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Make-up of gut microbiome may be linked to long Covid risk

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Microbiome ‘profiling’ might help identify those who are most susceptible to developing the condition, suggested the researchers. 

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

It is relatively common, with up to three out of four people reporting at least one symptom six months after recovery from Covid-19 infection. Fatigue, muscle weakness, and insomnia are the most commonly reported symptoms. 

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

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

And given that the gut has a major role in immunity, a disordered immune response to Covid-19 infection, induced by resident microbes, may affect the recovery process too. 

The researchers therefore wanted to find out if the make-up of the gut microbiome might be linked to long Covid, defined as at least one persistent symptom 4 weeks after clearance of SARS-CoV-2 from the body. 

They tracked changes in the gut microbiome of 106 patients with varying degrees of Covid-19 severity, treated at three different hospitals between February and August 2020, and in a comparison group of 68 people who didn’t have Covid-19, over the same period. 

They did this by analysing participants’ stool samples. Among the 106 patients with Covid-19, stool samples were collected on admission (68), and again after one month (64) and after six months (68). Stool samples were also collected from 11 patients nine months later.  

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

Among the 68 patients with Covid-19 whose stool samples were analysed at six months, 50 had long Covid. While initial viral load wasn’t associated with long Covid, their gut microbiome differed from that of patients without long Covid and those who hadn’t had Covid-19 infection. These patients had a less diverse and abundant microbiome; the gut microbiome of patients who didn’t develop long Covid was similar to that of those who hadn’t had Covid-19. 

Among the bacteria species found in patients with long Covid, 28 were reduced and 14 were enriched both at hospital admission and at three and six months after hospital discharge. At six months, patients with long Covid had significantly fewer ‘friendly’ and a greater abundance of ‘unfriendly’ than people who hadn’t had Covid-19. On the other hand, the gut microbiome of those who didn’t develop long Covid showed only 25 changes in bacteria species at hospital admission, and this recovered completely after six months.  

Interestingly the researchers also found that 81 bacterial species were associated with different categories of long Covid symptoms, and many species were associated with more than two categories of persistent symptoms.  

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 didn’t, suggesting that particular gut microbial profiles may indicate heightened susceptibility, say the researchers. 

This is an observational study, and as such can’t establish cause. And only a small number of participants were included in the study. But the findings echo those of other research, implicating a disordered gut microbiome in a range of long-term conditions, point out the researchers. 

And they conclude: “In summary, altered gut microbiome composition is strongly associated with persistent symptoms in patients with Covid-19 up to six months after clearance of SARS-CoV-2 virus.  

“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.” 

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