Demyelination in Patients with POST-COVID Depression
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Participants
2.2. Patient Survey
2.3. MRI Data Acquisition
- Magnetization-transfer (MT)-weighted pulse sequence: TR = 20 ms, echo time (TE) = 4.76 ms, flip angle (FA) = 8°, scan time 5 min 40 s;
- T1-weighted pulse sequence: TR = 16 ms, TE = 4.76 ms, FA = 18°, scan time: 4 min 32 s;
- Proton-density (PD)-weighted pulse sequence: TR = 16 ms, TE = 4.76 ms, FA = 3°, scan time: 4 min 32 s.
- The additional imaging sequences included the following:
- 3D Fluid attenuated inversion recovery (FLAIR) pulse sequence: TR = 5000 ms, TE = 390 ms, TI = 1800 ms;
- 3D T1-weighted pulse sequence: TR = 16 ms, TE = 4.76 ms;
- 3D T2-weighted pulse sequence: TR = 3000 ms, TE = 335 ms.
2.4. Image Processing
- Juxtacortical (superficial) WM: superior parietal, superior, middle, and inferior frontal; lateral and middle fronto-orbital; rectus; precentral; postcentral; angular; pre-cuneus; cuneus; lingual; fusiform; superior, inferior, and middle occipital; superior, inferior, and middle temporal; supramarginal; the cingulum (parts of the cingulate gyrus and hippocampus);
- WM pathways and fasciculi: corticospinal tract (CST); anterior, superior, and posterior corona radiata (CR); anterior limb, posterior limb, and retrolenticular part of internal capsule (IC); genu, body, and splenium of corpus callosum (CC); medial lemniscus; inferior, superior, and middle cerebellar peduncles (CPs); cerebral peduncles; posterior thalamic radiation; fornix (FX) (stria terminalis, column, and body); superior longitudinal (SL) fasciculus; superior (SFO) and inferior fronto-occipital (IFO) fasciculi; uncinate fasciculus; sagittal stratum; external capsule; pontine crossing tract; tapetum;
- Subcortical and allocortical GM structures: amygdala; caudate nucleus; putamen; globus pallidus; hippocampus; entorhinal area; thalamus;
- Brainstem structures: medulla; pons; midbrain.
2.5. Statistical Analysis
3. Results
3.1. Acute and Post-COVID Symptoms
3.2. Neuropsychological Results
3.3. Brain Demyelination in Patients with Post-COVID Depression
3.4. Specificity of Demyelination in Patients with Post-COVID Depression
4. Discussion
5. Conclusions
6. Study Limitations
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 | PCD | No-PCD | Control |
---|---|---|---|
Sample size | 25 | 38 | 19 |
Male (%) | 4 (16) | 14 (29) | 8 (42.1) |
Female (%) | 21 (84) | 24 (71) | 11 (57.9) |
Age, years ± SD | 36.96 ± 13.7 | 42.05 ± 9.17 | 38.53 ± 10.57 |
Age, median (min-max) | 42 (19–59) | 42 (21–58) | 37 (20–56) |
Vaccinated before the first COVID-19 episode (%) | 10 (40) * | 9 (23.7) *** | 14 (73.7) |
Vaccinated at the time of the study (%) | 20 (80) | 24 (63) | 14 (73.7) |
Parameter | PCD | noPCD | Statistics |
---|---|---|---|
Severity, mild/moderate/severe (%) | 88/8/4 | 73/24/3 | F(2, 79) = 1.74, p = 0.18 |
Number of COVID-19 episodes, mean ± SD | 1.6 ± 0.7 | 1.5 ± 0.7 | F(1, 61) = 0.33, p = 0.56 |
Time after the first COVID-19, months ± SD | 20.3 ± 8.2 | 19.7 ± 9.8 | F(1, 61) = 0.06, p = 0.81 |
Time after last COVID-19, months ± SD | 13.1 ± 10.3 | 13.8 ± 9.9 | F(1, 61) = 0.07, p = 0.79 |
Acute symptoms | |||
Anosmia, n (%) | 22 (88%) | 29 (76%) | Chi sq, p = 0.25 |
Ageusia, n (%) | 19 (76%) * | 19 (50%) | Chi sq, p = 0.04 |
Fever, n (%) | 22 (88%) | 36 (95%) | Chi sq, p = 0.33 |
Difficulty breathing, n (%) | 14 (56%) | 17 (45%) | Chi sq, p = 0.38 |
Cough, n (%) | 22 (88%) * | 24 (65%) | Chi sq, p = 0.04 |
Muscle weakness, n (%) | 24 (96%) | 35 (92%) | Chi sq, p = 0.53 |
Myalgia, n (%) | 20 (80%) | 22 (58%) | Chi sq, p = 0.07 |
Headache, n (%) | 22 (88%) * | 25 (66%) | Chi sq, p = 0.047 |
Dizziness, n (%) | 14 (56%) | 15 (39%) | Chi sq, p = 0.20 |
Number of acute symptoms | 7.24 ± 1.85 ** | 5.82 ± 2.13 | F(1, 61) = 7.45, p = 0.008 |
Post-COVID symptoms | |||
Headache, n (%) | 7 (28%) | 4 (11%) | Chi sq, p = 0.07 |
Dizziness, n (%) | 10 (40%) | 13 (34%) | Chi sq, p = 0.64 |
Brain fog, n (%) | 14 (56%) | 16 (42%) | Chi sq, p = 0.28 |
Anosmia, n (%) | 16 (64%) ** | 11 (29%) | Chi sq, p = 0.006 |
Ageusia, n (%) | 14 (56%) ** | 8 (21%) | Chi sq, p = 0.004 |
Sensitivity, n (%) | 3 (12%) | 4 (11%) | Chi sq, p = 0.86 |
Hypertensia/hypotensia, n (%) | 7 (28%) | 15 (39%) | Chi sq, p = 0.35 |
Insomnia, n (%) | 20 (80%) * | 19 (50%) | Chi sq, p = 0.02 |
Fatigue, n (%) | 24 (96%) ** | 25 (66%) | Chi sq, p = 0.005 |
Attention deficit, n (%) | 23 (92%) *** | 19 (50%) | Chi sq, p = 0.0005 |
Memory deficit, n (%) | 19 (76%) | 22 (58%) | Chi sq, p = 0.14 |
Myalgia, n (%) | 15 (60%) | 14 (37%) | Chi sq, p = 0.07 |
Depression 1, n (%) | 24 (96%) *** | 13 (34%) | Chi sq, p = 0.000 |
Panic attacks, n (%) | 5 (20%) * | 1 (3%) | Chi sq, p = 0.03 |
Number of post-COVID symptoms | 8.04 ± 2.23 *** | 4.84 ± 3.50 | F(1, 61) = 16.45, p = 0.000 |
Test | Parameter | Control | PCD | noPCD |
---|---|---|---|---|
HDRS | Hamilton score | 4.0 ± 3.40 | 18.36 ± 3.66 *** ### | 6.11 ± 3.52 * |
HADS | Anxiety | 4.42 ± 2.41 | 10.84 ± 3.25 *** ### | 5.32 ± 3.59 *** |
Depression | 3.47 ± 2.44 | 10.36 ± 4.78 *** ### | 4.05 ± 2.89 *** | |
Total score | 7.89 ± 3.75 | 21.04 ± 7.40 *** ### | 9.18 ± 4.73 *** |
Factor | Eigenvalue | % Total Variance | Cumulative % | Brain Structures with Scores > 0.7 |
---|---|---|---|---|
Factor 1 | 55.77 | 48.50 | 48.50 | Anterior, Superior, and Posterior CR (L+R); Genu, Body, and Splenium of CC (L+R); Posterior thal. rad.(L+R); Tapetum (L+R); SLF (L+R); SFOF (L+R); Sagittal stratum (L+R); Anterior, Posterior, and Retrolenticular IC (L+R); FX stria terminalis (R); Superior, Middle, and Inferior Frontal WM (L+R); Lateral Fronto-Orbital (R); Superior Parietal WM (L+R); Middle and Inferior Occipital WM (L+R); Superior Occipital (L); Middle Temporal WM (L+R); Angular WM (L+R); Cingulum (cingulate) (L), Precentral (L+R); Pre-cuneus (L); Thalamus (L) |
Factor 2 | 8.84 | 7.69 | 56.19 | CST (L+R); Cerebral peduncle (L+R); Medial lemniscus (L+R); Pontine crossing tract (L+R); Inferior, Superior, and Middle CP (L+R); FX stria terminalis (L); Globus pallidus (L); Midbrain, Pons, Medulla |
Factor 3 | 4.92 | 4.28 | 60.46 | Middle Fronto-Orbital (R); Rectus (L+R) |
Factor 4 | 4.20 | 3.65 | 64.12 | Amygdala (L+R) |
Factor 5 | 3.26 | 2.83 | 66.95 | Cuneus (R) |
Factor 6 | 2.85 | 2.48 | 69.42 | Globus Pallidus (R); Putamen (R); SFOF (R); Anterior IC (L+R); |
Factor 7 | 2.49 | 2.16 | 71.584 | IFOF (L+R); Uncinate fasciculus (L+R) |
Factor 8 | 2.22 | 1.93 | 73.52 | Entorhinal area (L) |
Factor 9 | 2.01 | 1.75 | 75.27 | Caudate Nucleus (L+R) |
Parameter | Total | PCD | noPCD | |||
---|---|---|---|---|---|---|
Multiple R | 0.64 | 0.70 | 0.36 | |||
Multiple R2 | 0.41 | 0.50 | 0.127 | |||
F | 19.45 | 10.57 | 5.24 | |||
p | 0.0000 | 0.0000 | 0.0281 | |||
Variables in the model | β coefficient | p | β coefficient | p | β coefficient | p |
Number of acute symptoms | 0.38 | 0.0019 | ||||
Number of post-COVID symptoms | 0.56 | 0.0000 | 0.36 | 0.0281 | ||
Factor 7 | −0.33 | 0.0010 | −0.66 | 0.0003 |
Statistic | Model 1 | Model 2 | ||
---|---|---|---|---|
Likelihood ratio Chi sq. test, p | p = 0.0001 | p = 0.00006 | ||
Goodness of fit, Logit likelihood | −33.19 | −30.32 | ||
Goodness of fit, AIC | 70.4 | 68.6 | ||
Goodness of fit, BIC | 76.8 | 77.2 | ||
Odds ratio | 6.77 | 14.03 | ||
Correct predicted cases (%PCD/%noPCD) | 60/78 | 68/87 | ||
Variables in the model | Wald stat., p | Logit likelihood, Chi-sqr, p | Wald stat., p | Logit likelihood, Chi-sqr, p |
Number of post-COVID symptoms | 11.7, p = 0.0006 | −34.9, 14.83, p = 0.0001 | 11.81, p = 0.0005 | −34.9, 14.35, p = 0.0001 |
Factor 7 | 4.65, p = 0.03 | −32.2, 5.4, p = 0.02 | 4.46, p = 0.03 | −32.2, 5.41, p = 0.02 |
Gender | - | - | 3.33, p = 0.05 | −30.3, p = 0.047 |
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Khodanovich, M.; Svetlik, M.; Kamaeva, D.; Usova, A.; Kudabaeva, M.; Anan’ina, T.; Vasserlauf, I.; Pashkevich, V.; Moshkina, M.; Obukhovskaya, V.; et al. Demyelination in Patients with POST-COVID Depression. J. Clin. Med. 2024, 13, 4692. https://doi.org/10.3390/jcm13164692
Khodanovich M, Svetlik M, Kamaeva D, Usova A, Kudabaeva M, Anan’ina T, Vasserlauf I, Pashkevich V, Moshkina M, Obukhovskaya V, et al. Demyelination in Patients with POST-COVID Depression. Journal of Clinical Medicine. 2024; 13(16):4692. https://doi.org/10.3390/jcm13164692
Chicago/Turabian StyleKhodanovich, Marina, Mikhail Svetlik, Daria Kamaeva, Anna Usova, Marina Kudabaeva, Tatyana Anan’ina, Irina Vasserlauf, Valentina Pashkevich, Marina Moshkina, Victoria Obukhovskaya, and et al. 2024. "Demyelination in Patients with POST-COVID Depression" Journal of Clinical Medicine 13, no. 16: 4692. https://doi.org/10.3390/jcm13164692