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Peer-reviewedCC BYInternational Journal of Infectious Diseases

Oral fluid inflammatory biomarker profile in long COVID: evaluation of oral active and total MMP-8, MMP-9, and TIMP-1 in relation to BMI and disease status

  • Nur Rahman Ahmad Seno Aji
  • Julie Toby Thomas1
  • Taina Tervahartiala2
  • Ismo T. Räisänen2
  • Mikko Varonen3
  • Helena Liira3
  • Mari Kanerva4
  • Velina Vangelova-Korpinen3
  • Timo Sorsa5
  • Hanna Välimaa6
6 affiliations
  1. 1Department of Oral and Maxillofacial Diseases, Faculty of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Periodontics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
  2. 2Department of Oral and Maxillofacial Diseases, Faculty of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
  3. 3Outpatient Clinic for Long-Term Effects of COVID-19, Helsinki University Central Hospital, Helsinki, Finland
  4. 4Outpatient Clinic for Long-Term Effects of COVID-19, Helsinki University Central Hospital, Helsinki, Finland; Department of Hospital Hygiene and Infection Control, TYKS Turku University Hospital, Turku, Finland
  5. 5Department of Oral and Maxillofacial Diseases, Faculty of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden
  6. 6Department of Oral and Maxillofacial Diseases, Faculty of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Virology, University of Helsinki, Helsinki, Finland; Department of Infectious Diseases, Meilahti Vaccine Research Center MeVac, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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Abstract

Background: Long COVID (LC) is characterized by persistent systemic symptoms, but its oral inflammatory profile remains unclear. This study evaluated oral inflammatory biomarkers, particularly matrix metalloproteinase (MMP) -8, -9 and their regulators in oral rinse samples from LC patients. Methods: This cross-sectional study analyzed oral rinse samples from 115 LC patients and 103 comparable controls. Periodontal inflammation was screened using a chair-side active MMP-8 (aMMP-8) point-of-care test (POCT). Biomarkers (aMMP-8, total MMP-8, MMP-9, TIMP-1, and MPO) were quantified and validated by Western blotting and gelatin zymography. Associations with LC and clinical variables were assessed using bivariate analysis and multivariable regression. Results: LC patients had significantly higher total MMP-8, MMP-9, TIMP-1, and MMP-9/TIMP-1 ratio (all P < 0.05 in both analyses). IFMA-measured active MMP-8 became independently associated with LC after multivariable adjustment. Chair-side aMMP-8 POCT showed a nonsignificant trend toward higher positivity in LC (16.5% vs 8.7%). BMI was positively associated with aMMP-8, tMMP-8 and tMMP-8/TIMP-1 molar ratio. Antidepressant use was associated with tMMP-8/TIMP-1 molar ratio. Western blotting confirmed active MMP-8 species and gingipain. Conclusion: These findings suggest an altered oral inflammatory biomarker profile in LC. The potential role of chair-side aMMP-8 POCT for screening oral inflammation in this population merits further investigation.

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Cite

BibTeXRIS
BibTeX
@article{aji2026oral,
  title = {{Oral fluid inflammatory biomarker profile in long COVID: evaluation of oral active and total MMP-8, MMP-9, and TIMP-1 in relation to BMI and disease status}},
  author = {Nur Rahman Ahmad Seno Aji and Julie Toby Thomas and Taina Tervahartiala and Ismo T. Räisänen and Mikko Varonen and Helena Liira and Mari Kanerva and Velina Vangelova-Korpinen and Timo Sorsa and Hanna Välimaa},
  journal = {International Journal of Infectious Diseases},
  year = {2026},
  month = nov,
  doi = {10.1016/j.ijid.2026.109183},
  url = {https://doi.org/10.1016/j.ijid.2026.109183},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Oral fluid inflammatory biomarker profile in long COVID: evaluation of oral active and total MMP-8, MMP-9, and TIMP-1 in relation to BMI and disease status
AU  - Nur Rahman Ahmad Seno Aji
AU  - Julie Toby Thomas
AU  - Taina Tervahartiala
AU  - Ismo T. Räisänen
AU  - Mikko Varonen
AU  - Helena Liira
AU  - Mari Kanerva
AU  - Velina Vangelova-Korpinen
AU  - Timo Sorsa
AU  - Hanna Välimaa
PY  - 2026
DA  - 2026/11/04
JO  - International Journal of Infectious Diseases
DO  - 10.1016/j.ijid.2026.109183
UR  - https://doi.org/10.1016/j.ijid.2026.109183
AB  - Background: Long COVID (LC) is characterized by persistent systemic symptoms, but its oral inflammatory profile remains unclear. This study evaluated oral inflammatory biomarkers, particularly matrix metalloproteinase (MMP) -8, -9 and their regulators in oral rinse samples from LC patients. Methods: This cross-sectional study analyzed oral rinse samples from 115 LC patients and 103 comparable controls. Periodontal inflammation was screened using a chair-side active MMP-8 (aMMP-8) point-of-care test (POCT). Biomarkers (aMMP-8, total MMP-8, MMP-9, TIMP-1, and MPO) were quantified and validated by Western blotting and gelatin zymography. Associations with LC and clinical variables were assessed using bivariate analysis and multivariable regression. Results: LC patients had significantly higher total MMP-8, MMP-9, TIMP-1, and MMP-9/TIMP-1 ratio (all P < 0.05 in both analyses). IFMA-measured active MMP-8 became independently associated with LC after multivariable adjustment. Chair-side aMMP-8 POCT showed a nonsignificant trend toward higher positivity in LC (16.5% vs 8.7%). BMI was positively associated with aMMP-8, tMMP-8 and tMMP-8/TIMP-1 molar ratio. Antidepressant use was associated with tMMP-8/TIMP-1 molar ratio. Western blotting confirmed active MMP-8 species and gingipain. Conclusion: These findings suggest an altered oral inflammatory biomarker profile in LC. The potential role of chair-side aMMP-8 POCT for screening oral inflammation in this population merits further investigation.
SN  - 1201-9712
SN  - 1878-3511
ER  -