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Triangle of cytokine storm, central nervous system involvement, and viral infection in COVID-19: the role of sFasL and neuropilin-1

  • Kiarash Saleki ORCID logo , Mohammad Banazadeh , Niloufar Sadat Miri and Abbas Azadmehr EMAIL logo
Published/Copyright: July 6, 2021
Become an author with De Gruyter Brill

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is identified as the cause of coronavirus disease 2019 (COVID-19), and is often linked to extreme inflammatory responses by over activation of neutrophil extracellular traps (NETs), cytokine storm, and sepsis. These are robust causes for multi-organ damage. In particular, potential routes of SARS-CoV2 entry, such as angiotensin-converting enzyme 2 (ACE2), have been linked to central nervous system (CNS) involvement. CNS has been recognized as one of the most susceptible compartments to cytokine storm, which can be affected by neuropilin-1 (NRP-1). ACE2 is widely-recognized as a SARS-CoV2 entry pathway; However, NRP-1 has been recently introduced as a novel path of viral entry. Apoptosis of cells invaded by this virus involves Fas receptor–Fas ligand (FasL) signaling; moreover, Fas receptor may function as a controller of inflammation. Furthermore, NRP-1 may influence FasL and modulate cytokine profile. The neuroimmunological insult by SARS-CoV2 infection may be inhibited by therapeutic approaches targeting soluble Fas ligand (sFasL), cytokine storm elements, or related viral entry pathways. In the current review, we explain pivotal players behind the activation of cytokine storm that are associated with vast CNS injury. We also hypothesize that sFasL may affect neuroinflammatory processes and trigger the cytokine storm in COVID-19.


Corresponding author: Abbas Azadmehr, Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, 47176-47745, Iran; Medical Immunology Department, Babol University of Medical Sciences, Babol, 47176-47745, Iran; and National Elite Foundation, Mazandaran Province Branch, 48157-66435, Iran, E-mail:

Acknowledgment

We thank the National Elite Foundation, Mazandaran Province Branch from Iran. Illustrations and figures were created with BioRender.com.

  1. Author contributions: K. Saleki, M. Banazadeh, and NS. Miri conceptualized the study and prepared the initial draft. K. Saleki and A. Azadmehr prepared the final draft. A. Azadmehr designed and supervised the project, and prepared the manuscript.

  2. Research funding: There is no funding for the present study.

  3. Conflict of interest statement: The authors declare that they have no competing interests.

  4. Consent for publication: All authors have approved and agreed to publish this manuscript.

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Received: 2021-03-21
Accepted: 2021-05-27
Published Online: 2021-07-06
Published in Print: 2022-02-23

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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