Cytokines Involved in COVID-19 Patients with Diabetes: A Systematic Review

Background: Hyperglycemic condition and compromised immune system may contribute to the progression of COVID-19 infection and increase the disease severity, relatively requiring a longer recovery period among diabetic patients. Objective: A systematic review was conducted to examine cytokine levels, the prevalence of risk factors, and other comorbidities in COVID-19 patients with and without diabetes mellitus during the early COVID-19 outbreak. Methods: A systematic literature search was conducted in PubMed central, PMC Europe databases, and Web of Science, evaluating the articles published between Dec 1st, 2019, and June 15th, 2020. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: The systematic search generated 14,960 articles and ended up with 9 articles, of which 8 articles involved data on the comparison of cytokines in diabetic and non-diabetic subjects with COVID-19, while 4 of them involved data on cytokines in the diabetes patients compared either by the severity of diseases or the rate of survival. Among the studied cytokines, interleukin-6, interleukin- 8, and tumor necrosis factor-α may cause the worst prognosis or fatality among diabetic patients. Increased cytokine levels indicate higher mortality and are linked to risk factors and comorbidities, such as hypertension and cardiovascular disease. Management of diabetes by insulin treatment may reduce the rate of mortality among diabetic patients but may be contraindicated in diabetic patients with COVID-19 who had at least one previous comorbidity, especially hypertension and CVD. Conclusion: The pathophysiological mechanisms linked to cytokine storm in diabetic patients may lead to the design of treatment strategies in the future, thus improving early diagnosis of the disease and mitigating cytokine storm-associated morbidity and mortality.