Immune system response during viral Infections: Immunomodulators, cytokine storm (CS) and Immunotherapeutics in COVID-19

Hyder Pottoo, Faheem; Abu-Izneid, Tareq; Mohammad Ibrahim, Abdallah; Noushad Javed, Md.; AlHajri, Noora; Hamrouni, Amar M.

Coronaviruses are non-segmented and single stranded positive-sense RNA (+ssRNA) viruses. To date, 06 human coronaviruses (HCoVs) are reported; α-CoVs (HCoVs-NL63 and HCoVs-229E) and β-CoVs (HCoVs-OC43, HCoVs-HKU1, SARS-CoV, MERS-CoV). While, novel coronavirus (SARS-CoV-2) is the most recent member. The genome sequence of SARS-CoV-2 is 82% similar to SARS–COV-1. The compelling evidences link the progression of viral infection of SARS-CoV-2 with excessive inflammation as a result of the exaggerated immune response and elevated production of “immunocytokines” resulting in cytokine storm (CS); followed by a series of events, like acute organ damage, acute respiratory distress syndrome (ARDS) as well as death. Hence attempts to reduce cytokine storm are now being considered as a new paradigm shift in the clinical management of SARS-CoV-2. Tocilizumab (IL-6 blocker), Baricitinib (JAKs and AAK1 inhibitor), TNFα inhibitors (Infliximab, Adalimumab, Certolizumab) are currently being evaluated for possible block of the CS. Hence, rationalizing anti-inflammatory therapeutics would be the most judicious approach for significant reduction in COVID-19 mortality. In order to elucidate optimized and rationaled use of different therapeutics in COVID-19, we collated latest available information from emerging scientific evidences, integrated previous attempts as well as clinical successes, and various adopted approaches to mitigate past outbreaks with of SARS-CoV and MERS CoV.