PD-1 blockade counteracts post-COVID-19 immune abnormalities and stimulates the anti-SARS-CoV-2 immune response.
JCI Insight
; 6(24)2021 12 22.
Article
in English
| MEDLINE | ID: covidwho-1518198
ABSTRACT
A substantial proportion of patients who have recovered from coronavirus disease-2019 (COVID-19) experience COVID-19-related symptoms even months after hospital discharge. We extensively immunologically characterized patients who recovered from COVID-19. In these patients, T cells were exhausted, with increased PD-1+ T cells, as compared with healthy controls. Plasma levels of IL-1ß, IL-1RA, and IL-8, among others, were also increased in patients who recovered from COVID-19. This altered immunophenotype was mirrored by a reduced ex vivo T cell response to both nonspecific and specific stimulation, revealing a dysfunctional status of T cells, including a poor response to SARS-CoV-2 antigens. Altered levels of plasma soluble PD-L1, as well as of PD1 promoter methylation and PD1-targeting miR-15-5p, in CD8+ T cells were also observed, suggesting abnormal function of the PD-1/PD-L1 immune checkpoint axis. Notably, ex vivo blockade of PD-1 nearly normalized the aforementioned immunophenotype and restored T cell function, reverting the observed post-COVID-19 immune abnormalities; indeed, we also noted an increased T cell-mediated response to SARS-CoV-2 peptides. Finally, in a neutralization assay, PD-1 blockade did not alter the ability of T cells to neutralize SARS-CoV-2 spike pseudotyped lentivirus infection. Immune checkpoint blockade ameliorates post-COVID-19 immune abnormalities and stimulates an anti-SARS-CoV-2 immune response.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
T-Lymphocytes
/
Cytokines
/
Programmed Cell Death 1 Receptor
/
Immune Checkpoint Inhibitors
/
SARS-CoV-2
/
COVID-19
Type of study:
Observational study
Topics:
Long Covid
/
Variants
Limits:
Female
/
Humans
/
Male
/
Middle aged
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
Jci.insight.146701
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