PD-1 blockade counteracts post–COVID-19 immune abnormalities and stimulates the anti–SARS-CoV-2 immune response
Year: 2021
Type: article
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.
Source: JCI Insight
Authors: 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
Institutions: University of Milan, Boston Children's Hospital, Harvard University, ASST Fatebenefratelli Sacco, Tongji Hospital, Huazhong University of Science and Technology, Brigham and Women's Hospital, Al-Azhar University, Ospedale dei Bambini Vittore Buzzi, Azienda Ospedaliera Ospedale Civile di Legnano, Aziende Socio Sanitarie Territoriale Ovest Milanese
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,100
Awards: G5500352322, G6130281517
OpenAlex ID: W3211891470