tetano
Editor, Senior Moderator
JCI Insight
. 2021 Nov 16;e146701.
doi: 10.1172/jci.insight.146701. Online ahead of print.
PD-1 blockade counteracts post-COVID-19 immune abnormalities and stimulates the anti-SARS-CoV-2 immune response
Cristian Loretelli[SUP] 1 [/SUP], Ahmed Abdelsalam[SUP] 1 [/SUP], Francesca D'Addio[SUP] 1 [/SUP], Moufida Ben Nasr[SUP] 2 [/SUP], Emma Assi[SUP] 1 [/SUP], Vera Usuelli[SUP] 1 [/SUP], Anna Maestroni[SUP] 1 [/SUP], Andy Joe Seelam[SUP] 1 [/SUP], Elio Ippolito[SUP] 1 [/SUP], Stefania Di Maggio[SUP] 1 [/SUP], Lara Loreggian[SUP] 1 [/SUP], Dejan Radovanovic[SUP] 3 [/SUP], Claudia Vanetti[SUP] 1 [/SUP], Jun Yang[SUP] 4 [/SUP], Basset El Essawy[SUP] 5 [/SUP], Antonio Rossi[SUP] 6 [/SUP], Ida Pastore[SUP] 6 [/SUP], Laura Montefusco[SUP] 6 [/SUP], Maria Elena Lunati[SUP] 6 [/SUP], Andrea M Bolla[SUP] 6 [/SUP], Mara Biasin[SUP] 1 [/SUP], Spinello Antinori[SUP] 1 [/SUP], Pierachille Santus[SUP] 1 [/SUP], Agostino Riva[SUP] 1 [/SUP], Gianvincenzo Zuccotti[SUP] 1 [/SUP], Massimo Galli[SUP] 1 [/SUP], Stefano Rusconi[SUP] 7 [/SUP], Paolo Fiorina[SUP] 2 [/SUP]
Affiliations
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 to 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: Anergy; COVID-19; Immunology; Immunotherapy.
. 2021 Nov 16;e146701.
doi: 10.1172/jci.insight.146701. Online ahead of print.
PD-1 blockade counteracts post-COVID-19 immune abnormalities and stimulates the anti-SARS-CoV-2 immune response
Cristian Loretelli[SUP] 1 [/SUP], Ahmed Abdelsalam[SUP] 1 [/SUP], Francesca D'Addio[SUP] 1 [/SUP], Moufida Ben Nasr[SUP] 2 [/SUP], Emma Assi[SUP] 1 [/SUP], Vera Usuelli[SUP] 1 [/SUP], Anna Maestroni[SUP] 1 [/SUP], Andy Joe Seelam[SUP] 1 [/SUP], Elio Ippolito[SUP] 1 [/SUP], Stefania Di Maggio[SUP] 1 [/SUP], Lara Loreggian[SUP] 1 [/SUP], Dejan Radovanovic[SUP] 3 [/SUP], Claudia Vanetti[SUP] 1 [/SUP], Jun Yang[SUP] 4 [/SUP], Basset El Essawy[SUP] 5 [/SUP], Antonio Rossi[SUP] 6 [/SUP], Ida Pastore[SUP] 6 [/SUP], Laura Montefusco[SUP] 6 [/SUP], Maria Elena Lunati[SUP] 6 [/SUP], Andrea M Bolla[SUP] 6 [/SUP], Mara Biasin[SUP] 1 [/SUP], Spinello Antinori[SUP] 1 [/SUP], Pierachille Santus[SUP] 1 [/SUP], Agostino Riva[SUP] 1 [/SUP], Gianvincenzo Zuccotti[SUP] 1 [/SUP], Massimo Galli[SUP] 1 [/SUP], Stefano Rusconi[SUP] 7 [/SUP], Paolo Fiorina[SUP] 2 [/SUP]
Affiliations
- PMID: 34784300
- DOI: 10.1172/jci.insight.146701
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 to 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: Anergy; COVID-19; Immunology; Immunotherapy.