TABLE 1.

Distinctive features of observational studies included in the systematic review (n = 21)

S. No.	Study Id	Study design	Sample (total no)	Age,Y, mean	Covid‐19 grade/Severity	Clinical signs and symptoms	Oral manifestations	Time of oral presentation	Diagnostic method of oral manifestations	Conclusion	Risk of bias
1	Gherlone EF et al (2021), Milan, Italy	Observational study	122 (M‐75%, F‐25%)	62.5 (53.9–74.1 y) for M, 30 (24.6) Y for F	Hospitalised (115), ICU (30 patients out of 122 transferred to ICU	Not reported (confirmed COVID‐19 cases included)	Salivary gland ectasia (46), both dry mouth and salivary gland ectasia (13), masticatory muscle weakness (23), TMJ abnormalities (9), dysgeusia (14), anosmia (12), facial tingling (4), trigeminal neuralgia(4), facial asymmetry (1)	Post‐recovery follow‐up	Extraoral and intraoral physical examination by experienced dental specialist	Oral cavity is a possible target of COVID‐19, with alterations persisting in the vast majority of survivors well after clinical recovery.	Low
2	Maia CMF et al, 2021, Brazil	Observational study	8695 (observed during covid period)	Not reported	Hospitalised and non‐hospitalised	Not reported (confirmed COVID‐19 cases included)	Herpes zoster	Before and during COVID‐19 infection	Medical records	There was an increase in HZ cases during the COVID‐19 pandemic, which suggests a correlation between these diseases.	Moderate
3	Nuno Gonzalez A et al, 2020, Spain	Observational study	666	55.67 years F‐ 58%, M‐42% (not reported)	Hospitalised	Confirmed cases of COVID‐19	Oral cavity findings were seen in 78 (25.65%) cases, including transient lingual papillitis (11.5%), glossitis with lateral indentations (6.6%), aphthous stomatitis (6.9%), glossitis with patchy depapillation (3.9%) and mucositis (3.9%), enanthema (0.5%), white tongue (1.6%), candidiasis (1%). Burning sensation was reported in 5.3% of patients and taste disturbances (dysgeusia) was commonly associated.	During COVID‐19 infection	Extraoral and intraoral physical examination	Almost half of patients with mild to moderate COVID‐19 admitted in a field‐hospital during a 2‐week period show mucocutaneous findings. Oral cavity is frequently involved and deserves specific examination under the appropriate circumstances to avoid contagion risk.	Low
4	Biadsee A et al, 2020, Israel	Observational study	128 (58 M, 70 F)	36.25 (18–73 Y)	Non‐hospitalised	Cough, weakness, myalgia, fever, headache, impaired sense of smell, sore throat, runny nose, nasal congestion, gastrointestinal symptoms.	Changes in taste sensation, dry mouth, facial pain, masticatory muscle pain, burning sensation, change in tongue sensation, plaque‐like changes in the tongue	During COVID‐19 infection	Web based questionnaire	A considerable number of patients presented with olfactory and oral disorders. Interestingly, women presented with a different cluster of symptoms than men, which may suggest a new clinical approach to diagnosing COVID‐19 disease.	Moderate
5	Fantozzi PJ et al, 2020, Italy	Observational study	111, 58 were males, 53 were females	Median age −57 years	Hospitalised, ICU	Fever, cough, dyspnoea, diarrhoea, sore throat, fatigue, myalgia, vomit	Taste dysfunction was the most common reported symptom (59.5%; n = 66), followed by xerostomia (45.9%; n = 51) and olfactory dysfunctions (41.4%; n = 46).	During COVID‐19 infection	Ouestionnaire based survey	Xerostomia, olfactory and gustatory dysfunctions are common symptoms reported as concomitant, and in some cases the sole manifestation of COVID‐19.	Low
6	Katz J and Yue S, 2021, Florida, USA	Observational study (retrospective cross‐sectional)	RAS and COVID‐19‐ (0.64%)	18–34 Yr (66%), 10–17 (33%)	Hospitalised and non‐hospitalised	Confirmed cases of COVID‐19	Prevalence of RAS in covid‐19 patients was 0.64%.	During COVID‐19 infection	Medical records	There is a strong association between COVID‐19 and aphthous ulcers	Low
7	Giacomelli A et al, 2020, Italy	Cross‐sectional study	59	60 years (50–74) M‐40, F‐19	Hospitalised	Fever, cough, dyspnoea, sore throat, arthralgia, coryza, headache, asthenia, abdominal symptoms	Olfactory and/or taste disorders (20), taste disorders only (6), olfactory disorders only (3), mixed taste and olfactory disorders (11)	12 patients (20.3%) presented the symptoms before the hospital admission, whereas 8 (13.5%) experienced the symptoms during the hospital stay. Taste alterations were more frequently (91%) before hospitalisation, whereas after hospitalisation taste and olfactory alteration appeared with equal frequency.	Questionnare based survey	OTDs are fairly frequent in patients with SARS‐CoV‐2 infection and may precede the onset of full‐blown clinical disease. I	Moderate
8	Sinjari B et al, 2020, Italy	Observational study	20	69.2 Y, 55% M, 45% F	Hospitalised	Confirmed cases of COVID‐19 (clinical manifestations not reported)	Xerostomia (30%), impaired taste (25%), burning sensation (15%), difficulty in swallowing (20%)	During COVID‐19 infection	Questionnaire based survey	This study demonstrates the importance of the close link between SARS‐CoV‐2 and oral manifestations. Dysgeusia may be a warning signal for the patients.	Low
9	Abubakr N et al, 2021, Egypt	Observational study	573	36.19 ± 9.11 years (range: 19–50 years).	Non‐hospitalised (mild to moderate cases)	Mild to moderate cases	Oral or dental pain (23%), pain in jaw bones or joint (12.0%), halitosis (10.5%), ulcerations (20.4%), and xerostomia (47.6%). Some patients (28.3%) showed 2 or 3 manifestations simultaneously.	During COVID‐19 infection		Mild‐to‐moderate cases of COVID‐19 infection are associated with oral symptoms, and thus the significance of dental examination of patients with communicable diseases should be emphasised.	Low
10	El Kady DM et al, 2021, Egypt	Observational study	58 (53.4% M, 46.6% F)	18–46 Y	Hospitalised	Fever, cough, shortness of breath, and myalgia or weakness, headache, sputum formation, haemoptysis, diarrhoea	The highest prevalence symptoms were dry mouth 39.7% (n = 23), gustatory dysfunction as 34.5% (n = 20) loss of salt sensation, 29.3% (n = 17) loss of sweet sensation, and 25.9% (n = 15) altered food taste, while the least prevalent symptoms were tongue redness 8.8% (n = 5), and gingival bleeding 7% (n = 4). The most frequently associated symptoms were loss of salt and sweetness, as reported by 27.6% of the participants.	During COVID‐19 infection	Questionnaire based survey (online)	COVID‐19 significantly impacts the oral cavity and salivary glands, as salivary gland‐related symptoms and taste disorders are highly prevalent in COVID‐19 patients.	Low
11	Moorthy A et al, 2021, Karnataka, India	Retrospective observational study	18 (15 M, 3 F)	35–73 years with a mean age of 54.6 years.	Hospitalised	Facial cellulitis, maxillary sinusitis, headache, necrosis of palatal bone/mucosa or acute loss of vision	The fungi noted was mucormycosis in 16 patients, aspergillosis in 1 patient and a mixed fungal infection in 1 patient.	During COVID‐19 infection	Physical extraoral and intraoral examination	There is a significant increase in the incidence of angioinvasive maxillofacial fungal infections in diabetic patients treated for SARS‐CoV‐2 with a strong association with corticosteroid administration.	Low
12	Bardellini E et al, 2021, Italy	Retrospective cross‐sectional study	27 children	4.2 years + 1.7)	Non‐hospitalised	Fever, cough, cutaneous flat papular lesions	Oral pseudomembranous candidiasis (7.4%), geographic tongue (3.7%), coated tongue (7.4%) and hyperaemic pharynx (37%). Taste alteration was reported by 3 patients.	During COVID‐19 infection	Medical records reviewed	As for paediatric sample, COVID‐19 resulted to be associated with non‐specific oral and cutaneous manifestations. There are no specific oral manifestations in children during a COVID‐19 infection.	Moderate
13	Klein H et al, 2021, Israel	Observational study	103 (64 M, 39 F)	35 ± 12 years	Non‐hospitalised	Headache, fever, muscle aches, dry cough, lack of appetite, runny nose, sore throat, productive cough, fatigue, smell change, diarrhoea, vomiting/nausea, breathing difficulty	Taste change. Taste and smell changes were the longest lasting symptoms	During COVID‐19 infection and during recovery period	Questionnaire (phone interview)	Long‐lasting effects of mild COVID‐19 manifested in almost half of the participants reporting at least one unresolved symptom after 6 months.	Moderate
14	Katz J, 2021, Florida, USA	Cross sectional study	889 (385 M, 504 F)	Children<18 = 38 (4%)	Hospitalised	Not reported	Dry mouth (Sicca dry mouth and non‐sicca dry mouth) in 9 patients (1.01%)	During COVID‐19 infection	i2b2 data repository platform of university of Florida health centre	Dry mouth related to Sicca and not related to Sicca are strongly associated with COVID‐19. The causes for this are not clear and may include autoimmunity & comorbidities.	Low
				Adults>18 = 851 (96%)
15	Villaroel‐Dorrego M et al, 2021, Spain	Observational study	55 (25 F and 30 M)	1–89 years, mean 51 ± 23.24 years	Hospitalised (19 in ICU)	Confirmed COVID‐19 cases (clinical manifestations not reported)	Candidiasis and ulcers (7 each), enanthems (2 pts.), geographic tongue and caviar tongue. Altered taste, dry mouth, and painful/burning mouth were noted in 60%, 27.3%, and 36.4% of patients, respectively. Oral mucosal alterations and lesions were prevalent in this series of COVID‐19 patients. Altered taste and a painful/burning mouth were common symptoms.	During COVID‐19 infection	Clinical examination of the lesions with findings recorded in a database	Ulcers were the most commonly observed lesions and included both haemorrhagic and aphthous‐like lesions. Both dysgeusia and oral pain or burning were common in patients with mucosal lesions (68.2% and 77.3%, respectively). In 22 patients (40%) at least one alteration or lesion was observed in the oral mucosa	Moderate
16	Katz J, 2021, USA	Cross sectional study	889	Not reported	Hospitalised	Not reported	Candidiasis only assessed.	During COVID‐19 infection	i2b2 data repository platform was used to analyse the interrelations between COVID‐19, oral candidiasis, and total candidiasis	Total candidiasis was significantly associated with increased risk for COVID‐19, whereas oral candidiasis showed an insignificant trend. COVID‐19 may be a risk factor for total candidiasis.	Low
17	Subramaniam T et al, 2021, Pune India	Observational study	713 patients, 416 M, 297 F	12–80 years	Hospitalised	Not reported	9 patients reported oral discomfort due to varied forms of oral lesions ranging from herpes simplex ulcers to angular cheilitis (1.26%).	During COVID‐19 infection	Photographs taken of the lesions from a camera, assessed by specialists.	No specific pattern or characteristic oral lesions were noted in a study of 713 COVID‐positive patients in this study to qualify these lesions as oral manifestations of SARS‐CoV‐2 infection.	Low
18	Freni F et al, 2020, Italy	Observational study	50 (30 M, 20 F)	37.7 ± 17.9	Non‐ hospitalised	Confirmed COVID‐19 cases	Xerostomia, difficult in swallowing food	During COVID‐ 19 infection	Questionnaire based survey	There was an alteration of the sense of taste, of the sense of smell, dry eyes and of the oral cavity and an auditory discomfort, symptoms probably linked to the neurotropism of the virus	Low
19	Omezli MM and Torul D, 2021, Ordu, Turkey	Observational study	107 (56 M, 51 F)	17–65 Y F, 13–70 Y M	Non‐ hospitalised	Confirmed COVID‐19 cases	Xerostomia, burning mouth, pain on chewing	After recovering from COVID‐ 19 infection	Questionnaire based survey	The most frequent finding in patients after the treatment was xerostomia. Taste and smell impairments were more frequently observed in females.	Low
20	D Giacomo P et al, 2021, Rome, Italy	Observational study	214	Not reported	Non hospitalised	Psychological impact of COVID‐19 pandemic on subjects with TMD	Temporomandibular disorders (TMD)	During COVID 19 pandemic	Questionnaire based survey	Awake and sleep bruxism, dental grinding, alteration in the quality and quantity of sleep and fatigue increased	Low
21	Colonna A et al, 2021, Ferrarra, Italy	Observational study	506	Not reported	Non hospitalised	Psychological status, bruxism in TMD reported individuals	Increase in symptoms of TMD	During COVID 19 pandemic	Online survey	36% and 32.2% of participants reported increased pain in the TMJ and facial muscles, respectively, and almost 50% of the subjects also reported more frequent migraines and/or headaches	Low

Abbreviation: TMJ, temporomandibular joint.