COVID-19 pandemic caused by the novel Coronavirus SARS-CoV-2 depicts a strange selectivity with mercurial clinical manifestations among humans. This differential pattern in disease severity, death toll and rate of recovery has been revealed worldwide. Symptoms range from mild cold or development of acute respiratory distress syndrome (ARDS); while few remain asymptomatic. Demographics reveal
that potential risk factors include age and underlying co-morbidities; nevertheless, several are often dying without comorbidities due to ARDS. In addition to ecological and viral factors, the host immunogenetic diversity is instrumental in the spectrum of clinical outcomes. Co-ordination of innate and adaptive immune responses can control viral infections, while a compromised immunity augments viral spreading leading to mortality. NK cells, heterogeneous macrophage subsets and T lymphocytes are crucial immune effectors during viral clearance in ARDS. Reports say that elevated pro-inflammatory serum cytokines, chemokines and interferon stimulated genes are associated with disease severity among SARS, MERS and COVID-19 patients. Moreover, critical COVID-19 patients had significant cytokine-upsurge than milder cases. Insufficient evidence exists which could associate COVID-19 disease severity to host immuno-genetic components. This study has been designed to identify, analyze and compare the host-specific immuno-genetic determinants triggering severe lung pathologies among COVID-19 patients, encompassing the endemic settings of India. Molecular characterization of the lung immune microenvironment and functional elucidation of the differentially regulated genes will be done from mild as well as severe COVID-19 patients. The immune determinants trigger disease severity in some, while protecting others might be targeted during drug development. Distinction between these alternative immuno-genetic profiles is essential during vaccine designing against SARS-CoV-2. Genetically predisposed higher-risk groups could be the first to be vaccinated when it becomes available.