Factors leading to high morbidity and mortality of COVID‐19 in patients with type 2 diabetes

Abstract

Coronavirus disease 2019 (COVID-19) is a recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus. Diabetes (mostly type 2 diabetes mellitus, T2DM) and hyperglycemia are among the major comorbidities in patients with COVID-19 leading to poor outcomes. Reports show that patients with diabetes and COVID-19 are at an increased risk for developing severe complications including acute respiratory distress syndrome, multi-organ failure, and death. Here we explore potential mechanistic links that could explain the observed higher morbidity and mortality in this patient population. Patients with T2DM have an underlying increased level of inflammation associated with obesity and insulin resistance in addition to other comorbidities including hypertension, obesity, cardiovascular disease, dyslipidemia, and being older. We review evidence that T2DM with hyperglycemia are among factors that lead to elevated expression of angiotensin-converting enzyme 2 (ACE2) in lungs and other tissues; ACE2 is the cellular "receptor" and port of viral entry. The preexisting chronic inflammation with augmented inflammatory response to the infection and the increasing viral load leads to extreme systemic immune response ("cytokine storm") that is strongly associated with increased severity of COVID-19. Based on the available evidence, it is recommended by a panel of experts that safe but stringent control of blood glucose, blood pressure, and lipids be carried out in patients with T2DM, measures that could potentially serve to decrease the severity of COVID-19 should these patients contract the viral infection. Once the infection occurs, then attention should be directed to proper glycemic control with use of insulin and frequent monitoring of blood glucose levels.

Clinical characteristics and short term outcomes after recovery from COVID-19 in patients with and without diabetes in Bangladesh

“…According to the present study, the occurrence of asymptomatic infection is less in COVID-19 patients with diabetes. The compromised immune response among cases with diabetes has been reported to play a role in disease expression and progression [ 26 ] and that can be a strong determinant for the higher frequency of symptomatic COVID-19 cases.…”

Investigating the Potential for Ultraviolet Light to Modulate Morbidity and Mortality From COVID-19: A Narrative Review and Update

“…Excessive oxidative stress and impaired immunity (particularly innate cell activity, such as natural killer cells) and pro-inflammatory pathways (including macrophages, T cells, B cells) may increase susceptibility for severe COVID-19 ( 126 , 127 ). The ACE2 receptor for SARS-CoV-2 is highly expressed by adipose tissue, and other relevant tissues [e.g., heart pericytes, pancreatic beta-cells ( 128 )], with adipose tissue a potential reservoir for viral infection ( 125 , 126 ). Entry of the virus may be promoted through pre-existing endothelial dysfunction ( 129 ).…”

Systematic review and patient-level meta-analysis of SARS-CoV-2 viral dynamics to model response to antiviral therapies

“…As a rapidly progressing, primarily respiratory viral infection, SARS-CoV-2 elimination from the body seems to be mainly driven by a combination of innate immune response and exhaustion of target cells available for infection 2 . Observational cohort studies published to date have shown that the rate of viral load decline seems slower in older patients, those with more severe disease and those with comorbidities such as diabetes mellitus and immunosuppression [3][4][5][6] . Interpreting these observational studies requires caution because patients have often received antiviral therapies.…”