IMPACT OF HYPERGLYCEMIA ON COVID-19
Evidence points to clinical and pathophysiological complications related to SARS (Severe Acute Respiratory Syndrome) in hyperglycemic patients, either by SARS-CoV or SARS-CoV-2. Analysis of clinical and biochemical characteristics of 135 patients who died of SARS-CoV, 385 survivors and 19 with non-SARS pneumonia, indicated a history of chronic and/or acute hyperglycemia as an independent predictor for morbidity and mortality in patients with SARS, and revealed metabolic control as the best prognostic factor [10].
A cohort of more than 7000 Sars-CoV- 2 infected patients (with or without DM2) showed correlated hyperglycemia with worse prognosis and higher risk of mortality [11]. This pathological condition favors inflammation and abnormal immune response, contributing to the development and progression of radiological findings [12]. When comparing groups of infected patients: without a history of diabetes (1), with secondary hyperglycemia (2) and diabetics (3), it was noticed that the proportion of critical patients and mortality in 2 and 3 was higher than in 1, besides needing a longer hospitalization time [13].
A retrospective analysis reinforced DM as the greatest risk for negative outcomes in COVID-19 infected [12]. However, acute or stress hyperglycemia may lead to additional complications in these patients (Figure 1). The glycosylation of the ACE2 receptor (Angiotensin 2 converting enzyme) facilitates the intrusion of the virus into the cell [14], since the spike protein of the virus binds to this receptor and promotes the fusion of the viral membrane with the host membrane [15]. In addition, monocytes and macrophages are the immune cells most present in the lungs. This virus effectively infects monocytes from peripheral blood and increases the expression of ACE2. Infected monocytes increase IFN expression α, β and λ and pro-inflammatory cytokines associated with the ”cytokine storm” triggered by SARS-CoV-2. It was also demonstrated that these monocytes increased the function of HIF-1, a strong inducer of glycolysis and transcription of IL-1β, contributing to the pro-inflammatory state. In addition, changes in oxidative metabolism were observed in critically ill patients with COVID-19, by reducing oxygen consumption in infected monocytes and increasing production of mitochondrial ROS (mtROS). Thus, it is suggested that infected monocytes can promote epithelial cell death in an mtROS/HIF-1α dependent manner [16]. Under conditions of hyperglycemia during infection, inhibition of T-cell proliferation may occur, resulting in dysfunction and lymphopenia [16-18]. There was also an increase in viral load, expression of ACE2 and IL-1β in a glucose dependent dose. In this sense, hyperglycemia promotes increased viral replication and expression of cytokines [16].
Based on the data found so far, hyperglycemia should not be neglected at the time of admission, but should be adequately treated, aiming at better outcomes in diabetic patients or not, contaminated by COVID-19[11]. Biguanides can represent auxiliary tools in treatment, thanks to their anti-hyperglicemiant, cardio-protective and modulating properties of the immune system, in addition to their potential antiviral effect.