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Peer-reviewedCC BY 4.0The European Respiratory Journal

Sputum and oral microbiota profiles are associated with long COVID severity and phenotype post-hospitalisation: a UK multicentre, prospective cohort study

  • Daniela Alferes de Lima Headley1
  • Hollian Richardson1
  • Chandani Hennayake1
  • Zsofia Eke1
  • Jamie Stobo1
  • Merete B. Long1
  • Olivia C. Leavy2,3
  • Matthew Richardson3
  • Omer Elneima3
  • Hamish J.C. McAuley3
  • Aarti Shikotra4
  • Amisha Singapuri3
68 more authors
  • Marco Sereno3
  • Ruth M. Saunders3
  • Victoria C. Harris3,5
  • Linzy Houchen-Wolloff6,7,8
  • Neil J. Greening3
  • Kimon Ntotsis3
  • Daniel Lozano-Rojas3
  • Beatriz Guillen-Guio2,3
  • Ewen M. Harrison9
  • Annemarie B. Docherty9
  • Steven Kerr9,10
  • Nazir I. Lone11,12
  • Jennifer K. Quint13
  • Aziz Sheikh14
  • Mathew Thorpe9
  • Bang Zheng15
  • Claudia Efstathiou16
  • Maxime Taquet17,18
  • Iain D. Stewart16
  • Trudie Chalder19,20
  • Melanie J. Davies4,5,21
  • Anthony De Soyza22,23
  • John R. Geddes24,18
  • William Greenhalf25,26,27
  • Luke S. Howard28,29
  • Joseph Jacob30,31
  • R. Gisli Jenkins16
  • William D-C. Man32,33,34
  • Gerry P. McCann4,35
  • Stefan Neubauer24,36
  • Peter J.M. Openshaw16
  • Joanna C. Porter37,38
  • Matthew J. Rowland39
  • David Thomas29
  • Mark Toshner40
  • Simon Heller
  • Janet T. Scott
  • Malcolm G. Semple
  • Sally J. Singh3
  • Raminder Aul
  • Paul Beirne
  • Charlotte E. Bolton
  • Jeremy S. Brown37
  • Gourab Choudhury
  • Nawar Diar Bakerly
  • Nicholas Easom
  • Carlos Echevarria
  • Jonathan Fuld

60 listed; 80 in total.

40 affiliations
  1. 1University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
  2. 2Department of Population Health Sciences, University of Leicester, Leicester, UK
  3. 3The Institute for Lung Health, NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK
  4. 4NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK
  5. 5University Hospitals of Leicester NHS Trust, Leicester, UK
  6. 6Centre for Exercise and Rehabilitation Science, NIHR Leicester Biomedical Research Centre-Respiratory, University of Leicester, Leicester, UK
  7. 7Department of Respiratory Sciences, University of Leicester, Leicester, UK
  8. 8Therapy Department, University Hospitals of Leicester, NHS Trust, Leicester, UK
  9. 9Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK
  10. 10London School of Hygiene and Tropical Medicine, London, UK
  11. 11Roslin Institute, University of Edinburgh, Edinburgh, UK
  12. 12The Usher Institute, University of Edinburgh, Edinburgh, UK
  13. 13Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, UK
  14. 14School of Public Health, Imperial College London, London, UK
  15. 15Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
  16. 16National Heart and Lung Institute, Imperial College London, London, UK
  17. 17Department of Psychiatry, University of Oxford, Oxford, UK
  18. 18Oxford Health NHS Foundation Trust, Oxford, UK
  19. 19Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK
  20. 20South London and Maudsley NHS Trust, London, UK
  21. 21Diabetes Research Centre, University of Leicester, Leicester, UK
  22. 22Population Health Sciences Institute, Newcastle University, Newcastle Upon Tyne, UK
  23. 23Newcastle upon Tyne Teaching Hospitals Trust, Newcastle upon Tyne, UK
  24. 24NIHR Oxford Health Biomedical Research Centre, University of Oxford, Oxford, UK
  25. 25University of Liverpool, Liverpool, UK
  26. 26The CRUK Liverpool Experimental Cancer Medicine Centre, Liverpool, UK
  27. 27Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
  28. 28Imperial College Healthcare NHS Trust, London, UK
  29. 29Imperial College London, London, UK
  30. 30Centre for Medical Image Computing, University College London, London, UK
  31. 31Lungs for Living Research Centre, University College London, London, UK
  32. 32Royal Brompton and Harefield Clinical Group, Guy's and St Thomas’ NHS Foundation Trust, London, UK
  33. 33NHLI, Imperial College London, London, UK
  34. 34King's Centre for Lung Health, Faculty of Life Sciences and Medicine, King's College London, London, UK
  35. 35Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
  36. 36Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
  37. 37UCL Respiratory, Department of Medicine, University College London, Rayne Institute, London, UK
  38. 38University College London Hospital (UCLH) NIHR Biomedical Research Centre, and ILD Service UCLH, London, UK
  39. 39Wellcome–Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, UK
  40. 40Cambridge NIHR Biomedical Research Centre, Cambridge, UK
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Abstract

Background: Acute COVID-19 alters the airway microbiota. Whether these changes persist post-COVID-19 and contribute to long COVID is unknown. We aimed to describe the microbiota by long COVID severity and subtype, and identify links with inflammation.

Methods: Adults were prospectively recruited to the longitudinal UK Post-hospitalisation COVID-19 study (PHOSP-COVID). Patients were grouped by previously described “severity clusters” (of ongoing health impairments) and symptom subgroups. Oral and sputum microbiota (at 6 months post-discharge) were characterised through 16S ribosomal RNA gene amplicon sequencing, and microbiota diversity was assessed. Co-occurrence network analysis identified keystone taxa. Associations between keystone taxa and plasma inflammatory proteins were assessed through Spearman's rank correlations.

Results: 771 participants had their microbiota assessed. Of participants with oral rinses and “severity cluster” assignment (mean age 57.5 years), 278 out of 722 (38.5%) were women. The “very severe” cluster, in which disease was predominantly pulmonary in nature, was associated with a distinct microbiota profile post-COVID-19. Reduced lung function was associated with a distinct oral microbiota profile. Persistent neurocognitive symptoms were associated with a distinct oral microbiota profile, while gastrointestinal symptoms were associated with a distinct sputum microbiota profile. Microbiota keystone taxa shifted to a higher prevalence of lactic acid bacteria associated with worse health outcomes. Lactic acid bacteria abundance was associated with elevated blood inflammatory proteins.

Conclusion: Distinct oral and sputum microbiota profiles were associated with pulmonary function and with neurocognitive and gastrointestinal symptoms in long COVID. Shifts in keystone microbiota taxa linked with inflammation, based on worse health outcomes, suggest a potential role change for lactic acid bacteria, which may be associated with the host immune response.

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Cite

BibTeXRIS
BibTeX
@article{headley2026sputum,
  title = {{Sputum and oral microbiota profiles are associated with long COVID severity and phenotype post-hospitalisation: a UK multicentre, prospective cohort study}},
  author = {Daniela Alferes de Lima Headley and Hollian Richardson and Chandani Hennayake and Zsofia Eke and Jamie Stobo and Merete B. Long and Olivia C. Leavy and Matthew Richardson and Omer Elneima and Hamish J.C. McAuley and Aarti Shikotra and Amisha Singapuri and Marco Sereno and Ruth M. Saunders and Victoria C. Harris and Linzy Houchen-Wolloff and Neil J. Greening and Kimon Ntotsis and Daniel Lozano-Rojas and Beatriz Guillen-Guio and Ewen M. Harrison and Annemarie B. Docherty and Steven Kerr and Nazir I. Lone and Jennifer K. Quint and Aziz Sheikh and Mathew Thorpe and Bang Zheng and Claudia Efstathiou and Maxime Taquet and Iain D. Stewart and Trudie Chalder and Melanie J. Davies and Anthony De Soyza and John R. Geddes and William Greenhalf and Luke S. Howard and Joseph Jacob and R. Gisli Jenkins and William D-C. Man and Gerry P. McCann and Stefan Neubauer and Peter J.M. Openshaw and Joanna C. Porter and Matthew J. Rowland and David Thomas and Mark Toshner and Simon Heller and Janet T. Scott and Malcolm G. Semple and Sally J. Singh and Raminder Aul and Paul Beirne and Charlotte E. Bolton and Jeremy S. Brown and Gourab Choudhury and Nawar Diar Bakerly and Nicholas Easom and Carlos Echevarria and Jonathan Fuld},
  journal = {The European Respiratory Journal},
  year = {2026},
  month = nov,
  doi = {10.1183/13993003.01162-2026},
  url = {https://doi.org/10.1183/13993003.01162-2026},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Sputum and oral microbiota profiles are associated with long COVID severity and phenotype post-hospitalisation: a UK multicentre, prospective cohort study
AU  - Daniela Alferes de Lima Headley
AU  - Hollian Richardson
AU  - Chandani Hennayake
AU  - Zsofia Eke
AU  - Jamie Stobo
AU  - Merete B. Long
AU  - Olivia C. Leavy
AU  - Matthew Richardson
AU  - Omer Elneima
AU  - Hamish J.C. McAuley
AU  - Aarti Shikotra
AU  - Amisha Singapuri
AU  - Marco Sereno
AU  - Ruth M. Saunders
AU  - Victoria C. Harris
AU  - Linzy Houchen-Wolloff
AU  - Neil J. Greening
AU  - Kimon Ntotsis
AU  - Daniel Lozano-Rojas
AU  - Beatriz Guillen-Guio
AU  - Ewen M. Harrison
AU  - Annemarie B. Docherty
AU  - Steven Kerr
AU  - Nazir I. Lone
AU  - Jennifer K. Quint
AU  - Aziz Sheikh
AU  - Mathew Thorpe
AU  - Bang Zheng
AU  - Claudia Efstathiou
AU  - Maxime Taquet
AU  - Iain D. Stewart
AU  - Trudie Chalder
AU  - Melanie J. Davies
AU  - Anthony De Soyza
AU  - John R. Geddes
AU  - William Greenhalf
AU  - Luke S. Howard
AU  - Joseph Jacob
AU  - R. Gisli Jenkins
AU  - William D-C. Man
AU  - Gerry P. McCann
AU  - Stefan Neubauer
AU  - Peter J.M. Openshaw
AU  - Joanna C. Porter
AU  - Matthew J. Rowland
AU  - David Thomas
AU  - Mark Toshner
AU  - Simon Heller
AU  - Janet T. Scott
AU  - Malcolm G. Semple
AU  - Sally J. Singh
AU  - Raminder Aul
AU  - Paul Beirne
AU  - Charlotte E. Bolton
AU  - Jeremy S. Brown
AU  - Gourab Choudhury
AU  - Nawar Diar Bakerly
AU  - Nicholas Easom
AU  - Carlos Echevarria
AU  - Jonathan Fuld
PY  - 2026
DA  - 2026/11/05
JO  - The European Respiratory Journal
DO  - 10.1183/13993003.01162-2026
UR  - https://doi.org/10.1183/13993003.01162-2026
AB  - Background: Acute COVID-19 alters the airway microbiota. Whether these changes persist post-COVID-19 and contribute to long COVID is unknown. We aimed to describe the microbiota by long COVID severity and subtype, and identify links with inflammation.  Methods: Adults were prospectively recruited to the longitudinal UK Post-hospitalisation COVID-19 study (PHOSP-COVID). Patients were grouped by previously described “severity clusters” (of ongoing health impairments) and symptom subgroups. Oral and sputum microbiota (at 6 months post-discharge) were characterised through 16S ribosomal RNA gene amplicon sequencing, and microbiota diversity was assessed. Co-occurrence network analysis identified keystone taxa. Associations between keystone taxa and plasma inflammatory proteins were assessed through Spearman's rank correlations.  Results: 771 participants had their microbiota assessed. Of participants with oral rinses and “severity cluster” assignment (mean age 57.5 years), 278 out of 722 (38.5%) were women. The “very severe” cluster, in which disease was predominantly pulmonary in nature, was associated with a distinct microbiota profile post-COVID-19. Reduced lung function was associated with a distinct oral microbiota profile. Persistent neurocognitive symptoms were associated with a distinct oral microbiota profile, while gastrointestinal symptoms were associated with a distinct sputum microbiota profile. Microbiota keystone taxa shifted to a higher prevalence of lactic acid bacteria associated with worse health outcomes. Lactic acid bacteria abundance was associated with elevated blood inflammatory proteins.  Conclusion: Distinct oral and sputum microbiota profiles were associated with pulmonary function and with neurocognitive and gastrointestinal symptoms in long COVID. Shifts in keystone microbiota taxa linked with inflammation, based on worse health outcomes, suggest a potential role change for lactic acid bacteria, which may be associated with the host immune response.
SN  - 0903-1936
SN  - 1399-3003
ER  -