Anxiety due to Long COVID is partially driven by activation of the tryptophan catabolite (TRYCAT) pathway

Abstract This study examines whether activation of the tryptophan catabolite (TRYCAT) pathway is associated with anxiety symptoms due to Long COVID. We selected 90 participants, 60 Long COVID patients and 30 individuals without any symptoms following acute CIVID-19 infection. Using cluster analysis and the Hamilton Anxiety Rating scale (HAMA) score, the pure HAMA anxiety score, serum tryptophan (TRP) and kynurenine (KYN), the KYN/TRP ratio (all measured during Long COVID), and oxygen saturation (SpO2) (measured during the acute phase of COVID-19), we were able to classify Long COVID patients into two distinct clusters with an adequate silhouette cohesion and separation index (0.58): cluster 1 (n=61) and cluster 2 (n=29). Cluster 2 patients had lower SpO2 and TRP levels, as well as higher KYN, KYN/TRP ratio, and HAMA scores than cluster 1. Regression analysis revealed that the KYN/TRP ratio explained 14.4% of the variance in the HAMA score (F=14.81, df=1/88, p=0.001). In addition, regression analysis revealed that SpO2 partially explained the variance in serum TRP (r=0.396, p=0.005), KYN/TRP ratio (r=-0.248, p=0.018), and the HAMA score (r=-0.279, p=0.008). The current data imply that decreased SpO2 during the acute phase of COVID-19 infection is predictive of anxiety caused by Long COVID. Our data reveal that around 32% of Long COVID patients have elevated IDO activity in association with elevated anxiety.