Gut imbalance linked to 'long COVID'

A study published in the journal Gut reveals that the gut microbiome may influence the severity of COVID-19 and the immune system’s response to the infection. The research also suggests that imbalances in the make-up of the microbiome may be implicated in ‘long COVID’ — the term used to describe persisting inflammatory symptoms.

With the gut’s resident microbes known to influence immune responses, the researchers from The Chinese University of Hong Kong wanted to explore whether the gut microbiome also affects the immune system’s response to COVID-19 infection. The research team studied blood and stool samples and medical records from 100 hospital inpatients with laboratory-confirmed COVID-19 infection between February and May 2020 and from 78 people without COVID-19 who were taking part in a microbiome study before the pandemic.

The severity of COVID-19 was classified as mild in the absence of X-ray evidence of pneumonia, moderate if pneumonia with fever and respiratory tract symptoms were detected, severe if patients found it very difficult to breathe normally, and critical if they needed mechanical ventilation or experienced organ failure requiring intensive care. To characterise the gut microbiome, 41 of the COVID patients provided multiple stool samples while in hospital, 27 of whom provided serial stool samples up to 30 days after clearance of SARS-CoV-2, the virus responsible for COVID-19.

Analysis of all 274 stool samples showed that the make-up of the gut microbiome differed significantly between patients with and without COVID-19, irrespective of whether they had been treated with drugs, including antibiotics.

COVID-19 patients had higher numbers of Ruminococcus gnavus, Ruminococcus torques and Bacteroides dorei species than people without the infection. They also had far fewer of the species that can influence immune system response, such as Bifidobacterium adolescentis, Faecalibacterium prausnitzii and Eubacterium rectale.

Lower numbers of F. prausnitzii and Bifidobacterium bifidum were particularly associated with infection severity after taking account of antibiotic use and patient age. Numbers of these bacteria remained low in the samples collected up to 30 days after infected patients had cleared the virus from their bodies.

COVID-19 infection prompts the immune system to produce inflammatory cytokines in response. In some cases, this response can be excessive (a ‘cytokine storm’), causing widespread tissue damage, septic shock and multiple organ failure.

Analysis of the blood samples showed that the microbial imbalance found in the COVID-19 patients was also associated with raised levels of inflammatory cytokines and blood markers of tissue damage, such as C-reactive protein and certain enzymes. This suggests that the gut microbiome might influence the immune system response to COVID-19 infection and potentially affect disease severity and outcome, the researchers said.

“In light of reports that a subset of recovered patients with COVID-19 experience persistent symptoms, such as fatigue, dyspnoea [breathlessness] and joint pains — some over 80 days after initial onset of symptoms — we posit that the dysbiotic gut microbiome could contribute to immune-related health problems post-COVID-19,” they wrote.

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