Insulin Treatment Increased Fatality in COVID-19 Patients with Diabetes (preprint)

Background: COVID-19 epidemic continues to spread rapidly around the world, causing severe multi-organ injury and high mortality in a subset of patients. Individuals with diabetes mellitus are at a higher risk of SARS-CoV-2 infection and worse outcomes than the general population without diabetes. While glucose control was observed to be associated with attenuated mortality, limited evidence is available to determine whether glucose control by insulin was beneficial for COVID-19 patients with diabetes.Methods: This retrospective study focused on a cohort of 689 COVID-19 patients from Wuhan, China, diagnosed with diabetes, and assessed the clinical outcomes associated with insulin treatment. Kaplan-Meier survival analysis and proportional Cox regression were employed to analyze the influence of insulin treatment on all cause death.Results: Among the 689 diabetic patients infected with COVID-19, 106 patients died (fatality was 15.4%). The fatality of COVID-19 patients with diabetes treated with insulin was significantly higher than those without insulin treatment (27.2% vs. 3.5%, p < 0.001). The HR was 6.57 (95% CI 3.09 to 13.99; p < 0.001) after adjustment for age, gender, coronary heart disease, COPD, chronic kidney disease, pulse, respiratory rate, SpO2, lymphocyte count, albumin, NT-proBNP and glucose. Further survival analysis in several subgroups and critically ill group showed the similar effect of insulin on adverse outcome in COVID-19 patients with diabetes.Conclusion: According to this retrospective study, insulin treatment increases the mortality in COVID-19 patients with diabetes. Thus, close observation especially glucose and vital signs monitoring are very important when COVID-19 patients with diabetes treated with insulin.Funding: This work was supported in part by projects from Ministry of Science and Technology of China (No. 2020YFC0844500), Nature Science Foundation of China (Nos. 31130031), Emergency project fund of Chinese Academy of Sciences (No. 2020YJFK0105) and Chinese Academy of Engineering and Ma Yun Foundation (No. 2020-CMKYGG-05). Conflict of Interest: The authors have declared that no competing interests exist.Ethical Approval: This study was approved by the institutional review board of Tongji Hospital (IRBID: TJ-IRB20200229). The written informed consent was waived by the Ethics Committee because of the retrospective and anonymous nature of the data.

Hydroxychloroquine application is associated with a decreased mortality in critically ill patients with COVID-19 (preprint)

Importance: Coronavirus disease 2019 (COVID-19) is a pandemic with no specific drugs and high mortality. The most urgent thing is to find effective treatments. Objective: To determine whether hydroxychloroquine application may be associated with a decreased risk of death in critically ill COVID-19 patients and what is potential mechanism. Design, Setting and Patients: This retrospective study included all 568 critically ill COVID-19 patients who were confirmed by pathogen laboratory tests despite antiviral treatment and had severe acute respiratory distress syndrome, PAO2/FIO2 <300 with need of mechanical ventilation in Tongji Hospital, Wuhan, between February 1 of 2020 to April 8 of 2020. All 568 patients received comparable basic treatments including antiviral drugs and antibiotics, and 48 of them additionally received oral hydroxychloroquine (HCQ) treatment (200 mg twice a day for 7-10 days). Primary endpoint is mortality of patients, and inflammatory cytokines levels were compared between hydroxychloroquine and non-hydroxychloroquine (NHCQ) treatments. MAIN OUTCOMES AND MEASURES: In-hospital death and hospital stay time (day) were obtained, level of inflammatory cytokine (IL-6) was measured and compared between HCQ and NHCQ treatments. RESULTS: The median age of 568 critically ill patients is 68 (57, 76) years old with 37.0% being female. Mortalities are 18.8% (9/48) in HCQ group and 45.8% (238/520) in NHCQ group (p<0.001). The time of hospital stay before patient death is 15 (10-21) days and 8 (4 - 14) days for the HCQ and NHCQ groups, respectively (p<0.05). The level of inflammatory cytokine IL-6 was significantly lowered from 22.2 (8.3-118.9) pg/mL at the beginning of the treatment to 5.2 (3.0-23.4) pg/ml (p<0.05) at the end of the treatment in the HCQ group but there is no change in the NHCQ group. CONCLUSIONS AND RELEVANCE: Hydroxychloroquine treatment is significantly associated with a decreased mortality in critically ill patients with COVID-19 through attenuation of inflammatory cytokine storm. Therefore, hydroxychloroquine should be prescribed for treatment of critically ill COVID-19 patients to save lives.