Alteration of the kynurenine pathway is inversely associated with the humoral immune response in patients with SARS-CoV-2.

BACKGROUND: The scale and the course of antibody production in patients with SARS-CoV-2 is highly variable. Factors involved in the immune regulation during the infection may play a major role in the antibody response. We investigated the relationship between the inflammatory markers of the kynurenine pathway and the concentration of antibodies against SARS-CoV-2 in infected patients 8 - 11 days after admission. METHODS: The study included 72 SARS-CoV-2 - positive inpatients hospitalized between August 2020 and April 2021. The plasma concentrations of tryptophan, kynurenine, anti-SARS-CoV-2 antibodies and the leucocyte count were measured 8 - 11 days after admission. The kynurenine/tryptophan ratio (KYN/TRP ratio) was calculated. Tertiles based on the values for tryptophan, kynurenine, KYN/TRP ratio and the leucocytes were generated. RESULTS: Statistically significant correlations were observed between anti-SARS-CoV-2 antibodies and tryptophan, kynurenine, KYN/TRP ratio and the leucocytes (p-values < 0.001-0.007). The high kynurenine and KYN/TRP ratio tertiles showed significantly lower antibody titers compared to the low tertiles (p-values 0.017 and < 0.001). The low tryptophan and leucocytes tertiles showed significantly lower antibody titers compared to the high tertiles (p-values 0.001 and 0.008). CONCLUSION: Patients with higher activation levels of the kynurenine pathway tended to develop lower anti-SARS-CoV-2 antibody titers.

A biopsychosocial model of severe fear of COVID-19.

INTRODUCTION: COVID-19 is a respiratory infection that causes not only somatic health issues, but also frequently psychosocial burdens. The aims of this study were to investigate biopsychosocial factors that might further aggravate fear of COVID-19, and to establish a biopsychosocial model of severe fear of COVID-19. METHODS: 368 participants were included in this study. Biopsychosocial factors observed comprised biological factors (somatic risk), psychological factors (state/trait anxiety, physical symptoms of anxiety, severe health anxiety, specific phobias, depression), and psychosocial factors (social support, financial losses, social media consumption, social contacts with COVID-19 infected people). Psychometric questionnaires included State-Trait Anxiety Inventory, Beck's Anxiety Inventory, Whiteley-Index / Illness Attitude Scales, Specific Phobia Questionnaire, WHO-5 and Social Support Survey. RESULTS: 162/368 (44.0%) participants had almost no fear, 170/368 (46.2%) participants had moderate fear, and 45/368 (12.2%) participants had severe fear of COVID-19. Female participants showed higher levels of fear of COVID-19 than male participants (gender: χ2 = 18.47, p<0.001). However, the level of fear of COVID-19 increased in male participants when they had contact with people who were infected with COVID-19, while in contrast the level of fear of COVID-19 decreased in female participants when they had such contacts [ANCOVA: fear of COVID-19 (contact x gender): F(1,363) = 5.596, p = .019]. Moreover, participants without relationships showed higher levels of fear of COVID-19 (marital status: χ2 = 14.582, p = 0.024). Furthermore, financial losses due to the COVID-19 were associated with higher levels of fear of COVID-19 [ANCOVA: fear of COVID-19(financial loss x gender): F(1, 363) = 22.853, p< .001]. Multiple regression analysis revealed female gender, severe health anxiety (WI-IAS) and state /trait anxiety (STAI) as significant predictors of severe fear of COVID-19. CONCLUSION: In this study significant predictors of severe fear of COVID-19 were female gender, pre-existing state and trait anxiety, as well as severe health anxiety. The finding of significant predictors of fear of COVID-19 might contribute to detect people who might suffer most from severe, overwhelming fear of COVID-19 at an early stage.

Assessment of tryptophan and kynurenine as prognostic markers in patients with SARS-CoV-2.

BACKGROUND: Immune dysregulation and inflammation in patients with SARS-CoV-2 is associated with a poor clinical outcome. We investigated the value of the inflammatory markers tryptophan and kynurenine in predicting the survival outcome of patients with SARS-CoV-2. METHODS: The study included 252 inpatients with a SARS-CoV-2 infection hospitalized between August 2020 and April 2021. Two groups were generated based on disease survival (survival group: n = 199; deceased group: n = 53). Plasma concentrations of tryptophan, kynurenine and interleukin-6 (IL-6) were measured on admission. In a subset of patients (n = 105; 81 survivors and 24 deceased) concentrations of tryptophan and kynurenine were checked 7 days after admission. The kynurenine/tryptophan ratio (TRP/KYN ratio) was calculated. RESULTS: On admission, the deceased group showed significantly higher concentrations of kynurenine and a significantly higher KYN/TRP ratio compared to the survival group (p-values < 0.001). Kynurenine and the KYN/TRP ratio significantly correlated with IL-6 (ρ = 0.441 and 0.448, p-values < 0.001). In the survival group, kynurenine and the KYN/TRPratio were significantly lower after seven days (p-values < 0.001). In the deceased group, no significant differences were found between the measurements. CONCLUSION: Kynurenine and the KYN/TRP ratio are potentially useful parameters in predicting the survival outcome in SARS-CoV-2 positive patients.