Objective COVID-19 mortality and outcomes differ significantly across the globe. Limited data exists from low-middle income countries (LMICs) on risk-factors for COVID-19 severity and mortality. We describe the clinical spectrum and predictors of mortality and severity of illness in COVID-19 from a single center in Karachi, Pakistan. Methods Retrospective cohort study of adults admitted with COVID-19 between February-June 2020 were reviewed and logistic regression applied on admission related risk-factors for severity and mortality. Results A total of 445 patients [66.97% males, mean age 51.6 (18-91) years] were admitted with PCR confirmed COVID-19 during the study period. Asymptomatic and severe/critical disease occurred in 55 (12.36%) and 137 (30.79%) patients, respectively. The proportion of severe disease increased with time and most (268, 60.22%) had ≥ 1 co-morbid. Disease severity was associated with age ≥ 60 (OR:1.92), shortness of breath (OR:4.43) , CRP ≥150mg/L (OR:1.77), LDH ≥ 500 I.U/L (OR:1.98), Neutrophil to Lymphocyte ratio (NLR) ≥5 (OR:2.80) and unit increase in serum creatinine (OR:1.32). All-cause mortality was 13%. Mortality was associated with septic shock (AOR= 13.2), age ≥ 60 (AOR: 3.25), Ferritin ≥ 1500ng/ml (AOR: 3.78) and NLR ≥ 5 (AOR: 4.04). Conclusion We describe the experience with COVID-19 from a tertiary-care hospital in a LMIC. Our study found a comparatively low inpatient mortality, high proportion of diabetics, and neutrophil to lymphocyte ratio of greater than 5 as a predictor of both severity of illness and as poor prognostic marker in COVID-19.