Researchers studying 771 hospital-treated COVID-19 patients have found distinct differences in oral and lung microbiomes linked to severe long COVID symptoms, including respiratory decline, cognitive fog, and digestive issues. Published in the European Respiratory Journal, the multicenter findings suggest airway microbial shifts may drive multi-organ illness.
Millions of people worldwide continue to deal with persistent, disabling symptoms months or years after their initial coronavirus infection. While previous investigations focused on the gut, a major multicenter study published in the European Respiratory Journal turned its attention higher up the respiratory tract.
The work forms part of PHOSP-COVID, a major U.K. research program, jointly funded by the National Institute for Health and Care Research and UK Research and Innovation. By analyzing DNA sequencing data from patient samples taken five to six months after hospital discharge, the team sought biological explanations for why certain individuals experience prolonged multi-organ debility while others fully recover.
Microbial Shifts and Systemic Inflammation in Severe Cases
DNA profiling revealed that patients suffering from very severe long COVID harbored starkly different bacterial populations in their mouths and airways compared to those with milder outcomes. Specifically, researchers observed an over-abundance of lactic acid-producing bacteria among patients experiencing poorer health trajectories.
These microbial shifts did not exist in isolation. Blood samples from affected patients showed elevated levels of inflammatory proteins, pointing toward a tangible link between altered airway flora and systemic inflammation.
“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.”
James Chalmers, Chair of Respiratory Research at the University of Dundee
Mapping Specific Bacteria to Respiratory, Cognitive, and Gut Symptoms
The data demonstrated clear alignments between distinct microbial profiles and specific clinical phenotypes. Reduced lung function—defined by impaired airflow or restricted lung capacity—mapped to unique oral microbiome patterns. Meanwhile, persistent neurocognitive deficits, including difficulties with memory, attention, and concentration often described as brain fog, also correlated with specific oral bacterial shifts.
Gastrointestinal complications such as abdominal pain, nausea, diarrhea, and loss of appetite showed distinct associations with sputum microbiome profiles gathered from the lungs. This crossover between airway bacteria and abdominal distress suggests that microbial imbalances in the respiratory tract might exert influences far beyond the chest cavity.
Unresolved Questions and Future Treatment Trials
Investigations have shed more light on the biological factors behind prolonged illness, but key chronological questions remain unanswered. It remains unproven whether the observed microbial differences preceded coronavirus infection or whether the virus itself permanently altered the airway environment. Scientists still do not know how these bacterial communities evolve over subsequent years or whether natural recovery coincides with microbial normalization.
Because the microbiome can be actively manipulated, researchers believe these discoveries point toward entirely new therapeutic avenues.
“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.”
James Chalmers, Chair of Respiratory Research at the University of Dundee
