Programmed Cell Death-1/Programmed Cell Death-1 Ligand as Prognostic Markers of Coronavirus Disease 2019 Severity
Paulina Niedźwiedzka-Rystwej1, Adam Majchrzak2, Bogusz Aksak-Wąs2
1Institute of Biology, University of Szczecin, 71-412 Szczecin, Poland.
Insights
Increased programmed cell death-1 (PD-1) and PD-1 ligand (PD-L1) on lymphocytes correlate with COVID-19 severity and mortality. These immune exhaustion markers show potential as biomarkers for coronavirus disease 2019 severity.
Area of Science:
- Immunology
- Virology
- Clinical Medicine
Background:
- Immune dysregulation and exhaustion are hallmarks of severe COVID-19, linked to increased mortality.
- Immune checkpoint molecules like programmed cell death-1 (PD-1) and its ligand (PD-L1) are implicated in disease severity.
Purpose of the Study:
- To evaluate the expression of PD-1 and PD-L1 in patients with moderate and severe COVID-19.
- To associate these immune checkpoint molecule expressions with clinical outcomes and lymphocyte profiles.
Main Methods:
- Blood immunophenotyping was performed on hospitalized COVID-19 patients (moderate and severe) and healthy controls.
- Expression of PD-1 and PD-L1 on T and B lymphocyte subsets was analyzed at baseline and during 14 days of treatment.
- Associations with clinical data, laboratory results, and survival were examined.
Main Results:
- Patients with moderate and severe COVID-19 showed significantly higher CD4+PD-1+, CD8+PD-1+, and CD19+PD-1+ T and B cells compared to controls.
- Elevated levels of PD-L1-positive lymphocytes (CD4+, CD8+, CD19+) were also observed in COVID-19 patients.
- Increased PD-1 and PD-L1 expression on lymphocytes was associated with greater disease severity and mortality and remained stable over time.
Conclusions:
- Elevated PD-1 and PD-L1 expression on lymphocytes are linked to COVID-19 severity and mortality.
- These immune exhaustion markers may serve as valuable biomarkers for assessing COVID-19 severity.
Abstract:
Current research proves that immune dysregulation is a common feature of coronavirus disease 2019 (COVID-19), and immune exhaustion is associated with increased disease mortality. Immune checkpoint molecules, including the programmed cell death-1 (PD-1)/PD-1 ligand (PD-L1) axis, may serve as markers of disease severity. Accordingly, in this study, we evaluated the expression of PD-1/PD-L1 in patients with COVID-19. Blood immunophenotypes of hospitalized patients with moderate (n = 17, requiring oxygen support) and severe (n = 35, requiring mechanical ventilation in the intensive care setting) COVID-19 were compared and associated with clinical, laboratory, and survival data. The associations between severity and lymphocyte profiles were analysed at baseline and after 7 and 14 days of in-hospital treatment. Forty patients without COVID-19 infection were used as controls. For PD-1-positive T and B lymphocyte subsets, notable increases were observed between controls and patients with moderate or severe COVID-19 for CD4+PD-1+ T cells, CD8+PD-1+ T and CD19+PD-1+ B cells. Similar trends were observed for PD-L1-positive lymphocytes, namely, CD4+PD-L1+ T cells, CD8+PD-L1+ T cells and CD19+PD-L1+ B cells. Importantly, all markers associated with PD-1 and PD-L1 were stable over time for the analysed time points in the moderate and severe COVID-19 groups. Increased abundances of PD-1+ and PD-L1+ lymphocytes were associated with disease severity and mortality and were stable over time in patients with moderate to severe COVID-19. These immune exhaustion parameters may be attractive biomarkers of COVID-19 severity.
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