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Amal Ahmed Mohamed,1 Abdulmohsen H Alrohaimi,2 Asmaa Sayed Abdelgeliel,3 Sarah Albogami,4 Ibrahim Jafri,4 Eman Fayad,4 Nouran Mohamed,5 Nourelhuda Ahmed Nassar,6 Ahmad Sobhy Adaroas,6 Hala H Eldeeb,6 Ahmed Abdel Halim,7 Ahmed Ramadan,8 Rehab M Elnagar,9 Reem Ahmed Mohamed Abdelghafour,10 Amira Yones Mohamed,11 Maha O Mahmoud,12 Ahmed El-Kasses,13 Marwa El-Sayed,14 Mostafa Ahmed Mohammed,15 Eman A Alwaleed,3 Shrook Mousa,16 Sherief Abdel Salam,17 Soha M Abd el salam18 1Biochemistry and Molecular Biology Department, National Hepatology & Tropical Medicine Research Institute, Cairo, Egypt; 2Department of Pharmacy Practice, College of Pharmacy, Shaqra University, Shaqra, Saudi Arabia; 3Department of Botany and Microbiology, South Valley University, Qena, Egypt; 4Department of Biotechnology, College of Science, Taif University, Taif, Saudi Arabia; 5Faculty of Biotechnology, Misr University for Science and Technology, Giza, Egypt; 6Clinical Pathology Department, Elsahel Teaching Hospital, Cairo, Egypt; 7Tropical Medicine Department, National Hepatology & Tropical Medicine Research Institute, Cairo, Egypt; 8Endemic Medicine Department, Cairo University, Cairo, Egypt; 9Radiology Department, Faculty of Medicine, Tanta University, Tanta, Egypt; 10Internal Medicine Department, Damnohour Teaching Hospital, Cairo, Egypt; 11Internal Medicine Department, Mataria Teaching Hospital, Cairo, Egypt; 12Biochemistry Department, Faculty of Pharmacy, Egyptian Russian University, Cairo, Egypt; 13Radiology Department, Elsahel Teaching Hospital, Cairo, Egypt; 14Department of Microbiology and Immunology, Faculty of Medicine, South Valley University, Qena, Egypt; 15Department of Microbiology and Immunology, Faculty of Pharmacy, Al Azhar University, Assiut Branch, Assiut, Egypt; 16Internal Medicine Department, Cairo University, Cairo, Egypt; 17Department of Hepatogastroenterology and Infectious Diseases, Tanta University, Tanta, Egypt; 18Department of Medical Microbiology and Immunology, Faculty of Medicine, Suez University, Suez, EgyptCorrespondence: Sherief Abdel Salam, Department of Hepatogastroenterology and Infectious Diseases, Tanta University, Tanta, Egypt, Email sheriefabdelsalam@yahoo.comBackground and Aims: SARS-CoV-2 infection has been recorded in 230 countries to date. Obesity has a negative impact on one’s quality of life and is one of the main causes of mortality globally. Obesity affects the immune system, making the host more susceptible to infectious infections. Also, obesity commonly provokes the severity of respiratory diseases so the correlation of LEP rs7799039 Polymorphism in corpulent patients with COVID-19 infection was clearly investigated in the current study.Methods: A total of 232 patients were recruited, 116 patients were obese with COVID-19 infection, and 116 patients were non obese COVID-19. Fasting blood glucose test (FBG), hemoglobin A1C (HbA1C), complete blood count (CBC), international normalized ratio (INR), urea, alanine transaminase (ALT), aspartate aminotransferase (AST), D dimer and C-reactive protein (CRP) were estimated. C.T. scan was performed for each patient, and C.T. severity score was calculated. Genotyping for the leptin rs7799039 SNPs was performed by TaqMan® (Applied Biosystems Step One TM Real-time PCR).Results: Regarding LEP polymorphism, all individuals of non-obese groups significantly had the homozygous allele GG (100%), whereas only 56% of obese groups had GG alleles (P = 0.001). The severity scores significantly (P = 0.001) varied regarding LEP polymorphism regarding Rs7799039, where the largest proportion of those with Grade IV had the homozygous allele AA (57.1%).Conclusion: There was a correlation between the leptin gene allelic discrimination and COVID-19 CT brutality in obese patients. The A allele was considered a risk factor for severity in COVID-19 patients while the G allele contributes to decreasing that risk.Keywords: COVID-19, leptin, gene polymorphism, immunity, obesity