Impaired Cellular and Antibody immunity after COVID-19 in Chronically Immunosuppressed Transplant Recipients

Author(s): Chethan Ashokkumar, Vinayak Rohan, Alexander H Kroemer, Sohail Rao, George Mazariegos, Brandon W Higgs, Satish Nadig, Jose Almeda, Harmeet Dhani, Khalid Khan, Nada Yazigi, Udeme Ekong, Stuart Kaufman, Monica M Betancourt-Garcia, Kavitha Mukund, Pradeep Sethi, Shikhar Mehrotra, Kyle Soltys, Manasi S Singh, Geoffrey Bond, Ajai Khanna, Mylarappa Ningappa, Brianna Spishock, Elizabeth Sindhi, Neha Atale, Maggie Saunders, Prabhakar Baliga, Thomas Fishbein, Shankar Subramaniam, and Rakesh Sindhi

Assessment of cellular immunity to the SARS-CoV-2 coronavirus is of great interest in chronically immunosuppressed transplant recipients (Tr), who are predisposed to infections and vaccination failures. We evaluated CD154-expressing T-cells induced by spike (S) antigenic peptides in 204 subjects-103 COVID-19 patients and 101 healthy unexposed subjects. Sreactive CD154+T-cell frequencies were a) higher in 42 healthy unexposed Tr who were sampled pre-pandemic, compared with healthy NT (p=0.02), b) lower in Tr COVID-19 patients compared with healthy Tr (p<0.0001) and were accompanied by lower S-reactive B-cell frequencies (p<0.05), c) lower in Tr with severe COVID-19 (p<0.0001), or COVID-19 requiring hospitalization (p<0.05), compared with healthy Tr. Among Tr with COVID-19, cytomegalovirus co-infection occurred in 34%; further, incidence of anti-receptor-binding-domain IgG (p=0.011) was lower compared with NT COVID-19 patients. Healthy unexposed Tr exhibit pre-existing T-cell immunity to SARS-CoV-2. COVID-19 impairs anti-S T-cell and antibody and predisposes to CMV co-infection in transplant recipients.