Diagnosing gastrointestinal symptoms and gut microbiome changes that precede respiratory problems during COVID-19 may help improve early detection and treatment for both acute and long-haul forms of the condition, according to a Houston Methodist study.

The study, a review of existing literature on coronavirus and the microbiome, suggests that delineating the composition of gut bacteria in the context of the infection can help identify novel disease biomarkers and therapeutic targets.

"Depending on your microbiome, we think we should be able to tell if you're likely to develop a more severe or moderate form of COVID-19 and if you are high risk for suffering long-haul COVID-19, says Sonia Villapol, a Houston Methodist neuroscientist and the study's author. "It looks like an overlooked piece of the disease puzzle."

Digging deep into the role the microbiome plays with long-haul COVID-19

Villapol calls for further investigation into the role the microbiome plays and possible therapy, such as dietary changes, prebiotics and probotics, and fecal transplants.

Villapol, whose lab is analyzing and interpreting gut microbiome dysbiosis, or changes, during the development of COVID-19, undertook the review because of the challenges posed by the coronavirus' ability to spread, even when the patient is asymptomatic. In the paper, she writes that identifying the virus' symptoms and different phases is "a complicated but necessary task to slow expansion."

The study, published last fall in Translational Research, is one of the first to review the existing literature on COVID-19 and the microbiome. Numerous studies have looked at the microbiome's role in the context of COVID-19, but there have been few attempts to put them all together and make sense of the big picture.

Villapol wants to see the well-established correlation between the microbiome and COVID-19 severity probed deeper. Her hypothesis is that, in addition to influencing prognosis, changes in gut microbiota might trigger prolonged inflammatory responses in patients with long-haul COVID.

COVID-19 is primarily a respiratory disease, but during early stages of infection many patients experience gastrointestinal symptoms such as nausea, vomiting or diarrhea. Such gastrointestinal changes create an imbalance in gut microflora that can cause the release of proinflammatory cytokines.

That stands to reason. The intestinal tract, the largest immune organ in the body, houses millions of microbes critical for regulating the body's defenses.

Linking diarrhea to severe acute respiratory syndrome (SARS)

The review notes that diarrhea occurred in 40% of patients with severe acute respiratory syndrome (SARS), the 2002 coronavirus that preceded the COVID-19 virus. Such patients had an increased need for respiratory assistance and intensive care.

For COVID-19, one study of 206 patients with low severity disease found 48 presenting digestive symptoms alone had a longer duration between symptom onset and viral clearance and were more likely to be fecal virus-positive than those with respiratory symptoms.

Another study, which compared 100 hospitalized COVID-19 patients and 78 healthy people, found that species of certain bacteria known to play a role in the immune system were present in much lower numbers in the guts of the infected patients.

Still, study results are nothing if not murky. One systematic meta-analysis showed a diarrhea incidence rate from as low as 2% to as high as 50% of the positive cases in clinical studies. Villapol cites the finding in calling for more clinical studies to elucidate the percentage of COVID-19 patients who develop intestinal symptoms and the role of factors such as age, gender or comorbidities.

"Detecting these symptoms might not only lead to slowdown in transmission, but also open the door to novel treatments that could reduce the severity of COVID-19," Villapol writes in the study. "More studies are necessary to interpret the phases of the disease correctly, including long-haul COVID-19, especially if the viral load detected is considered infectious."