key: cord-0723678-9rfwspf8
authors: Chesnut, Walter M; MacDonald, Scott; Gustavo Wambier, Carlos
title: Could diet and exercise reduce risk of COVID-19 syndemic?
date: 2021-01-24
journal: Med Hypotheses
DOI: 10.1016/j.mehy.2021.110502
sha: 5c950b01e5438f3d9ca71d3edcac02dca1c7089f
doc_id: 723678
cord_uid: 9rfwspf8

We present a hypothesis for increased sugar consumption and a lack of physical exercise as possible determinants of COVID-19 disease severity by impaired glucose metabolism, concurring into a syndemic. National data demonstrate that increased sugar consumption, a high daily caloric intake, and low levels of daily physical activity are independently associated with COVID-19 mortality. Further, genetic factors such as variations in the androgen receptor may compound the effects of an unhealthy lifestyle and increase the risk of severe COVID-19 symptoms in some patients. A diet high in sugar in combination with a low level of physical activity may increase blood glucose levels and impair glucose metabolism. Recent data show that patients admitted to the hospital with high levels of fasting blood glucose are at an increased risk for severe COVID-19 symptoms. Moreover, elevated glucose levels resulted in increased SARS-CoV-2 viral loads in vitro. We believe that healthier habits of diet and exercise, by improving glucose homeostasis could modulate the individual risk of severe COVID-19 symptoms.

We present a hypothesis for increased sugar consumption and a lack of physical exercise as possible determinants of COVID-19 disease severity by impaired glucose metabolism, concurring into a syndemic. National data demonstrate that increased sugar consumption, a high daily caloric intake, and low levels of daily physical activity are independently associated with COVID-19 mortality. Further, genetic factors such as variations in the androgen receptor may compound the effects of an unhealthy lifestyle and increase the risk of severe COVID-19 symptoms in some patients. A diet high in sugar in combination with a low level of physical activity may increase blood glucose levels and impair glucose metabolism. Recent data show that patients admitted to the hospital with high levels of fasting blood glucose are at an increased risk for severe COVID-19 symptoms. Moreover, elevated glucose levels resulted in increased SARS-CoV-2 viral loads in vitro. We believe that healthier habits of diet and exercise, by improving glucose homeostasis could modulate the individual risk of severe COVID-19 symptoms.

To the editor: The COVID-19 pandemic has affected over 31 million people and taking over 1 million lives. 1 Individual vulnerability still needs further elucidation. High levels of fasting blood glucose (FBG) upon hospital admission has been associated with an increased risk for more severe COVID-19 symptoms. 2 Elevated glucose levels has been observed to enhance viral replication trigger increased cytokine production by monocytes in vitro. 3 Here we hypothesize that reduced consumption of added sugars (refined carbohydrates), as well as increased physical activity per capita, could lead to increased individual resistance to COVID-19 pathogenicity.

A meta-analysis of 35 studies revealed that each 1 mmol/L increase in FBG levels augmented the risk of COVID-19 severity by 33% (risk ratio 1.33 [95% CI: 1.26-1.40]). The odds ratio of ICU admission with a FBG of 5.5-6.9 mmol/L was 1.69 and increased to 19.21 when FBG was over 7.0 mmol/L. 3 Furthermore, elevated Hemoglobin A1c levels has been associated with worse COVID-19 prognosis. 4 Hyperglycemia was also associated with requirement for mechanical ventilation, intensive care unit (ICU) admission and mortality. 5 After adjusting for age, diabetes, hypertension and other confounding factors, hyperglycemia was reported to be an independent risk factor of mortality: when >180 mg/dL (hazard ratio 1.50 [95% CI: 1.31-1.73]), when 140-180 mg/dL (hazard ratio 1.48 [95%CI: 1.29-1.70]). 5 Patients with higher blood glucose levels have more severe symptoms associated with SARS-CoV-2 infection (weighted mean difference 2.21 [95% CI: 1.30-3.13, P <0.001]). 6 Genetic factors may put some individuals at additional risk of severe COVID-19. It is known that AR regulates transcription of the transmembrane protease, serine 2, which is required for SARS-CoV-2 infectivity. 7 The AR gene contains a polymorphic CAG repeat sequence which varies in length between 12 and 30 repeats. 8 COVID-19 patients with longer CAG repeats were shown to have longer hospitalizations and an increased likelihood of being admitted to the intensive care unit than patients with shorter CAG repeats. 7, 9 Longer CAG repeats have been associated with higher body fat mass, plasma insulin, and leptin levels. 10 The concurrent syndemic in which socially disadvantaged groups such as minorities, poorly paid key workers and the elderly lack the resources and knowledge necessary to conduct and maintain a healthy lifestyle. 11 There is a marked difference is COVID-19 mortality globally. In Western and Central Africa, death rates are remarkedly low. For example, the death rates in Niger and Chad are 2.85 per million respectively. An exception to this trend is Singapore; despite a high rate of sugar consumption per capita at 46 Kg, the country has a remarkedly low mortality rate of 4.79 per million. One possible explanation is that Singapore has instituted strict lockdown policies and excellent testing and contact tracing efforts, which have proven effective in halting the spread of SARS-CoV-2. 15 

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