Interferon-gamma Mediated Metabolic Pathways in Hospitalized Patients During Acute and Reconvalescent COVID-19

Mario Gietl; Francesco Burkert; Stefanie Seiwald; Anna Böhm; Stefanie Hofer; Johanna M Gostner; Talia Piater; Simon Geisler; Guenter Weiss; Judith Loeffler-Ragg; Thomas Sonnweber; Ivan Tancevski; Alex Pizzini; Sabina Sahanic; Dietmar Fuchs; Rosa Bellmann-Weiler; Katharina Kurz

doi:10.1177/11786469231154244

Interferon-gamma Mediated Metabolic Pathways in Hospitalized Patients During Acute and Reconvalescent COVID-19

Int J Tryptophan Res. 2023 Feb 13:16:11786469231154244. doi: 10.1177/11786469231154244. eCollection 2023.

Authors

Mario Gietl¹, Francesco Burkert¹, Stefanie Seiwald¹, Anna Böhm¹, Stefanie Hofer¹, Johanna M Gostner¹, Talia Piater¹, Simon Geisler¹, Guenter Weiss¹, Judith Loeffler-Ragg¹, Thomas Sonnweber¹, Ivan Tancevski¹, Alex Pizzini¹, Sabina Sahanic¹, Dietmar Fuchs¹, Rosa Bellmann-Weiler¹, Katharina Kurz¹

Affiliation

¹ Department of Internal Medicine II, Medical University Innsbruck, Biocentre, Medical Biochemistry, Innsbruck, Austria.

Abstract

Background: Fatigue, sleep disturbance, and neurological symptoms during and after COVID-19 are common and might be associated with inflammation-induced changes in tryptophan (Trp) and phenylalanine (Phe) metabolism.

Aim: This pilot study investigated interferon gamma inducible biochemical pathways (namely Trp catabolism, neopterin, tyrosine [Tyr], and nitrite formation) during acute COVID-19 and reconvalescence.

Patients and methods: Thirty one patients with moderate to severe COVID-19 admitted to the University Hospital of Innsbruck in early 2020 (March-May) were followed up. Neurotransmitter precursors Trp, Phe, Tyr as well as kynurenine (Kyn), neopterin, nitrite, and routine laboratory parameters were analyzed during acute infection and at a follow-up (FU) 60 days thereafter. Clinical symptoms of patients (neurological symptoms, fatigue, sleep disturbance) were recorded and associations with concentrations of laboratory parameters investigated.

Results and conclusion: Almost half of the patients suffered from neurological symptoms (48.4%), the majority of patients experienced sleep difficulties (56.7%) during acute COVID-19. Fatigue was present in nearly all patients. C-reactive protein (CRP), interleukin-6 (IL-6), neopterin, Kyn, Phe concentrations were significantly increased, and Trp levels depleted during acute COVID-19. Patients with sleep impairment and neurological symptoms during acute illness presented with increased CRP and IL-6 concentrations, Trp levels were lower in patients with sleep disturbance. In general, inflammatory markers declined during reconvalescence. A high percentage of patients suffered from persistent symptoms at FU (neurological symptoms: 17.2%, fatigue: 51.7%, sleeping disturbance: 34.5%) and had higher CRP concentrations. Nitrite and Phe levels were lower in patients with sleeping difficulties at FU and Kyn/Trp ratio, as indicator of IDO activity, was significantly lower in patients with neurological symptoms compared to patients without them at FU. In summary, inflammation induced alterations of amino acid metabolism might be related to acute and persisting symptoms of COVID-19.

Keywords: COVID-19; IDO; Long Covid; interferon-gamma; neopterin; phenylalanine; tryptophan.