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.

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 non-significant 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.