Cytokine storms may underlay the molecular basis of covid-19 severity in infected patients

The world is currently battling with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that originated in Wuhan, China late December 2019 and has now become a global pandemic. Objective: From the available scientific evidence, attempt was made to elucidate the possible molecular basis that underlays the severity of this disease with the aim of unveiling a novel therapeutic target for the development of effective therapy against this menace. Methods: Systematic MEDLINE (Ovid) and other databases such as EMBASE were searched for published articles up to June 2020. The subject heading/keywords – “novel coronavirus”, “2019 novel coronavirus”, “2019-nCoV”, “COVID-19”, “SARS-CoV-2 and Cytokines” were used. Results: The investigation revealed that SARS-CoV-2 having distinct tropism of nasal mucosa, negotiates its way into the host’s cells prominently through type II pneumocytes of the lungs using its SPIKE (S protein) recognition binding domain (RBD) on the host’s angiotensin-converting enzyme 2 (ACE2) receptors. Inside the cells, they rapidly replicate, avoiding the type I interferons (IFN-1) signaling crucial to the initial viral control. The delayed IFN-1 marshaling results to the encroachment of the neutrophils, mononuclear macrophages as well as cytokines/chemokines to the site of infections well above the threshold resulting in conditions known as hyper-cytokineamia (cytokine storm). This socalled “cytokine storm” orchestrates and exacerbates systemic hyper-inflammation, which induces lung injury and subsequently acute respiratory distress syndrome (ARDS), multiple system organ failure (MSOF) and eventual death of the patients. Conclusions: Modulating the expression and exacerbation of cytokines such as IL-6 and IL-1β may be a novel therapeutic approach against late stage COVID-19.