People with long Covid have drastically different microbiome in their lungs and mouth

A study of more than 700 people has shown that those with long Covid have distinct differences in the mix of bacteria that live in their mouths and lungs, according to a study published in the European Respiratory Journal [1].

The research also shows that these differences in the lung microbiome are linked to respiratory symptoms, as well as the cognitive and digestive problems known to occur in long Covid.

Researchers say their findings may shed light on why some people develop long Covid and they could point to new ways to treat the condition.

The lead author of the study was Dr Daniela Alferes de Lima Headley from the University of Dundee, UK. She said: “We know that millions of people worldwide are still affected by long Covid and its cause is still unknown. Long Covid affects multiple organs. The microbiome is important to maintain health throughout the body, so it is a strong candidate for something that may contribute to long Covid. Prior studies have shown some changes in the gut microbiome with long Covid, but Covid is a lung disease and so it makes sense to look to see if the lung microbiome is changed in long Covid.”

This research is part of PHOSP-COVID, jointly funded by the National Institute for Health and Care Research (NIHR) and UK Research and Innovation. The research included 771 people who had been treated for Covid-19 between February 2020 and March 2021 at one of 38 UK hospitals [2].

Researchers divided the participants into four groups based on how bad their symptoms were five months after being discharged from hospital. These were ‘very severe’, with serious physical, mental, and cognitive impairments; ‘severe’, with serious mental and physical, but not cognitive problems; ‘moderate’, with primarily cognitive difficulties; and ‘mild’, with few symptoms and good recovery.

Six months after patients were discharged, researchers took samples from their mouths, via a saliva sample, and from their lungs, via a sputum sample, and used DNA sequencing to identify which microbes were present. Researchers analysed the variety and quantities of the microbes and compared this with patient’s symptoms.

This showed that people who have very severe long Covid had very obvious differences in the microbiome in their mouth and lungs, compared to people who did not have severe long Covid. It also showed that there were differences linked to specific symptoms, including reduced lung function (meaning your lungs cannot hold as much air as normal or air cannot flow in and out of your lungs as easily as normal), neurocognitive symptoms (including ‘brain fog’, difficulties with memory, attention and concentration), and gut symptoms (including pain, nausea, diarrhoea and loss of appetite).

Among the changes associated with long-Covid symptoms, was an over-abundance of bacteria that produce lactic acid, and this was also linked to signs of inflammation found in samples of patients’ blood.

The study was led by Professor James Chalmers, Chair of Respiratory Research at the University of Dundee, UK. He said: “People who had the worst symptoms five to six months after Covid infection had big changes in the microbiome in their mouth and lungs. We also found that changes in the airway microbiome were linked not just to lung problems, but also to symptoms like brain fog and gut symptoms, suggesting the lung microbiome could have effects on health more broadly.

“What we don’t know is whether these changes came before a Covid infection, or whether the changes happened following a Covid infection. We also do not know what will happen to the microbiome in patients in subsequent years. We would love to know whether these changes get better with time.

“We urgently need to know what causes long Covid because it remains a major healthcare problem. Understanding what causes it could lead to better treatments; the microbiome can be changed using antibiotics, probiotics or other measures. We hope our findings will stimulate more research into long Covid and in the future, we would love to see treatment trials to help people with this devastating condition.”

PHOSP-COVID is the UK’s flagship long Covid project, and its researchers are continuing to investigate the burden and management of long Covid. For example, researchers are studying the role of inflammation in long Covid and what kind of treatments might be able to reverse it.

Professor Raquel Duarte is head of the European Respiratory Society’s assembly on infectious diseases, based at the University of Porto, Portugal, and was not involved in the research. She said: “Millions of people worldwide continue to live with the disabling consequences of long Covid. For some, persistent respiratory, cognitive and other symptoms affect their ability to work, study or manage everyday activities, with consequences not only for patients but also for their families, health services and society.

“Six years after the start of the pandemic, we still do not fully understand why some people develop long Covid or how best to support their recovery. This large, multicentre study identifies distinct patterns in the oral and airway microbiota of people with the most severe symptoms following hospitalisation for Covid-19. Importantly, these patterns were associated not only with respiratory impairment, but also with cognitive and gastrointestinal symptoms. These findings provide an important basis for further longitudinal and mechanistic research. If these associations are confirmed, they may ultimately help us identify new ways to predict, prevent or treat the most disabling forms of long Covid.”

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Notes to editors
[1] ‘Sputum and oral microbiota profiles are associated with long COVID severity and phenotype post-hospitalisation: a UK multicentre, prospective cohort study’, by Daniela Alferes de Lima Headley et al., European Respiratory Journal, in press (https://doi.org/10.1183/13993003.01162-2026).

[2] the Post-hospitalisation COVID-19 study: a national consortium to understand and improve long-term health outcomes: https://www.phosp.org/

Hospitals taking part: Addenbrookes, Aintree, Belfast, Castle Hill, Glasgow Queen Elizabeth, Glasgow Royal Infirmary, Glenfield, Guys & St Thomas, Hammersmith, Harefield, Kings College, Lanarkshire Wishaw, Manchester RI, Ninewells, North Middlesex, Nottingham City Campus, Oxford Churchill, Prince Philip, QE Birmingham, RI Edinburgh Raigmore NHS, Highlands, Royal Brompton, Royal Free Hampstead, Royal Gwent, Royal Hallamshire, Royal London Barts, Royal Papworth, Royal Victoria Infirmary, Salford Royal, Southampton General, Southmead Hospital, St Georges Tooting, St James University, St Marys, Tameside and Glossop, The Whittington Hospital, University College London, Wythenshawe.

Funding: This work is independent research jointly funded by the National Institute for Health and Care Research (NIHR) and UK Research and Innovation (UKRI) [PHOSP COVID, grant references: MR/V027859/1 and COV0319]. The views expressed in this publication are those of the author(s) and not necessarily those of the National Health Service (NHS), NIHR, The Department of Health and Social Care or UKRI.