Patients presenting with COVID-19, GI symptoms have reduced mortality
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Patients with COVID-19 who presented with gastrointestinal symptoms had reduced mortality, according to research published in Gastroenterology.
Saurabh Mehandru, MD, from the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai, explored how an intestinal infection with SARS-CoV-2 affected disease pathogenesis.
First, they collected intestinal biopsies from 19 patients with COVID-19 and 10 uninfected control individuals for microscopic examination, CyTOF analysis and RNA sequencing.
Researchers detected SARS-CoV-2 in small intestinal epithelial cells in 14 of 16 patients in the study. In their analysis, they found low levels of inflammations, downregulation of key inflammatory genes and reduced frequencies of proinflammatory dendritic cells compared with controls.
In a separate patient cohort, investigators examined disease severity and mortality in hospitalized patients with and without GI symptoms both in the United States (n = 634) and Italy (n = 287).
Mehandru and colleagues found that patients who presented with GI symptoms had a significant reduction in disease severity and mortality independent of comorbid illness, similar nasopharyngeal SARS-CoV-2 viral load and other factors.
Mehandru said they were surprised by their findings.
“We can only hypothesize why,” he said in a press release. “It could be that the virus traveled into the GI tract and got neutralized by the significant enzyme activity or IgA immunoglobulin presence in the intestinal tract, and as a result, did not unleash the extent of inflammation that we sometimes see in in the lungs. The finding surprised us because the receptor that the virus uses to enter the body – the ACE 2 – is abundantly expressed by intestinal epithelial cells.”
The investigators wrote that something in the gut could have a role in attenuating SARS-CoV-2 associated inflammation.
“Looking ahead, our study points to the need to better understand how infection in the intestines relates to long COVID symptoms and the emergence of viral variants, which will require further investigation,” Mehandru said in the release.
Perspective
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Sara El Ouali, MD
Early in the pandemic, data from several studies showed SARS-CoV-2 infection could affect the GI tract and that up to 50% of patients could experience GI symptoms. However, whether GI symptoms are associated with better COVID-19 outcomes remains uncertain.
Early studies revealed that GI symptoms are associated with worse COVID-19 outcomes, including increased rates of hospitalization and mechanical ventilation. However, other studies found no association with negative outcomes, including a study that showed lower short-term mortality rates among patients with GI symptoms.
This study by Livanos and colleagues further contributes to our understanding of COVID-19 outcomes among patients with GI symptoms. The authors found that GI symptoms in COVID-19 were associated with reduced disease severity, including lower inflammatory biomarkers and decreased mortality in two different distinct cohorts of patients in the U.S. and Europe. Moreover, this study nicely contributes to the current body of literature as it tries to provide insight into a possible mechanistic explanation for the reduced morbidity seen in patients with GI symptoms.
It is still unclear why studies thus far have had different conclusions regarding the impact of GI symptoms. Possible explanations may include differences linked to different variants, distinct patient populations and variations in reporting. This may be because GI symptoms are now widely recognized as possible COVID-19 symptoms and perhaps these patients are seeking medical care sooner, leading to better outcomes. More studies are therefore needed to understand the true impact of GI manifestations on COVID-19 outcomes.
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