Abdullah A Alharbi,1 Khalid I Alqumaizi,2 Ibrahim Bin Hussain,3– 5 Abdullah Alsabaani,6 Amr Arkoubi,7 Abdulaziz Alkaabba,8 Arwa AlHazmi,5 Nasser S Alharbi,9 Hussam M Suhail,10 Abdullah K Alqumaizi11 1Family and Community Medicine Department, Faculty of Medicine, Jazan University, Jazan City, Saudi Arabia; 2Family Medicine Department, Faculty of Medicine, AlMaarefa University, Riyadh, Saudi Arabia; 3Department of Pediatrics, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia; 4Department of Pediatrics, College of Medicine, Al Faisal University, Riyadh, Saudi Arabia; 5Southern Business Unit, Health Holding Company Project, Healthcare Transformation, Vision Realization Office, Ministry of Health, Riyadh, Saudi Arabia; 6Department of Family and Community Medicine, College of Medicine, King Khalid University, Abha, Saudi Arabia; 7Department of Surgery, College of Medicine, Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia; 8Department of Family Medicine, Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia; 9Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 10Faculty of Medicine, Jazan University, Jazan City, Saudi Arabia; 11College of Medicine, Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi ArabiaCorrespondence: Abdullah A Alharbi, Family and Community Medicine Department, Faculty of Medicine, Jazan University, 12501 Dar Al-Nassr St., Abu Arish, Jazan, 45911, Saudi Arabia, Email aaalharbi@jazanu.edu.saBackground: This is the first descriptive and comparative study conducted of COVID-19 inpatients from multi-centers in the four administrative southern regions and proposed Southern Business Unit (Jazan, Najran, Bisha, and Aseer) of the Kingdom of Saudi Arabia (KSA).Methods: Participants were 809 randomly selected patients admitted to the eight sampled hospitals with confirmed COVID-19 between March 2020 and February 2021. We assessed and compared socio-demographics, clinical characteristics, and clinical outcomes of the four regions.Results: Socio-demographic and clinical characteristics of the participants are a mean age of 60 ± 17.7 years, 70% Saudi male, the prevalence of diabetes (DM2) 58%, hypertension (HTN) 48%, obesity 43%, cardiac diseases 15%, and immunity or cancer diseases almost 1%. The prevalence of complications during admission were bacterial pneumonia 65%, acquired respiratory distress syndrome (ARDS) 32%, sepsis 20%, multi-organ failure 18%, acute kidney diseases 15%, and arrhythmia 4%. Clinical outcomes were: admitted to intensive care unit (ICU) 52%, mortality rate 25%, referred to other facilities 9%, and mean length of stay (LOS) was 11± 9.5 days. We observed statistically significant variation in many variables among the four regions. Najran and Aseer had a higher prevalence of risk factors for severity including age and comorbidities accompanied by higher rates of complications, ICU admissions, LOS, and mortality. Bisha and Jazan had lower prevalence of risk factors and LOS with lower rates of complications, ICU admissions, and mortality.Conclusion: This study reveals that the geographic region in which the patient was cared for was related to the severity and outcome of COVID-19 infection. Policy makers should search for solutions to regional differences in underlying health conditions such as DM2, HTN, and obesity to plan for improvements in preventive care as well as resource distribution to ensure quality for all Saudi citizens. This study will serve as guidance to begin to form strategies for these improvements as envisioned in the future New Model of Care.Keywords: COVID-19, inpatient characteristics, demographic and clinical characteristics, clinical course, outcomes, and complications, Southern Business Unit, Saudi Arabia