JCI Insight . PD-1 blockade counteracts post-COVID-19 immune abnormalities and stimulates the anti-SARS-CoV-2 immune response

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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 ¹ , Ahmed Abdelsalam ¹ , Francesca D'Addio ¹ , Moufida Ben Nasr ² , Emma Assi ¹ , Vera Usuelli ¹ , Anna Maestroni ¹ , Andy Joe Seelam ¹ , Elio Ippolito ¹ , Stefania Di Maggio ¹ , Lara Loreggian ¹ , Dejan Radovanovic ³ , Claudia Vanetti ¹ , Jun Yang ⁴ , Basset El Essawy ⁵ , Antonio Rossi ⁶ , Ida Pastore ⁶ , Laura Montefusco ⁶ , Maria Elena Lunati ⁶ , Andrea M Bolla ⁶ , Mara Biasin ¹ , Spinello Antinori ¹ , Pierachille Santus ¹ , Agostino Riva ¹ , Gianvincenzo Zuccotti ¹ , Massimo Galli ¹ , Stefano Rusconi ⁷ , Paolo Fiorina ²



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.