Delayed Kinetics of IgG, but not IgA, Anti-spike Antibodies in Transplant Recipients following SARS-CoV-2 Infection.

Cravedi, Paolo; Ahearn, Patrick; Wang, Lin; Yalamarti, Tanuja; Hartzell, Susan; Azzi, Yorg; Menon, Madhav; Jain, Aditya; Billah, Marzuq; Fernandez-Vina, Marcelo; Gebel, Howard; Woodle, E; Haddad, Natalie; Morrison-Porter, Andrea; Lee, F Eun-Hyung; Sanz, Ignacio; Akalin, Enver; Girnita, Alin; Maltzman, Jonathan

Background: Kidney organ transplant recipients are at increased risk of severe outcomes during COVID-19. Antibodies directed against the virus are thought to offer protection, but a thorough characterization of anti-SARS-CoV-2 immune globulin isotypes in kidney transplant recipients following SARS-CoV-2 infection has not been reported. Methods: We performed a cross-sectional study of 49 kidney transplant recipients and 42 immunocompetent controls at early (≤14 days) or late (>14 days) time points after documented SARS-CoV-2 infection. Using a validated semi-quantitative Luminex-based multiplex assay, we determined IgM, IgG, IgG1-4 and IgA antibodies against 5 distinct viral epitopes. Results: Kidney transplant recipients showed lower levels of total IgG anti-trimeric spike (S), S1, S2, and receptor-binding domain (RBD), but not nucleocapsid (NC) at early versus late time points after SARS-CoV-2 infection. Early levels of IgG anti-spike protein epitopes were also lower than in immunocompetent controls. Anti-SARS-CoV-2 antibodies were predominantly IgG1 and IgG3 with modest class switching to IgG2 or IgG4 in either cohort. Later levels of IgG anti-Spike, S1, S2, RBD and NC were not significantly different between cohorts. There was no significant difference in the kinetics of either IgM or IgA anti-Spike, S1, RBD or S2 based on timing after diagnosis or transplant status. Conclusions: Kidney transplant recipients mount early anti-SARS-CoV-2 IgA and IgM responses while IgG responses are delayed compared to immunocompetent individuals. These findings might explain the poor outcomes in transplant recipients with COVID-19.