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Tonny Kyagambiddwa,1,&ast; Timothy Mwanje Kintu,1,&ast; Emmanuel Miiro,1,&ast; Franchesca Nabalamba,1 Gloria Suubi Asiimwe,1 Anne Marion Namutebi,2 Fardous C Abeya,3 Boniface A Lumori,3 Isaac Ijuka,4 Rose K Muhindo,1,3 Andrew Mutekanga,1,3 Richard Musinguzi,5 Francis Natuhwera,6 Joseph Ngonzi,1,7 Edwin Nuwagira3,8 1Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda; 2Kabale Regional Referral Hospital, Kabale, Uganda; 3Department of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda; 4Mayanja Memorial Hospital, Mbarara, Uganda; 5Masaka Regional Referral Hospital, Masaka, Uganda; 6Fort Portal Regional Referral Hospital, Fort Portal, Uganda; 7Department of Obstetrics and Gynecology, Mbarara University of Science and Technology, Mbarara, Uganda; 8Tuberculosis Treatment Unit, Mbarara Regional Referral Hospital, Mbarara, Uganda&ast;These authors contributed equally to this workCorrespondence: Tonny Kyagambiddwa; Edwin Nuwagira, Mbarara University of Science and Technology, Tel +256782980116 ; +256779096887, Email tonnykyagambiddwa97@gmail.com; enuwagira@must.ac.ugBackground: There is scarcity of data regarding young and middle-aged adults hospitalized with severe Corona Virus Disease 2019 (COVID-19) in Africa. In this study, we describe the clinical characteristics and 30-day survival among adults aged 18 to 49 years admitted with severe COVID-19 in Uganda.Methods: We reviewed treatment records of patients admitted with severe COVID-19 across five COVID-19 treatment units (CTU) in Uganda. We included individuals aged 18 to 49 years, who had a positive test or met the clinical criteria for COVID-19. We defined severe COVID-19 as having an oxygen saturation < 94%, lung infiltrates > 50% on imaging and presence of a co-morbidity that required admission in the CTU. Our main outcome was the 30-day survival from the time of admission. We used a Cox proportional hazards model to determine the factors associated with 30-day survival at a 5% level of significance.Results: Of the 246 patient files reviewed, 50.8% (n = 125) were male, the mean ± (standard deviation) age was 39 ± 8 years, majority presented with cough, 85.8% (n = 211) and median C-reactive protein (interquartile range) was 48 (47.5, 178.8) mg/L. The 30-day mortality was 23.9% (59/246). At admission, anemia (hazard ratio (HR): 3.00, 95% confidence interval (CI), 1.32– 6.82; p = 0.009) and altered mental state (GCS < 15) (HR: 6.89, 95% CI: 1.48– 32.08, p = 0.014) were significant predictors of 30-day mortality.Conclusion: There was a high 30-day mortality among young and middle-aged adults with severe COVID-19 in Uganda. Early recognition and targeted management of anemia and altered consciousness are needed to improve clinical outcomes.Keywords: COVID-19, Uganda, mortality, young and middle-aged adults