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Post-COVID-19 patients suffer from chemosensory, trigeminal, and salivary dysfunctions – Scientific Reports


Study design and participants

This cross-sectional, case-controlled study was conducted at the Institute of Clinical Dentistry (ICD), Faculty of Dentistry, University of Oslo (UiO), Norway, between October 2020 and June 2023. Patients from all parts of Norway are referred to the university clinic for treatment of persisting smell, taste and trigeminal dysfunction. The “Clinic of Smell, Taste and Oral Pain” has recently been established at the ICD, dedicated specifically to help post-COVID-19 patients. Information about our services was provided through Facebook, newspaper articles, radio programs, national news channel on television and clinical workshop and seminar for ENT-surgeons, neurologists, dentists, and family doctors. One hundred post-COVID-19 patients referred to ICD were consecutively recruited for participation in this study. Seventy-six pre-COVID-19, healthy controls were used to ascertain that controls were not asymptomatic COVID-19 patients. These pre-pandemic controls had undergone the same assessments as the post-COVID-19 patients and were enrolled in previous studies at the ICD47,48. The exclusion criteria for controls were oral dryness, and presence of chronic diseases or medications that could affect smell, taste, trigeminal and salivary functions. The study was approved by the Norwegian Regional Committee for Medical and Health Research Ethics (REK 2021/274615) and was performed in compliance with the tenets of the Declaration of Helsinki. Written informed consent was obtained from all participants. The participants were instructed to refrain from eating, drinking, and smoking one hour prior to examination. The assessments of olfaction, gustation, trigeminal, and salivary function were carried out according to the protocol described below.

The Oslo COVID-19 questionnaire

Participants’ medical history was obtained through standard health forms used at the university clinic at ICD. Post-COVID-19 patients then completed a questionnaire designed specifically for this study, called the Oslo COVID-19 questionnaire (Supplement). This questionnaire contained both binary, multiple choice and open-ended questions. In section “Introduction”, patients’ age, gender, occupational status, and use of tobacco was recorded. In section “Methods”, information about COVID-19 infection was obtained; date of diagnosis, mode of confirmation of diagnosis (PCR test, home test, antibody test or clinical symptoms), and course of illness (mild, moderate, or severe). Finally, time for onset of loss of smell and taste, burning sensation and oral dryness was recorded (number of days before or after the confirmation of COVID-19 infection). Possible aetiology of chemosensory, trigeminal and salivary dysfunctions was also recorded (other viral or bacterial infections, menopause, trauma in head and neck region, head and neck surgery, dental surgery). In section “Results”, more specific questions about parosmia, dysgeusia, dysesthesia, and oral dryness were recorded as described below. This questionnaire did not assess phantosmia or phantogeusia.

Olfactory assessment

Prior to objective olfactory testing, the participants were asked to score their smell perception on a linear visual analogue scale (VAS) from 0 to 10, where 0 indicated no smell perception and 10 very good smell perception. Score 5 was chosen as the cut-off point and scores 0– < 5 indicated low, 5– < 9 moderate, and 9–10 very good perception of smell, respectively. An Olfactory identification test was then performed using Sniffin’ Sticks test (Burghart Messtechnik GmbH, Holm, Germany). Twelve felt-tip odor pens were used for non-lateralized psychophysical testing of the olfactory function. The participants were informed about the procedure before the test started. The responses were recorded as either 1 = correct or 0 = incorrect and summated (score range 0–12). A normative classification49 was used to categorize participants into anosmic (score 0–6), hyposmic (score 7–10) and normosmic (score 11–12).

Gustatory assessment

Prior to objective gustatory testing, the participants were asked to score their taste perception on a VAS from 0 to 10, where 0 indicated no taste perception and 10 very good taste perception. Score 5 was chosen as the cut-off point where scores 0– < 5 indicated low, 5– < 9 moderate, and 9–10 very good perception of taste, respectively.

Gustatory function was then measured using Taste Strips impregnated with solutions in four different concentrations of four different taste qualities: sweet, sour, salty and bitter (Burghart Messtechnik GmbH, Holm, Germany). The responses were recorded as either 1 = correct, or 0 = incorrect, and summated (score range 0–16). Participants were classified into ageusic (score 0), hypogeusic (score 1–8) and normogeusic (score 9–16) using a normative classification50. Participants were considered to have a specific ageusia if they were unable to detect all four different concentrations of one specific tastant.

Assessment of self-reported parosmia, dysgeusia, dysesthesia and xerostomia

The categorization of parosmia was based on results from the questionnaire, where participants had either no parosmia (score 0), or parosmia (score 1). Further, if they had parosmia they were asked to describe how often they experienced parosmia: constantly, daily, sometimes, during meals, in between meals, or only when in contact with certain odorants. They were also asked to report which smells that were distorted from a list of 35 odors, as well as describe the character of the distortion.

Similarly, absence or presence of dysgeusia was categorized as follows: no dysgeusia (score 0), or dysgeusia (score 1). Participants with dysgeusia were asked how often they experienced dysgeusia (constantly, daily, sometimes, periodically, during meals, in between meals), and to describe the character of dysgeusia (metallic, rotten, harsh, salty, bitter, other).

Dysesthesia was categorized as either no dysesthesia (score 0), or dysesthesia (score 1). Participants reported how often they experienced dysesthesia (constantly, daily, sometimes, periodically, during meals, in between meals), asked to describe where in the mouth they experienced dysesthesia (whole tongue, anterior tongue, lips, palate, buccal mucosa, other), and identify food items that enhanced the dysesthesia (spicy, sweet, sour, salty, bitter).

Xerostomia was categorized according to participants’ self-reported perception as either no dry mouth (score 0), or dry mouth (score 1). Participants were asked whether the symptoms of xerostomia started before or after COVID-19 infection and were asked open-ended questions where they could describe their experience of oral dryness. Finally, they were asked to report whether there were food items that they had to refrain from eating because of parosmia, dysgeusia, dysesthesia or xerostomia.

Statistical analyses

The statistical analyses were performed using SPSS (SPSS Statistics version 28.0, IBM, Armonk, NY, USA), and Excel (Microsoft Excel version 2302, Microsoft, Redmond, Washington, USA). The results of descriptive analyses were presented as percentages, histograms and median/interquartile range (IQR)/range. Chi-square (χ2) or Fisher’s exact test were used to compare categorical variables and determine dependence between variables. A non-parametric test, Mann–Whitney U, was used to describe median differences between the groups in case of non-normal distribution. Pearson’s correlation coefficient (r) was used to measure the strength and direction of linear relationships between pairs. Statistical significance was considered at p < 0.05.



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