COVID-19 Works With Bacteria to Become More Virulent in Diabetics

COVID-19 works with body's microbiota in the lungs to become more severe and virulent in people with obesity and diabetes, according to a new article published in eLife. "There is rapidly emerging evidence highlighting obesity and type 2 diabetes as key risk factors linked to severity of COVID-19 infections in all ethnic groups, but the detailed underlying connections with these risk factors remain largely unknown," says author Philipp Scherer, Professor at the Department of Internal Medicine, and Director of the Touchstone Diabetes Center, at the University of Texas Southwestern Medical Center, Dallas, US.

"There is a paradox that people with obesity and diabetes are generally known to recover better from lung conditions than others. So, what is it about COVID-19 that makes this group of people more susceptible?"

In their article, Scherer and his coauthors revisit the factors and disease pathways that connect obesity and diabetes to the severity of COVID-19 infection. The mechanisms can be roughly divided into two groups: those connected with the ACE2 receptor, and those providing an interaction between COVID-19 and pre-existing bacterial conditions.

One theory is that increased amounts of ACE2 in people with obesity or diabetes makes it easier for the virus to enter cells and increases the viral load - an important factor in determining disease severity. Alternatively, increased shedding of ACE2 in people with obesity causes it to move to the lungs, where the virus can use it.

It is possible that lipopolysaccharides molecules join forces with COVID-19 in humans and trigger a chain of events that causes healthy tissue to transform into scarred tissue - as COVID-19 does in the lungs.

"While all of these potential mechanisms can contribute to the severity of COVID-19, we believe that one of them plays the predominant role, and that this must be present not only in obese and diabetic patients, but also in other groups of increased risk in COVID-19," Scherer explains.

The authors propose that a combined deficiency in ACE2 caused by COVID-19, together with obesity or diabetes, leads to impaired gut barrier function, allowing bacteria and their toxins to leak into the circulation. In the lungs, these bacteria and toxins work with the virus to cause more severe lung injury than either would do alone.

"Our theory is supported by experiments showing that the combination of bacterial and viral infection can lead to a 'cytokine storm' - an extreme inflammatory reaction - which is a hallmark of COVID-19", Scherer concludes.

"Moreover, the involvement of viral-bacterial interactions can also explain the increased risk of severe COVID-19 seen in older people, those with heart disease and in some ethnic groups."



Source-Eurekalert