SARS-CoV-2 Viral Clearance and Evolution Varies by Extent of Immunodeficiency
Li, Y.; Choudhary, M. C.; Regan, J.; Boucau, J.; Nathan, A.; Speidel, T.; Liew, M. Y.; Edelstein, G. E.; Kawano, Y.; Uddin, R.; Deo, R.; Marino, C.; Getz, M. A.; Reynold, Z.; Barry, M.; Gilbert, R. F.; Tien, D.; Sagar, S.; Vyas, T. D.; Flynn, J. P.; Hammond, S. P.; Novack, L. A.; Choi, B.; Cernadas, M.; Wallace, Z. S.; Sparks, J. A.; Vyas, J. M.; Seaman, M. S.; Gaiha, G. D.; Siedner, M. J.; Barczak, A. K.; Lemieux, J. E.; Li, J. Z.
Show abstract
Despite vaccination and antiviral therapies, immunocompromised individuals are at risk for prolonged SARS-CoV-2 infection, but the immune defects that predispose to persistent 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 time to nasal viral RNA and culture clearance in the severe hematologic malignancy/transplant group (S-HT) were 72 and 40 days, respectively, which were significantly longer than clearance rates in the severe autoimmune/B-cell deficient (S-A), non-severe, and non-immunocompromised groups (P<0.001). Participants who were severely immunocompromised had greater SARS-CoV-2 evolution and a higher risk of developing antiviral treatment resistance. Both S-HT and S-A participants had diminished SARS-CoV-2-specific humoral, while only the S-HT group had reduced T cell-mediated responses. This highlights the varied risk of persistent COVID-19 across immunosuppressive conditions and suggests that suppression of both B and T cell responses results in the highest contributing risk of persistent infection.
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