COVID-19 risk increases with comorbidities, and the effect is magnified due to the contribution of individual and combined comorbidities to the overall clinical outcomes. We aimed to explore the influence of demographic factors, clinical manifestations, and underlying comorbidities on mortality, severity, and hospital stay in COVID-19 patients. Therefore, retrospective chart reviews were performed to identify all laboratory-confirmed cases of SARS-CoV-2 infection in Apollo Hospitals, Hyderabad, between March 2020 and August 2020.A total of 369 confirmed SARS-CoV-2 cases were identified: 272 (73.7%) patients were male, and 97 (26.2%) were female. Of the confirmed cases, 218 (59.1%) had comorbidities, and 151 (40.9%) were devoid of comorbidities. This study showed that old age and underlying comorbidities significantly increase mortality, hospital stay, and severity due to COVID-19 infection. The presence of all four comorbidities,
diabetes
mellitus
DM
+
Hypertension
HTN
+
coronary
artery
disease
CAD
+
chronic
kidney
disease
CKD
, conferred the most severity (81%). The highest mortality (OR: 44.03, 95% CI: 8.64-224.27) was observed during the hospital stay (
12.73
±
11.38
; 95% CI: 5.08-20.38) in the above group. Multivariate analysis revealed that nonsurvivors are highest (81%) in (
DM
+
HTN
+
CAD
+
CKD
) category with an odds ratio (95% CI) of 44.03 (8.64-224.27). Age, gender, and comorbidities adjusted odds ratio decreased to 20.25 (3.77-108.77). Median survival of 7 days was observed in the (
DM
+
HTN
+
CAD
+
CKD
) category. In summary, the presence of underlying comorbidities has contributed to a higher mortality rate, greater risk of severe disease, and extended hospitalization periods, hence, resulting in overall poorer clinical outcomes in hospitalized COVID-19 patients.