COVID-19 has emerged as a global pandemic. It is mainly manifested as pneumonia which may deteriorate into severe respiratory failure. The major hallmark of the disease is the systemic inflammatory immune response characterized by Cytokine Storm (CS). CS is marked by elevated levels of inflammatory cytokines, mainly interleukin-6 (IL-6), IL-8, IL-10, tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Of these, IL-6 is found to be significantly associated with higher mortality. IL-6 is also a robust marker for predicting disease prognosis and deterioration of clinical profile. In this review, the pivotal role played by IL-6 in the immuno-pathology of COVID-19 has been illustrated. The role of IL-6 as a pleiotropic cytokine executing both pro and anti-inflammatory activities has been reviewed. ADAM 10, a metalloproteinase switches the anti-inflammatory pathway of IL-6 to pro inflammatory hence blocking the action of ADAM 10 could be a new therapeutic strategy to mitigate the proinflammatory action of IL-6. Furthermore, we explore the role of anti-IL6 agents, IL-6 receptor antibodies which were being used for autoimmune diseases but now are being repurposed for the therapy of COVID-19.

Most people infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV2) are mildly symptomatic while few progress to critical illness and succumb to the infection. The disease severity is seen to be associated with increasing age and underlying comorbid conditions. Obesity, responsible for various metabolic disorders, appears to be a risk factor in determining the severity of infection despite any age group. Though this association is clinically relevant, the mechanisms underlying are not fully elucidated. SARS CoV2 enters host cell via Angiotensin Converting Enzyme 2 receptor, expression of which is upregulated in visceral fat tissue in obese people, underscoring the fact that adipose tissue is a potential reservoir for virus. Adipose tissue is also a source of many proinflammatory mediators and adipokines. High baseline C-Reactive Protein, interleukin 6, hyperleptinemia with Leptin resistance and hypoadiponectinemia associated with obesity explains the preexisting inflammatory state in obese individuals which predisposes them to worse outcomes and fatality. Keywords COVID-19 Á Obesity Á Interleukin-6 Á Creactive protein Á ACE 2 Á Leptin Abbreviations SARS CoV2 Severe acute respiratory syndrome coronavirus 2 CoV Coronavirus COVID-19 Coronavirus disease 2019 IL-6 Interleukin-6 TNF-a Tumor necrosis factor alpha BMI Basal metabolic index IMV Invasive mechanical ventilation ARDS Acute respiratory distress syndrome RAS Renin angiotensin system ACE 2 Angiotensin converting enzyme 2 AT1R Angiotensin II type 1 receptor TMPRSS2 Trans membrane serine protease 2 CRP C-reactive protein hs-CRP High sensitivity C-reactive protein IL-6R Interleukin-6 receptor sIL-6R

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