Paolo Cravedi1, Patrick Ahearn2, Lin Wang3, Tanuja Yalamarti2, Susan Hartzell1, Yorg Azzi4, Madhav C Menon1,5, Aditya Jain6, Marzuq Billah6, Marcelo Fernandez-Vina3, Howard M Gebel7, E Steve Woodle8, Natalie S Haddad9, Andrea Morrison-Porter9, F Eun-Hyung Lee9, Ignacio Sanz9, Enver Akalin4, Alin Girnita3, Jonathan S Maltzman10,11. 1. Department of Medicine, Translational Transplant Research Center, Icahn School of Medicine at Mount Sinai, New York, New York. 2. Department of Medicine, Stanford University School of Medicine, Palo Alto, California. 3. Department of Pathology, Stanford University School of Medicine, Palo Alto, California. 4. Department of Medicine, Einstein-Montefiore Abdominal Transplant Program, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York. 5. Department of Medicine, Division of Nephrology, Yale University School of Medicine, New Haven, Connecticut. 6. Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York. 7. Department of Pathology, Emory University, Atlanta, Georgia. 8. Department of Surgery, Division of Transplantation, University of Cincinnati, Cincinnati, Ohio. 9. Department of Medicine, Emory University, Atlanta, Georgia. 10. Department of Medicine, Stanford University School of Medicine, Palo Alto, California maltzman@stanford.edu. 11. Geriatric Research Education and Clinical Center, VA Palo Alto Health Care System, Palo Alto, California.
Abstract
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.
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.
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