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BackgroundRisk factors for the development of severe COVID-19 disease and death have been widely reported across several studies. Knowledge about the determinants of severe disease and mortality in the Indian context can guide early clinical management.MethodsWe conducted a hospital-based case control study across nine sites in India to identify the determinants of severe and critical COVID-19 disease.FindingsWe identified age above 60 years, duration before admission >5 days, chronic kidney disease, leucocytosis, prothrombin time > 14 sec, serum ferritin >250 ng/mL, d-dimer >0.5 ng/mL, pro-calcitonin >0.15 μg/L, fibrin degradation products >5 μg/mL, C-reactive protein >5 mg/L, lactate dehydrogenase >150 U/L, interleukin-6 >25 pg/mL, NLR ≥3, and deranged liver function, renal function and serum electrolytes as significant factors associated with severe COVID-19 disease.InterpretationWe have identified a set of parameters that can help in characterising severe COVID-19 cases in India. These parameters are part of routinely available investigations within Indian hospital settings, both public and private. Study findings have the potential to inform clinical management protocols and identify patients at high risk of severe outcomes at an early stage.