SARS-CoV-2 viral clearance and evolution varies by type and severity of immunodeficiency
Yijia Li, Manish C. Choudhary, James Regan, Julie Boucau, Anusha Nathan, Tessa Speidel, May Y. Liew, Gregory E. Edelstein, Yumeko Kawano, Rockib Uddin, Rinki Deo, Caitlin Marino, Matthew A. Getz, Zahra Reynolds, Mamadou Barry, Rebecca F. Gilbert, Dessie Tien, Shruti Sagar, Tammy D. Vyas, James P. Flynn, Sarah P. Hammond, Lewis A. Novack, Bina Choi, Manuela Cernadas, Zachary S. Wallace, Jeffrey A. Sparks, Jatin M. Vyas, Michael S. Seaman, Gaurav D. Gaiha, Mark J. Siedner, Amy K. Barczak, Jacob E. Lemieux, Jonathan Z. Li
Abstract
Despite vaccination and antiviral therapies, immunocompromised individuals are at risk for prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but the immune defects that predispose an individual to persistent coronavirus disease 2019 (COVID-19) remain incompletely understood. In this study, we performed detailed viro-immunologic analyses of a prospective cohort of participants with COVID-19. The median times to nasal viral RNA and culture clearance in individuals with severe immunosuppression due to hematologic malignancy or transplant (S-HT) were 72 and 40 days, respectively, both of which were significantly longer than clearance rates in individuals with severe immunosuppression due to autoimmunity or B cell deficiency (S-A), individuals with nonsevere immunodeficiency, and nonimmunocompromised groups ( P < 0.01). Participants who were severely immunocompromised had greater SARS-CoV-2 evolution and a higher risk of developing resistance against therapeutic monoclonal antibodies. Both S-HT and S-A participants had diminished SARS-CoV-2–specific humoral responses, whereas only the S-HT group had reduced T cell–mediated responses. This highlights the varied risk of persistent COVID-19 across distinct immunosuppressive conditions and suggests that suppression of both B and T cell responses results in the highest contributing risk of persistent infection.