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.
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
This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.
Having trouble reading a PDF?
PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.
Having trouble saving a PDF?
Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.
Having trouble printing a PDF?
- Try printing one page at a time or to a newer printer.
- Try saving the file to disk before printing rather than opening it "on the fly." This requires that you configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can usually be done in the "Helper Applications" options.
- Make sure you are using the latest version of Adobe's Acrobat Reader.
