A pilot study from Hong Kong has provided evidence of prolonged gut dysbiosis in patients hospitalized with COVID-19. Findings from this study were published in Gastroenterology.
Researchers from the Chinese University of Hong Kong gathered data from 15 patients receiving treatment for COVID-19. Fecal samples were obtained 2 or 3 times per week from the time of hospitalization until discharge. Patients’ illnesses were classified as: mild, defined as showing no radiographic evidence of pneumonia; moderate, defined as disease in the presence of pneumonia; severe, defined as a respiratory rate ≥30/min or oxygen saturation ≤93% when breathing ambient air; or critical, defined as respiratory failure requiring mechanical ventilation, shock, or organ failure requiring intensive care.
Researchers compared microbiome data from these patients with patients who had community-acquired pneumonia (n=6) and healthy controls (n=15). Additionally, they assessed gut microbiome profiles in relation to disease severity and changes in the fecal shedding of the SARS-CoV-2 virus.
The median ages of patients with COVID-19, community-acquired pneumonia, and healthy controls were 55, 50 and 48 years, respectively. Approximately 40% of patients with COVID-19 and 100% of patients with pneumonia had underlying comorbidities. Compared with the fecal microbiota of healthy controls, significant alterations were observed in the microbiota of patients with COVID-19. These changes were demonstrated by enrichment of opportunistic pathogens and drastic reduction in beneficial commensal microbes. Changes were observed at the time of admission and at each time point during hospitalization.
Patients with COVID-19, who received empirical antibiotics at baseline, had greater depletion of symbionts beneficial to host immunity compared with antibiotic-naïve patients. These symbionts included the anti-inflammatory bacterium Fecalibacterium prausnitzii as well as Lachnospiraceae bacterium, Eubacterium rectale, Ruminococcus obeum, and Dorea formicigenerans. After the SARS-CoV-2 was cleared and respiratory symptoms were resolved, the fecal microbiota of patients with COVID-19 continued to demonstrate depleted symbionts and gut dysbiosis.
During hospitalization, bacteria that downregulate ACE2 expression in mouse models — namely Bacteroides dorei, Bacteroides thetaiotaomicron, Bacteroides massiliensis, and Bacteroides ovatus — were inversely associated with SARS-CoV-2 viral load in fecal samples of patients with COVID-19.
Limitations of this study included the small sample size, and the sole inclusion of patients with COVID-19 requiring hospitalization, which may have restricted the generalizability of findings across patients who are asymptomatic or who have mild cases of infection that do not require hospital admission.
According to the researchers, these findings “highlight a new concept that novel and targeted approach of modulation of the gut microbiota may represent a therapeutic avenue for COVID-19 and its co-morbidities.”
Zuo T, Zhang F, Lui GCY, et al. Alterations in gut microbiota of patients with COVID-19 during time of hospitalization [published online May 19, 2020]. Gastroenterology. doi: 10.1053/j.gastro.2020.05.048.