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

ACE inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19

March 23, 2020

Science Daily/Louisiana State University Health Sciences Center

James Diaz, MD, MHA, MPH & TM, Dr PH, Professor and Head of Environmental Health Sciences at LSU Health New Orleans School of Public Health, has proposed a possible explanation for the severe lung complications being seen in some people diagnosed with COVID-19. The manuscript was published by Oxford University Press online in the Journal of Travel Medicine.

The SARS beta coronaviruses, SARS-CoV, which caused the SARS (Severe Acute Respiratory Syndrome) outbreak in 2003 and the new SARS-CoV-2, which causes COVID-19, bind to angiotensin converting enzyme 2 (ACE2) receptors in the lower respiratory tracts of infected patients to gain entry into the lungs. Viral pneumonia and potentially fatal respiratory failure may result in susceptible persons after 10-14 days.

"Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are highly recommended medications for patients with cardiovascular diseases including heart attacks, high blood pressure, diabetes and chronic kidney disease to name a few," notes Dr. Diaz. "Many of those who develop these diseases are older adults. They are prescribed these medications and take them every day."

Research in experimental models has shown an increase in the number of ACE2 receptors in the cardiopulmonary circulation after intravenous infusions of ACE inhibitors.

"Since patients treated with ACEIs and ARBS will have increased numbers of ACE2 receptors in their lungs for coronavirus S proteins to bind to, they may be at increased risk of severe disease outcomes due to SARS-CoV-2infections," explains Diaz.

Diaz writes, this hypothesis is supported by a recent descriptive analysis of 1,099 patients with laboratory-confirmed COVID-19 infections treated in China during the reporting period, December 11, 2019, to January 29, 2020. This study reported more severe disease outcomes in patients with hypertension, coronary artery disease, diabetes and chronic renal disease. All patients with the diagnoses noted met the recommended indications for treatment with ACEIs or ARBs. Diaz says that two mechanisms may protect children from COVID-19 infections -- cross-protective antibodies from multiple upper respiratory tract infections caused by the common cold-causing alpha coronaviruses, and fewer ACE2 receptors in their lower respiratory tracts to attract the binding S proteins of the beta coronaviruses.

He recommends future case-control studies in patients with COVID-19 infections to further confirm chronic therapy with ACEIs or ARBs may raise the risk for severe outcomes.

In the meantime he cautions, "Patients treated with ACEIs and ARBs for cardiovascular diseases should not stop taking their medicine, but should avoid crowds, mass events, ocean cruises, prolonged air travel, and all persons with respiratory illnesses during the current COVID-19 outbreak in order to reduce their risks of infection."

https://www.sciencedaily.com/releases/2020/03/200323101354.htm