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Assim A Alfadda,1– 3 Khalid Siddiqui,2 Mohamed Rafiullah,2 Mohammad AlKhowaiter,1 Naif Alotaibi,4 Musa Alzahrani,5 Khalifa Binkhamis,6 Amira M Youssef,2 Haifa Altalhi,7 Ibrahim Almaghlouth,8 Mohammed Alarifi,9 Saleh Albanyan,1 Mohammed F Alosaimi,10 Arthur Isnani,3 Shaik S Nawaz,2 Khalid Alayed5 1Department of Internal Medicine, College of Medicine, and King Khalid University Hospital, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 2Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 3Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 4Department of Medicine, College of Medicine, and King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 5Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 6Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 7Infection Control Department, King Khalid University Hospital, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 8Rheumatology Unit, Department of Internal Medicine, King Khalid University Hospital, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 9Intensive Care Department, King Khalid University Hospital, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 10Pediatric Department, King Khalid University Hospital, King Saud University Medical City, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Assim A Alfadda, Department of Internal Medicine and the Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925(98), Riyadh, 11461, Saudi Arabia, Tel + 966 11 467 1315, Email aalfadda@ksu.edu.saBackground: The severe manifestation of coronavirus disease 2019 (COVID-19) is known to be mediated by several cytokines and chemokines. The study aimed to compare the early cytokine profile of mild and severe COVID-19 patients to that with COVID-19-like symptoms and tested negative for Severe Acute Respiratory Syndrome Coronavirus-2 in the Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) test.Methods: This was a prospective, observational study on COVID-19 patients admitted to King Khalid University Hospital, King Saud University Medical City from June to November 2020. Clinical and biochemical data were collected from hospital charts. Blood samples were collected at the time of hospital admission to measure cytokines. A Cytokine and Growth Factor High-Sensitivity Array was used to quantitatively measure cytokines.Results: The study included 202 RT-PCR-positive individuals and 61 RT-PCR-negative individuals. C-Reactive protein (CRP) and Interleukin-10 (IL-10) levels were found significantly elevated in the RT-PCR positive group compared to the RT-PCR negative group (p=0.001). Patients with severe COVID-19 had significantly longer median hospital stays than those with mild COVID-19 cases (7 vs 6 days). They also had higher CRP and Vascular Endothelial Growth Factor (VEGF) levels and lower Interleukin-4 (IL-4) levels compared to the mild cases. CRP, interleukin-6, IL-10, VEGF, and Monocyte Chemoattractant Protein-1 (MCP-1) levels were significantly elevated in men and IL-10 was significantly higher and interleukin-8 was significantly lower in women compared to negative controls. Elevated Interferon-ɣ (IFN-γ) and IL-10 levels were seen in mild COVID-19 cases and elevated level of MCP-1 was seen in severe COVID-19 cases when categorized according to the length of stay in the hospital.Conclusion: CRP and IL-10 levels were elevated in the RT-PCR positive group. People with severe COVID-19 had higher CRP and VEGF levels and lower IL-4 levels. Elevated IFN-γ and IL-10 levels were seen in mild COVID-19 cases and elevated level of MCP-1 was seen in severe COVID-19 cases when categorized according to the length of stay in the hospital.Keywords: SARS-CoV-2, early inflammation, asymptomatic patient, proinflammatory cytokines, regulatory cytokines