Ramsay-Hunt-Syndrome Associated with Unilateral Parotitis Following COVID-19 Vaccine

Ramsay-Hunt-Syndrome Associated with Unilateral Parotitis Following COVID-19 Vaccine | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Ramsay-Hunt-Syndrome Associated with Unilateral Parotitis Following COVID-19 Vaccine Masood Soltanipur, Hossein Yarmohammadi, Seyed Fatah Mahdavi Anari, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3811498/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Apr, 2025 Read the published version in European Archives of Oto-Rhino-Laryngology → Version 1 posted You are reading this latest preprint version Abstract Varicella-zoster-virus (VZV) reactivation is a recognized complication following COVID-19 vaccination; however, Ramsey-hunt-syndrome (RHS) rarely has been reported. This case presents a 36-year-old immunocompetent man with features of RHS three weeks following the second dose of the BBIBP-CorV (Sinopharm) vaccine. Interestingly, he developed acute unilateral parotitis on his left side and the ultrasonography showed a 55*44*18 mm parotid gland with decreased parenchymal echogenicity. He was treated with valacyclovir, and after seven days he was discharged. Also, his parotitis was resolved by day 29 following the presentation of the first symptoms with no further complications. The possibility of VZV reactivation after COVID-19 vaccination is an important point and it should be noted that this reactivation might present in unusual clinical scenarios. Varicella-zoster-virus (VZV) Ramsey-hunt-syndrome (RHS) COVID-19 Vaccine Unilateral parotitis Figures Figure 1 Figure 2 1. Introduction The COVID-19 pandemic made a negative impact on many aspects of human lives from its cardiopulmonary complications to the psychosocial burden that it imposed on individuals worldwide ( 1 – 4 ). With the development of different vaccines, the mortality of COVID-19 was dramatically reduced and its burden started to lighten over time ( 5 ). However, complications following the vaccination instead became a health concern. Different complications affecting cardiorespiratory, autoimmune, and, nervous systems were reported in the literature and the reactivation of varicella-zoster-virus was one of the well-recognized complications ( 6 – 8 ). The Ramsay-Hunt-Syndrome (RHS) is a clinical diagnosis and classically recognized as a triad of vesicles around the ear or auditory canal, otalgia, and ipsilateral facial paralysis ( 9 ). RHS induced by VZV mostly responds to treatment with valacyclovir and steroids, also physiotherapy could help those who suffer from synkinesis in the long term ( 9 , 10 ). The presentation of RHS following COVID-19 vaccination has been rarely reported in the literature. We describe the clinical course, management, and, follow-up of a 36-year-old immunocompetent man presenting with RHS three weeks after COVID-19 vaccination. 2. Case presentation A 36-year-old male with no significant past medical history started to have fever and flu symptoms three weeks after the second dose of the BBIBP-CorV (Sinopharm) vaccine. He developed pain, erythema, and, tenderness of the left antitragus in the following four days. He made an appointment with the otolaryngology clinic and received a prescription including ciprofloxacin drop, glucocorticoid drop, and oral analgesia, as the initial diagnosis was otitis externa. However, he did not sleep due to severe pain which made him visit the emergency department (ED) that night. At the time in ED, he had also developed some difficulties of swallowing and the swelling of the left side of his neck was evident. At day six, sonography of the left neck revealed the parotid size 55*44*18 mm with decreased parenchymal echogenicity. Also, multiple reactive adenopathies with a maximum diameter of 13 mm were shown. At the left cervical chain, enlarged lymph nodes with small echogenic centers and approximate sizes of 16*6 mm and 15*6 mm were observed (Fig. 1 ). Hours later after sonography, a painful nodular erythematous lesion on the left temporal side was noticed by the patient and the swelling of the parotid increased dramatically (Fig. 2 , a). On day seven, he had odynophagia and dysgeusia with painful ulcerous buccal nodules. The outer half of his tongue on the left side had similar lesions without ulcer. The left side of his lips and his left auditory canal and antitragus were also involved (Fig. 2 , b). He also started left facial weakness and paraesthesia with nausea and dizziness. The next day, the left lower eyelid and external epicanthus developed painful erythematous nodules (Fig. 2 , c). At this point, skin lesions were characteristic of zona and due to the distribution of lesions and facial weakness, the diagnosis of Ramsy-Hunt-Syndrome (RHS) was made. All his previously prescribed drugs were discontinued immediately and valacyclovir (500 mg, three times a day) in combination with analgesia was initiated for him at the hospital on day nine. On day 13th his lesions gradually improved; first on the tongue and lips and then lesions on the antitragus (Fig. 2 , d). He was discharged after seven days of being hospitalized on day 16th when valacyclovir was discontinued. His facial weakness and paraesthesia sensation gradually improved, however, the swelling of the neck was not resolved until the following 14 days on day 29th. At this follow-up visit, he also had complaints regarding post-herpetic neuralgia that were managed with nortriptyline. At the second follow-up visit on day 61, he had no longer any complications. 3. Discussion Varicella-zoster-virus belongs to the Herpesviridae family which tends to reactivate even many years after the primary infection and is capable of inducing different complications such as skin lesions to meningoencephalitis ( 11 ). Different presentations of VZV reactivation have been reported from characteristic skin lesions to RHS following COVID-19 vaccination. The exact pathogenesis of RHS following COVID-19 vaccination is not clear but some indirect links between herpes virus reactivation, COVID-19 vaccination, and autoimmunity could be drawn which needs more studies to be tested ( 11 ). Hyperviscosity induced by mRNA vaccinations is another suggested related mechanism ( 12 ). Nevertheless, this case report presented a healthy young immunocompetent man who developed RHS following Sinopharm vaccination. His first symptoms were pain and skin lesions. Zona is the most reported presentation of VZV reactivation following COVID-19 vaccination. The systematic review by Desai et al gathered clinical data of 54 cases that developed reactivation of VZV following COVID-19 vaccination. The most reported vaccine was the mRNA vaccine and the mean interval between vaccination to presentation of symptoms was almost seven days ( 13 ). Additionally, the systematic review by Katsikas Triantafyllidis et al reported similar results on 91 cases. Comorbidities such as hypertension, autoimmune conditions, and, receiving immunosuppressants were considered risk factors for VZV reactivation. However, younger cases with no significant past medical history were also reported in the review similar to our case. They also found that valacyclovir was the most used treatment ( 14 ). The review article by Iwanaga et al gathered data from 399 reported cases of herpes zoster infection following COVID-19 vaccination. The majority of cases reported the herpes zoster infection following the BNT162b2 vaccine. The authors concluded that the duration since vaccination to VZV reactivation could be 1 to 24 days, as in our case it took 21 days ( 15 ). Other than cutaneous manifestation of VZV reactivation among patients with COVID-19 or following vaccination, RHS has been rarely reported in the literature. There have been six cases of RHS presented after COVID-19 infection. Al Rida Ayoub et al just recently reported an interesting case of an asymptomatic 60-year-old man, who was diagnosed with COVID-19 based on a positive PCR test. Three days later he developed a skin rash and facial weakness and was treated with valacyclovir for RHS. The authors also made a thorough literature search and found five case reports of RHS presented among COVID-19 patients ( 16 ). The case reported by Mehta et al reported a 32-year-old man with left-sided lower motor neuron facial palsy which occurred after COVID-19 and eventually was resolved after five days of using steroids ( 17 ). The case described by Alonzo‑Correa was a 25‑year‑old woman with positive COVID-19 PCR who developed herpes zoster oticus, otalgia, and acute peripheral facial nerve palsy which consequently improved after administering steroids ( 18 ). Other three cases could be found in the review done by Al Rida Ayoub et al and it generally could be concluded that the management of most cases was administering valacyclovir with favorable outcomes ( 16 , 19 – 21 ). Additionally, RHS has also been reported following COVID-19 vaccination in three previously published articles. Rodríguez-Martín et al reported a 78-year-old woman who developed otalgia and other related symptoms including House-Brackmann grade IV right peripheral facial paralysis, three days after BNT162b2 mRNA vaccination ( 22 ). Woo et al described a 37-year-old man presenting with RHS two days after BNT162b2 mRNA vaccination. A swab sample from exudates was studied with PCR and it was positive for VZV ( 23 ). Finally, Lakhoua et al reported a 65-year-old who was presented with RHS seven days after BNT162b2 mRNA vaccination. He was treated with valacyclovir and pregabalin with improvement in lesions but he was still complaining of post-herpetic neuralgia at six-month follow-up ( 24 ). To the best of our knowledge, our case is the first describing RHS following Sinopharm vaccination in a healthy young man. Our case had also parotitis which was evaluated with ultrasonography. Some case reports have described acute parotitis following the COVID-19. Lechien et al reported three cases with COVID-19 who developed parotitis. Symptoms lasted 3 to 10 days and all three were managed with paracetamol. MRI was done for three cases and intraparotid lymphadenitis was shown in all of them. It was suggested that intraparotid lymphadenitis due to COVID-19 could be the cause of the presentation of parotitis ( 25 ). A 32-year-old man with COVID-19 was reported by Taha Ismail and Mohamed Naser who had unilateral parotitis. Ultrasonography showed an enlarged and diffuse hypoechoic parotid gland structure. He received intravenous steroids and his symptoms were resolved on day seven ( 26 ). Also, Capaccio et al described a 26-year-old man with positive COVID-19 PCR who was initially presented with acute unilateral parotitis ( 27 ). Another 79-year-old man has been reported to be admitted due to COVID-19 and required non-invasive mechanical ventilation. Five days after admission he developed sudden unilateral parotitis and he expired after nine days ( 28 ). The treatment of parotitis in our case consisted of conservative management with analgesia which was resolved on day 29th with no further complications. The interesting point of this case was the associated unilateral parotitis which rarely has been reported in association with VZV reactivation in the literature. It is not clear if these two problems are linked or not, however, it seems that both could be attributed to COVID-19. To the best of our knowledge, only two studies have reported simultaneous presentation of parotitis and VZV reactivation in adults ( 29 , 30 ). The case reported by Banno et al described a 43-year-old man who had unilateral right parotitis simultaneous with ophthalmicus involvement due to VZV. The serologic test showed positive antibodies for VZV in the absence of r herpes simplex virus 1 and 2 and mumps. He was treated with valacyclovir, antibiotics, and, steroids which led to complete improvement in symptoms after three weeks ( 29 ). Additionally, the case reported by Tally et al was a 36-year-old woman with VZV ophthalmicus and unilateral left parotitis. The neck computed tomography confirmed the parotitis with no other concerning problem. She received valacyclovir, antibiotics, and, analgesia and she was symptom-free after three weeks follow-up ( 30 ). The exact mechanism of this simultaneous presentation is not known. The auriculotemporal nerve involvement following the VZV reactivation of the trigeminal nerve is one proposed theory. However, the immune response to the VZV reactivation, or also the possibility of autoimmunity following the COVID-19 vaccination might be another explanation ( 5 , 31 ). Nevertheless, being familiar with such rare presentations could be useful for timely diagnosis and proper management. Declarations Ethics approval and consent to participate The patient permitted us to use clinical information and photographs to be published. Consent for publication Signed written informed consent was obtained from the patient. Availability of data and material Data are available based on the request from the corresponding author. Competing interests The authors confirm that there are no known conflicts of interest associated with this publication. Funding There has been no financial support for this work. Authors' contributions S.D.S. contributed to conceptualizing the study and finalized the manuscript. M.S. and M.K.N gathered data and contributed to writing the initial draft. H.Y. contributed to performing the literature search and wrote the draft of the search result. S.F.M.A contributed to the visualization of figures and writing the initial draft. All authors reviewed the manuscript. Acknowledgments Not applicable References Ramandi MMA, Yarmohammadi H, Beikmohammadi S, Fahimi BHH, Hatami F, Beydokhti H et al (2021) Comparison of the cardiovascular presentations, complications and outcomes following different coronaviruses’ infection: A systematic review. J Cardiovasc Thorac Res 13(2):92 Yarmohammadi H, Motevalizadeh S-A, Asgari A-M, Keshavarzi M, Azimi G (2023) COVID-19 Patients Presenting With Pneumothorax and Bronchopleural Fistula: Incidence and Case Description. Infect Dis Clin Pract 31(6):e1316 Montazeri A, Mohammadi S, Hesari M, Yarmohammadi P, Bahabadi H, Naghizadeh Moghari MR (2023) Exposure to the COVID-19 news on social media and consequent psychological distress and potential behavioral change. Sci Rep 13(1):15224 Ansari Ramandi M, Yarmohammadi H, Beikmohammadi S, Hosseiny Fahimi B, Amirabadizadeh A (2020) Factors affecting the psychological status of an Iranian population during Coronavirus pandemic. 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Eur Arch Otorhinolaryngol 277:1235–1245 Goswami Y, Gaurkar SS (2023) Ramsay Hunt Syndrome: An Introduction, Signs and Symptoms, and Treatment. Cureus. ;15(1) Yarmohammadi H, Razavi A, Shahrabi Farahani M, Soltanipur M, Amini M (2023) Characteristics of HHV-7 meningitis: a systematic review. J Neurol 270(12):5711–5718 Mungmunpuntipantip R, Wiwanitkit V (2022) Ramsay Hunt syndrome and mRNA SARS-COV-2 vaccination. Enfermedades infecciosas y microbiologia clinica (English ed). 40(1):48 Desai HD, Sharma K, Shah A, Patoliya J, Patil A, Hooshanginezhad Z et al (2021) Can SARS-CoV‐2 vaccine increase the risk of reactivation of Varicella zoster? A systematic review. J Cosmet Dermatol 20(11):3350–3361 Katsikas Triantafyllidis K, Giannos P, Mian IT, Kyrtsonis G, Kechagias KS (2021) Varicella zoster virus reactivation following COVID-19 vaccination: a systematic review of case reports. Vaccines 9(9):1013 Iwanaga J, Fukuoka H, Fukuoka N, Yutori H, Ibaragi S, Tubbs RS (2022) A narrative review and clinical anatomy of Herpes zoster infection following COVID-19 vaccination. Clin Anat 35(1):45–51 Al Rida Ayoub W, Lizzeik D, Berro J, Faddoul S, El Dassouki M, Shatila AR et al (2023) Ramsay Hunt Syndrome in Asymptomatic COVID-19 Infection: A Case Report and a Literature Review. J Clin Med 12(23):7407 Mehta M, Jain A, Mehta N (2021) Ramsay Hunt Syndrome: Viral Infection Coexisting with COVID-19. Annals of Otology and Neurotology 4(02):079–82 Alonzo-Correa CP, Camacho-Martínez E, Bustamante-Arias A, Rodriguez-Garcia A (2021) Ramsay Hunt syndrome in a young COVID-19 patient. Pan-American J Ophthalmol 3(1):33 López-Blanco R, Cazorla-Garcia R, Barbero-Bordallo N, Fernández-Ferro J (2020) Neurological infections during the COVID-19 epidemic. Neurología (English Edition) 35(4):273 Chu W-K, Lin K-Y, Sun H-Y, Chen Y-C, Cheng A (2023) Herpes zoster aseptic meningitis and Ramsay Hunt syndrome in an immunocompetent young adult post mild COVID-19–A coincidence? J Microbiol Immunol Infect. Antonescu F, Butnariu I, Cojocaru FM, Anghel DN, Mihai ED, Tuţă S (2021) Zoster cranial polyneuropathy in a COVID-19 patient. Am J Case Rep 22:e934658–e934651 Rodríguez-Martín M, Corriols-Noval P, López-Simón E, Morales-Angulo C (2022) Ramsay Hunt syndrome following mRNA SARS-COV-2 vaccine. Enfermedades infecciosas y microbiologia clinica (English ed). 40(1):47 Woo CJ, Chou OHI, Cheung BMY (2022) Ramsay Hunt syndrome following COVID-19 vaccination. Postgrad Med J 98(1164):738–739 Lakhoua G, Charfi O, Dabbehce S, Zaiem A, Kastalli S, Daghfous R et al (2022) An atypical Ramsey Hunt syndrome after covid 19 immunization. Therapie. Lechien JR, Chetrit A, Chekkoury-Idrissi Y, Distinguin L, Circiu M, Saussez S et al (2020) Parotitis-like symptoms associated with COVID-19, France, March–April 2020. Emerg Infect Dis 26(9):2270 Ismail MT, Naser MM (2020) Parotitis as clinical manifestation of COVID-19 infection, emergency physician experience: A case report. Medicine 9(4):1089–1092 Capaccio P, Pignataro L, Corbellino M, Popescu-Dutruit S, Torretta S (2020) Acute parotitis: a possible precocious clinical manifestation of SARS-CoV-2 infection? Otolaryngology–Head and Neck Surgery 163(1):182–183 Marcano A, Nanduri A, Saleem T, Bonk M (2021) ATYPICAL PAROTITIS AS A RESULT OF SEVERE COVID-19 INFECTION. Chest 160(4):A315 Banno F, Riccelli T, Banno M (2019) Simultaneous parotitis and ipsilateral herpes zoster ophthalmicus: coincidence? BMJ Case Reports CP 12(3):e228897 Tally S, Brown M, Hsu E (2023) Case Report of Herpes Zoster Ophthalmicus with Concurrent Parotitis. J Educ Teach Emerg Med. ;8(2) Yoshida M, Higuchi T (2012) Herpes zoster ophthalmicus with ipsilateral parotitis. Int J Dermatol 52(6):769–770 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 01 Apr, 2025 Read the published version in European Archives of Oto-Rhino-Laryngology → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3811498","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":263643177,"identity":"8d7012d1-3bc9-472e-9539-accb0738a0f8","order_by":0,"name":"Masood Soltanipur","email":"","orcid":"","institution":"Motamed Cancer Institute, ACECR","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Masood","middleName":"","lastName":"Soltanipur","suffix":""},{"id":263643178,"identity":"0da3faf4-a0a2-496b-be88-32c517565b3a","order_by":1,"name":"Hossein Yarmohammadi","email":"","orcid":"","institution":"Motamed Cancer Institute, ACECR","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hossein","middleName":"","lastName":"Yarmohammadi","suffix":""},{"id":263643179,"identity":"590fcd42-ac17-45a4-a045-118960340bc7","order_by":2,"name":"Seyed Fatah Mahdavi Anari","email":"","orcid":"","institution":"Shiraz University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Seyed","middleName":"Fatah Mahdavi","lastName":"Anari","suffix":""},{"id":263643182,"identity":"34d37b1d-7af1-4308-a2ba-916c1e22c5dc","order_by":3,"name":"Seyed Davar Siadat","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0klEQVRIiWNgGAWjYDCCAyDExsDAD+IkFJCgRUKyAaTFgEgtDCAtBmAGMVr4DrA/PPCjzK7O+PzqxA8PDBjk+cUO4NcieYDH4GDPuWQJsxtvN0sAHWY4c3YCfi0GB3gYDvC2MQO1nN0A0pJgcJugFvYHB/+21UsYzzi7+QeRWhgMDvO2HZYw4O/dRpwtkod5DA7LnDsuOeMG7zaLBAMJwn7hO97++OObsmp+/v6zm2/+qLCR55cmoIWBGcaQAKuUIKAcBfAfIEX1KBgFo2AUjCQAAIoARuiQTHN+AAAAAElFTkSuQmCC","orcid":"","institution":"Pasteur Institute of Iran","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Seyed","middleName":"Davar","lastName":"Siadat","suffix":""},{"id":263643183,"identity":"684a90b9-9dd2-4edc-9cde-6e62b5ca7d71","order_by":4,"name":"Mohammadreza Karimi Nemch","email":"","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mohammadreza","middleName":"Karimi","lastName":"Nemch","suffix":""}],"badges":[],"createdAt":"2023-12-27 09:14:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3811498/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3811498/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00405-025-09330-y","type":"published","date":"2025-04-02T00:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":49088334,"identity":"9b243c8e-681b-4d60-9c10-bcbb56b71d1c","added_by":"auto","created_at":"2024-01-03 01:22:09","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":551507,"visible":true,"origin":"","legend":"\u003cp\u003eFindings of the sonography on day six show enlarged lymph nodes of the left cervical region (a and b), and an enlarged left parotid with decreased echogenicity (c).\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3811498/v1/f24a2eef197d1c8f0076ebb7.jpg"},{"id":49088335,"identity":"562d78b6-2e75-48ce-9098-f071558cce7e","added_by":"auto","created_at":"2024-01-03 01:22:09","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":556677,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of lesions through the time: a) painful nodular erythematous lesion on the left temporal side and parotitis on day 6\u003csup\u003eth\u003c/sup\u003e, b) involvement of the left auditory canal and antitragus on day 7\u003csup\u003eth\u003c/sup\u003e, c) involvement of the left lower eyelid and external epicanthus at day 8\u003csup\u003eth\u003c/sup\u003e, d) gradual improvement of lesions on day 13\u003csup\u003eth\u003c/sup\u003e.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3811498/v1/1e47aac7e619b52c32ea1570.jpg"},{"id":80091464,"identity":"cd8e0302-2ba0-4650-b664-ea238cc9f1b1","added_by":"auto","created_at":"2025-04-07 19:22:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1484294,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3811498/v1/4c61446d-f832-423d-ae5e-f01b4c81cf53.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Ramsay-Hunt-Syndrome Associated with Unilateral Parotitis Following COVID-19 Vaccine","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eThe COVID-19 pandemic made a negative impact on many aspects of human lives from its cardiopulmonary complications to the psychosocial burden that it imposed on individuals worldwide (\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). With the development of different vaccines, the mortality of COVID-19 was dramatically reduced and its burden started to lighten over time (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). However, complications following the vaccination instead became a health concern. Different complications affecting cardiorespiratory, autoimmune, and, nervous systems were reported in the literature and the reactivation of varicella-zoster-virus was one of the well-recognized complications (\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). The Ramsay-Hunt-Syndrome (RHS) is a clinical diagnosis and classically recognized as a triad of vesicles around the ear or auditory canal, otalgia, and ipsilateral facial paralysis (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). RHS induced by VZV mostly responds to treatment with valacyclovir and steroids, also physiotherapy could help those who suffer from synkinesis in the long term (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). The presentation of RHS following COVID-19 vaccination has been rarely reported in the literature. We describe the clinical course, management, and, follow-up of a 36-year-old immunocompetent man presenting with RHS three weeks after COVID-19 vaccination.\u003c/p\u003e"},{"header":"2. Case presentation","content":"\u003cp\u003eA 36-year-old male with no significant past medical history started to have fever and flu symptoms three weeks after the second dose of the BBIBP-CorV (Sinopharm) vaccine. He developed pain, erythema, and, tenderness of the left antitragus in the following four days. He made an appointment with the otolaryngology clinic and received a prescription including ciprofloxacin drop, glucocorticoid drop, and oral analgesia, as the initial diagnosis was otitis externa. However, he did not sleep due to severe pain which made him visit the emergency department (ED) that night. At the time in ED, he had also developed some difficulties of swallowing and the swelling of the left side of his neck was evident. At day six, sonography of the left neck revealed the parotid size 55*44*18 mm with decreased parenchymal echogenicity. Also, multiple reactive adenopathies with a maximum diameter of 13 mm were shown. At the left cervical chain, enlarged lymph nodes with small echogenic centers and approximate sizes of 16*6 mm and 15*6 mm were observed (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eHours later after sonography, a painful nodular erythematous lesion on the left temporal side was noticed by the patient and the swelling of the parotid increased dramatically (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, a). On day seven, he had odynophagia and dysgeusia with painful ulcerous buccal nodules. The outer half of his tongue on the left side had similar lesions without ulcer. The left side of his lips and his left auditory canal and antitragus were also involved (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, b). He also started left facial weakness and paraesthesia with nausea and dizziness. The next day, the left lower eyelid and external epicanthus developed painful erythematous nodules (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, c). At this point, skin lesions were characteristic of zona and due to the distribution of lesions and facial weakness, the diagnosis of Ramsy-Hunt-Syndrome (RHS) was made. All his previously prescribed drugs were discontinued immediately and valacyclovir (500 mg, three times a day) in combination with analgesia was initiated for him at the hospital on day nine. On day 13th his lesions gradually improved; first on the tongue and lips and then lesions on the antitragus (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, d). He was discharged after seven days of being hospitalized on day 16th when valacyclovir was discontinued. His facial weakness and paraesthesia sensation gradually improved, however, the swelling of the neck was not resolved until the following 14 days on day 29th. At this follow-up visit, he also had complaints regarding post-herpetic neuralgia that were managed with nortriptyline. At the second follow-up visit on day 61, he had no longer any complications.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"3. Discussion","content":"\u003cp\u003eVaricella-zoster-virus belongs to the Herpesviridae family which tends to reactivate even many years after the primary infection and is capable of inducing different complications such as skin lesions to meningoencephalitis (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Different presentations of VZV reactivation have been reported from characteristic skin lesions to RHS following COVID-19 vaccination. The exact pathogenesis of RHS following COVID-19 vaccination is not clear but some indirect links between herpes virus reactivation, COVID-19 vaccination, and autoimmunity could be drawn which needs more studies to be tested (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Hyperviscosity induced by mRNA vaccinations is another suggested related mechanism (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Nevertheless, this case report presented a healthy young immunocompetent man who developed RHS following Sinopharm vaccination.\u003c/p\u003e \u003cp\u003eHis first symptoms were pain and skin lesions. Zona is the most reported presentation of VZV reactivation following COVID-19 vaccination. The systematic review by Desai et al gathered clinical data of 54 cases that developed reactivation of VZV following COVID-19 vaccination. The most reported vaccine was the mRNA vaccine and the mean interval between vaccination to presentation of symptoms was almost seven days (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Additionally, the systematic review by Katsikas Triantafyllidis et al reported similar results on 91 cases. Comorbidities such as hypertension, autoimmune conditions, and, receiving immunosuppressants were considered risk factors for VZV reactivation. However, younger cases with no significant past medical history were also reported in the review similar to our case. They also found that valacyclovir was the most used treatment (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). The review article by Iwanaga et al gathered data from 399 reported cases of herpes zoster infection following COVID-19 vaccination. The majority of cases reported the herpes zoster infection following the BNT162b2 vaccine. The authors concluded that the duration since vaccination to VZV reactivation could be 1 to 24 days, as in our case it took 21 days (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOther than cutaneous manifestation of VZV reactivation among patients with COVID-19 or following vaccination, RHS has been rarely reported in the literature. There have been six cases of RHS presented after COVID-19 infection. Al Rida Ayoub et al just recently reported an interesting case of an asymptomatic 60-year-old man, who was diagnosed with COVID-19 based on a positive PCR test. Three days later he developed a skin rash and facial weakness and was treated with valacyclovir for RHS. The authors also made a thorough literature search and found five case reports of RHS presented among COVID-19 patients (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). The case reported by Mehta et al reported a 32-year-old man with left-sided lower motor neuron facial palsy which occurred after COVID-19 and eventually was resolved after five days of using steroids (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). The case described by Alonzo‑Correa was a 25‑year‑old woman with positive COVID-19 PCR who developed herpes zoster oticus, otalgia, and acute peripheral facial nerve palsy which consequently improved after administering steroids (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Other three cases could be found in the review done by Al Rida Ayoub et al and it generally could be concluded that the management of most cases was administering valacyclovir with favorable outcomes (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAdditionally, RHS has also been reported following COVID-19 vaccination in three previously published articles. Rodr\u0026iacute;guez-Mart\u0026iacute;n et al reported a 78-year-old woman who developed otalgia and other related symptoms including House-Brackmann grade IV right peripheral facial paralysis, three days after BNT162b2 mRNA vaccination (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Woo et al described a 37-year-old man presenting with RHS two days after BNT162b2 mRNA vaccination. A swab sample from exudates was studied with PCR and it was positive for VZV (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Finally, Lakhoua et al reported a 65-year-old who was presented with RHS seven days after BNT162b2 mRNA vaccination. He was treated with valacyclovir and pregabalin with improvement in lesions but he was still complaining of post-herpetic neuralgia at six-month follow-up (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). To the best of our knowledge, our case is the first describing RHS following Sinopharm vaccination in a healthy young man.\u003c/p\u003e \u003cp\u003eOur case had also parotitis which was evaluated with ultrasonography. Some case reports have described acute parotitis following the COVID-19. Lechien et al reported three cases with COVID-19 who developed parotitis. Symptoms lasted 3 to 10 days and all three were managed with paracetamol. MRI was done for three cases and intraparotid lymphadenitis was shown in all of them. It was suggested that intraparotid lymphadenitis due to COVID-19 could be the cause of the presentation of parotitis (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). A 32-year-old man with COVID-19 was reported by Taha Ismail and Mohamed Naser who had unilateral parotitis. Ultrasonography showed an enlarged and diffuse hypoechoic parotid gland structure. He received intravenous steroids and his symptoms were resolved on day seven (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Also, Capaccio et al described a 26-year-old man with positive COVID-19 PCR who was initially presented with acute unilateral parotitis (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Another 79-year-old man has been reported to be admitted due to COVID-19 and required non-invasive mechanical ventilation. Five days after admission he developed sudden unilateral parotitis and he expired after nine days (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). The treatment of parotitis in our case consisted of conservative management with analgesia which was resolved on day 29th with no further complications.\u003c/p\u003e \u003cp\u003eThe interesting point of this case was the associated unilateral parotitis which rarely has been reported in association with VZV reactivation in the literature. It is not clear if these two problems are linked or not, however, it seems that both could be attributed to COVID-19. To the best of our knowledge, only two studies have reported simultaneous presentation of parotitis and VZV reactivation in adults (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). The case reported by Banno et al described a 43-year-old man who had unilateral right parotitis simultaneous with ophthalmicus involvement due to VZV. The serologic test showed positive antibodies for VZV in the absence of r herpes simplex virus 1 and 2 and mumps. He was treated with valacyclovir, antibiotics, and, steroids which led to complete improvement in symptoms after three weeks (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). Additionally, the case reported by Tally et al was a 36-year-old woman with VZV ophthalmicus and unilateral left parotitis. The neck computed tomography confirmed the parotitis with no other concerning problem. She received valacyclovir, antibiotics, and, analgesia and she was symptom-free after three weeks follow-up (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). The exact mechanism of this simultaneous presentation is not known. The auriculotemporal nerve involvement following the VZV reactivation of the trigeminal nerve is one proposed theory. However, the immune response to the VZV reactivation, or also the possibility of autoimmunity following the COVID-19 vaccination might be another explanation (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Nevertheless, being familiar with such rare presentations could be useful for timely diagnosis and proper management.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient permitted us to use clinical information and photographs to be published.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSigned written informed consent was obtained from the patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData are available based on the request from the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors confirm that there are no known conflicts of interest associated with this publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere has been no financial support for this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eS.D.S. contributed to conceptualizing the study and finalized the manuscript. M.S. and M.K.N gathered data and contributed to writing the initial draft. H.Y. contributed to performing the literature search and wrote the draft of the search result. S.F.M.A contributed to\u0026nbsp;the visualization of figures and writing the initial draft. All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRamandi MMA, Yarmohammadi H, Beikmohammadi S, Fahimi BHH, Hatami F, Beydokhti H et al (2021) Comparison of the cardiovascular presentations, complications and outcomes following different coronaviruses\u0026rsquo; infection: A systematic review. 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Chest 160(4):A315\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBanno F, Riccelli T, Banno M (2019) Simultaneous parotitis and ipsilateral herpes zoster ophthalmicus: coincidence? BMJ Case Reports CP 12(3):e228897\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTally S, Brown M, Hsu E (2023) Case Report of Herpes Zoster Ophthalmicus with Concurrent Parotitis. J Educ Teach Emerg Med. ;8(2)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoshida M, Higuchi T (2012) Herpes zoster ophthalmicus with ipsilateral parotitis. Int J Dermatol 52(6):769\u0026ndash;770\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Varicella-zoster-virus (VZV), Ramsey-hunt-syndrome (RHS), COVID-19, Vaccine, Unilateral parotitis","lastPublishedDoi":"10.21203/rs.3.rs-3811498/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3811498/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eVaricella-zoster-virus (VZV) reactivation is a recognized complication following COVID-19 vaccination; however, Ramsey-hunt-syndrome (RHS) rarely has been reported. This case presents a 36-year-old immunocompetent man with features of RHS three weeks following the second dose of the BBIBP-CorV (Sinopharm) vaccine. Interestingly, he developed acute unilateral parotitis on his left side and the ultrasonography showed a 55*44*18 mm parotid gland with decreased parenchymal echogenicity. He was treated with valacyclovir, and after seven days he was discharged. Also, his parotitis was resolved by day 29 following the presentation of the first symptoms with no further complications. The possibility of VZV reactivation after COVID-19 vaccination is an important point and it should be noted that this reactivation might present in unusual clinical scenarios.\u003c/p\u003e","manuscriptTitle":"Ramsay-Hunt-Syndrome Associated with Unilateral Parotitis Following COVID-19 Vaccine","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-03 01:22:05","doi":"10.21203/rs.3.rs-3811498/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5354e400-d3ed-4a8f-b543-a772c82879d9","owner":[],"postedDate":"January 3rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-04-07T19:22:51+00:00","versionOfRecord":{"articleIdentity":"rs-3811498","link":"https://doi.org/10.1007/s00405-025-09330-y","journal":{"identity":"european-archives-of-oto-rhino-laryngology","isVorOnly":false,"title":"European Archives of Oto-Rhino-Laryngology"},"publishedOn":"2025-04-02 00:00:00","publishedOnDateReadable":"April 2nd, 2025"},"versionCreatedAt":"2024-01-03 01:22:05","video":"","vorDoi":"10.1007/s00405-025-09330-y","vorDoiUrl":"https://doi.org/10.1007/s00405-025-09330-y","workflowStages":[]},"version":"v1","identity":"rs-3811498","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3811498","identity":"rs-3811498","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}