Plasma taurine level is linked to symptom burden and clinical outcomes in post-COVID condition

Abstract

Background: A subset of individuals (10-20%) experience post-COVID condition (PCC) subsequent to initial SARS-CoV-2 infection, which lacks effective treatment. PCC carries a substantial global burden associated with negative economic and health impacts. This study aims to evaluate the association between plasma taurine levels with self-reported symptoms and adverse clinical outcomes in patients with PCC.

Methods and findings: We analyzed the plasma proteome and metabolome of 117 individuals during their acute COVID-19 hospitalization and at the convalescence phase six-month post infection. Findings were compared with 28 age and sex-matched healthy controls. Plasma taurine levels were negatively associated with PCC symptoms and correlated with markers of inflammation, tryptophan metabolism, and gut dysbiosis. Stratifying patients based on the trajectories of plasma taurine levels during six-month follow-up revealed a significant association with adverse clinical events. Increase in taurine levels during the transition to convalescence were associated with a reduction in adverse events independent of comorbidities and acute COVID-19 severity. In a multivariate analysis, increased plasma taurine level between acute and convalescence phase was associated with marked protection from adverse clinical events with a hazard ratio of 0.13 (95% CI: 0.05-0.35; p<0.001).

Conclusions: Taurine emerges as a promising predictive biomarker and potential therapeutic target in PCC. Taurine supplementation has already demonstrated clinical benefits in various diseases and warrants exploration in large-scale clinical trials for alleviating PCC.

Fig 1. Taurine in acute and convalescence phase of SARS-CoV-2 infection.

(A) Schematic of study design. (B) Differentially expressed metabolites between convalescence samples with age and sex-matched healthy controls. (C) Box and whisker plot showing taurine levels between cohorts. Mann-Whitney U test with Benjamini-Hochberg correction was performed for pairwise comparison. (D) Schematic representation of taurine mediated effects on various pathways and physiological processes. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.

Fig 2. Taurine correlates with biomarkers of inflammation and gut dysbiosis.

Scatter plots show the correlations between plasma taurine levels and plasma CRP (A), IL10 (B), IL6 (C), tryptophan (D), serotonin (E), quinolinic acid (F), TMAO (G), phenylacetic acid (H), and LBP (I) levels. CRP, C-reactive protein; IL10, Interleukin 10; IL6, Interleukin 6; TMAO, Trimethylamine N-oxide; LBP, Lipopolysaccharide binding protein.

Fig 3. Analysis of plasma taurine levels in the convalescence phase following SARS-CoV-2 infection.

(A) Heatmap showing the top five molecules with the most significant p values between patients with and without adverse events based on analysis of variance (ANOVA). (B) Box and whisker plot showing the level of taurine in event-free and with-event individuals. Mann-Whitney U test with Benjamini-Hochberg correction performed for pairwise comparison. (C) Paired box and whisker plots illustrating the trajectory of change in plasma taurine level from acute to convalescence phase in individual patients. Paired Wilcoxon signed-rank test was performed for pairwise comparison. (D) Heatmap showing the association between taurine levels with self-reported symptoms in the convalescence phase (OR: odds ratio) adjusted for clinical variables such as age, sex, diabetes, CKD, acute COVID-19 treatment (dexamethasone, antibiotics, tocilizumab, remdesivir), WHO Ordinal Scale for acute COVID-19 severity, and SARS-CoV-2 vaccination status. (E) Box and whisker plot illustrating taurine levels amongst PCC severity groups (severe: >3 symptoms, mild: ≦3 symptoms, recovered: no PCC symptoms). Mann-Whitney U test with Benjamini-Hochberg correction performed for pairwise comparison. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.

Fig 4. Relationship between temporal changes in plasma taurine and adverse clinical outcomes.

(A) Paired box and whisker plots illustrating the trajectory of plasma taurine level from acute to convalescence phase. Paired Wilcoxon signed-rank test was performed for pairwise comparison. (B) Association between the trajectory of plasma taurine levels with adverse clinical outcomes (all-cause mortality and re-hospitalization) following discharge from acute COVID-19 hospitalization. Log-rank p = 0.0066. (C) Stack bar plot showing the proportion of event-free and with-event individuals between patients with either reduced or increased taurine levels from acute to convalescence phase. Chi-square test. P = 0.02. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.

Fig 5. Multivariate analysis of predictive factors for adverse clinical outcome.

Forest plot showing the adjusted hazard ratios, confidence intervals, and p values for plasma taurine level along with other variables such as age, sex, diabetes, CKD, acute COVID-19 treatment (dexamethasone, antibiotics, tocilizumab, remdesivir), WHO Ordinal Scale for acute COVID-19 severity, and SARS-CoV-2 vaccination status.

Fig 6. Plasma taurine alteration and correlations with biomarkers in PCC patients with diabetes.

(A) Box and whisker plot illustrating the level of taurine in PCC patients with and without diabetes during the convalescence phase compared with healthy controls. Mann-Whitney U test with Benjamini-Hochberg correction was performed for pairwise comparison. (B-H) Scatter plots showing the correlations between plasma taurine levels with IL-4 (B), IL-13 (C), antithrombin III (D), peroxiredoxin I (E), APOA-I (F), creatine (G), and quinolinic acid (H) in PCC patients with diabetes. IL-4, Interleukin-4; IL-13, Interleukin-13; APOA-I, apolipoprotein A1. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.