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

## TL;DR

The study suggests that quinolinic acid and the kynurenine-to-tryptophan ratio could be biomarkers for smell and taste loss in acute COVID-19, and vaccination may help prevent these symptoms.

## Contribution

The study identifies serum quinolinic acid and Kyn–Trp ratio as potential biomarkers for dysosmia/dysgeusia in acute COVID-19.

## Key findings

- Group A (with dysosmia/dysgeusia) had significantly lower tryptophan levels and higher Kyn–Trp ratio and quinolinic acid levels.
- Dysosmia was significantly correlated with non-vaccination status, while dysgeusia was not.
- Serum KTR and QUIN levels may serve as useful biomarkers for assessing dysgeusia/dysosmia in acute COVID-19.

## Abstract

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.

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.

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.

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.

•Neurological signs with COVID-19 may be due to neuromediator imbalance.•COVID-19 patients stratified by presence/absence of dysgeusia/dysosmia were tested.•Serum Kyn-Trp ratio & QUIN levels are potent biomarkers of dysgeusia/dysosmia.•Targeting kynurenine pathway is a promising strategy to manage dysosmia/dysgeusia.•Vaccination could serve as an effective measure for preventing dysosmia.

Neurological signs with COVID-19 may be due to neuromediator imbalance.

COVID-19 patients stratified by presence/absence of dysgeusia/dysosmia were tested.

Serum Kyn-Trp ratio & QUIN levels are potent biomarkers of dysgeusia/dysosmia.

Targeting kynurenine pathway is a promising strategy to manage dysosmia/dysgeusia.

Vaccination could serve as an effective measure for preventing dysosmia.