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

• DOI: 10.1016/j.ccell.2022.05.013
• Publication Date: 2022-05-30T06:50:43Z
• Authors: 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
• Keywords: Humoral immunity; 2019-20 coronavirus outbreak; Cellular immunity; Cell mediated immunity

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.