Usage Information
Citation Information: JCI Insight. 2021;6(24):e146701. https://doi.org/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 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
Usage data is cumulative from June 2022 through June 2023.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 12,282 | 3,227 |
| 951 | 567 | |
| Figure | 2,489 | 34 |
| Table | 276 | 0 |
| Supplemental data | 149 | 36 |
| Citation downloads | 108 | 0 |
| Totals | 16,255 | 3,864 |
| Total Views | 20,119 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
