International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2026
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.
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Seno Aji Nur Rahman Ahmad, Thomas Julie Toby, Tervahartiala Taina, Räisänen Ismo T, Varonen Mikko, Liira Helena, Kanerva Mari, Vangelova-Korpinen Velina, Sorsa Timo, Välimaa Hanna
Аннотация
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.
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.