Lowered Quality of Life in Long COVID Is Predicted by Affective Symptoms, Chronic Fatigue Syndrome, Inflammation and Neuroimmunotoxic Pathways
Abstract
:1. Introduction
2. Methods
2.1. Participants
2.2. Clinical Assessments
2.3. Biomarker Assessments
2.4. Statistics
2.5. Avoiding Bias
3. Results
3.1. Results of Cluster Analysis
3.2. The Physio-Affective Phenome Scores and Biomarkers in WHO-QoL Clusters
3.3. Associations of the Physio-Affective Phenome with WHO-QoL Scores
3.4. Associations of the Biomarkers with WHO-QoL Scores
4. Discussion
4.1. Lowered HR-Qol in Long COVID
4.2. The Physio-Affective Phenome of Long COVID Predict Lowered HR-QoL
4.3. Lowered HR-Qol in Long COVID Is Predicted by Neuroimmunotoxic and Oxidative Pathways
4.4. The Effects of SARS-CoV-2 Infection on Lowered HR-QoL in Long COVID Are Mediated by Acute and Chronic Immune-Inflammatory Processes
4.5. Additional Explanatory Variables
4.6. Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameter | Normal WHO-QoL A n = 42 | Moderate Low WHO-QoL B n = 37 | Very Low WHO-QoL C n = 46 | F/χ2 | df | p |
---|---|---|---|---|---|---|
WHO-QoL, physical * | 27.46 ± 0.66 B,C | 21.60 ± 0.51 A,C | 16.83 ± 0.49 A,B | 66.83 | 2/114 | <0.001 |
WHO-QoL, psychological * | 25.70 ± 0.57 B,C | 21.40 ± 0.43 A,C | 16.43 ± 0.42 A,B | 77.50 | 2/114 | <0.001 |
WHO-QoL, social * | 11.92 ± 0.43 | 10.58 ± 0.33 | 10.56 ± 0.32 | 2.50 | 2/114 | 0.086 |
WHO-QoL, environment * | 33.60 ± 0.71 B,C | 26.78 ± 0.54 A,C | 22.89 ± 0.53 A,B | 54.03 | 2/114 | <0.001 |
PC 4 WHO-QoL domains * | 1.121 ± 0.087 | −0.124 ± 0.066 | −0.924 ± 0.064 | 135.31 | 2/114 | <0.001 |
HC/Long COVID | 38/4 | 1/36 | 0/46 | FFHE | <0.001 | |
Age (years) | 28.0 ± 7.4 | 29.3 ± 6.5 | 27.9 ± 5.9 | 0.35 | 2/127 | 0.706 |
Female/Male ratio | 19/23 | 15/22 | 20/26 | 0.18 | 2 | 0.914 |
BMI (kg/m2) | 25.84 ± 4.08 | 25.83 ± 3.53 | 26.21 ± 5.23 | 0.05 | 2/127 | 0.950 |
Education (years) | 15.0 ±1.2 B,C | 15.8 ± 1.9 A,C | 15.6 ± 1.7 A,B | 9.99 | 2/127 | <0.001 |
Married/Single (No/Yes) | 19/23 | 21/31 | 15/21 | 0.23 | 2 | 0.901 |
Rural/Urban (No/Yes) | 8/34 | 8/29 | 7/39 | 0.58 | 2 | 0.749 |
TUD (No/Yes) | 29/13 | 24/13 | 32/14 | 2.40 | 2 | 0.887 |
Vaccination A/Pf/S | 9/23/10 | 5/23/9 | 15/23/8 | 4.46 | 4 | 0.347 |
Dexamethasone (No/Yes) | 39/3 | 24/13 | 23/23 | 19.17 | 2 | <0.001 |
Ceftriaxone (No/Yes) | 41/1 | 18/19 | 16/30 | 38.94 | 2 | <0.001 |
Azithromycine (No/Yes) | 38/4 | 17/20 | 25/21 | 19.87 | 2 | <0.001 |
Enoxaparin sodium (No/Yes) | 38/4 | 4/33 | 8/38 | 67.52 | 2 | <0.001 |
Bromhexine (No/Yes) | 39/3 | 10/27 | 8/38 | 57.71 | 2 | <0.001 |
Variables | Normal WHO-QoL A n = 42 | Moderate Lower WHO-QoL B n = 52 | Very Low WHO-QoL C n = 36 | F (df = 2/122) | p |
---|---|---|---|---|---|
Total FF score | 11.0 ± 4.1 B,C | 20.4 ± 10.1 A,C | 36.0 ± 12.1 A,B | 78.42 | <0.001 |
Total HAMA score | 7.9 ± 3.9 B,C | 13.8 ± 6.6 A,C | 19.7 ± 8.5 A,B | 34.26 | <0.001 |
Total BDI-II score | 9.1 ± 4.1 B,C | 20.3 ± 5.8 A,C | 28.9 ± 6.4 A,B | 140.46 | <0.001 |
Total HAMD score | 6.4 ± 3.7 B,C | 14.5 ± 4.8 A,C | 18.8 ± 4.5 A,B | 90.23 | <0.001 |
Pure FF | −0.867 ± 0.385 B,C | −0.079 ± 0.746 A,C | 0.855 ± 0.849 A,B | 68.31 | <0.001 |
Pure HAMD | −0.987 ± 0.395 B,C | 0.136 ± 0.636 A,C | 0.792 ± 0.851 A,B | 80.21 | <0.001 |
Physiosom HMD | −0.862 ± 0.672 B,C | 0.247 ± 0.949 A,C | 0.588 ± 0.726 A,B | 40.35 | <0.001 |
Pure HAMA | −0.547 ± 0.766 B,C | −0.084 ± 0.853 A,C | 0.568 ± 1.012 A,B | 17.53 | <0.001 |
Physiosom HAMA | −0.517 ± 0.564 B,C | 0.002 ± 0.958 A | 0.470 ± 1.120 A | 12.73 | <0.001 |
Pure BDI | −0.998 ± 0.605 B,C | 0.209 ± 0.663 A,C | 0.743 ± 0.735 A,B | 76.11 | <0.001 |
PC Physio-affective phenome | −0.963 ± 0.368 B,C | 0.0498 ± 0.706 A,C | 0.839 ± 0.804 A,B | 82.90 | <0.001 |
Peak body temperature | 37.07 (0.78) B,C | 38.30 (0.74) A,C | 38.75 (0.93) A,B | 47.85 | <0.001 |
Lowest SpO2 (%) | 94.86 ± 1.96 B,C | 91.62 ± 3.59 A | 90.37 ± 4.29 A | 19.46 | <0.001 |
TO2 index (zBT-zSpO2 in z scores) | −0.880 ± 0.586 B,C | 0.218 ± 0.759 A,C | 0.628 ± 0.903 A,B | 44.71 | <0.001 |
NLRP3 (z scores) | −0.406 ± 0.945 B,C | 0.030 ± 0.833 A | 0.347 ± 1.052 A | 6.85 | 0.002 |
OSTOX (z scores) | −0.380 ± 1.018 B,C | 0.140 ± 0.478 A | 0.269 ± 1.057 A | 5.45 | 0.005 |
OSTOX+NLRP3 (z scores) | −0.527 ± 0.880 B,C | 0.088 ± 0.794 A,C | 0.492 ± 0.905 A,B | 15.23 | <0.001 |
zIR (z scores) | −0.426 ± 0.678 B,C | 0.307 ± 1.112 A | 0.142 ± 1.040 A | 6.57 | 0.002 |
OSTOX+NLRP3+IR (NT) | −0.625 ± 0.892 B,C | 0.188 ± 0.741 A | 0.419 ± 1.010 A | 16.04 | <0.001 |
NT+TO2 (z scores) | −0.857 ± 0.795 B,C | 0.240 ± 0.677 A,C | 0.589 ± 0.851 A,B | 39.76 | <0.001 |
Dependent Variables | Explanatory Variables | B | t | p | F Model | df | p | R2 |
---|---|---|---|---|---|---|---|---|
PC_WHO-QoL domains | Model#1 | 132.74 | 2/121 | <0.001 | 0.767 | |||
Pure BDI | −0.476 | −6.96 | <0.001 | |||||
Pure FF | −0.292 | −5.04 | <0.001 | |||||
Total HAMD | −0.238 | −3.02 | 0.003 | |||||
WHO-QoL physical | Model#2 | 90.00 | 3/120 | <0.001 | 0.750 | |||
Pure FF | −0.523 | −8.63 | <0.001 | |||||
Pure BDI | −0.254 | −3.56 | <0.001 | |||||
Sex | −0.125 | −2.72 | 0.007 | |||||
Total HAMD | −0.221 | −2.69 | 0.008 | |||||
WHO-QoL psychological | Model#3 | 133.17 | 2/122 | <0.001 | 0.686 | |||
Pure BDI | −0.619 | −10.41 | <0.001 | |||||
Total FF | −0.316 | −5.31 | <0.001 | |||||
WHO-QoL social | Model#4 | 24.61 | 1/123 | <0.001 | 0.167 | |||
Total HAMD | −0.408 | −4.96 | <0.001 | |||||
WHO-QoL environmental | Model#5 | 85.53 | 2/122 | <0.001 | 0.584 | |||
Pure BDI | −0.586 | −8.78 | <0.001 | |||||
Pure FF | −0.283 | −4.24 | <0.001 |
Dependent Variables | Explanatory Variables | B | t | p | F Model | df | p | R2 |
---|---|---|---|---|---|---|---|---|
PC_WHO-QoL domains | Model#1 | 57.47 | 3/120 | <0.001 | 0.590 | |||
PBT | −0.290 | −3.02 | 0.003 | |||||
Calcium | 0.302 | 4.57 | <0.001 | |||||
NT+TO2 | −0.329 | −3.56 | <0.001 | |||||
WHO-QoL physical | Model#2 | 54.93 | 3/120 | <0.001 | 0.579 | |||
PBT | −0.465 | −6.22 | <0.001 | |||||
Calcium | 0.256 | 3.82 | <0.001 | |||||
NT | −0.241 | −3.58 | <0.001 | |||||
WHO-QoL psychological | Model#3 | 40.13 | 2/121 | <0.001 | 0.399 | |||
NT+TO2 | −0.446 | −5.83 | <0.001 | |||||
Calcium | 0.305 | 3.99 | <0.001 | |||||
WHO-QoL social | Model#4 | 21.33 | 2/121 | <0.001 | 0.261 | |||
Calcium | 0.401 | 5.04 | <0.001 | |||||
NT | −0.251 | −3.16 | 0.002 | |||||
WHO-QoL environmental | Model#5 | 37.87 | 3/120 | <0.001 | 0.486 | |||
PBT | −0.276 | −2.57 | 0.011 | |||||
Calcium | 0.288 | 3.89 | <0.001 | |||||
NT+TO2 | −0.274 | −2.65 | 0.009 | |||||
PC phenome | Model#6 | 47.71 | 4/119 | <0.001 | 0.616 | |||
PBT | 0.480 | 6.70 | <0.001 | |||||
Calcium | −0.266 | −4.13 | <0.001 | |||||
Female sex | −0.206 | −3.61 | <0.001 | |||||
NT | 0.223 | 3.45 | <0.001 |
Dependent Variables | Explanatory Variables | B | t | p | F Model | df | p | R2 |
---|---|---|---|---|---|---|---|---|
PC_WHO-QoL 4 domains | Model#1 | 167.94 | 4/120 | <0.001 | 0.848 | |||
Acute infection | −0.644 | −8.50 | <0.001 | |||||
Pure BDI | −0.354 | −6.95 | <0.001 | |||||
Pure FF | −0.274 | −6.10 | <0.001 | |||||
Enoxaparin | 0.262 | 4.08 | <0.001 | |||||
WHO-QoL physical | Model#2 | 65.39 | 4/120 | <0.001 | 0.686 | |||
Acute infection | −0.525 | −6.49 | <0.001 | |||||
PBT | −0.238 | −3.16 | 0.002 | |||||
Ceftriaxone | −0.165 | −2.68 | 0.008 | |||||
Vaccination A | −0.103 | −2.00 | 0.048 | |||||
WHO-QoL environmental | Model#3 | 89.82 | 2/122 | <0.001 | 0.596 | |||
Acute infection | −1.054 | −10.35 | <0.001 | |||||
Enoxaparin | 0.379 | 3.72 | <0.001 |
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Maes, M.; Al-Rubaye, H.T.; Almulla, A.F.; Al-Hadrawi, D.S.; Stoyanova, K.; Kubera, M.; Al-Hakeim, H.K. Lowered Quality of Life in Long COVID Is Predicted by Affective Symptoms, Chronic Fatigue Syndrome, Inflammation and Neuroimmunotoxic Pathways. Int. J. Environ. Res. Public Health 2022, 19, 10362. https://doi.org/10.3390/ijerph191610362
Maes M, Al-Rubaye HT, Almulla AF, Al-Hadrawi DS, Stoyanova K, Kubera M, Al-Hakeim HK. Lowered Quality of Life in Long COVID Is Predicted by Affective Symptoms, Chronic Fatigue Syndrome, Inflammation and Neuroimmunotoxic Pathways. International Journal of Environmental Research and Public Health. 2022; 19(16):10362. https://doi.org/10.3390/ijerph191610362
Chicago/Turabian StyleMaes, Michael, Haneen Tahseen Al-Rubaye, Abbas F. Almulla, Dhurgham Shihab Al-Hadrawi, Kristina Stoyanova, Marta Kubera, and Hussein Kadhem Al-Hakeim. 2022. "Lowered Quality of Life in Long COVID Is Predicted by Affective Symptoms, Chronic Fatigue Syndrome, Inflammation and Neuroimmunotoxic Pathways" International Journal of Environmental Research and Public Health 19, no. 16: 10362. https://doi.org/10.3390/ijerph191610362