Journal Article

Effect of antiviral and immunomodulatory treatment on a cytokine profile in patients with COVID-19

Martonik, Diana, Starosz, Aleksandra, Flisiak, Robert, Parfieniuk-Kowerda, Anna, Moniuszko, Marcin, Grubczak, Kamil

2023

Overview

The severity of COVID-19 is associated with an elevated level of a variety of inflammatory mediators. Increasing evidence suggests that the Th17 response contributes to the severity of COVID-19 pneumonia, whereas Th22 response plays a regulatory role in SARS-CoV-2 infection. Two main types of available COVID-19 treatments are antivirals and immunomodulatory drugs; however, their effect on a cytokine profile is yet to be determined. This study aim to analyse a cytokine profile in peripheral blood from patients with COVID-19 (n=44) undergoing antiviral or/and immunomodulatory treatment and healthy controls (n=20). Circulating CD4+ and CD8+ T cells and their intracellular expression of IL-17A and IL-22 were assessed by flow cytometry. Initial results showed an overexpression of IL-17F, IL-17A, CCL5/RANTES, GM-CSF, IL-4, IL-10, CXCL-10/IP-10 and IL-6 in COVID-19 patients compared to healthy controls. Treatment with remdesivir resulted in a significant decline in concentrations of IL-6, IL-10, IFN-alpha and CXCL10/IP-10. Immunomodulatory treatment contributed to a significant downregulation of IL-10, IFN-alpha, CXCL10/IP-10 and B7-H3 as well as upregulation of IL-22 and IL-1 beta. A combination of an antiviral and immunomodulatory treatment resulted in a significant decrease in IL-17F, IL-10, IFN-alpha, CXCL10/IP-10 and B7-H3 levels as well as an increase in IL-17A and IL-1 beta. We found significantly higher percentage of both CD4+ and CD8+ T cells producing IL-17A and CD4+ T cells producing IL-22 in patients with COVID-19. Administration of antiviral or/and immunomodulatory treatment resulted in a significant downregulation of pro-inflammatory cytokine expression and an upregulation of T cell absolute counts in most cases, thus showing effectiveness of treatment in COVID-19. SARS-CoV-2 infection induced cytokine overexpression in hospitalized patients with COVID-19 as well as lymphopenia, particularly a decrease in CD4+ and CD8+ T cell counts. Moreover, despite the reduced counts of CD4+ and CD8+ T cells, both subsets showed overactivation and increased expression of IL-17A and IL-22, thus targeting Th17 response might alleviate inflammatory response in severe disease.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Aged / Antiviral agents / Antiviral Agents - therapeutic use / Asymptomatic / Biomarkers / Case-Control Studies / CD4 antigen / CD4+ T cells / CD8 antigen / CD8+ T cells / Cloning / COVID-19 / COVID-19 - blood / COVID-19 - diagnosis / CXCL10 protein / Cytokines / Cytokines - blood / Cytokines - drug effects / Down-regulation / Female / Flow cytometry / Granulocyte-macrophage colony-stimulating factor / Helper cells / Hepatology / Hospitals / Humans / Immune system / Immunology / Immunomodulating Agents - therapeutic use / Immunomodulation / Immunomodulators / Infectious diseases / Interleukin 1 / Interleukin 10 / Interleukin 22 / Interleukin 6 / Interleukin-17 - metabolism / Interleukins - metabolism / IP-10 protein / Lymphocytes / Lymphocytes T / Lymphopenia / Male / Middle Aged / Oxygen saturation / Oxygen therapy / Peripheral blood / Pneumonia / RANTES / Respiratory diseases / RNA polymerase / SARS-CoV-2 / Severe acute respiratory syndrome coronavirus 2 / Th17 cells / Tumor necrosis factor-TNF / Up-regulation / Viral infections / α-Interferon