Concentrations of Uremic Bacterial Metabolites in Patients with Post-COVID-19 Syndrome

Natascha Brigo ^1* Wolfram Mayr ¹ Maja Taenzer ¹ Judith Löffler-Ragg ¹ Andrea Schroll ¹ Sabine Engl ¹ Burkhard Schütz ² Peter Rappl ² Till Heine ² Guenter Weiss ¹ Katharina Kurz ^1*

• ¹ Department of Internal Medicine II, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria, Innsbruck, Austria
• ² Biovis Diagnostik, Limburg, Germany, Limburg, Germany

Post-COVID-19 syndrome (PCS) is marked by persistent symptoms and reduced mental and physical performance after the acute phase of COVID-19. The mechanisms behind PCS are unclear but may involve gut microbiota dysbiosis and immune-related changes in amino acid metabolism.This pilot study examined bacterial uremic metabolites (BUM) in 25 PCS patients, 8 Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients, and 8 healthy controls (Ctrls). Concentrations of BUM were determined in the second morning urine by mass spectrometry (Biovis Diagnostik, Limburg, Germany). Questionnaires assessed physical, cognitive, psychological, and somatic symptoms, along with mental health. The aim of the study was to investigate, whether specific BUM are altered in patients with post-infectious syndromes and whether these are associated with PCS symptoms.PCS and ME/CFS patients presented with significantly higher scores for post-exertional malaise (PEM) and somatic symptom severity compared to Ctrls (p<0.001). Elevated BUM concentrations were found in 64% PCS patients, compared to 37.5% of healthy Ctrls and ME/CFS patients (3 of 8 patients). While overall BUM levels were not significantly different between groups, heatmap clustering revealed distinct metabolic patterns. Elevated tryptamine and 4-hydroxyphenylpropionic acid (HPHPA), as well as higher hippuric acid and trimethylamine concentrations, were only found in patients with post-infectious syndromes. Our pilot study suggests that altered amino acid metabolism is frequently found in PCS and associated with symptoms. This may be a consequence of subclinical inflammation and/or gut dysbiosis. Determination of specific metabolites may be helpful in the diagnosis of PCS and provide hints for potential targeted therapy.