Oral Cavity Serves as Long-Term COVID-19 Reservoir with Increased Periodontal and Viral Disease Risk

Schwartz, J.; Capistrano, K.; Naqvi, R.; Elshourbagy, S.; Hezarkhani, A.; Etminan, S.; Bland, J.; Kadkol, S.; Shukla, D.; Nares, S.; Tomar, S.; Naqvi, A.

doi:10.1101/2025.02.17.638734

bioRxiv · 10.1101/2025.02.17.638734

Oral Cavity Serves as Long-Term COVID-19 Reservoir with Increased Periodontal and Viral Disease Risk

Schwartz, J.·Capistrano, K.·Naqvi, R.·Elshourbagy, S.·Hezarkhani, A.·Etminan, S.·Bland, J.·Kadkol, S.·Shukla, D.·Nares, S.·Tomar, S.·Naqvi, A.

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Abstract

BackgroundSARS-CoV-2 infection can lead to long-term health problems affecting multiple body systems termed long COVID. Currently, limited information exists about long-term oral health manifestations in COVID-19 patients with limited healthcare access. MethodsWe conducted a sequential, cross-sectional study (December 2020-March 2024) to assess how racial/ethnic differences (Black/Hispanic vs White/Asian) and health disparities affect oral and non-oral long COVID symptoms and their relationship with COVID-19 vaccination. We retrospectively reviewed patients oral health record from University of Illinois Chicago dental clinics before vaccination (December 2020; N=1150; Covid+/- N=575/group) and after vaccination (December 2021; N=592; Covid+/- N=292/group). Participants were recruited in two separate prospective groups of COVID-19 positive subjects (February-April 2021; pre-vaccination: N=158; January-March 2024; post-vaccination: N=171), we examined clinical indicators of oral (periodontal and salivary glands) and non-oral (neurologic) sequalae 3-6 months after initial exposure. We measured viral S protein by flow cytometry and quantified inflammatory markers, viral entry receptors, and oral viral load to correlate molecular, and cellular changes in COVID-19 positive subjects before and after vaccination. ResultsOur results identified racial disparity indicating oral associated post-acute sequelae (PASC) primarily manifested as periodontal (gum) disease (COVID-19 positive: 73.1{+/-}18.9% vs COVID-19 negative: 33.1{+/-}14.3%) and correlated with higher rates of dry mouth (57.5%), taste disturbance (47%), and smell loss (20%). Vaccination reduced oral PASC in COVID-19 positive subjects; however, periodontal disease indicators persisted compared to the COVID-19 negative group. Notably, 3-6 months post-infection, while SARS-CoV-2 Spike (S) transcript was rarely detected in saliva ([~]6%), its protein was commonly detected ([~]70%) in the COVID-19 positive subjects indicating incomplete viral clearance. This correlates with significantly higher salivary expression of viral entry receptors (ACE2, and TRMPSS2), and inflammatory mediators (IL-6, IL-8 and MMP-8), in COVID-19 positive subjects. This finding was further supported by higher prevalence of other oral viruses including Epstein-Barr Virus (70.5%), Herpes Simplex Virus (8.1%), and Human Papillomavirus (17.5%) in COVID-19 positive subjects. InterpretationCOVID-19 history significantly correlates with severe oral health complications in predominantly Black communities, while vaccination reduced but did not eliminate these issues. The oral cavity serves as a long-term viral reservoir, and periodontal inflammation with increased oral viral presence in COVID-positive patients may increase susceptibility to oral and non-oral viral diseases and identify risk for long COVID.

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Schwartz, J., Capistrano, K., Naqvi, R., Elshourbagy, S., Hezarkhani, A., Etminan, S., Bland, J., Kadkol, S., Shukla, D., Nares, S., Tomar, S., Naqvi, A.. 2025-02-19. Oral Cavity Serves as Long-Term COVID-19 Reservoir with Increased Periodontal and Viral Disease Risk. https://doi.org/10.1101/2025.02.17.638734

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