Obesity and metabolic syndrome are risk factors for severe influenza, COVID-19

July 15, 2020

Science Daily/American Society for Microbiology

Metabolic syndrome increases the risk of severe disease from viral infection, according to a review of the literature performed by a team of researchers from St. Jude Graduate School of Biomedical Sciences and the University of Tennessee Health Science Center, both in Memphis. The research appears this week in the Journal of Virology, a publication of the American Society for Microbiology.

Metabolic syndrome is a cluster of at least 3 co-occurring conditions that raise the risk of heart disease, stroke and type 2 diabetes mellitus (T2DM). These conditions include excess abdominal fat, high blood pressure, excess blood sugar, abnormalities of lipids (including excess triglycerides and cholesterol), insulin resistance and a proinflammatory state.

Multiple studies have shown that obesity is associated with increased severity of influenza A, higher viral titers in exhaled breath and prolonged transmission of the virus, according to the report. Changes in the viral population may abet the emergence of more pathogenic influenza variants, according to the report. Despite the fact that influenza vaccines generate robust antibody titers in obese subjects, obesity doubles the likelihood of developing influenza.

As with influenza virus, the Centers for Disease Control and Prevention recently recognized obesity as a risk factor for severe illness caused by SARS-CoV-2. "This is not surprising because excess body weight and fat deposition apply pressure to the diaphragm, which further increases the difficulty of breathing during a viral infection," the researchers write.

But the risk goes beyond the burden of excess weight. A recent study highlighted in the literature review looked at 174 diabetes patients with confirmed cases of COVID-19. The study found that these patients were at significantly higher risk for severe pneumonia compared to non-diabetic COVID-19 patients. CT scans revealed a greater severity of lung abnormalities in these patients.

There was also a profound increase in serum IL-6 levels, a predictive biomarker for disease severity, the investigators write. These data imply that SARS-CoV-2 causes severe disease in obese patients and in those with T2DM by inducing bilateral pneumonia and a cytokine storm that damages the lung epithelial-endothelial barrier. (The epithelium lines surfaces exposed to the outer environment, such as the respiratory tract, the endothelium lines inner pathways such as those of the vasculature.)

However, one hypothetical risk for patients with T2DM who have hypertension or heart disease appears not to be a problem, after all, according to the report. These patients are commonly treated with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). These increase expression of ACE2, the receptor that SARS-CoV-2 uses to gain entry into cells.

Clinicians and researchers were initially concerned that ACE inhibitors and ARBs could promote adhesion and entry of SARS-CoV-2 into host cells, thereby increasing the risk of severe COVID-19. Contrary to concerns, multiple studies now suggest that ACE inhibitors and ARBs do not lead to poorer outcomes in COVID-19 infection.

"Future research should seek to [determine] how metabolic abnormalities increase viral pathogenesis, as this information will play an essential role in global preparedness against emerging seasonal and pandemic virus strains," the investigators conclude.

https://www.sciencedaily.com/releases/2020/07/200715131234.htm

Researchers propose novel approach to limit organ damage for patients with severe COVID-19

July 8, 2020

Science Daily/Beth Israel Deaconess Medical Center

Patients with severe COVID-19 frequently experience a life-threatening immune reaction, sometimes called a cytokine storm, which can lead to respiratory failure, organ damage and potentially death. With no FDA-approved treatment currently available for SARS-CoV-2, the virus that causes COVID-19, researchers are racing to find ways to stop the virus or the inflammatory overreaction it provokes in its tracks.

In a paper published in Cancer and Metastasis Reviews and selected by the journal as the featured publication, a team of researchers from Beth Israel Deaconess Medical Center and Brigham and Women's Hospital propose that controlling the local and systemic inflammatory response in COVID-19 may be as important as anti-viral and other therapies.

Led by Dipak Panigrahy, MD, of the Cancer Center at BIDMC, and Charles N. Serhan, PhD, DSc, director of the Center of Experimental Therapeutics and a member of the Department of Anesthesiology, Perioperative and Pain Medicine at Brigham and Women's Hospital, the researchers suggest that a family of molecules naturally produced by the human body may be harnessed to resolve inflammation in patients with severe COVID-19, thereby reducing the acute respiratory distress and other life-threatening complications associated with the viral infection.

"Controlling the body's inflammatory response is key to the management of COVID-19 and may be as important to managing the pandemic as anti-viral therapies or a vaccine," Panigrahy said. "Our team proposes using molecules made by the body called pro-resolution lipid mediators -- which are currently in clinical trials for other inflammatory diseases -- as a novel approach to turning off the inflammation and preventing the cytokine storm caused by COVID-19."

Cytokines are released by the body as part of its normal immune response to injured or infected tissues. Typically, the body also releases chemicals to put an end to -- or resolve -- the inflammatory response. But in a significant percentage of patients with severe COVID-19, the cytokines unleashed to kill the virus also do damage to infected lung cells. In turn, this injury to the lung tissues triggers additional inflammation, and the so-called "cytokine storm" begins to spiral out of control.

Naturally occurring molecules called resolvins -- discovered by Serhan and colleagues at BWH in 2002 -- actively turn off inflammation. Panigrahy, Serhan and colleagues have previously demonstrated that resolvins and related pro-resolution molecules could play a role in preventing cancer metastasis and progression. This class of molecules are also currently in clinical trials investigating their use against other inflammatory diseases, such as ocular, periodontal, and inflammatory bowel disease. Now, the scientists suggest, they could be re-deployed for the management of COVID-19.

"A paradigm shift is emerging in our understanding of the resolution of inflammation as an active biochemical process," said Serhan. "Activating the body's own resolution pathways with the use of resolvins and related pro-resolution molecules -- which, importantly, promote blog clot removal -- may complement current treatment strategies while limiting severe organ damage and improving outcomes in COVID-19 patients."

https://www.sciencedaily.com/releases/2020/07/200708135950.htm