Elevated Fecal Calprotectin Points to Intestinal Inflammation in COVID-19 Patients

By Scott Baltic

May 20, 2020

NEW YORK (Reuters Health) - New data showing elevated fecal calprotectin (FC) levels in COVID-19 patients add to mounting evidence that SARS-CoV-2 infection provokes an inflammatory response in the gut.

"These findings highlight a potential role of non-invasive FC monitoring in the diagnosis and especially in the follow-up of COVID-19-related diarrhea," said Dr. Flavio Caprioli of the Department of Pathophysiology and Transplantation at the University of Milan, in Italy, who was not involved in the research.

"It is plausible that COVID-related diarrhea may be secondary to viral-induced mucosal inflammation, which in turn is due to the influx of inflammatory cells in the intestinal mucosa, including neutrophils and lymphocytes," Dr. Caprioli told Reuters Health by email. Dr. Caprioli recently published a case report of an elderly patient with severe acute ulcerative colitis who died after becoming infected with SARS-CoV-2 (https://bit.ly/36bRZzI).

More than a quarter of COVID-19 patients may suffer gastrointestinal (GI) symptoms, and the underlying pathophysiology is not well understood, Dr. Herbert Tilg of Medical University Innsbruck, in Austria, and colleagues note in Gut.

To investigate, they probed the link between GI symptoms, fecal SARS-CoV-2 RNA and FC, a biomarker of intestinal inflammation in inflammatory bowel disease (IBD) and infectious colitis, in 40 hospitalized patients who did not need intensive care. Other causes of acute gastrointestinal infection were ruled out.

The patients were divided into three groups: 18 patients (mean age, 58) without diarrhea, 13 patients (mean age, 66) whose diarrhea had stopped at least 48 hours earlier, and nine patients (mean age, 78) with active diarrhea within the previous 48 hours.

FC concentrations were significantly higher in patients who had had (37.2 ug/g) or still had (123.2 ug/g) diarrhea than in those without (17.3 ug/g). The elevated FC levels correlated significantly with higher serum interleukin-6 concentrations.

SARS-CoV-2 RNA was not found in stools from patients with ongoing diarrhea, but was detected in samples from four patients without diarrhea and eight patients with ceased diarrhea.

This indicates that viral particles can still be detected in feces even though immune-cell activation is already decreasing from the peak of inflammation, Dr. Tilg told Reuters Health by email. He added that more and more data have been reported that certain IBD drugs such as anti-TNF agents might be beneficial in COVID-19 infection, because they suppress inflammation, immune-cell activation and calprotectin synthesis.

Dr. Caprioli echoed this message, nothing that the new findings suggest COVID-related diarrhea may be driven by acute inflammatory mechanisms and thus is potentially treatable with anti-inflammatory drugs. The data also suggest the infection could worsen existing inflammatory conditions of the digestive tract, including IBD, he added.

"It has been suggested that COVID-19 disease is biphasic," Dr. Caprioli said, with the first, viral phase marked by high viral load and reduced inflammatory activity. The second phase is characterized in a proportion of patients by a vigorous inflammatory response (which can culminate in "cytokine storm syndrome") and a reduced viral load. This might explain why COVID-19-related inflammatory diarrhea is associated with reduced levels of fecal SARS-CoV-2 RNA, Dr. Caprioli said.

The study had no commercial funding, and the authors declare no conflicts of interest.

SOURCE: https://bit.ly/2Tot0Ei Gut, online April 20, 2020.

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