RGUHS Nat. J. Pub. Heal. Sci Vol No: 16 Issue No: 3 pISSN:
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Sahana NS1 , Meghashyama Kulkarni1*, Abhisikta Chakrabarty1 , Renuga S1 , Hajira Khatoon1 , Srinath SK2
1 Department of Oral Pathology and Microbiology, Government Dental College and Research Institute, Bengaluru-560002.
2 Department of Pediatric and Preventive Dentistry, Government Dental College and Research Institute, Bengaluru-560002.
*Corresponding author:
Dr. Meghashyama Kulkarni, Postgraduate Student, Department of Oral Pathology and Microbiology, Government Dental College and Research Institute, Bengaluru-560002. E-mail: meghashyamakulkarni@gmail.com
Received date: June 25, 2021; Accepted date: February 12, 2022; Published date: June 30, 2022
Abstract
Since the inception of COVID-19 pandemic in November 2019, caused by SARS-CoV-2 virus, relationship between corona virus disease and oral effects caused due to viral enanthema have been studied with great interest. Owing to the existence of many ACE2 receptors (which permit entry of virus in the host cell) in the oral cavity, a multitude of oral manifestations have been described. Among various oral symptoms, dysgeusia is the most prevalent. Other oral lesions included ulcer, erosion, vesicle, bulla, depapillated tongue, macule, papule, plaque, pigmentation, whitish areas, petechiae and erythema. Aphthous stomatitis, mucositis were also diagnosed among COVID-19 affected patients. Kawasaki-like disease and atypical Sweet syndrome was also noted in some patients. People with severe disease state and older individuals had significantly more oral lesions. Many oral symptoms were seen in patients post the corona virus disease recovery as well. This may be due to the diverse treatment given to the patients which may have ill-effects. Older age group, underlying diseases, opportunistic infections, poor oral hygiene and stress are the important factors for the development of oral manifestations in COVID-19 patients. Health care workers should be vigilant to identify the various oral manifestations and provide extensive treatment with an intent to improve general status as well as oral health of COVID affected individuals.
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Introduction
The corona virus disease was first described in November 2019 as pneumonia of unknown origin in Wuhan city of Hubei Province in China. It soon went on to affect thousands and millions of individuals worldwide, causing life-threatening complications in people with comorbidities as well as in healthy individuals with a tendency towards the medically compromised individuals and elderly with reduced immune response.1 On 30th January 2020, WHO delineated the coronavirus disease as ‘Public Health Emergency of International Concern’ and on February 11, 2020 the nomenclature ‘COVID-19’ for the disease caused by novel corona virus Severe Acute Respiratory Syndrome Corona Virus – 2 (SARS-CoV-2) was given.2
The COVID-19 disease is the third only reported pandemic affecting humans in which coronavirus crossed the species barrier and caused severe morbidity and mortality. The first incidence of corona virus disease in humans was Severe acute respiratory syndrome (SARS) which occurred in the year 2003 and the second was Middle East respiratory syndrome corona virus (MERS) in 2012. Before this, corona virus diseases were associated only in animals.3
SARS-CoV-2 is a single-stranded RNA-enveloped virus. The spike protein of the virus plays a vital role in the receptor recognition, cell membrane fusion process and makes way for the entry of virus in the host cell.4 The spikes on the surface of virus’ cell-membrane are coated with polysaccharide molecules to conceal them, evading surveillance of the host immune system during entry.5
Since the onset of the pandemic, there has been mutation in the spike protein with emergence of different variants. Researchers are tracking the trail and effects of the mutations in the variants that have arisen so far, while keeping an eye peeled for new ones.6
The main route of transmission is by spread of respiratory droplets secreted by the affected individual during coughing, sneezing, breathing and even normal speech. Other route of viral transmission is through contaminated objects or fomites.7
Ensuing studies have proved that virus is present in the saliva as well. There is evidence of viral transmission from asymptomatic individuals.8
There is conflicting evidence for airborne transmission of the virus. Several studies have reported positive air sampling in closed (non-ventilated) areas and foreground the transmission of corona virus through air.9,10
The presence of the virus in stool sample evinces that gastrointestinal transmission is also possible.8
The most common symptoms of COVID-19 are fatigue, fever and dry cough. The symptoms that are less commonly affecting some patients include loss of taste or smell, nasal congestion, sore throat, headache, muscle or joint pain, different types of skin rash, conjunctivitis, nausea or vomiting, diarrhoea, chills or dizziness. Severe symptoms include shortness of breath, loss of appetite, confusion, persistent pain or pressure in the chest, high temperature.11
Complications leading to mortality include respiratory failure, acute respiratory distress syndrome (ARDS), sepsis and septic shock, thromboembolism, multiorgan failure, including injury of the heart, kidneys or liver.12
At the beginning of the pandemic, it was presumed that paucity of oral involvement is a differentiating attribute of COVID-19 from other viral diseases. But later SARSCoV-2 was detected from saliva of the patients and it has been noted that RT-PCR test from salivary samples can be more sensitive when compared to nasopharyngeal samples.13
The COVID-19 virus enters into the host by binding to two cell receptors which are angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2.14
The oral mucosa is also rich in ACE2, especially in salivary glands and on dorsal region of the tongue.15 Dysgeusia was the first recognized oral symptom. Later on, many signs and symptoms of the disease in relation to the oral cavity have been described. In this review article, various oral manifestations of COVID-19 are described.
Material & Methods
Articles from PubMed library and Google Scholar were searched for published literature from February 2020 to January 2021 using keywords ‘COVID-19’, ‘SARSCoV-2’ and ‘Oral manifestations’. The related articles in the reference lists of the articles found were also searched. Eventually 35 articles were selected. After deletion of non-English literature and papers without clear background, 28 articles were chosen for the review.
Results
Oral manifestations included dysgeusia (most common), ulcer, erosion, vesicle, bulla, depapillated tongue, macule, papule, plaque, pigmentation, halitosis, whitish areas, haemorrhagic crust, petechiae and erythema.
The diagnoses put forward based on these lesions were aphthous stomatitis, herpetiform lesions, candidiasis, Kawasaki-like disease, mucositis, gingival and periodontal diseases, Sweet syndrome, mucormycosis, cervical lymphadenopathy and others.
Discussion
Dysguesia/Ageusia
Dysgeusia is seen in 5.6% to 88.8% of patients.13 The epithelial cells of the oral tissues and nasal mucosa have abundant ACE2. The presence of viral RNA in saliva before pulmonary regions has been illustrated. Hence it can be possible that the salivary glands get affected primarily by the infection which results in salivary gland dysfunction followed by reduced/impaired salivary flow.16
The expression of ACE2 receptors is more in the gustatory receptors present on dorsum of the tongue than the other areas of the oral mucosa which results in certain chemosensory changes leading to ageusia.17
Oral Ulcers Aphthous like ulcers The definite aetiology of occurrence of ulcers in the oral cavity in patients with COVID-19 is still unknown. Most of the investigators concluded that aphthous ulcers are caused secondary to mental stress.18
Sweet syndrome
In a case report, 61-year-old COVID positive female patient presented with fever, arthralgia, myalgia, fatigue, several erythematous nodules on the scalp, abdomen, upper and lower extremities. The oral finding was presence of multiple minor aphthous ulcers on the buccal mucosa and the anterior portion of the hard palate. The skin biopsy confirmed the diagnosis of erythema nodosum like Sweet syndrome.19
Vesicles/Bullae
Herpetiform/Zosteriform lesions may be caused due to reactivation or new infection of herpes virus mainly due to immunosuppression seen in virus affected individuals.20
White/Red Patches
White and red patches were reported on dorsum of the tongue, gingiva and palate in patients with confirmed cases of corona virus disease. Candidiasis was reported as well. This can be due to long-term antibiotic therapy, deterioration of general health status and improper oral hygiene maintenance in diseased.21
Gingival/Periodontal Diseases
Gingival inflammation, bleeding, desquamative gingivitis are commonly seen in patients with the coronavirus disease which is seen in many viral enanthemas as well. One case of necrotizing periodontal disease has been reported. It was caused due to bacterial coinfections along with COVID-19.22
Mucormycosis
Mucormycosis is a fatal fungal infection, rhino cerebral mucormycosis being the most common type. It has emerged as one of the most prevalent complication in COVID-19 patients. It occurs mainly in immunocompromised individuals, in uncontrolled diabetes and in patients with prolonged steroid treatment.
Oral involvement is seen in the form of palatal ulceration/necrosis and later as palatal perforation which occurs due to infection in the para nasal sinuses or the nasal cavity which evades the oral mucosa via the palatal vessels.23 In the initial stages of the disease, patients often exhibit cellulitis and anaesthesia/paraesthesia in the oral and para-oral regions.24
Mucormycosis has created a lot of havoc as the fatality rate is very high and the treatment is strenuous. It has been classified as an epidemic in different regions of India.
Mucositis
Presence of erythematous macules and papules in the oral mucosa was reported in many studies. Thrombotic vascular diseases, hypersensitivity seen in COVID-19 patients could be associated with mucositis.25
Gingival Pigmentation
Cases with pigmentation associated with papillary and attached gingiva have been described post COVID recovery. This is attributed to ‘Cytokine Storm’ that is seen in the pathogenesis of the COVID infection. The levels of the inflammatory cytokines like interleukin1(IL-1) and tumour necrosis factor alpha (TNF-a) are raised which increases the keratinocyte growth factor (FGF-7) in the basal layer of the epithelium which sources melanin production ultimately leading to post inflammatory pigmentations.26
Kawasaki-Like Multisystem Inflammatory Disease
The latest reports have described a secondary Multisystem Inflammatory Syndrome in Children abbreviated as MIS-C which is observed after recovery of COVID-19 infection. The children affected presented with features of Kawasaki disease (KD). Along with younger children, many young adults in their late teenage years and early twenties also showed similar symptoms of KD.27
Oral lesions like glossitis, cheilitis and swollen tongue with erythema i.e. red strawberry tongue were seen in COVID-19 patients with Kawasaki like disease.
KD associated with COVID patients is known as ‘KawaCOVID’.28
COVID Tongue
It clinically appears as glossitis with patchy depapillation. There is presence of lateral clefts and anterior lingual papillitis which is due to swollen tongue and friction with the teeth.29 These features are in line with geographic tongue which is a common entity and not associated with viral infections. Hence Covid tongue cannot be considered as a pathognomonic sign of the disease.30
Lymphadenopathies in Association with Oral Symptoms
In patients with symptoms like dysgeusia and nasal obstruction, MRI was performed. Bilateral cervical lymphadenopathy was noted. Along with cervical lymph nodes, there was enlargement of parotid lymph nodes too. There was also enlargement of the palatine tonsils in some patients. In one of the patient, radiologists observed complete enlargement of the Waldeyer’s ring.31
Conclusion
Most of the lesions in the oral cavity associated with COVID-19 infection are either due to viral enanthema or as a consequence of the treatment given. There is a very strong correlation between COVID-19 and oral manifestations. The fact that there exists numerous ACE2 receptors in the oral mucosa that have great affinity to the corona virus should be considered significantly. Older age group, underlying diseases, opportunistic infections, lack of oral hygiene, stress are the important factors for the development of oral lesions in COVID-19 patients. Health care providers should be vigilant to concede the myriad of symptoms of the coronavirus disease.
Supporting File
References
1. Paradowska-Stolarz AM. Oral manifestations of COVID-19: Brief review. Dent Med Probl 2021; 58(1):123-6.
2. He F, Deng Y, Li W. Coronavirus disease 2019: What we know? J Med Virol 2020;92(7):719-725.
3. Singh G, Priya H, Mishra D. Oral manifestations and dental practice recommendations during COVID-19 pandemic. J Family Med Prim Care 2021;10(1): 98-102.
4. Huang Y, Yang C, Xu XF, Xu W, Liu SW. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin 2020;41(9): 1141-9.
5. Wu C, Liu Y, Yang Y, Zhang P, Zhong W, Wang Y et al. Analysis of therapeutic targets for SARSCoV-2 and discovery of potential drugs by computational methods. Acta Pharmaceutica Sinica B 2020;10(5):766-88.
6. Callaway E. Beyond Omicron: what’s next for COVID’s viral evolution. Nature 2021; 600(7888): 204-7.
7. Falahi S, Kenarkoohi A. Transmission routes for SARS-CoV-2 infection: review of evidence. New Microbes New Infect 2020;27(38):141-47.
8. Wei WE, Li Z, Chiew CJ, Yong SE, Toh MP, Lee VJ, et al. Presymptomatic transmission of SARSCoV-2—Singapore, January 23–March 16, 2020. MMWR 2020;69(14):411-14.
9. Zhang R, Li Y, Zhang AL,,Wang Y, Molina MJ.. Identifying airborne transmission as the dominant route for the spread of COVID-19. PNAS USA 2020; 117(26):14857-63.
10. Morawska L, Cao J. Airborne transmission of SARS-CoV-2: The world should face the reality. Environ Int 2020;139:10-17.
11. Gu J, Han B, Wang J. COVID-19: gastrointestinal manifestations and potential fecal–oral transmission. Gastroenterol 2020;158(6):1518-9.
12. Larsen JR, Martin MR, Martin JD, Kuhn P, Hicks JB. Modeling the Onset of Symptoms of COVID-19. Front. Public Health 2020;8:473.
13. Iranmanesh B, Khalili M, Amiri R, Zartab H, Aflatoonian M. Oral manifestations of COVID-19 disease: A review article. Dermatol Ther 2021; 34(1):e14578.
14. Kipshidze N, Dangas G, White CJ, Kipshidze N, Siddiqui F, Lattimer CR,. et al. Viral coagulopathy in patients with COVID-19: treatment and care. CATH 2020;26:107-110.
15. Seirafianpour F, Sodagar S, Pour Mohammad A,Panahi P, Mozafarpoor S, Almasi S, Goodarzi A. et al. Cutaneous manifestations and considerations in COVID-19 pandemic: a systematic review. Dermatol Ther 2020;33(6):e13986.
16. Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, et al. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Oto-Rhino-L 2020;277(8):2251-61.
17. Wang WK, Chen SY, Liu IJ, Chen YC, Chen HL, Yang CF, et al. Detection of SARS-associated coronavirus in throat wash and saliva in early diagnosis. Emerg Infect Dis 2020;10(7):121-3.
18. Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X, et al. High expression of ACE2 receptor of 2019- nCoV on the epithelial cells of oral mucosa. Int J Oral Sci 2020;12(1):1-5.
19. Indu S. Multiple oral ulcerations–An initial manifestation of COVID 19 infection: A personal experience!! J Oral Maxillofac Pathol 2020; 24(2): 227-231.
20. Taşkın B, Vural S, Altuğ E, Demirkesen C, Kocatürk E, Çelebi İ,et al. Coronavirus 19 presenting with atypical Sweet›s syndrome. J. Eur. Acad. Dermatol. Venereol 2020;34(10):534-5.
21. Corchuelo J, Ulloa FC. Oral manifestations in a patient with a history of asymptomatic COVID-19: Case report. Int J Infect Dis 2020;100:154-7.
22. Patel J, Woolley J. Necrotizing periodontal disease: Oral manifestation of COVID-19. Oral Dis 2020; 32(4):124-28
23. Pauli MA, de Melo Pereira L, Monteiro ML, de Camargo AR, Rabelo GD. et al. Painful palatal lesion in a patient with COVID-19. J Oral Med Oral Surg Oral Pathol Oral Radiol 2021;24(2):254-57.
24. Roden MM, Zaoutis TE, Buchanan WL Knudsen TA, Sarkisova TA, Schaufele RL, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis 2005;41(5):634-53.
25. Tapia ROC, Labrador AJP, Guimaraes DM, Valdez LHM.. Oral mucosal lesions in patients with SARSCoV-2 infection. Report of four cases. Are they a true sign of COVID-19 disease? Spec Care Dentist 2020;40(6):555-60.
26. Feller L, Masilana A, Khammissa RA, Altini M, Jadwat Y, Lemmer J. et al. Melanin: the biophysiology of oral melanocytes and physiological oral pigmentation. Head Face Med 2014;10(1):1-7.
27. Sokolovsky S, Soni P, Hoffman T, Kahn P, ScheersMasters J.. COVID-19 associated Kawasaki-like multisystem inflammatory disease in an adult. Am J Emerg Med 2021;39:253-59.
28. Labé P, Ly A, Sin C, Nasser M, ChapelonFromont E, Saïd PB, et al. Erythema multiforme and Kawasaki disease associated with COVID-19 infection in children. J Eur Acad Dermatol Venereol 2020;34(10):539-41.
29. Pérez-Sayáns M, Ortega KL, Braz-Silva PH, Carreras-Presas CM, Carrión AB., et al. Can “COVID-19 tongue” be considered a pathognomonic finding in SARS-CoV-2 infection? Oral Dis 2021; 25(2):124-6.
30. Hathway RW. COVID tongue. Br Dent J 2021; 230(3):114.
31. Distinguin L, Ammar A, Lechien JR, Chetrit A, Idrissi YC, Circiu M, et al. MRI of patients infected with COVID-19 revealed cervical lymphadenopathy. ENT Journal 2021;100(1):26-28.