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Background: The outbreak of the novel coronavirus disease (COVID-19) that began in December 2019 has posed a great threat to human health and caused a significant loss of life. In Shenzhen, 465 patients were confirmed to have COVID-19 as of August 31, 2020. In the present study, we aimed to describe the clinical characteristics of COVID-19 patients in Shenzhen and identify risk factors for the development of viral sepsis.Methods: In this retrospective study, patients who were confirmed to have a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and were admitted to the Third People's Hospital of Shenzhen from January 11 to April 27, 2020 were included in the cohort. Clinical data were extracted and followed up to May 10, 2020, by using predesigned data collection forms.Results: A total of 422 hospitalized COVID-19 patients were enrolled in this study, including 97 (23%) patients with viral sepsis at hospital admission and 325 (77%) non-septic patients. Patients with sepsis were much older than those without sepsis (57 vs. 43 years, P < 0.001) and presented with more comorbidities. Septic patients showed multiple organ dysfunction and significant abnormalities in immune- and inflammation-related biomarkers, and had poorer outcomes when compared to those without sepsis. Increased levels of interleukin-6, blood urea nitrogen, and creatine kinase were associated with the development of SARS-CoV-2-induced sepsis, and an elevated production of interleukin-6 was found to be an independent risk factor for the progression to critical illness among septic COVID-19 patients.Conclusions: SARS-CoV-2 infection-induced sepsis is critically involved in the severity and prognosis of COVID-19 patients by characterizing both aberrant immune response and uncontrolled inflammation. The development of sepsis might contribute to multiple organ dysfunction and poor outcomes in COVID-19 patients during hospitalization.