Quinolinic acid as trigger/biomarker of dysosmia/dysgeusia in patients with acute coronavirus disease 2019: A retrospective case-control study

Background: Impaired smell/taste sensation (dysosmia/dysgeusia) are common manifestations of coronavirus disease 2019 (COVID-19). Scattered peripheral chemoreceptors and directly innervating central nerves from the brain to the receptors are responsible systems for perception in the human body. The shared neurotransmitter serotonin (5-HT) and neuroimmune modulators of the kynurenine (Kyn) pathway (KP) are metabolites derived from tryptophan (Trp). The synthesis of KP metabolites is initiated by the rate-limiting enzymes indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can activate Trp metabolism. Therefore, we investigated whether serum metabolites of Trp and IDO/TDO activity could serve as biomarkers for assessing smell/taste impairment (dysosmia/dysgeusia) in patients during the acute phase of COVID-19. Methods: We conducted a retrospective case-control study. Among patients admitted with acute COVID-19 to our hospital between September 13, 2021, and September 30, 2023, those whose chief complaints included dysosmia/dysgeusia at admission were identified. These symptoms were confirmed by the attending physician for COVID-19. Patients were stratified based on the presence or absence of dysosmia and/or dysgeusia.In both patient groups, serum concentrations of Trp, 5-HT, Kyn, kynurenic acid (KYNA), and quinolinic acid (QUIN) were measured using enzyme-linked immunosorbent assay. IDO/TDO activity was expressed as Kyn–Trp ratio (KTR). The relationships between these biomarkers and dysosmia/dysgeusia, as well as other clinical parameters and outcomes, were evaluated. Results: Of 520 patients admitted with COVID-19, 95 met the inclusion and exclusion criteria. Among them, 26 patients with dysosmia/dysgeusia (group A) and 26 patients without these symptoms (group B) were analyzed. No significant intergroup difference was observed in the average timepoint at blood sampling after COVID-19 onset (post-day from onset: pdo) (4.69 ± 2.51 days in group A vs. 3.62 ± 2.22 in group B). Group A showed significantly lower Trp levels [median 9.70 μg/mL (range 4.59–13.89) vs. 10.40 (7.52–13.34), p = 0.031], and higher KTR [61.34 (40.47–384.2) vs. 53.52 (26.13–86.64), p < 0.037] and QUIN levels [574.39 nM (100.39–11909) vs. 443.65 (83.09–998.3), p < 0.0169]. No significant differences were observed in 5-HT or KYNA levels between groups. Almost all cases of dysosmia involved anosmia/hyposmia and were significantly correlated with non-vaccination status with mRNA vaccine (p = 0.017). In contrast, dysgeusia exhibited heterogeneous manifestations, primarily ageusia or hypogeusia, followed by hypersensitivity to salty taste, and was not correlated with vaccination status. Conclusion: Clinically, serum KTR and QUIN levels may serve as useful biomarkers for assessing dysgeusia/dysomia during acute COVID-19. Furthermore, vaccination may play an important preventive role, particularly against dysosmia.