{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T23:18:48Z","timestamp":1788218328516,"version":"build-2803163510"},"reference-count":56,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Long COVID, potentially emerging post COVID-19 infection, involves extreme health challenges. Based on current literature in the field, we propose a novel approach to Long COVID treatment based on epipharyngeal abrasive therapy targeting ostia of the oral and nasal mucosa, having been identified for the first time. The presented case report documents the application of innovative oronasal drainage (OND), a novel treatment integrating physiological, biochemical, and fluid mechanical components simultaneously. OND led to remarkable improvements and even remissions of various symptoms, along with enhanced hand blood circulation. While the case suggests potential efficacy in Long COVID therapy, acknowledging inherent limitations is essential and its impact needs further validation through clinical trials.<\/jats:p>","DOI":"10.3390\/v17020210","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T06:42:36Z","timestamp":1738305756000},"page":"210","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Novel Oronasal Drainage for Long COVID: Proposed Mechanisms\u2014Case Report"],"prefix":"10.3390","volume":"17","author":[{"given":"Claudia","family":"Lorenz","sequence":"first","affiliation":[{"name":"Department of Operative Dentistry, Sanit\u00e4tszentrum Pfreimd, Schlo\u00dfbergstr. 1, 92536 Pfreimd, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Frankenberger","sequence":"additional","affiliation":[{"name":"Department of Operative Dentistry and Endodontics, Dental School, University of Marburg and University Medical Center Giessen and Marburg, 35039 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ivanova, N., Sotirova, Y., Gavrailov, G., Nikolova, K., and Andonova, V. (2022). Advances in the Prophylaxis of Respiratory Infections by the Nasal and the Oromucosal Route: Relevance to the Fight with the SARS-CoV-2 Pandemic. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14030530"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Bellocchio, L., Dipalma, G., Inchingolo, A.M., Inchingolo, A.D., Ferrante, L., Del Vecchio, G., Malcangi, G., Palermo, A., Qendro, A., and Inchingolo, F. (2023). COVID-19 on Oral Health: A New Bilateral Connection for the Pandemic. Biomedicines, 12.","DOI":"10.3390\/biomedicines12010060"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101762","DOI":"10.1016\/j.eclinm.2022.101762","article-title":"The prevalence and long-term health effects of Long Covid among hospitalised and non-hospitalised populations: A systematic review and meta-analysis","volume":"55","author":"Routen","year":"2023","journal-title":"EClinicalMedicine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"611.e9","DOI":"10.1016\/j.cmi.2021.11.002","article-title":"Female gender is associated with long COVID syndrome: A prospective cohort study","volume":"28","author":"Bai","year":"2022","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1038\/s41591-023-02521-2","article-title":"Postacute sequelae of COVID-19 at 2 years","volume":"29","author":"Bowe","year":"2023","journal-title":"Nat. Med."},{"key":"ref_6","first-page":"e51543","article-title":"Differences Between Patients With Chronic Epipharyngitis With and Without Previous COVID-19 Infection","volume":"16","author":"Mogitate","year":"2024","journal-title":"Cureus"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Imai, K., Yamano, T., Nishi, S., Nishi, R., Nishi, T., Tanaka, H., Tsunoda, T., Yoshimoto, S., Tanaka, A., and Hiromatsu, K. (2022). Epipharyngeal Abrasive Therapy (EAT) Has Potential as a Novel Method for Long COVID Treatment. Viruses, 14.","DOI":"10.3390\/v14050907"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Nishi, K., Yoshimoto, S., Nishi, S., Nishi, T., Nishi, R., Tanaka, T., Tsunoda, T., Imai, K., Tanaka, H., and Hotta, O. (2022). Epipharyngeal Abrasive Therapy (EAT) Reduces the mRNA Expression of Major Proinflammatory Cytokine IL-6 in Chronic Epipharyngitis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23169205"},{"key":"ref_9","first-page":"e33421","article-title":"A Potential Novel Treatment for Chronic Cough in Long COVID Patients: Clearance of Epipharyngeal Residual SARS-CoV-2 Spike RNA by Epipharyngeal Abrasive Therapy","volume":"15","author":"Nishi","year":"2023","journal-title":"Cureus"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yao, Q., Doyle, M.E., Liu, Q.R., Appleton, A., O\u2019Connell, J.F., Weng, N.P., and Egan, J.M. (2023). Long-Term Dysfunction of Taste Papillae in SARS-CoV-2. NEJM Evid., 2.","DOI":"10.1056\/EVIDoa2300046"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e9","DOI":"10.1136\/gutjnl-2021-324280","article-title":"Residual SARS-CoV-2 viral antigens detected in GI and hepatic tissues from five recovered patients with COVID-19","volume":"71","author":"Cheung","year":"2022","journal-title":"Gut"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/s41586-021-03207-w","article-title":"Evolution of antibody immunity to SARS-CoV-2","volume":"591","author":"Gaebler","year":"2021","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1038\/s41590-023-01601-2","article-title":"SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC)","volume":"24","author":"Proal","year":"2023","journal-title":"Nat. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1038\/s41586-022-05542-y","article-title":"SARS-CoV-2 infection and persistence in the human body and brain at autopsy","volume":"612","author":"Stein","year":"2022","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1038\/s41586-024-07029-4","article-title":"Prevalence of persistent SARS-CoV-2 in a large community surveillance study","volume":"626","author":"Ghafari","year":"2024","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Silva, J., Lucas, C., Sundaram, M., Israelow, B., Wong, P., Klein, J., Tokuyama, M., Lu, P., Venkataraman, A., and Liu, F. (2021). Saliva viral load is a dynamic unifying correlate of COVID-19 severity and mortality. medRxiv.","DOI":"10.1101\/2021.01.04.21249236"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Cappare, P., D\u2019Ambrosio, R., De Cunto, R., Darvizeh, A., Nagni, M., and Gherlone, E. (2022). The Usage of an Air Purifier Device with HEPA 14 Filter during Dental Procedures in COVID-19 Pandemic: A Randomized Clinical Trial. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19095139"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1159\/000511166","article-title":"A Kidney Transplant Recipient with Recurrent Henoch-Schonlein Purpura Nephritis Successfully Treated with Steroid Pulse Therapy and Epipharyngeal Abrasive Therapy","volume":"144","author":"Fujimoto","year":"2020","journal-title":"Nephron"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5067","DOI":"10.1007\/s00464-021-08868-2","article-title":"Comparative effectiveness of lidocaine sprays between sitting and supine position for patients undergoing upper gastrointestinal endoscopy: A prospective randomized controlled trial","volume":"36","author":"Mahawongkajit","year":"2022","journal-title":"Surg. Endosc."},{"key":"ref_20","unstructured":"BMG, and B.f.G. (2024). Long COVID\u2014Arzneimittel: Ma\u00dfnahmen zur Verbesserung der Versorgung von Long COVID-Erkrankten. Eine Ausarbeitung der Expertengruppe Long COVID Off-Label-Use im Auftrag des Bundesministeriums f\u00fcr Gesundheit (BMG), BMG Initiative LONG COVID."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.jcpa.2022.07.011","article-title":"Morphological and Phenotypic Characteristics of the Bovine Nasopharyngeal Mucosa and Associated Lymphoid Tissue","volume":"198","author":"Meek","year":"2022","journal-title":"J. Comp. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1038\/s41385-020-00359-2","article-title":"The central role of the nasal microenvironment in the transmission, modulation, and clinical progression of SARS-CoV-2 infection","volume":"14","author":"Gallo","year":"2021","journal-title":"Mucosal Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"de Freitas Santoro, D., de Sousa, L.B., Camara, N.O.S., de Freitas, D., and de Oliveira, L.A. (2021). SARS-CoV-2 and Ocular Surface: From Physiology to Pathology, a Route to Understand Transmission and Disease. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.612319"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1038\/s41591-021-01296-8","article-title":"SARS-CoV-2 infection of the oral cavity and saliva","volume":"27","author":"Huang","year":"2021","journal-title":"Nat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/s41590-022-01367-z","article-title":"Adaptive immune responses to SARS-CoV-2 persist in the pharyngeal lymphoid tissue of children","volume":"24","author":"Xu","year":"2023","journal-title":"Nat. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.anorl.2017.12.004","article-title":"Physiology of the paransal sinus ostia: Endoscopic findings","volume":"135","author":"Jankowski","year":"2018","journal-title":"Eur. Ann. Otorhinolaryngol. Head Neck Dis."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Baldassarri, M., Zguro, K., Tomati, V., Pastorino, C., Fava, F., Croci, S., Bruttini, M., Picchiotti, N., Furini, S., and Pedemonte, N. (2022). Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes. Cells, 11.","DOI":"10.3390\/cells11244096"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Marquez-Miranda, V., Rojas, M., Duarte, Y., Diaz-Franulic, I., Holmgren, M., Cachau, R.E., and Gonzalez-Nilo, F.D. (2020). Analysis of SARS-CoV-2 ORF3a structure reveals chloride binding sites. bioRxiv.","DOI":"10.1101\/2020.10.22.349522"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.archoralbio.2011.10.001","article-title":"Effect of ZnCl2 on plaque growth and biofilm vitality","volume":"57","author":"Gu","year":"2012","journal-title":"Arch. Oral Biol."},{"key":"ref_30","first-page":"e50288","article-title":"Epipharynegal Abrasive Therapy Downregulates the Number of Epipharyngeal Abrasive CD4 Cells With Symptomatic Recovery","volume":"15","author":"Mogitate","year":"2023","journal-title":"Cureus"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Bao, Y., Wu, S., Chu, L.T., Kwong, H.K., Hartanto, H., Huang, Y., Lam, M.L., Lam, R.H.W., and Chen, T.H. (2020). Early Committed Clockwise Cell Chirality Upregulates Adipogenic Differentiation of Mesenchymal Stem Cells. Adv. Biosyst., 4.","DOI":"10.1002\/adbi.202000161"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3331","DOI":"10.1038\/s41467-023-38882-y","article-title":"The preference signature of the SARS-CoV-2 Nucleocapsid NTD for its 5\u2032-genomic RNA elements","volume":"14","author":"Korn","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ceb.2018.09.001","article-title":"The balance between adhesion and contraction during cell division","volume":"56","author":"Taneja","year":"2019","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"103482","DOI":"10.1016\/j.rinp.2020.103482","article-title":"Dynamics of respiratory droplets carrying SARS-CoV-2 virus in closed atmosphere","volume":"19","author":"Bavi","year":"2020","journal-title":"Results Phys."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Gusev, E., Sarapultsev, A., Solomatina, L., and Chereshnev, V. (2022). SARS-CoV-2-Specific Immune Response and the Pathogenesis of COVID-19. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031716"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e2248","DOI":"10.1002\/rmv.2248","article-title":"Oral manifestations of COVID-19-A literature review","volume":"32","author":"Farid","year":"2022","journal-title":"Rev. Med. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.adaj.2021.08.007","article-title":"Long COVID and oral health care considerations","volume":"153","author":"France","year":"2022","journal-title":"J. Am. Dent. Assoc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"101019","DOI":"10.1016\/j.eclinm.2021.101019","article-title":"Characterizing long COVID in an international cohort: 7 months of symptoms and their impact","volume":"38","author":"Davis","year":"2021","journal-title":"EClinicalMedicine"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1016\/j.mayocp.2023.07.032","article-title":"Diagnosis and Management of Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome","volume":"98","author":"Grach","year":"2023","journal-title":"Mayo Clin. Proc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/jocn.16471","article-title":"Persistent symptoms among post-COVID-19 survivors: A systematic review and meta-analysis","volume":"33","author":"Rochmawati","year":"2024","journal-title":"J. Clin. Nurs."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Stengel, A., Malek, N., Zipfel, S., and Goepel, S. (2021). Long Haulers-What Is the Evidence for Post-COVID Fatigue?. Front. Psychiatry, 12.","DOI":"10.3389\/fpsyt.2021.677934"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Tanikawa, T., Kiba, Y., Yu, J., Hsu, K., Chen, S., Ishii, A., Yokogawa, T., Suzuki, R., Inoue, Y., and Kitamura, M. (2022). Degradative Effect of Nattokinase on Spike Protein of SARS-CoV-2. Molecules, 27.","DOI":"10.3390\/molecules27175405"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Leitzke, M. (2023). Is the post-COVID-19 syndrome a severe impairment of acetylcholine-orchestrated neuromodulation that responds to nicotine administration?. Bioelectron. Med., 9.","DOI":"10.1186\/s42234-023-00104-7"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/s41579-021-00630-8","article-title":"Structural biology of SARS-CoV-2 and implications for therapeutic development","volume":"19","author":"Yang","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1007\/s12275-019-9218-0","article-title":"Bacterial persistence: Fundamentals and clinical importance","volume":"57","author":"Jung","year":"2019","journal-title":"J. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e210018","DOI":"10.1590\/0074-02760210018","article-title":"Comparison of viral load between saliva and nasopharyngeal swabs for SARS-CoV2: The role of days of symptoms onset on diagnosis","volume":"116","author":"Justo","year":"2021","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e14150","DOI":"10.15252\/emmm.202114150","article-title":"Long-lived macrophage reprogramming drives spike protein-mediated inflammasome activation in COVID-19","volume":"13","author":"Theobald","year":"2021","journal-title":"EMBO Mol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1038\/s44161-023-00358-z","article-title":"SARS-CoV-2 infection boosts inflammation in atherosclerotic plaques","volume":"2","author":"Giacca","year":"2023","journal-title":"Nat. Cardiovasc. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2658","DOI":"10.1080\/22221751.2022.2128887","article-title":"Pathogen-host adhesion between SARS-CoV-2 spike proteins from different variants and human ACE2 studied at single-molecule and single-cell levels","volume":"11","author":"Zhang","year":"2022","journal-title":"Emerg. Microbes Infect."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Tromp, J., Wong, M., Ouwerkerk, W., Wu, M.-Z., Ren, Q.-W., Chandramouli, C., Teramoto, K., Teng, K.T.-H., Huang, J., and To, K.-K.-W. (2024). The association between baseline viral load and long-term risk in patients with COVID-19 in Hong Kong: A territory-wide study. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-65764-0"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1186\/s12967-021-02774-w","article-title":"Hand grip strength and fatigability: Correlation with clinical parameters and diagnostic suitability in ME\/CFS","volume":"19","author":"Jakel","year":"2021","journal-title":"J. Transl. Med."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Gamage, A.M., Tan, K.S., Chan, W.O.Y., Lew, Z.Z.R., Liu, J., Tan, C.W., Rajagopalan, D., Lin, Q.X.X., Tan, L.M., and Venkatesh, P.N. (2022). Human Nasal Epithelial Cells Sustain Persistent SARS-CoV-2 Infection In Vitro, despite Eliciting a Prolonged Antiviral Response. mBio, 13.","DOI":"10.1128\/mbio.03436-21"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"102","DOI":"10.4103\/jfmpc.jfmpc_1605_20","article-title":"Oral manifestations and dental practice recommendations during COVID-19 pandemic","volume":"10","author":"Singh","year":"2021","journal-title":"J. Fam. Med. Prim. Care"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Sun, Y., Luo, B., Liu, Y., Wu, Y., and Chen, Y. (2023). Immune damage mechanisms of COVID-19 and novel strategies in prevention and control of epidemic. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1130398"},{"key":"ref_55","first-page":"236","article-title":"Does the Thymus Index Predict COVID-19 Severity?","volume":"47","author":"Berkan","year":"2023","journal-title":"J. Comput. Assist. Tomogr."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"For\u010di\u0107, D., Mr\u0161i\u0107, K., Peri\u0107-Balja, M., Kurtovi\u0107, T., Rami\u0107, S., Silovski, T., Pedi\u0161i\u0107, I., Milas, I., and Halassy, B. (2024). An Unconventional Case Study of Neoadjuvant Oncolytic Virotherapy for Recurrent Breast Cancer. Vaccines, 12.","DOI":"10.3390\/vaccines12090958"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/2\/210\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:24:52Z","timestamp":1760027092000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/2\/210"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,31]]},"references-count":56,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["v17020210"],"URL":"https:\/\/doi.org\/10.3390\/v17020210","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,31]]}}}