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.