Impaired humoral immunity is associated with prolonged COVID-19 despite robust CD8 T cell responses

Olga Lyudovyk, Justin Y Kim, David Qualls, Madeline A Hwee, Ya-Hui Lin, Sawsan R Boutemine, Yuval Elhanati, Alexander Solovyov, Melanie Douglas, Eunise Chen, N Esther Babady, Lakshmi Ramanathan, Pallavi Vedantam, Chaitanya Bandlamudi, Sigrid Gouma, Philip Wong, Scott E Hensley, Benjamin Greenbaum, Alexander C Huang, Santosha A Vardhana

Cancer Cell. 2022 Jul 11;40(7):738-753.e5.


How immune dysregulation affects recovery from COVID-19 infection in patients with cancer remains unclear. We analyzed cellular and humoral immune responses in 103 patients with prior COVID-19 infection, more than 20% of whom had delayed viral clearance. Delayed clearance was associated with loss of antibodies to nucleocapsid and spike proteins with a compensatory increase in functional T cell responses. High-dimensional analysis of peripheral blood samples demonstrated increased CD8+ effector T cell differentiation and a broad but poorly converged COVID-specific T cell receptor (TCR) repertoire in patients with prolonged disease. Conversely, patients with a CD4+ dominant immunophenotype had a lower incidence of prolonged disease and exhibited a deep and highly select COVID-associated TCR repertoire, consistent with effective viral clearance and development of T cell memory. These results highlight the importance of B cells and CD4+ T cells in promoting durable SARS-CoV-2 clearance and the significance of coordinated cellular and humoral immunity for long-term disease control.