Persistent Symptoms and IFN-γ-Mediated Pathways after COVID-19.
Study Design
- अध्ययन प्रकार
- Cross-sectional
- नमूना आकार
- 142
- हस्तक्षेप
- Persistent Symptoms and IFN-γ-Mediated Pathways after COVID-19. None
- तुलनित्र
- Placebo
- प्रभाव की दिशा
- Mixed
- पूर्वाग्रह का जोखिम
- Moderate
Abstract
After COVID-19, patients have reported various complaints such as fatigue, neurological symptoms, and insomnia. Immune-mediated changes in amino acid metabolism might contribute to the development of these symptoms. Patients who had had acute, PCR-confirmed COVID-19 infection about 60 days earlier were recruited within the scope of the prospective CovILD study. We determined the inflammatory parameters and alterations in tryptophan and phenylalanine metabolism in 142 patients cross-sectionally. Symptom persistence (pain, gastrointestinal symptoms, anosmia, sleep disturbance, and neurological symptoms) and patients' physical levels of functioning were recorded. Symptoms improved in many patients after acute COVID-19 (n = 73, 51.4%). Still, a high percentage of patients had complaints, and women were affected more often. In many patients, ongoing immune activation (as indicated by high neopterin and CRP concentrations) and enhanced tryptophan catabolism were found. A higher phenylalanine to tyrosine ratio (Phe/Tyr) was found in women with a lower level of functioning. Patients who reported improvements in pain had lower Phe/Tyr ratios, while patients with improved gastrointestinal symptoms presented with higher tryptophan and kynurenine values. Our results suggest that women have persistent symptoms after COVID-19 more often than men. In addition, the physical level of functioning and the improvements in certain symptoms appear to be associated with immune-mediated changes in amino acid metabolism.
Full Text
Figures
Figure 1
Study design or participant characteristics for the investigation of persistent symptoms and IFN-gamma-mediated metabolic pathways following COVID-19 infection.
diagram
Figure 2
Comparison of amino acid metabolism markers between post-COVID patients with persistent symptoms and recovered controls, suggesting alterations in IFN-gamma-mediated pathways.
chart
Figure 3
Analysis of inflammatory or tryptophan-kynurenine pathway metabolites in post-COVID participants, indicating associations with fatigue, neurological symptoms, or insomnia.
chart
Figure 4
Correlation or pathway analysis linking IFN-gamma-driven immune changes to persistent post-COVID symptoms including fatigue and insomnia.
diagramTables
Table 1
| Gender [f/m] | |||||
|---|---|---|---|---|---|
| Female ( | Male ( | ||||
| Laboratory Values | Mean (SEM) | Mean (SEM) | Reference Value | ||
| Neopterin 1 (nM/L) | 11.9 (0.5) | 11.7 (0.7) | 12.2 (0.7) | 5.9 ± 1.6 | n.s. |
| Nitrite 1 (µM/L) | 36.1 (2.6) | 36.7 (4.1) | 35.5 (3.3) | 44.9 ± 32.0 | n.s. |
| Kynurenine 1 (µM/L) | 2.56 (0.07) | 2.47 (0.08) | 2.64 (0.10) | 1.78 ± 0.42 | n.s. |
| Tryptophan 1 (µM/L) | 54.08 (0.99) | 52.29 (1.46) | 55.50 (1.33) | 67.4 ± 10.2 | n.s. |
| Phenylalanine 1 (µM/L) | 71.98 (1.22) | 70.05 (1.8) | 73.53 (1.66) | 65.2 ± 11.1 | n.s. |
| Tyrosine 1 (µM/L) | 63.89 (1.48) | 64.14 (2.13) | 63.69 (2.07) | 90.6 ± 22.9 | n.s. |
| Kyn/Trp 1 (µM/mM) | 49.46 (1.63) | 49.35 (2.19) | 49.56 (2.36) | 26.7 ± 6.2 | n.s. |
| Phe/Tyr 1 (µM/µM) | 1.18 (0.03) | 1.14 (0.03) | 1.22 (0.04) | 0.75 ± 0.14 | n.s. |
| CRP (mg/dL) | 0.38 (0.09) | 0.31 (0.06) | 0.45 (0.15) | <0.5 | n.s. |
| IL-6 (ng/L) | 3.8 (0.5) | 3.9 (0.9) | 3.7 (0.7) | <7.0 | n.s. |
| WBC (G/L) | 6.45 (0.19) | 6.32 (0.23) | 6.55 (0.29) | 4.0–10.0 | n.s. |
| Neutrophils % | 3.86 (0.16) | 3.78 (0.21) | 3.92 (0.23) | 46.0–66.0 | n.s. |
| Hemoglobin (g/L) | 137.51 (1.26) | 132.32 (1.37) | 141.66 (1.85) | 120.0–180.0 2 |
|
| Thrombocytes (G/L) | 260.98 (6.30) | 268.24 (8.19) | 255.19 (9.25) | 150.0–380.0 | n.s. |
| Iron (µM/L) | 15.6 (0.5) | 15.2 (0.6) | 16 (0.7) | 5.8–34.5 | n.s. |
| Transferrin (mg/dL) | 249 (3.0) | 253 (6.0) | 246 (4.0) | 200.0–360.0 | n.s. |
| Ferritin (µmol/L) | 262 (20) | 167 (23.0) | 339 (29.0) | 15.0–400.0 2 |
|
| Transferrin saturation (%) | 25.0 (1.0) | 25 (1.0) | 26 (1.0) | 16.0–45.0 | n.s. |
| sTfR (mg/L) | 3.4 (0.1) | 3.2 (0.1) | 3.5 (0.1) | 1.80–4.7 2 |
|
| Hepcidin-25 (µg/L) | 20.6 (1.4) | 17 (1.7) | 23.6 (2.0) | 1.5–41.5 |
|
| Folate (μg/L) | 7.41 (0.36) | 7.02 (0.46) | 7.72 (0.54) | 3.9–26.8 |
|
| Vit B12 (pg/mL) | 292.18 (20.42) | 303 (14.0) | 292 (20.0) | 145.0–569.0 |
|
| 25-OH Vit D (nM/L) | 55 (2.0) | 60 (3.0) | 50 (2.0) | 75.0–150.0 |
|
| Troponin T (ng/L) | 10.1 (0.7) | 7.2 (0.6) | 12.4 (1.1) | <14.0 |
|
| Creatine kinase (CK, U/L) | 92 (5.0) | 81 (8.0) | 102 (7.0) | 26.0–190.0 |
|
| NT-proBNP (ng/L) | 243 (45) | 161 (26.0) | 309 (77.0) | <486.0 2 | n.s. |
| Creatinine (mg/dL) | 0.84 (0.02) | 0.74 (0.02) | 0.92 (0.03) | 0.51–1.17 |
|
Table 2
| Total ( | Female ( | Male ( | ||
|---|---|---|---|---|
| Pain COVID |
| 37 (58.7) | 34 (54.4) |
|
| Follow-up | 26 (18.3) | 15 (23.8) | 11 (13.9) | n.s. |
| GI COVID | 58 (40.8) | 31 (49.2) | 27 (34.2) |
|
| Follow-up | 11 (7.7) | 8 (12.7) | 3 (3.8) |
|
| Anosmia COVID | 59 (41.5) | 37 (58.7) | 22 (27.8) |
|
| Follow-up | 20 (14.1) | 15 (23.8) | 5 (6.3) |
|
| Sleep COVID | 48 (33.8) | 22 (34.9) | 26 (32.9) | n.s. |
| Follow-up | 36 (25.3) | 22 (34.9) | 14 (17.7) |
|
| Neuro COVID | 61 (42.9) | 27 (42.9) | 34 (43.0) | n.s. |
| Follow-up | 23 (16.2) | 9 (14.3) | 14 (17.7) | n.s. |
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