Research published in the European Respiratory Journal, drawing on data from over 700 participants, found that the oral and pulmonary microbiomes of people with long Covid differ measurably from those without the condition. Lung microbiome variations of this kind have also been tied to the breathing difficulties, cognitive impairment, and gastrointestinal disturbances that patients with long Covid commonly experience.
The findings, according to the research team, open a potential avenue for understanding why long Covid takes hold in certain individuals, and may inform treatment approaches going forward. Dr Daniela Alferes de Lima Headley, based at the University of Dundee in the UK and the lead author on the research, noted that tens of millions of people around the world continue to live with long Covid, and that what drives the condition remains poorly understood.
Research has found that long Covid can place strain on more than one organ system within the body. Researchers have identified the microbiome — the community of microorganisms living throughout the body — as one factor that warrants investigation in understanding why some people develop long Covid, given its established role in supporting bodily health.
Earlier research had documented shifts in the gut microbiome among those experiencing long Covid, and given that Covid primarily affects the lungs, investigators considered it worthwhile to examine whether the lung microbiome undergoes comparable alterations in the same condition — work carried out under the PHOSP-COVID programme, which draws joint funding from the National Institute for Health and Care Research and UK Research and Innovation.
Among the 771 participants enrolled in the study, all had undergone treatment for Covid-19 at one of 38 hospital sites across the UK, with admissions spanning from February 2020 through to March 2021. Four groups of participants took shape according to how their symptoms stood at the five-month mark following hospital discharge, a sorting the researchers carried out to structure their analysis.
Four groupings were defined by the breadth of impairment each patient presented: at the most affected end, those carrying physical, mental, and cognitive difficulties together; next, those whose burdens were physical and mental but left cognition intact; then a third tier in which cognitive difficulties predominated; and finally, at the least affected end, those whose symptoms were few and whose recovery held up relatively well.
At the half-year mark following discharge, the research team gathered oral specimens through saliva collection and airway specimens through sputum, then ran DNA sequencing across both to map the microbial populations present. Microbial diversity and abundance in patient samples were catalogued by the research team, then set against the clinical symptoms each patient presented.
Measurable distinctions in the microbial communities of the mouth and lungs were recorded among individuals whose long Covid symptoms fell at the most severe end of the spectrum, when their samples were set alongside those from people whose condition did not reach that level of severity. Among the symptom-specific patterns the data revealed were diminished lung capacity, a cluster of neurocognitive difficulties — among them brain fog, impaired memory, and problems sustaining attention or concentration — alongside gastrointestinal complaints such as abdominal pain, nausea, loose stools, and a reduced desire to eat.
Elevated counts of lactic-acid-producing bacteria were among the gut microbiome shifts observed in long Covid patients, a pattern that also correlated with inflammatory markers detected in their blood. A respiratory research team at the University of Dundee, led by Professor James Chalmers — who holds the chair in that discipline — found that patients whose post-Covid symptoms remained most pronounced at the five-to-six-month mark showed notable alterations in the microbial communities of both the mouth and the lungs.
Shifts in the microbial population of the airways showed ties not only to respiratory conditions but also to neurological and gastrointestinal complaints, pointing toward a broader role for the lung microbiome in overall health. Researchers have yet to determine whether those physiological alterations preceded a Covid infection or arose in its aftermath.
How microbiome conditions in these patients may evolve over the years ahead remains an open question for researchers to address. Whether those changes improve over time remains an open question. Understanding what drives long Covid remains an open question in medicine, one that researchers and clinicians alike regard as unresolved given its continued burden on health systems.
Pinpointing the origins of the condition may open pathways to improved therapies, given that the microbiome lends itself to modification through antibiotics, probiotics, and related interventions. The PHOSP-COVID team expressed hope that their findings would prompt further investigation into long Covid, and noted that treatment trials for those affected by the condition remain a goal for the future, as the project continues its work on understanding the burden and management of long Covid across the UK.
Inflammation's potential part in post-Covid persistence is now under examination by researchers, who are also mapping out which therapeutic approaches might hold the capacity to reverse that process.
Professor Raquel Duarte, affiliated with the University of Porto in Portugal and serving as chair of the European Respiratory Society's infectious diseases assembly, held no part in conducting the research. She noted that persistent health consequences tied to post-acute Covid infection affect an estimated tens of millions of people across the globe. Breathing difficulties, problems with memory and concentration, and a range of other lingering complaints leave a portion of those affected unable to hold down work, keep up with studies, or handle the demands of daily life — placing strain not just on the individuals involved but on their households, healthcare systems, and the broader community.
Six years after the pandemic took hold, researchers have yet to pin down what drives long Covid in affected patients or which treatment paths offer the best chance of recovery. Conducted across multiple hospitals and drawing on a broad participant base, the research mapped out contrasting microbial profiles in the mouths and airways of patients who went on to experience the worst outcomes after being admitted with Covid-19. The observed patterns extended beyond respiratory impairment, with links to cognitive and gastrointestinal symptoms also recorded.
The data, at this stage, provide a foundation from which longitudinal tracking and mechanistic inquiry can proceed. Should those associations hold up under further scrutiny, they could open a path toward better tools for forecasting, forestalling, or treating the long Covid presentations that leave patients most debilitated.
