgG and IgA antibodies specific for multiple epitopes of SARS-CoV-2. The 14 remaining subjects displayed a mixture of immunoglobulin isotypes. Of three subjects indeterminant for IgG antibodies, two had developed IgM, suggesting that they were early in the course of their immune response. Longitudinal samples from one subject demonstrated dynamic changes from IgM+IgG+ -> IgM-IgG+. Utilizing the semi-quantitative aspect of the assay, we found that IgG antibodies to the full Spike and Spike S1 domains were present at a statistically reduced level compared to immunocompetent controls while those directed against the Spike S2 domain were statistically higher. Interestingly, 77% of these subjects had detectable IgA directed against combinations of spike and/ or nucleocapsid specificity. IgG subtype analysis and correlation between antibody expression patterns with clinical severity is under investigation. Conclusions: Overall, these studies indicate that solid organ transplant recipients have the capacity to mount a dynamic antibody response to SARS-CoV-2 infection and that this response differs from immunocompetent individuals.