CD8 T cells compensate for impaired humoral immunity in COVID-19 patients with hematologic cancer.
Journal
Research square
Titre abrégé: Res Sq
Pays: United States
ID NLM: 101768035
Informations de publication
Date de publication:
02 Feb 2021
02 Feb 2021
Historique:
entrez:
10
2
2021
pubmed:
11
2
2021
medline:
11
2
2021
Statut:
epublish
Résumé
Cancer patients have increased morbidity and mortality from Coronavirus Disease 2019 (COVID-19), but the underlying immune mechanisms are unknown. In a cohort of 100 cancer patients hospitalized for COVID-19 at the University of Pennsylvania Health System, we found that patients with hematologic cancers had a significantly higher mortality relative to patients with solid cancers after accounting for confounders including ECOG performance status and active cancer status. We performed flow cytometric and serologic analyses of 106 cancer patients and 113 non-cancer controls from two additional cohorts at Penn and Memorial Sloan Kettering Cancer Center. Patients with solid cancers exhibited an immune phenotype similar to non-cancer patients during acute COVID-19 whereas patients with hematologic cancers had significant impairment of B cells and SARS-CoV-2-specific antibody responses. High dimensional analysis of flow cytometric data revealed 5 distinct immune phenotypes. An immune phenotype characterized by CD8 T cell depletion was associated with a high viral load and the highest mortality of 71%, among all cancer patients. In contrast, despite impaired B cell responses, patients with hematologic cancers and preserved CD8 T cells had a lower viral load and mortality. These data highlight the importance of CD8 T cells in acute COVID-19, particularly in the setting of impaired humoral immunity. Further, depletion of B cells with anti-CD20 therapy resulted in almost complete abrogation of SARS-CoV-2-specific IgG and IgM antibodies, but was not associated with increased mortality compared to other hematologic cancers, when adequate CD8 T cells were present. Finally, higher CD8 T cell counts were associated with improved overall survival in patients with hematologic cancers. Thus, CD8 T cells likely compensate for deficient humoral immunity and influence clinical recovery of COVID-19. These observations have important implications for cancer and COVID-19-directed treatments, immunosuppressive therapies, and for understanding the role of B and T cells in acute COVID-19.
Identifiants
pubmed: 33564756
doi: 10.21203/rs.3.rs-162289/v1
pmc: PMC7872363
pii:
doi:
Types de publication
Preprint
Langues
eng
Subventions
Organisme : NCI NIH HHS
ID : T32 CA009140
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009679
Pays : United States
Commentaires et corrections
Type : UpdateIn
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