PD-L1 Dysregulation in COVID-19 Patients

• Main Authors: Francesco Sabbatino, Valeria Conti, Gianluigi Franci, Carmine Sellitto, Valentina Manzo, Pasquale Pagliano, Emanuela De Bellis, Alfonso Masullo, Francesco Antonio Salzano, Alessandro Caputo, Ilaria Peluso, Pio Zeppa, Giosuè Scognamiglio, Giuseppe Greco, Carla Zannella, Michele Ciccarelli, Claudia Cicala, Carmine Vecchione, Amelia Filippelli, Stefano Pepe
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-06-01
• Series: Frontiers in Immunology
• Subjects: SARS-CoV-2; PD-L1; immune checkpoint molecules; innate immune response; adaptive immune response; COVID-19
• Online Access: https://www.frontiersin.org/articles/10.3389/fimmu.2021.695242/full

The COVID-19 pandemic has reached direct and indirect medical and social consequences with a subset of patients who rapidly worsen and die from severe-critical manifestations. As a result, there is still an urgent need to identify prognostic biomarkers and effective therapeutic approaches. Severe-critical manifestations of COVID-19 are caused by a dysregulated immune response. Immune checkpoint molecules such as Programmed death-1 (PD-1) and its ligand programmed death-ligand 1 (PD-L1) play an important role in regulating the host immune response and several lines of evidence underly the role of PD-1 modulation in COVID-19. Here, by analyzing blood sample collection from both hospitalized COVID-19 patients and healthy donors, as well as levels of PD-L1 RNA expression in a variety of model systems of SARS-CoV-2, including in vitro tissue cultures, ex-vivo infections of primary epithelial cells and biological samples obtained from tissue biopsies and blood sample collection of COVID-19 and healthy individuals, we demonstrate that serum levels of PD-L1 have a prognostic role in COVID-19 patients and that PD-L1 dysregulation is associated to COVID-19 pathogenesis. Specifically, PD-L1 upregulation is induced by SARS-CoV-2 in infected epithelial cells and is dysregulated in several types of immune cells of COVID-19 patients including monocytes, neutrophils, gamma delta T cells and CD4+ T cells. These results have clinical significance since highlighted the potential role of PD-1/PD-L1 axis in COVID-19, suggest a prognostic role of PD-L1 and provide a further rationale to implement novel clinical studies in COVID-19 patients with PD-1/PD-L1 inhibitors.