PD-L1 Dysregulation in COVID-19 Patients

Abstract

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.

NK cell receptor and ligand composition influences the clearance of SARS-CoV-2

“…After mice were injected with expanded primary NK cells, preferential killing of uninfected Calu-1 cells was observed (uninfected vs. infected: 75.88% vs. 48.35%, P = 0.0248; Figure 3, E and F), suggesting that the virally infected cells can escape from the immunosurveillance mediated by NK cells. Interestingly, the ligands HLA-ABC and PDL-1 are also induced by SARS-CoV-2 infection (Figure 3A) and could potentially contribute to the immune escape mediated by SARS-CoV-2 (41).…”

IFN-γ Induces PD-L1 Expression in Primed Human Basophils

“…PD-L1 interacts with the programmed death receptor 1 (PD-1) on T cells and induces tolerance or/and exhaustion [ 25 ]. More recently, due to the COVID-19 pandemic, research focus on immune checkpoint molecules has increased [ 26 ]. As evident from the literature, PD-L1 dysregulation is observed in COVID-19 patients [ 26 ].…”

“…More recently, due to the COVID-19 pandemic, research focus on immune checkpoint molecules has increased [ 26 ]. As evident from the literature, PD-L1 dysregulation is observed in COVID-19 patients [ 26 ]. Moreover, studies have reported the link between PD-L1-expressing basophils and the severity of COVID-19.…”

“…Analyses of PBMCs from severe COVID-19 patients have revealed a dysregulated expression of PD-L1 in various immune cells [ 26 ]. However, contradictory results have been published regarding the changes in basophil PD-L1 in COVID-19 patients [ 6 , 7 ].…”

Depressive and Neurocognitive Disorders in the Context of the Inflammatory Background of COVID-19

“…Elevated LDH levels are associated with cell damage. In approximately 80% of patients, lymphopenia and an increased ratio of neutrophils to lymphocytes are observed [16,18,97,98]. Mahat et al in their review and meta-analysis concluded that in patients with severe COVID-19, serum levels of CRP, ESR, PCT (procalcitonin), IL-6, IL-10, IL-2R, ferritin, SAA (serum amyloid A) and NLR (neutrophil-to-lymphocyte ratio) are significantly increased compared with people with a mild COVID-19.…”