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Italians who had COVID-19 during the early waves last year were at substantial risk of showing continued gastrointestinal symptoms long after recovering from the infection -- especially those who experienced diarrhea during the acute phase, a researcher reported.

Some 18% of COVID-19 survivors in the Lombardy region who responded to a survey said they were still having loose stools, and a number of other GI symptoms appeared more severe in these individuals than in controls who had avoided infection, said Daniele Noviello, MD, of the University of Milan.

Moreover, one-third of the COVID survivors reported chronic fatigue, compared with 14% of controls, Noviello told attendees at the virtual Digestive Disease Week annual meeting.

The report follows many others documenting persistent post-recovery symptoms in a significant minority of COVID survivors, which appear to run the gamut from respiratory difficulties to neurological and psychiatric abnormalities, and now gastrointestinal symptoms.

Because diarrhea and other GI complaints are among the hallmark non-respiratory symptoms of COVID-19, and because Italy was an early hotbed for the infection -- centered in the region around Milan -- Noviello and colleagues sought to examine how their patients were faring in terms of continued symptoms.

The group emailed a survey to patients treated for COVID-19 at Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico in Milan during the first two waves of the pandemic there, in March and May 2020, and also to workers at the hospital who had tested negative for COVID, who would serve as controls. The survey asked about the presence and severity of specific GI abnormalities, as well as others including neuropsychiatric and general symptoms.

After excluding respondents with pre-existing diagnoses of irritable bowel syndrome, inflammatory bowel disease, or celiac disease, the researchers had 347 completed surveys for analysis (reflecting a response rate of 12%, a significant limitation of the study), of which 164 were from COVID survivors and 183 from uninfected controls. These were submitted a mean of 4.8 months after acute-phase recovery.

Mean ages of survivors and controls were 44 and 40, respectively. About 40% of survivors were women versus 61% of controls. Oddly, perhaps, nearly 20% of controls were current smokers, compared with 7% of the COVID survivors.

During the survivors' acute COVID phase, half had experienced diarrhea; about 25% reported having nausea, and 20% had had abdominal pain. Rates of other symptoms were similar to those reported elsewhere.

Loose stool was the predominant GI symptom that appeared more frequently among survivors versus controls -- numerically almost twice as common, in fact (adjusted relative risk 1.88, 95% CI 0.99-3.54). Noviello didn't report rates of other symptoms, but mean severity of abdominal pain/discomfort, diarrhea/incontinence, and gastroesophageal reflux on standard scoring instruments were all numerically greater by 50%, though these differences fell just short of statistical significance.

Among other domains analyzed, chronic fatigue was clearly more common in survivors, with an adjusted relative risk of 2.24 (95% CI 1.48-3.37). Also, so-called somatoform symptoms, as evaluated with questions derived from the 12-item Symptom Checklist, were reported more frequently, with total scores of 54.6 in survivors versus 50.5 for controls (P<0.05).

Noviello also reported that risks for persistent symptoms were greater in the subset of survivors who had diarrhea in the acute phase. Fully one-third of this group would qualify for a diagnosis of irritable bowel syndrome by Rome IV criteria at follow-up, based on the respondents' self-reports, and 21% were still having loose stools. Among survivors without acute-phase diarrhea, the corresponding figures were 19% and 10%, respectively.

"Key takeaways" from the study include that patients with diarrhea during acute COVID-19 are especially likely to show persistent symptoms after recovery, Noviello said. These findings suggest a three-way interaction among SARS-CoV-2 and the GI and central nervous systems, he added.

Besides the low survey response rate, limitations to the analysis included the reliance on participant self-report and the sample's restriction to northern Italy.

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