The make-up of a person’s gut microbiome may be linked to their risk of developing “long Covid” many months after initial Covid-19 infection, according to scientists.

“Profiling” the microbe mix in the digestive tract might help identify those who are most susceptible to developing the condition, suggest the researchers. Their findings were published in the journal Gut on Tuesday.

Post-acute Covid-19 syndrome, dubbed long Covid, is characterised by complications and/or persistent symptoms weeks and months after initial Covid-19 infection.

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Up to three out of four people report at least one symptom six months after recovery from Covid-19. Fatigue, muscle weakness and insomnia are most commonly reported.

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An exaggerated immune system response, cell damage or the physiological consequences of a critical illness may contribute to development of long Covid. It is not clear exactly what causes it, or why some people seem to be more susceptible.

A growing body of evidence has implicated the gut microbiome – the trillions of bacteria, fungi and other microbes inhabiting the digestive tract – in Covid-19’s severity.

Given the gut has a major role in immunity, a disordered immune response to infection induced by resident microbes may affect recovery too, conclude the team based at the Chinese University of Hong Kong.

It investigated if the make-up of the gut microbiome might be linked to long Covid, defined as at least one persistent symptom four weeks after clearance of Sars-CoV-2 virus from the body.

Breathing capacity

They tracked changes in the gut microbiome of 106 patients with varying degrees of Covid-19 severity and in a comparison group of 68 people who did not have Covid-19 by analysing stool samples over a period.

The researchers checked for presence of the 30 most commonly reported long Covid symptoms three and six months after initial Covid-19 infection. Breathing capacity and endurance, an indicator of long Covid, was also measured in a six-minute distance walk test.

Long Covid was reported in 86 (81 per cent) of these patients at three months and in 81 (76.5 per cent) at six months. Most common symptoms at six months were fatigue (31 per cent), poor memory (28 per cent), hair loss (22 per cent), anxiety (21 per cent) and sleep disturbances (21 per cent).

There were no significant differences in potentially influential factors such as age, gender, prevalence of underlying conditions, use of antibiotics or antiviral drugs, or Covid-19 severity between patients with and without long Covid, six months after initial infection.

Among the 68 patients with Covid-19 whose stool samples were analysed at six months, 50 had long Covid. While initial viral load was not associated with long Covid, their gut microbiome differed from that of patients without long Covid and those who did not have Covid-19. These patients had a less diverse and abundant microbiome.

Long Covid symptoms

The researchers looked at the make-up of the microbiome to see if it was associated with different categories of long Covid symptoms such as headache, dizziness, loss of taste and smell, anxiety, poor concentration, disrupted sleep, low mood, poor memory, blurred vision, gastrointestinal effects, hair loss and fatigue.

A total of 81 bacterial species were associated with different categories of long Covid and many species were associated with more than two categories of persistent symptoms. Similarly, several “unfriendly” bacteria species were associated with poorer performance on the six-minute walk test among those with long Covid.

At hospital admission, the diversity and richness of gut bacteria in patients who subsequently developed long Covid was significantly lower than that of patients who did not – suggesting “particular gut microbial profiles may indicate heightened susceptibility”, they suggest.

As this is an observational study, it cannot establish cause. But the findings echo other studies implicating "a disordered gut microbiome" in a range of long-term conditions, noted lead author Prof Siew Ng.

“Considering the millions of people infected during the ongoing pandemic, our findings are a strong impetus for consideration of microbiota modulation to facilitate timely recovery and reduce the burden of post-acute Covid-19 syndrome,” he added.

Meanwhile €5.6 million in funding has been awarded to Prof Subrata Ghosh, a global expert in Crohn’s disease and ulcerative colitis, to establish a world-leading research lab at UCC through a Science Foundation Ireland research professorship programme award.

He will lead the AUGMENT project at the APC Microbiome Ireland SFI Research Centre, investigating precision medicine in treating gut inflammation and the microbiome.

This will also benefit research in irritable bowel disease; Crohn’s disease and ulcerative colitis, which affect 40,000 people in Ireland and 10 million people globally every year.

The grant will resource a research laboratory with 13 personnel, and investigate the microbiome in relation to gut inflammation and how it can be influenced by precision medicine to address critical health challenges.

“Chronic inflammatory diseases and cancer are major causes of disability and death in Ireland and in the world. Current treatments are limited by their efficacy ceiling and adverse effects,” said Prof Ghosh.

“Increasing the efficacy of currently used targeted therapies and minimising adverse events through modulation of the gut microbiome may have a major impact on the life of the sufferers and address the economic burden of expensive therapies that prove to be ineffective,” he added.

The funding aims to support work with those affected by chronic inflammatory diseases and cancer to find novel solutions that enhance efficacy of currently available drugs and minimise harmful side effects “by understanding the role of the gut microbiome in mediating the action of drugs”.