Microbiome and COVID-19: Lower levels of key gut bacteria linked to severity of disease and immune response – China data

Imbalances in the make-up of the microbiome may also be implicated in persisting inflammatory symptoms, so-called ‘long COVID’, the findings suggest.

Researchers from The Chinese University of Hong Kong obtained 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 patients had higher numbers of Ruminococcus gnavus​, Ruminococcus torques​ and Bacteroides dorei ​species than people without the infection.

And they 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.

The numbers of these bacteria remained low in the samples collected up to 30 days after infected patients had cleared the virus from their bodies.

Writing in the journal, Gut​, the researchers noted: “​In identifying microbial species associated with disease severity, we found that F. prausnitzii and Bifidobacterium bifidum were negatively correlated with severity after adjusting for antibiotic use and patients’ age. Relative abundances of several other microbial species typically abundant in the human gut including B. adolescentis and E. rectale also showed reductions with increasing disease severity although these were not statistically significant.”​

Cytokine storm

Analysis of the blood samples showed that the microbial imbalance found in the COVID 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, say the researchers.

The researchers added: “​Associations between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in the magnitude of COVID-19 severity possibly via modulating host immune responses. Furthermore, the gut microbiota dysbiosis after disease resolution could contribute to persistent symptoms, highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19.”​

They went on to state: “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.”​

The researchers cautioned that as this is an observational study, they can’t establish cause. They added that the gut microbiome varies widely among different populations, so the changes observed in this study may not be applicable to other COVID patients elsewhere.

However, they concluded: “Bolstering of beneficial gut species depleted in COVID-19 could serve as a novel avenue to mitigate severe disease, underscoring the importance of managing patients’ gut microbiota during and after COVID-19.”​

Source: Gut​

http://dx.doi.org/10.1136/ gutjnl-2020-323020

'Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19'​

Authors: Professor Siew C Ng, et al.​