Researchers in the United States have shown that a Western diet may affect viral replication, disease severity, and immune protection following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the agent that causes coronavirus disease 2019 (COVID-19).
Western Diet. Image Credit: Ceinny Kusuma/Shutterstock.com
In a study of SARS-CoV-2-infected Syrian hamsters, those that were fed a continuous high-fat high-sugar (HFHS) diet exhibited increased weight loss and lung pathology, delayed viral clearance, and delayed lung recovery, compared with mice that were fed a regular diet.
These outcomes were accompanied by trending increases in systemic interleukin 10 (IL-10) and IL-6 and a dysregulated serum lipid response that recapitulated the cytokine and lipid responses seen in human cases of severe COVID-19.
“For the first time in the Syrian hamster model, we demonstrate the detrimental impact of a continuous high-fat high-sugar diet on COVID-19 outcome,” says the team from the National Institutes of Health in Montana.
“Our data support the hamster model for testing restrictive or targeted diets and immunomodulatory therapies to mediate the adverse effects of metabolic disease on COVID-19,” says Vincent Munster and colleagues.
A pre-print version of the research paper is available on the bioRxiv* server, while the article undergoes peer review.
Detrimental effects of a Western diet
The presence of comorbidities such as obesity, metabolic disease, and chronic lung disease can adversely affect clinical outcomes in cases of COVID-19.
Chronic metabolic disorders, which are on the rise globally, are often a consequence of an unhealthy diet comprised of processed foods that are rich in saturated fats and refined sugars.
Long-term consumption of a Western diet may result in chronic activation of the immune system, impairing both innate and adaptive responses,”
The Western diet has been associated with non-alcoholic steatohepatitis and non-alcoholic fatty liver disease (NAFLD) – conditions that predispose to multiple comorbidities, include cirrhosis and liver failure.
The risk of hospitalization and severe COVID-19 outcomes are significantly increased among patients with these comorbidities.
Animal models that recapitulate aspects of COVID-19 in humans are a priority
It is not currently clear how certain pre-existing comorbidities might determine disease outcomes in COVID-19.
The development of animal models that accurately recapitulate different aspects of COVID-19 in humans is a top priority in SARS-CoV-2 research, says Munster and colleagues.
Various studies have shown that the Syrian hamster model is suitable for capturing aspects of obesity, diabetes, and lipid metabolism.
The researchers say that following SARS-CoV-2 infection, Syrian hamsters develop a mild-to-moderate disease that is similar to the disease seen in most human cases.
“However, they do not exhibit the more severe respiratory disease seen in humans with comorbidities such as obesity, diabetes, or other chronic illness,” writes the team.
What did the researchers do?
The researchers developed an experimental infection model of hamsters that were exclusively fed a high-fat high-sugar diet (HFHS) to investigate the impact of a Western Diet on COVID-19 severity.
A continuous HFHS diet-induced morbidity increased weight gain, and led to increased glucose tolerance, systemic hyperlipidemia, and high total cholesterol, compared with animals that were fed a regular diet. The HFHS diet also led to a NAFLD-like pathology.
Following infection with SARS-CoV-2, animals that were fed the HFHS diet exhibited delayed lower and upper respiratory tract viral clearance and more severe disease than those fed a regular diet.
Functional lung analysis showed that the Syrian hamster model of SARS-CoV-2 infection recapitulates the increased total airway resistance and decreased inspiratory capacity observed in humans.
The researchers say the Syrian hamster may be a useful model for mechanistic studies of the respiratory parameters affected by COVID-19.
Alteration in cytokine profile resembled those seen in humans
Importantly, the HFHS hamsters exhibited increasing trends in serum levels of IL-10 and IL-6, which is also a unique feature of the cytokine profile seen in humans with COVID-19.
Furthermore, the HFHS animals had higher levels of serum lipids at seven days post-infection.
The lipids that dominated this response were free- polyunsaturated fatty acids (PUFAs) and PUFA-containing phosphatidylethanolamine. These lipid responses are also associated with severe COVID-19 in humans.
The findings suggested that the serum lipid changes are dependent on pre-existing serum hyperlipidemia and are stimulated by infection with SARS-CoV-2.
The Syrian hamster model could be useful in further studies
Despite the lack of obesity in these animals, the matching of clinical SARS-CoV-2-associated lipid patterns and cytokine profile in this model supports its utility in examining lipid and inflammation dynamics associated immune dysregulation during infection,”
The researchers say the findings also point to the potential suitability of the Syrian hamster model for assessing immunomodulatory therapies.
“While dietary advice for those suffering from metabolic diseases is proposed to reduce the burden of severe COVID-19, it remains doubtful if any change in diet can impact disease outcome favorably after infection has occurred,” they write. “Targeted immunomodulatory therapies, such as anti-IL-6 therapies, may be more efficient.”
The Syrian hamster model could also be applied in studies of selected aspects of NAFLD.
“It may be useful for assessing long term post-COVID-19 NAFLD, to document further deterioration of liver damage and the relation to infection sequelae,” says Munster and colleagues.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.