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Abstract Introduction COVID-19 has spread across the African continent, including Niger. Yet very little is known about the phenotype of people who tested positive for COVID-19. In this humanitarian crises region, we aimed at characterizing variation in clinical features among hospitalized patients with COVID-19-like syndrome and to determine predictors associated with COVID-19 mortality among those with confirmed COVID-19. Methods The study was a retrospective nationwide cohort of hospitalized patients isolated for COVID-19 infection, using the health data of the National Health Information System from 19 March 2020 (onset of the pandemic) to 17 November 2020. All hospitalized patients with COVID-19-like syndrome at admission were included. A Cox-proportional regression model was built to identify predictors of in-hospital death among patients with confirmed COVID-19. Results Sixty-five percent (472/729) of patients hospitalized with COVID-19 like syndrome tested positive for SARS-CoV-2 among which, 70 (15%) died. Among the patients with confirmed COVID-19 infection, age was significantly associated with increased odds of reporting cough (adjusted odds ratio [aOR] 1.02; 95% confidence interval [CI] 1.01–1.03) and fever/chills (aOR 1.02; 95% CI 1.02–1.04). Comorbidity was associated with increased odds of presenting with cough (aOR 1.59; 95% CI 1.03–2.45) and shortness of breath (aOR 2.03; 95% CI 1.27–3.26) at admission. In addition, comorbidity (adjusted hazards ratio [aHR] 2.04; 95% CI 2.38–6.35), shortness of breath at baseline (aHR 2.04; 95% CI 2.38–6.35) and being 60 years or older (aHR 5.34; 95% CI 3.25–8.75) increased the risk of COVID-19 mortality two to five folds. Conclusion Comorbidity, shortness of breath on admission, and being aged 60 years or older are associated with a higher risk of death among patients hospitalized with COVID-19 in a humanitarian crisis setting. While robust prospective data are needed to guide evidence, our data might aid intensive care resource allocation in Niger.