Results from EDIFICE : A French pilot study on COVID-19 and the gut microbiome in a hospital environment

BACKGROUND & AIMS: Early reports suggest that both fecal shedding and dysbiosis of the gut microbiome are associated to disease severity in COVID-19 patients. We investigated the gut microbiome as well as the prevalence of SARS-CoV-2 in stool samples from two French populations: exposed healthcare workers and elderly hospitalized COVID-19 patients. The predictive power of bacterial loss of diversity and detection of SARS-CoV-2 in stool was assessed at 4 weeks against clinical outcomes in the patient group. METHODS: 79 healthcare workers in contact with COVID-19 patients and 64 elderly patients hospitalised in a COVID-19 unit in France were included in the EDIFICE trial from April 2020 until May 2021. Stool samples were collected at inclusion. Loss of bacterial diversity was diagnosed based on 16S rRNA gene sequencing. Stool positivity to SARS-CoV-2 was determined by RT-PCR. Clinical outcomes were recorded at a 4 weeks follow up visit. In particular, these include whether the patient had been put under oxygen during the 4 weeks follow up, whether he had been discharged with or without aggravation from initial symptoms or whether the patient had died. The primary end point was to validate the hypothesis that hospitalized COVID-19 patients had more often lost their bacterial diversity than highly exposed active healthcare workers. RESULTS: Elderly hospitalised patients with COVID-19 had more frequently lost their bacterial diversity when compared to exposed healthcare workers (p-value = 0.005), their severe dysbiosis was characterized by enrichment of the family Erysipelotrichaceae and depletion of beneficial bacteria at the genus level such as butyrate producers (Butyrivibrio, Roseburia, Faecalibacterium) and Bifidobacterium. The virus was detected in 61% of hospitalized patients and in only one healthcare workers (2%) who had previously been diagnosed with COVID-19 (p-value<0.001). No significant difference in the gut microbiome composition at the genus level of patients that tested positive in stool versus patients that tested negative was observed. Neither bacterial loss of diversity nor positivity to SARS-CoV-2 were associated to clinical outcome at 4 weeks. CONCLUSIONS: We report findings of the first French trial investigating the clinical interest of stool based diagnosis of SARS-CoV-2 and loss of bacterial diversity in a population of elderly hospitalised COVID-19 patients and highly exposed healthcare workers. Our findings of reduced bacterial diversity and a strong gut dysbiosis in elderly hospitalized COVID-19 patients are highly consistent with previous reports mostly from Chinese populations. A major limitation is that observed differences in the gut microbiome between the two studied groups cannot be attributed to COVID-19 per se given the large number of confounding factors. SARS-CoV-2 was detected in the stool of the majority of hospitalized patients even several weeks after initial diagnosis by nasopharyngeal swabs. This high prevalence warrants further investigation by the scientific community into mechanism.