Fecal microbiota transplant (FMT) was safe in two hospitalized patients who were co-infected with cases of COVID-19 that quickly resolved, raising questions about the procedure’s effect on the virus.

FMT was effective for the two patients, who were receiving the treatment for Clostridium difficile (C. difficile) infections and subsequently tested positive for COVID-19, reported Jaroslaw Bilinski, MD, PhD, of the Medical University of Warsaw in Poland, and colleagues.

“A further more speculative question is whether FMT may impact the clinical course of COVID-19,” the authors wrote in Gut, noting that both patients had risk factors for severe COVID-19, such as comorbidities and immunosuppression, yet contracted mild cases.

Mark Corkins, MD, from the University of Tennessee Health Science Center in Memphis, told MedPage Today that the coronavirus tends to interact with cells expressing the ACE2 receptor, and “the gut lining is loaded with these.”

“A few studies have shown that the virus is excreted longer from the GI tract than in the respiratory [tract],” said Corkins, who was not involved with the study.

He noted that during the pandemic, the FDA initiated a moratorium on fecal transplants, which was due to the concerns of bacterial infection via stool transplants. Despite this, Corkins explained that a fecal transplant by changing intestinal flora has the potential of altering the immune response people have to the virus, and under the right conditions, could blunt the effects of the virus.

Bilinski and colleagues noted that FMT may have “mitigated more adverse outcomes, potentially through impacting microbiome-immune interactions.” SARS-CoV-2 has been known to shed via stool.

“In this report, we found that both patients, who had many risk factors to have really severe COVID-19, had a fever for two days and all their symptoms resolved. We also found a very quick resolution of the virus shedding in the stool,” Bilinski told MedPage Today in response to his surprise of the findings. Viral shedding is normally seen for about one month in duration, but in his patients, it was seen occurring within just one to two weeks, he added.

The authors described the cases of two C. difficile patients, both men, one age 80 and one age 19.

The 80-year-old was hospitalized for pneumonia as well as sepsis. He had a fever and increased C-reactive protein (CRP) level on the day the nasojejunal stool transplant was administered, and later tested positive for early COVID-19 infection. The patient was given vancomycin with the transplant and had been taking meropenem before the transplant. He was started on remdesivir (Veklury) post-transplant in addition to being given convalescent plasma. The patient’s fever resolved and pneumonia subsided just two days after the FMT.

“Clinical benefits from remdesivir usually occur after a median of 10 days, and clinical trials show limited benefits of [convalescent plasma] in COVID-19,” the authors noted.

The 19-year-old patient had ulcerative colitis and immunosuppression and was admitted due to a relapse in C. difficile infection. He received vancomycin and was given colonoscopic FMT as a preventive measure. Fifteen hours after the procedure, he developed a fever, along with increased CRP and interleukin-6 levels, and tested positive for SARS-CoV-2. Bilinski’s group noted that other than two isolated incidences of fever, the patient’s temperature “subsequently” stabilized and lab values returned to normal. He received no COVID-19-specific therapy.

Stool samples for both patients tested positive for COVID-19 at 7 days after FMT, though donor stool tested negative. Prior to hospitalization, both patients did not have a COVID-19 infection. The authors noted that SARS-CoV-2 can persist in a patient’s stools on average for 27.9 days, “which appears far longer than in our patients.”

Bilinski and co-authors described similar previous findings, where FMT for C. difficile “appeared safe and associated with rapid resolution of coexisting COVID-19” in two additional patients.

Addressing the generalization of the findings to Americans, “It is fully generalizable. Although the gut microbiota of the American people is a bit different than that of Europeans,” Bilinski told MedPage Today while adding, the results should proceed in a similar fashion.

“Based on our experience here (and other data demonstrating gut microbiome-immune interactions in humans), we are progressing to a clinical trial to assess the impact of FMT added to standard COVID-19 treatment on the risk reduction of disease progression,” Bilinski and co-authors stated.

“I really want to perform the clinical trial we have prepared, which involves adding fecal microbiota capsules versus placebo in patients during their early stage of COVID-19 to test if our proposed hypothesis for FMT could reverse the initiation of a cytokine storm,” he added in regards to his newest study. “We faced great obstacles in attempting to conduct this study, since FMT is not formally approved by the Polish government as a medicinal product,” Bilinski explained to MedPage Today. He hopes a solution from the Polish Ministry of Health will be available soon to allow him to continue his research in this area.