Attenuated Cd8+ T Cell Activation and Infiltration of the Lungs in Severe COVID-19

The SARS-CoV-2 genome encodes many proteins that directly compromise Type I interferon-mediated innate immunity. In acute COVID-19 the consequent dysregulated hyper-inflammatory state alters the milieu of draining lymph nodes and indirectly induces anatomically restricted, weeks-long transient defects in adaptive immunity. The striking attenuation of discrete aspects of T cell immunity may facilitate the evolution of more transmissible viral variants. No techniques employed to date, including single nuclear sequencing, have revealed information on pulmonary T cell subsets in severe COVID-19. Here we demonstrate an unexpected paucity of total CD8+T cells and CD8+Granzyme B+ T cells in the lung parenchyma in acute COVID-19. Apart from broadly compromising the generation of T FH cells in draining lymph nodes, acute COVID-19 is also linked to attenuated CD8+ T cell activation and infiltration of the lungs, and the delayed pulmonary accumulation of CD4+T cells with a cytotoxic phenotype. Funding Information: This work was supported by NIH U19 AI110495 to SP. Funding for these studies from the Massachusetts Consortium of Pathogen Readiness, the Mark and Lisa Schwartz Foundation and Enid Schwartz is also acknowledged. Declaration of Interests: SP is on the Scientific Advisory Board of Abpro Inc and BeBio. There are no other competing interests for any of the authors. Ethics Approval Statement: This study was conducted with the approval of the Institutional Review Boards at the Massachusetts General Hospital and the Brigham and Women’s Hospital.