학술논문
PD-1 blockade counteracts post–COVID-19 immune abnormalities and stimulates the anti–SARS-CoV-2 immune response
Document Type
article
Author
Cristian Loretelli; Ahmed Abdelsalam; Francesca D’Addio; Moufida Ben Nasr; Emma Assi; Vera Usuelli; Anna Maestroni; Andy Joe Seelam; Elio Ippolito; Stefania Di Maggio; Lara Loreggian; Dejan Radovanovic; Claudia Vanetti; Jun Yang; Basset El Essawy; Antonio Rossi; Ida Pastore; Laura Montefusco; Maria Elena Lunati; Andrea M. Bolla; Mara Biasin; Spinello Antinori; Pierachille Santus; Agostino Riva; Gian Vincenzo Zuccotti; Massimo Galli; Stefano Rusconi; Paolo Fiorina
Source
JCI Insight, Vol 6, Iss 24 (2021)
Subject
Language
English
ISSN
2379-3708
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-1β, 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.