Association between the expression of toll-like receptors, cytokines, and homeostatic chemokines in SARS-CoV-2 infection and COVID-19 severity

Wael Alturaiki; Haitham Alkadi; Saad Alamri; Maaweya E Awadalla; Abdulkarim Alfaez; Ayman Mubarak; Mona Awad Alanazi; Faris Q Alenzi; Brian F Flanagan; Bandar Alosaimi

doi:10.1016/j.heliyon.2022.e12653

Association between the expression of toll-like receptors, cytokines, and homeostatic chemokines in SARS-CoV-2 infection and COVID-19 severity

Heliyon. 2023 Jan;9(1):e12653. doi: 10.1016/j.heliyon.2022.e12653. Epub 2022 Dec 24.

Authors

Affiliations

¹ Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah, Saudi Arabia.
² Research Center, Riyadh Second Health Cluster, King Fahad Medical City, Riyadh, Saudi Arabia.
³ Department of Pathology, Immunology and Laboratory, College of Medicine, University of Florida, Gainesville, Florida, 32610, USA.
⁴ Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia.
⁵ Prince Mohammed Bin Abdulaziz Hospital, Riyadh Second Health Cluster, Ministry of Health, Riyadh, Saudi Arabia.
⁶ Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia.
⁷ Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Alder Hey Children's NHS Foundation Trust Hospital, Eaton Road, Liverpool L12 2AP, UK.

Abstract

The recent identification of the involvement of the immune system response in the severity and mortality of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection highlights the importance of cytokines and chemokines as important factors in the clinical outcomes of COVID-19. However, the impact and roles of the BAFF/APRIL cytokine system, homeostatic chemokines (CXCL12, CXCL13, CCL19, and CCL21), as well as Toll-like receptor (TLR)-3/4 in COVID-19, have not been investigated. We sought to assess the expression levels and roles of TLR3/4, BAFF, APRIL, IFN-β, homeostatic chemokines (CXCL12, CXCL13, CCL19, and CCL21), SARS-CoV-2 IgG and IgM antibodies in patients with critical (ICU) and non-ICU (mild) COVID-19 and their association with mortality and disease severity. Significant high levels of TLR-4 mRNA, IFN-β, APRIL, CXCL13, and IgM and IgG antibodies were observed in ICU patients with severe COVID-19 compared to non-ICU COVID-19 patients and healthy controls. On the other hand, BAFF and CCL21 expression were significantly upregulated in non-ICU patients with COVID-19 compared with that in critical COVID-19 patients. The two groups did not differ in TLR-3, CXCL12, and CCL19 levels. Our findings show high expression levels of some inflammatory chemokines in ICU patients with COVID-19. These findings highlight the potential utility of chemokine antagonists as an immune-based treatment for the severe form of COVID-19. We also believe that selective targeting of TLR/spike protein interactions might lead to the development of a new COVID-19 therapy.

Keywords: COVID-19 severity; Cytokines; Homeostatic chemokines; SARS-CoV-2; Toll-like receptors.