Gut dysbiosis linked to COVID-19 severity and persistent symptoms after viral clearance

Altered gut microbiota composition in patients with coronavirus disease 2019 (COVID-19) compared with controls is linked to COVID-19 severity and may contribute to persistent symptoms after viral clearance, according to a study by the Chinese University of Hong Kong (CUHK).

The researchers collected blood and stool samples from 100 patients (mean age, 36.4 years; male, 53 percent) with COVID-19 admitted to the Prince of Wales Hospital or United Christian Hospital between February and May 2020. At baseline, 47 percent of the patients had mild COVID-19, 45 percent had moderate disease, and 8 percent had severe or critical disease. [Gut 2021, doi: 10.1136/gutjnl-2020-323020]

Compared with stool samples from 78 individuals without COVID-19 (mean age, 45.5 years; male, 42 percent) recruited before the pandemic, stool samples from 87 patients with COVID-19 collected during hospitalization showed alterations in relative abundance of bacteria species that were significantly associated with the disease.

“The gut microbiota of patients with COVID-19 showed depletion of ‘good bacteria’ that play an immunomodulatory role, including a 2.2-fold depletion of several bifidobacterial species, a 2.6-fold depletion of Eubacterium rectale, and a 1.6-fold depletion of Faecalibacterium prausnitzii,” reported Professor Siew Ng of the Centre for Gut Microbiota Research, CUHK. “Their gut microbiota was also enriched with ‘bad bacteria’, including Ruminococcus gnavus, R. torques and Bacteroides dorei.”

F. prausnitzii and Bifidobacterium bifidum were found to be negatively correlated with COVID-19 severity after adjustment for antibiotic use and patients’ age.

Moreover, the relative abundance of species depleted in the COVID-19 cohort, including B. adolescentis, F. prausnitzii and E. rectale, negatively correlated with plasma concentrations of inflammatory markers, such as C-X-C motif ligan 10 (CXCL10), tumour necrosis factor-a (TNF-a) and C-C motif ligand 2 (CCL2).

“The gut dysbosis in COVID-19 patients persisted even after discharge from hospital,” pointed out Ng.

Stool samples collected from 27 recovered patients up to 30 days after clearance of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) showed enrichment of species including B. dentium and Lactobacillus ruminis irrespective of antibiotic use, as well as depletion of E. rectale, R. bromii, F. prausnitzii and B. longum.

“Gut dysbiosis that persists after SARS-CoV-2 clearance may contribute to persistent symptoms and/or multisystem inflammation syndromes, also known as long COVID-19,” suggested Ng.

“Our recent survey of 30 patients [age, 20–72 years; male, 40 percent] hospitalized for COVID-19 between February and April 2020 showed that 80 percent of the patients had at least one symptom at 6 months after recovery. One-third of the patients reported more than three symptoms at 6 months,” said Dr Joyce Mak of the Division of Gastroenterology and Hepatology, CUHK. “The symptoms included fatigue [26.67 percent], memory problems [26.67 percent], difficulty in sleeping [23.33 percent], difficulty in breathing [20 percent], and hair loss [20 percent].”

These findings are similar to recent reports from China and Europe, which showed persistent symptoms in 22–87.4 percent of patients 2–6 months after discharge from hospital. [Lancet 2021;397:220-232; JAMA 2020;324:603-605]

“We believe that bolstering of beneficial gut species depleted in COVID-19 could serve as a novel avenue to mitigate severe disease, before and after the infection. We are studying whether restoration of microbiome balance could reduce the risk of long COVID-19,” said Ng.