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In Severe COVID-19, What Happens in the Gut Doesn’t Stay in the Gut

Shortly after the pandemic began, when doctors and scientists knew little to nothing about the novel coronavirus that has been sweeping across the globe for almost a year now, one thing became clear quickly: people who get severely ill or die of COVID-19 experience generalized inflammation and extensive damage to their lungs and often to other vital organs, sometimes leading to multi-organ failure.

Fast forward a few months. The amount of knowledge has grown exponentially and scientists are now unraveling the factors that determine whether SARS-CoV-2 infection will be mild, or even asymptomatic, or cause severe illness and possibly become fatal.

The Wistar lab of Dr. Mohamed Abdel-Mohsen is one of the first to investigate the link between SARS-CoV-2 infection, inflammation and gut integrity, based on previous knowledge from other respiratory conditions.

Dr. Abdel-Mohsen and team are dissecting the so-called "gut-lung" axis, whereby a disruption of the normal crosstalk between gut microbiota and the lungs contributes to the severity of respiratory diseases.

We tend to think of the lungs and the gut as two unrelated, distant organs. It takes some effort to understand their interaction and the influence microorganisms that colonize the intestine can have on the lungs.

Let’s break it down. Conditions that damage the intestinal wall and cause it to become abnormally permeable allow gut-resident microbes and their products to translocate into the blood stream and reach the lungs. This has a pro-inflammatory effect on the whole body — and the lungs in particular. Other lung-associated diseases, including asthma and acute respiratory distress syndrome, are known to disrupt gut integrity and cause a similar translocation of inflammatory molecules.

Now, Wistar scientists are testing this hypothesis, as it might be the case in COVID-19 as well. A  vicious cycle may become established whereby SARS-CoV-2 infection in the lungs causes a generalized inflammation that results in breakdown of the gut barrier, which causes microbial translocation that in turns hastens inflammation and lung injury.

The fact that SARS-CoV-2 can also infect intestinal cells and directly damage the gut structure and barrier strengthens the scientists’ case.

To test this hypothesis, the Abdel-Mohsen lab is studying blood samples from COVID-19 patients with varying degrees of disease severity and from age-matched healthy individuals and comparing the levels of several biologically active molecules to detect any meaningful shifts.

One type of microbial products that escape from the gut into the blood stream are special enzymes that microbes use to break down the intestinal mucus layer as a source of nutrients. While these enzymes are not harmful in the gut, once in the blood they can alter the sugar molecules present on circulating proteins and antibodies, resulting in enhanced inflammation. These enzymes are among the molecules Dr. Abdel-Mohsen and team are focusing on in their studies.

By shedding light on the link between gut barrier breakdown and COVID-19 pathogenesis, this research might help identify biomarkers for risk of severe disease and pave the way towards new strategies to prevent or reduce the severity of COVID-19.

Dr. Abdel-Mohsen thinks the information acquired through work will be useful to understand some of the health issues experienced by COVID-19 ‘long haulers’. COVID-19 symptoms can persist for months after infection has been cleared and may cause long-term health complications. The team’s preliminary data suggest that the disrupted gut barrier and gut dysfunction observed during severe COVID-19 may persist after recovery from acute disease and play a role in prolonged symptoms.

This research is made possible by urgent funding provided by the National Institutes of Health in response to the COVID-19 crisis.