Delayed Kinetics of IgG, but Not IgA, Antispike Antibodies in Transplant Recipients following SARS-CoV-2 Infection
Paolo Cravedi, Patrick Ahearn, Lin Wang, Tanuja Yalamarti, Susan Hartzell, Yorg Azzi, Madhav C. Menon, Aditya V. Jain, Marzuq Billah, Marcelo Fernández-Viña, Howard M. Gebel, E. Steve Woodle, Natalie S. Haddad, Andrea Morrison-Porter, F. Eun‐Hyung Lee, Igñacio Sanz, Enver Akalin, Alin Girnita, Jonathan S. Maltzman
Abstract
Significance Statement Analyses of the incidence, relative kinetics, and spectrum of anti–SARS-CoV-2 antibodies in kidney transplant recipients are not as detailed as they are for immunocompetent controls. In this multicenter, cross-sectional study of 49 kidney transplant recipients with PCR-confirmed SARS-CoV-2 infection, we found that anti–SARS-CoV-2 IgG production is delayed but that IgM and IgA responses are similar compared with those observed in immunocompetent controls. Therefore, antiviral humoral immunity is delayed but preserved in kidney transplant recipients. This finding is important in understanding the immune response against SARS-CoV-2 in patients on chronic immunosuppression and may provide insights into devising strategies to monitor antibody responses to infection and vaccination. Background Kidney transplant recipients are at increased risk of severe outcomes during COVID-19. Antibodies 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 semiquantitative Luminex-based multiplex assay, we determined the abundances of IgM, IgG, IgG1–4, and IgA antibodies against five distinct viral epitopes. Results Kidney transplant recipients showed lower levels of total IgG antitrimeric 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 antispike 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 antispike, S1, S2, RBD, and NC did not significantly differ between cohorts. There was no significant difference in the kinetics of either IgM or IgA antispike, S1, RBD, or S2 on the basis of timing after diagnosis or transplant status. Conclusions Kidney transplant recipients mount early anti–SARS-CoV-2 IgA and IgM responses, whereas IgG responses are delayed compared with immunocompetent individuals. These findings might explain the poor outcomes in transplant recipients with COVID-19. Podcast This article contains a podcast athttps://www.asn-online.org/media/podcast/JASN/2021_11_23_briggsgriffin112321.mp3