The present study is a sub-analysis of a broader investigation focused on the pathophysiology of long COVID-19, approved by the ethics committee of the European University of Madrid (Internal code CIPI/20/207). All patients provided informed consent to participate prior to inclusion.
The definition of the study groups was as follows:
1. Case group: subjects diagnosed with long COVID-19. Sixty-three subjects, all adults, belonging to the Long Covid ACTS association of the Community of Madrid were recruited. None had active infection or severe systemic diseases in cases where examination is not recommended due to the life-threatening risk to the patient (ASA IV and V).
2. Control group: subjects who had experienced infection with the SARS-CoV-2 virus and either did not present with symptoms associated or whose symptoms resolved upon remission of the infection. Thirty-nine volunteer subjects were recruited via a social media campaign who met the inclusion criteria: over 18 years of age, from the Community of Madrid, and who had experienced the infection without sequelae.
The study was divided into two phases. In the first phase, the recruitment of the sample for both study groups was conducted, from September to November 2021. In the second phase, an oral examination and clinical interview of the subjects were performed.
This second phase was conducted at the University Dental Clinic of the European University of Madrid between November 2021 and April 2022. Before the clinical appointment, each patient completed a 20-item questionnaire covering demographic data, stress factors before and after infection, general health, and aspects related to SARS-CoV-2 infection. At the clinic, a full medical history and oral examination were performed, which included:
• Extraoral examination for the collection of data on pathologies and/or abnormalities such as tumours, cellulitis, adenopathies, cutaneous lesions, and asymmetries located in the head and neck regions.
• Assessment of temporomandibular joint (TMJ) status: degree of mouth opening, presence of articular clicks, deviation, and presence of pain on palpation during mouth opening and closure.
• Intraoral examination for the detection of soft tissue alterations (lips, buccal mucosa, tongue, floor of the mouth, retromolar region, palate, gingiva, and pharynx), evaluation of oral hygiene status (OHI-S index), recording of the number of carious lesions, obfillings, absences, fractures, root remnants, crowns, bridges, removable prostheses, as well as calculation of the DMFT and DMFM indices. Finally, periodontal status was assessed (probing depth, recessions, attachment loss, tooth mobility, furcation involvement) and the Community Periodontal Index of Treatment Needs (CPITN) was calculated.

Statistical analysis
For the descriptive study, relative frequencies were calculated for qualitative variables and, for quantitative variables, the mean and standard deviation were calculated.
In cases where the quantitative variables followed a normal distribution and were categorised by qualitative variables, parametric tests were performed. For variables with two categories, the Student’s t-test was performed; if the variable had three or more categories, Levene’s test for homogeneity of variances was conducted prior to ANOVA.
For those without a normal distribution, non-parametric tests were performed: the Mann-Whitney U test for variables with two categories, and the Kruskal-Wallis test for those with three or more.
Additionally, Pearson’s Chi-square test was applied in cases where the independence between two qualitative variables was analysed. Similarly, in these tests of independence, when the p-value is significant (p<0.05), we can accept the hypothesis with 95% confidence that there is a statistically significant difference in the mean value of the variable between the different groups.
All statistical tests were conducted with a 95% confidence level, and version 26 of the IBM SPSS statistical software was utilised.

The study was conducted on a total of 102 subjects, of whom 20 were men (20%) and 82 were women (80%), with ages ranging from 23 to 68 years.

By study group, there was a higher proportion of subjects in the mild COVID group within the 26 to 45 years age range. However, in the long COVID group, there was a greater number of subjects within the age range of 36 to 65 years.

To analyse the level of oral health in subjects with long COVID, 34 related variables were examined. Of all these oral health markers explored both extraorally and intraorally, and subsequently analysed according to the study group, the following were observed to a greater extent and with high statistical significance in the long COVID group (Table):

Stress was identified as one of the most influential factors in oral health. As shown in Figure 11, mild COVID subjects with a higher current subjective stress level (7 ± 1.48) also exhibited greater pharyngeal irritation compared to those with a lower stress level (5.11 ± 2.69) and consequently an unaltered pharynx, this difference being statistically significant.

However, this did not occur in subjects with long COVID because, although they exhibited higher levels of stress, the differences observed in pharyngeal irritation were attributable to chance.

Conversely, it is the long COVID study subjects with higher levels of stress (7.73 ± 2.02) who experienced greater xerostomia compared to those with lower levels (5.63 ± 2.73), this difference being significant according to the Mann-Whitney U statistic (p<0.01) (Figure 12).

Among the possible systemic conditions caused by the SARS-CoV-2 virus, it is necessary to analyse in depth its impact on the oral cavity. COVID-19 infection may give rise to various oral manifestations, primarily at the mucosal level. In the present study, it was observed that the number of dental symptoms—such as periodontal and peri-implant involvement, the presence of aphthae, mucosal irritation due to outbreaks, halitosis, dentine hypersensitivity, or the presence of caries—was higher in subjects belonging to the long COVID group. A possible explanation for this set of manifestations may be posited given that the oral cavity forms part of the upper respiratory tract and represents one of the potential direct routes for the entry of the SARS-CoV-2 virus, owing to the presence of ACE2 receptors in the oral mucosa and in the epithelial cells of the salivary glands¹⁶.

It should be emphasised that individuals who exhibited persistent systemic symptoms related to COVID-19 also presented certain oral manifestations, such as the presence of adenopathies, the subjective sensation of dry mouth (xerostomia), pharyngeal irritation, and temporomandibular joint pain as a consequence of bruxism. Of these, the presence of adenopathies, xerostomia, and mucosal irritation at the pharyngeal level are clinical manifestations that are likewise observed in certain autoimmune pathologies, such as Sjögren’s syndrome, rheumatoid arthritis, systemic lupus erythematosus, type I diabetes, or multiple sclerosis, among others¹⁷. This raises the possibility of an autoimmune nature for long COVID.

In the case of pain experienced at the level of the temporomandibular joint, generated by dental clenching, predominantly nocturnal, it may be closely related to the level of stress currently perceived by individuals with long COVID, largely due to their complex medical condition¹⁸.

Moreover, during the lockdown, dental clinics suspended their activities, limiting dental care solely to specific dental emergencies and, as far as possible, avoiding clinical treatments that generated aerosols¹⁹. This reduction in dental care, home confinement as a social distancing measure, the socio-economic crisis experienced, increased levels of stress, as well as anxious-depressive symptoms, together with the pathophysiological situation in which individuals with long COVID found themselves, complicated such a routine act as daily oral hygiene through tooth brushing and frequent visits to the dentist. This may account for the significant deterioration in oral health status observed in patients with long COVID, as evidenced by a higher number of restorations, missing teeth, crowns, and caries index in comparison with those with mild COVID.

Among the limitations, the biases of our study arise from the selection of cases from a single patient association, which hinders the extrapolation of the results. The imbalance between the number of cases and controls is also recognised, which was addressed through a multivariate analysis to adjust for variables that could affect the confidence level of the results. Robust studies are required to develop follow-up and control protocols at the onset of the disease, in order to evaluate the factors involved in resolution without sequelae or, conversely, in progression to long COVID.

Accordingly, the advancement of clinical practice in dentistry necessitates the promotion of research strategies that enable the expansion of our understanding of long COVID and its early diagnosis, as well as its prevention, potentially within the remit of dental professionals.

Individuals affected by long COVID demonstrate various related oral manifestations, some of which are attributable to the oral cavity serving as an entry route for the virus, such as mucosal irritation or the presence of aphthae; others to the possible autoimmune nature of this new syndrome, such as xerostomia or the presence of adenopathies, and, finally, other manifestations may be associated with stress, such as the presence of TMJ pain, indicative of bruxism.