21 Dec, 2020
Its very essential to understand the interaction between SARS-CoV-2 and the host immune system as this will help in developing targeted therapeutics as well as vaccines. The scientific community throughout the world is trying to analyze the various characteristics of this nasty virus and how it affects the host and in which circumstances it causes severe disease leading to acute respiratory distress syndrome (ARDS) ,multiple organ failure or death.
At present some studies have highlighted the unpredictable hyperimmune response to this virus leading to humungous release of cytokines and leading to a “cytokine storm”. Whenever a pathogen invades , the host immune system gets alerted to clear off the pathogen. The first line of rapid defense is the innate immune system cells and subsequently cells of the adaptive immune system take necessary action. For this complex process to occur multiple chemical signals or cytokines are secreted by the participant cells however if the proinflammatory cytokines go overboard it becomes dangerous for the host body itself. The cytokines involved namely with SARS-CoV-2 defense are IFN( this is antiviral), IL-1ß, IL-6, and tumour necrosis factor(TNF). The cytokine storm is responsible for inflammatory lung injury, circulatory problems and eventually death. Several drugs like corticosteroids, tocilizumab( IL-6 antagonist), TNF inhibitors target this process.
Interestingly, recently one study by Keneth et al from U.S pointed severe immunosuppression in COVID-19. They used a functional immunoassay called ELISpot to evaluate innate and adaptive immune system and found very low levels of circulating T cell subsets in COVID-19 patients. Few research studies prior to this have also discussed about T cell exhaustion in COVID-19. Well , this is quite opposite of cytokine storm hypothesis. Hence, much more scientific evidence is required to understand the complex host and SARS-CoV-2 interactions for targeted treatment.
References:
Remy KE, Mazer M, Striker DA, Ellebedy AH, Walton AH, Unsinger J, Blood TM, Mudd PA, Yi DJ, Mannion DA, Osborne DF, Martin RS, Anand NJ, Bosanquet JP, Blood J, Drewry AM, Caldwell CC, Turnbull IR, Brakenridge SC, Moldwawer LL, Hotchkiss RS. Severe immunosuppression and not a cytokine storm characterizes COVID-19 infections. JCI Insight. 2020 Sep 3;5(17):e140329. doi: 10.1172/jci.insight.140329. PMID: 32687484; PMCID: PMC7526441.
Ye Q, Wang B, Mao J. The pathogenesis and treatment of the `Cytokine Storm' in COVID-19. J Infect. 2020 Jun;80(6):607-613. doi: 10.1016/j.jinf.2020.03.037. Epub 2020 Apr 10. PMID: 32283152; PMCID: PMC7194613.
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