The exaggerated immune response induced in the lower respiratory tract against coronaviruses (CoVs), including CoViD-19 (2019-nCoV), appears to contribute to the overwhelming lung damage caused by the disease in comparison to the effect of the direct viral invasion and replication in the host. While it has resulted in high global rates of morbidity (4,618,821 infected cases), a sizeable number of individuals have already succumbed (311,847 deaths) 1 (case fatality rate of 1–10%) to severe pathological manifestations involving the lower respiratory tract (1) as of May 18, 2020, as reported by the World Health Organization1. This has, however, been documented to be less severe when compared to influenza (2).

CoViD-19 reportedly has four stages: a pre-symptomatic phase of fever, cough, and generalized malaise heralded by high viral loads in severely affected cases. After about a week, the second stage manifests with viral pneumonia that involves the lower respiratory tract (while viral loads in the upper respiratory tract decrease exponentially). A vast majority of patients show clinical improvement as protective humoral responses are developed at this stage of the disease. A minor proportion of individuals progress to the third phase of CoViD-19 by developing symptoms of hypercytokinemia (cytokine release syndrome (CRS)/cytokine storm) characterized by exaggerated levels of pro-inflammatory cytokines and other pathognomonic biomarkers of inflammation, leading to the rapid onset of acute respiratory distress syndrome (ARDS) and multi-organ failure (Stage 4). It is also intriguing to know that many individuals with CoViD-19 have not developed ARDS. The median time from development of symptomatic disease to death from CoViD-19 is∼ 2–8 weeks (3). SARS-CoV-2 appears to trigger a prolonged phase of hypercytokinemia (also called as macrophage activation syndrome) that encompasses a broad array of pro-inflammatory mediators like IL-6, IL-1β, TNF-α, and CXCL8 (IL-8) together with the infiltration of inflammatory and degranulating cells into the lungs, usually 7–10 days following the onset of symptoms during the second stage of CoViD-19 (3–7). Variations in human genetic make-up have been shown to affect disease progression and prognosis of infectious diseases. A more recent emergence of interest surrounds individuals harboring mutations in the Mediterranean fever gene (mefv), which likely could predispose the onset of severe CoViD-19 disease manifestations resulting from local and systemic cytokine storm (8).