The Role of Cytotoxic T-Cells in COVID-19: Potential Therapeutic Targeting

Amirhossein  Hessami; Keyvan  Heydari; Aref  Hosseini; Negar  Asgari

doi:10.18502/igj.v7i3.17876

Amirhossein Hessami Non-communicable Disease Institute, Mazandaran University of Medical Sciences, Sari, Iran
Keyvan Heydari Gastrointestinal Cancer Research Center, Non-Communicable Disease Institute, Mazandaran University of Medical Sciences, Sari, Iran
Aref Hosseini Non-communicable Disease Institute, Mazandaran University of Medical Sciences, Sari, Iran
Negar Asgari Department of Medical Laboratory, Golestan University of Medical Sciences, Gorgan, Iran

DOI: https://doi.org/10.18502/igj.v7i3.17876

Keywords: COVID-19; PD-1; PD-L1; anti-PD-1/PD-L1; CRISPR

Abstract

A novel coronavirus disease (COVID-19) have raised in Whuan in December 2019. This disease kept spread-ing rapidly until World Health Organization have declared a pandemic on COVID-19. Despite all the effortsmade there are no definite treatments for this disease. Recent papers on pathophysiology of COVID-19have shown possible mechanism of T-Cell exhaustion caused by virus is responsible for lymphopenia ob-served in these patients. PD-1/PD-L1 have a major role in T-Cell exhaustion so we have proposed targetingPD-1/PD-L1 using anti-PD-1/PD-L1 agent. Using anti-PD-1/PD-L1 agents including Pembrolizumab andNivolumab could potentially decrease T-Cell exhaustion and increases survival of COVID-19 patients. Inorder to overcome the shortcoming of this approach we have proposed using clustered regularly interspacedshort palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) which can be highly efficient intargeting PD-1/PD-L1. Using CRISPR/Cas9 in this regard could be more efficient, feasible and economicaland potentially lower side effects. In conclusion targeting PD-1/PD-L1 through approved medications orCRISPR/Cas9, in order to block their interactions, may remarkably prevent the cytotoxic lymphocytes func-tional exhaustion, especially CD8+ T-cells and help to decrease the mortality rate in COVID-19 patients.In addition, to evaluate the clinical outcome of using anti-PD-1/PD-L1 agents or CRISPR/Cas9 system inCOVID-19 patients, it is recommended to measure lymphocyte, CD8+ T-cells, NK cells and total T-cellscount.