Long COVID Neuropsychological Deficits after Severe, Moderate, or Mild Infection
Abstract
:1. Introduction
2. Materials and Methods
2.1. Participants
2.2. General Procedure and Ethics
2.3. Neuropsychological Assessment
2.4. Other Clinical Outcomes
2.5. Statistical Analyses
2.5.1. Prevalence of Neuropsychological Deficits and Psychiatric Symptoms (Objective 1)
2.5.2. Neuropsychological Deficits as a Function of Disease Severity (Objective 2)
2.5.3. Relationships between Neuropsychological Deficits, Psychiatric Symptoms, and Other Secondary Variables (Objective 3)
3. Results
3.1. Neuropsychological, Psychiatric, and Olfactory Profiles 6–9 Months Post-Infection
Mild (No Hospitalization) n = 15 | Moderate (Conventional Hospitalization) n = 15 | Severe (ICU Hospitalization) n = 15 | ||||
---|---|---|---|---|---|---|
Function | Prevalence under P5 (mean%) | Prevalence under P16 (mean%) | Prevalence under P5 (mean%) | Prevalence under P16 (mean%) | Prevalence under P5 (mean%) | Prevalence under P16 (mean%) |
Memory | ||||||
Verbal episodic memory (/5) | 1.34 | 6.67 | 6.67 | 13.26 | 8.00 | 17.33 |
Visuospatial episodic memory (/4) | 1.67 | 3.34 | 15.00 | 20.00 | 1.67 | 5.00 |
Verbal short-term memory (/1) | 0.00 | 6.67 | 6.67 | 33.33 | 6.67 | 6.67 |
Visuospatial short-term memory (/1) | 0.00 | 6.67 | 0.00 | 0.00 | 0.00 | 0.00 |
Executive functions | ||||||
Inhibition (/3) | 15.56 | 22.22 | 11.90 | 23.81 | 13.33 | 28.89 |
Verbal Working memory (/1) | 6.67 | 6.67 | 0.00 | 13.33 | 0.00 | 0.00 |
Visuospatial working memory (/3) | 6.67 | 13.34 | 4.45 | 11.11 | 6.82 | 13.33 |
Mental flexibility (/6) | 3.33 | 7.78 | 14.44 | 18.89 | 11.11 | 18.89 |
Verbal fluency (/2) | 6.67 | 26.67 | 13.33 | 53.33 | 6.67 | 26.67 |
Incompatibility (/4) | 0.00 | 13.33 | 5.00 | 21.67 | 6.67 | 10.00 |
Interhemispheric transfer (/2) | 10.00 | 20.00 | 6.67 | 30.00 | 6.67 | 26.67 |
Attentional functions | ||||||
Phasic alertness (/5) | 10.67 | 18.67 | 0.00 | 20.00 | 1.33 | 14.67 |
Sustained attention (/2) | 10.00 | 16.67 | 26.93 | 34.62 | 7.69 | 11.54 |
Divided attention (/4) | 8.34 | 21.67 | 6.67 | 16.67 | 8.33 | 21.67 |
Instrumental functions | ||||||
Language (/5) | 4.00 | 9.34 | 5.33 | 8.00 | 6.67 | 16.00 |
Ideomotor praxis (/3) | 4.44 | - | 0.00 | - | 2.22 | - |
Object perception (/2) | 10.00 | - | 20.00 | - | 0.00 | - |
Spatial perception (/2) | 0.00 | - | 13.33 | - | 3.33 | - |
Logical reasoning (/2) | 3.33 | 10.00 | 10.00 | 13.33 | 0.00 | 6.67 |
Anosognosia for memory | 0.00 | - | 40.00 | - | 40.00 | - |
Anosognosia-Executive functions-Inhibition | 20.00 | - | 26.67 | - | 53.33 | - |
Anosognosia-Executive functions-Flexibility | 20.00 | - | 33.33 | - | 33.33 | - |
Anosognosia-Executive functions-Working memory | 6.67 | - | 6.67 | - | 0.00 | - |
Cognitive complaints | 6.67 | - | 13.33 | - | 0 | - |
Psychiatric Symptoms | Mild (No Hospitalization) n = 15 | Moderate (Conventional Hospitalization) n = 15 | Severe (ICU Hospitalization) n = 15 | Kruskal–Wallis p Value |
---|---|---|---|---|
Depression (BDI-II) (prevalence) | Minor = 46.67% | Minor = 66.67% | Minor = 80% | 0.009 |
Mild = 20% | Mild = 20% | Mild = 20% | ||
Moderate = 33.33% | Moderate = 13.33% | Moderate = 0% | ||
Severe = 0% | Severe = 0% | Severe = 0% | ||
State anxiety (STAI-state) (prevalence) | Very low = 26.67% | Very low = 60% | Very low = 86.67% | 0.002 |
Low = 33.33% | Low = 6.67% | Low = 6.67% | ||
Moderate = 13.33% | Moderate = 20% | Moderate = 6.67% | ||
High = 26.67% | High = 13.33% | High = 0% | ||
Very high = 0% | Very high = 0% | Very high = 0% | ||
Trait anxiety (STAI-trait) (prevalence) | Very low = 46.67% | Very low = 73.33% | Very low = 60% | 0.100 |
Low = 26.67% | Low = 0% | Low = 33.33% | ||
Moderate = 13.33% | Moderate = 20% | Moderate = 6.67% | ||
High = 13.33% | High = 6.67% | High = 0% | ||
Very high = 0% | Very high = 0% | Very high = 0% | ||
Mania (Goldberg Inventory) (prevalence) | Probably absent = 26.67% | Probably absent = 13.33% | Probably absent = 20% | 0.909 |
Hypomania = 26.67% | Hypomania = 26.67% | Hypomania = 46.67% | ||
Close to mania = 20% | Close to mania = 20% | Close to mania = 6.67% | ||
Moderate = 26.67% | Moderate = 40% | Moderate = 26.67% | ||
Ordinary to severe = 0% | Ordinary to severe = 0% | Ordinary to severe = 0% | ||
Severe = 0% | Severe = 0% | Severe = 0% | ||
Apathy (AMI-total) (prevalence) | Absent = 86.67% | Absent = 93.33% | Absent = 73.33% | 0.602 |
Moderate = 13.33% | Moderate = 6.67% | Moderate = 26.67% | ||
High = 0% | High = 0% | High = 0% | ||
Behavioral apathy (AMI-behavioral) (prevalence) | Absent = 100% | Absent = 100% | Absent = 93.33% | 0.211 |
Moderate = 0% | Moderate = 0% | Moderate = 6.67% | ||
High = 0% | High = 0% | High = 0% | ||
Social apathy (AMI-social) (prevalence) | Absent = 93.33% | Absent = 86.67% | Absent = 73.33% | 0.940 |
Moderate = 6.67% | Moderate = 6.67% | Moderate = 26.67% | ||
High = 0% | High = 6.67% | High = 0% | ||
Emotional apathy (AMI-emotional) (prevalence) | Absent = 73.33% | Absent = 60% | Absent = 40% | 0.029 |
Moderate = 26.67% | Moderate = 40% | Moderate = 33.33% | ||
High = 0% | High = 0% | High = 26.67% | ||
Posttraumatic stress disorder (PCL-5) (prevalence) | Absent = 86.67% | Absent = 86.67% | Absent = 93.33% | 0.054 |
Present = 13.33% | Present = 13.33% | Present = 6.67% | ||
Stress (PSS-14) Mean (±SD) | 26.13 (±9.53) | 19.6 (±7.47) | 14.93 (±9.42) | 0.023 |
Dissociative disorder (DES) Mean (±SD) | 7.68 (±11.89) | 10.45 (±9.23) | 3.98 (±3.03) | 0.140 |
Emotional contagion (ECS) Mean (±SD) | 41.40 (±7.20) | 44.6 (±4.22) | 36.13 (±8.38) | 0.002 |
Emotion regulation (ERQ) Mean (±SD) | 41.6 (±7.39) | 44.2 (±8.33) | 39.80 (±11.77) | 0.416 |
Somnolence (Epworth) (prevalence) | Pathological = 40.00% | Pathological = 53.33% | Pathological = 26.67% | 0.036 |
Insomnia (ISI) (prevalence) | Absent = 20% | Absent = 46.67% | Absent = 60% | 0.040 |
Mild = 40% | Mild = 40% | Mild = 26.67% | ||
Moderate = 40% | Moderate = 13.33% | Moderate = 13.33% | ||
Severe = 0% | Severe = 0% | Severe = 0% | ||
Fatigue (EMIF-SEP) (prevalence) | Present = 13.33% | Present = 20% | Present = 6.67% | 0.088 |
Sniff test (anosmia) Mean (±SD) | 13.07 (±1.44) | 11.53 (±2.13) | 11.47 (±2.90) | 0.067 |
3.2. Neuropsychological and Psychiatric Symptoms as a Function of Disease Severity
3.2.1. Neuropsychological Data
3.2.2. Psychiatric Data
3.2.3. Fatigue and Quality of Life
3.3. Relationships between Neuropsychological Deficits, Psychiatric Symptoms, and Other Secondary Variables
Regressor | R2 | p Value | ||
---|---|---|---|---|
Memory Functions | ||||
Verbal episodic memory | Grober & Buschke (RL/RI 16)-Immediate recall | ns | ns | ns |
Grober & Buschke (RL/RI 16)-Delayed free recall | AMI–Emotional apathy | 0.45 | 0.006 | |
Epworth-Sleepiness | 0.20 | 0.022 | ||
ERQ–Emotion regulation | 0.13 | 0.034 | ||
ECS–Emotional contagion | 0.08 | 0.034 | ||
Grober & Buschke (RL/RI 16)-Delayed total recall | AMI–Emotional apathy | 0.34 | 0.022 | |
Epworth-Sleepiness | 0.22 | 0.031 | ||
AMI–Social apathy | 0.15 | 0.034 | ||
Visuospatial episodic memory | Rey Figure-Copy time | ISI-Insomnia | 0.46 | 0.005 |
ERQ–Emotion regulation | 0.18 | 0.035 | ||
Rey Figure-Score | ns | ns | ns | |
Rey Figure-Immediate recall (3’) | ns | ns | ns | |
Rey Figure-Delayed recall (20’) | ISI–Insomnia | 0.30 | 0.034 | |
Days of hospitalization | 0.22 | 0.039 | ||
Sniff test (anosmia) | 0.21 | 0.013 | ||
Verbal short-term memory | MEM III-Spans | ns | ns | ns |
Visuospatial short-term memory | WAIS IV-Spans | DES–Dissociation | 0.30 | 0.035 |
Executive functions | ||||
Inhibition | Stroop (GREFEX)-Interference-Time | ns | ns | ns |
Stroop (GREFEX)-Interference-Errors | AMI–Total apathy | 0.37 | 0.015 | |
ERQ–Emotion regulation | 0.21 | 0.030 | ||
Stroop (GREFEX)-Interference/Naming-Score | ns | ns | ns | |
Working memory | MEM III–Verbal working memory | AMI–Behavioral apathy | 0.33 | 0.026 |
WAIS IV-Visuospatial working memory | STAI-T Anxiety | 0.39 | 0.013 | |
Diabetes | 0.25 | 0.014 | ||
STAI-S Anxiety | 0.13 | 0.03 | ||
TAP-Working memory item omissions | AMI–Emotional apathy | 0.30 | 0.035 | |
TAP-Working memory false alarms | Diabetes | 0.47 | 0.005 | |
Mania–Goldberg Inventory | 0.16 | 0.044 | ||
Mental flexibility | TMT A (GREFEX)-Time | ns | ns | ns |
TMT A (GREFEX)-Errors | ns | ns | ns | |
TMT B (GREFEX)-Time | ns | ns | ns | |
TMT B (GREFEX)-Errors | AMI–Total apathy | 0.41 | 0.010 | |
ERQ–Emotion regulation | 0.14 | 0.024 | ||
Gender | 0.13 | 0.025 | ||
TMT B (GREFEX)-Perseverations | STAI-T Anxiety | 0.55 | 0.002 | |
BDI-II-Depression | 0.16 | 0.026 | ||
ISI–Insomnia | 0.20 | <0.001 | ||
TMT B-A (GREFEX)-Score | ns | ns | ns | |
Verbal fluency (GREFEX)-Literal (2’) | ns | ns | ns | |
Verbal fluency (GREFEX)-Categorical fluency (2’) | DES–Dissociation | 0.28 | 0.047 | |
Incompatibility | TAP-Compatibility-Reaction time | AMI–Social apathy | 0.50 | 0.003 |
TAP-Compatibility-False alarms | ns | ns | ns | |
TAP-Incompatibility-Reaction Time | Sniff test (anosmia) | 0.28 | 0.043 | |
DES–Dissociation | 0.25 | 0.026 | ||
ERQ–Emotion regulation | 0.13 | 0.028 | ||
Epworth-Sleepiness | 0.10 | 0.017 | ||
TAP-Incompatibility-False alarms | Sniff test (anosmia) | 0.27 | 0.045 | |
TAP-Incompatibility-Visual field score | Days of hospitalization | 0.39 | 0.013 | |
Diabetes | 0.23 | 0.007 | ||
STAI-T Anxiety | 0.08 | 0.041 | ||
PCL-5 Posttraumatic stress disorder | 0.06 | 0.041 | ||
TAP-Incompatibility task-Hands score | AMI–Social apathy | 0.44 | 0.008 | |
TAP-Incompatibility task-Visual fields * Hands score | ISI–Insomnia | 0.33 | 0.025 | |
STAI-T Anxiety | 0.24 | 0.025 | ||
BDI-II-Depression | 0.18 | 0.019 | ||
Attentional functions | ||||
Phasic alertness | TAP-Without warning sound-Reaction time | Gender | 0.35 | 0.019 |
TAP-Without warning sound-SD of reaction time | AMI–Social apathy | 0.64 | <0.001 | |
Diabetes | 0.11 | 0.041 | ||
Sniff test (anosmia) | 0.10 | 0.023 | ||
TAP-With warning sound-Reaction time | DES–Dissociation | 0.30 | 0.033 | |
TAP-With warning sound-SD of reaction time | ns | ns | ns | |
TAP-Alertness index | Gender | 0.28 | 0.041 | |
Sustained attention | TAP-Items Omissions | STAI-Trait Anxiety | 0.46 | 0.005 |
TAP-False alarm | ns | ns | ns | |
Divided attention | TAP-Audio condition-Reaction time | DES–Dissociation | 0.41 | 0.010 |
AMI–Behavioral apathy | 0.27 | 0.008 | ||
TAP-Visual condition-Reaction time | Days of hospitalization | 0.38 | 0.014 | |
Sniff test (anosmia) | 0.27 | 0.009 | ||
ISI-Insomnia | 0.23 | <0.001 | ||
AMI–Emotional apathy | 0.05 | 0.016 | ||
TAP-Total omissions | ns | ns | ns | |
TAP-Total false alarms | AMI–Emotional apathy | 0.32 | 0.029 | |
Epworth-Sleepiness | 0.28 | 0.015 | ||
AMI–Social apathy | 0.16 | 0.023 | ||
Instrumental functions | ||||
Language | BECLA-Semantic image matching | ns | ns | ns |
BECLA-Semantic word matching | ns | ns | ns | |
BECLA-Object and action image naming | ECS–Emotional contagion | 0.38 | 0.014 | |
STAI-State Anxiety | 0.29 | 0.007 | ||
AMI–Emotional apathy | 0.10 | 0.014 | ||
ISI-Insomnia | 0.08 | 0.012 | ||
BECLA-Word repetition | NV | NV | NV | |
BECLA-Nonword repetition | ns | ns | ns | |
Ideomotor praxis | Symbolic gestures | ERQ–Emotion regulation | 0.35 | 0.019 |
AMI–Behavioral apathy | 0.33 | 0.004 | ||
Action pantomimes | BDI-II-Depression | 0.51 | 0.003 | |
Meaningless gestures | AMI–Total apathy | 0.30 | 0.033 | |
AMI–Social apathy | 0.18 | 0.035 | ||
Object perception | VOSP-Fragmented letters | AMI–Total apathy | 0.26 | 0.029 |
VOSP-Object decision | ns | ns | ns | |
Spatial perception | VOSP-Number localization | ns | ns | ns |
VOSP-Cubic counting | Mania–Goldberg Inventory | 0.27 | 0.047 | |
PSS-14-Stress | 0.24 | 0.034 | ||
Logical reasoning | WAIS IV-Puzzle | Diabetes | 0.34 | 0.021 |
WAIS IV-Matrix | DES–Dissociation | 0.28 | 0.041 | |
Gender | 0.40 | 0.002 | ||
Emotion recognition | GERT | ERQ–Emotion regulation | 0.33 | 0.023 |
AMI–Emotional apathy | 0.28 | 0.011 | ||
AMI–Behavioral apathy | 0.16 | 0.004 | ||
Sniff test (anosmia) | 0.06 | 0.008 | ||
AMI–Social apathy | 0.02 | 0.027 | ||
Anosognosia | Memory dysfunctions | BDI-II-Depression | 0.62 | <0.001 |
ISI-Insomnia | 0.12 | 0.038 | ||
AMI–Behavioral apathy | 0.09 | 0.040 | ||
Epworth-Sleepiness | 0.05 | 0.033 | ||
Executive functions-Inhibition | AMI–Total apathy | 0.40 | 0.011 | |
Executive functions-Flexibility | AMI–Behavioral score | 0.28 | 0.043 | |
Executive functions–Working memory | Epworth-Sleepiness | 0.38 | 0.015 | |
Sniff test (anosmia) | 0.25 | 0.015 |
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Mild (No Hospitalization) n = 15 | Moderate (Conventional Hospitalization) n = 15 | Severe (ICU Hospitalization) n = 15 | p Value b | |
---|---|---|---|---|
Age in years (mean ± SD) (range) | 53.33 (±8.93) (39–65) | 55.87 (±11.45) (38–74) | 61.80 (±10.42) (44–78) | ns |
Education level in years [level 1 to 3] a (mean ± SD) | 2.67 (±0.49) | 2.53 (±0.74) | 2.40 (±0.63) | ns |
Gender (F/M) | 8/7 | 9/6 | 2/13 | 0.021 |
Number of day’s post-discharge (mean ± SD) and (range) | 247.33 (±19.61) (216–282) | 226.53 (±24.85) (195–273) | 236.00 (±20.30) (195–270) | ns |
Days of hospitalization (mean ± SD) | - | 9.27 (±9.52) | 37.40 (±30.50) | - |
Diabetes | 0/15 | 2/15 | 5/15 | 0.041 |
Smoking | 2/15 | 0/15 | 1/15 | ns |
History of respiratory disorders | 3/15 | 3/15 | 5/15 | ns |
History of cardiovascular disorders | 3/15 | 2/15 | 4/15 | ns |
History of neurological disorders | 0/15 | 0/15 | 0/15 | - |
History of psychiatric disorders | 1/15 | 0/15 | 1/15 | ns |
History of cancer | 0/15 | 0/15 | 0/15 | - |
History of severe immunosuppression | 0/15 | 0/15 | 0/15 | - |
History of developmental disorders | 0/15 | 0/15 | 0/15 | - |
Chronic renal failure | 0/15 | 0/15 | 2/15 | ns |
Sleep apnea syndrome | 1/15 | 1/15 | 3/15 | ns |
Quality-of-Life Domains (SF-36) + | Mild (No Hospitalization) (n = 15) Mean (±SD) | Moderate (Conventional Hospitalization) (n = 15) Mean (±SD) | Severe (ICU Hospitalization) (n = 15) Mean (±SD) | Kruskal–Wallis p Value |
---|---|---|---|---|
Overall health | 62.67 (±16.89) | 59.33 (±27.31) | 66.00 (±24.14) | 0.808 |
Physical function | 80.00 (±17.22) | 82.33 (±19.44) | 77.33 (±24.41) | 0.806 |
Physical role | 58.33 (±30.86) | 53.33 (±43.16) | 71.67 (±36.43) | 0.353 |
Emotional role | 64.45 (±36.67) | 73.34 (±36.08) | 80.00 (±37.38) | 0.314 |
Social function | 57.50 (±23.05) | 66.67 (±31.93) | 85.00 (±18.42) ** | 0.011 |
Physical pain | 57.83 (±20.81) | 72.00 (±29.40) | 71.83 (±25.61) | 0.153 |
Emotional well-being | 58.13 (±17.75) | 61.33 (±24.96) | 79.2 (±17.90) **’’ | 0.010 |
Vitality score | 38.66 (±16.20) | 49.00 (±27.14) | 56.00 (±14.17) ** | 0.039 |
Health modification | 30.00 (±16.90) | 35.00 (±24.64) | 43.33 (±17.59) | 0.143 |
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Voruz, P.; Allali, G.; Benzakour, L.; Nuber-Champier, A.; Thomasson, M.; Jacot de Alcântara, I.; Pierce, J.; Lalive, P.H.; Lövblad, K.-O.; Braillard, O.; et al. Long COVID Neuropsychological Deficits after Severe, Moderate, or Mild Infection. Clin. Transl. Neurosci. 2022, 6, 9. https://doi.org/10.3390/ctn6020009
Voruz P, Allali G, Benzakour L, Nuber-Champier A, Thomasson M, Jacot de Alcântara I, Pierce J, Lalive PH, Lövblad K-O, Braillard O, et al. Long COVID Neuropsychological Deficits after Severe, Moderate, or Mild Infection. Clinical and Translational Neuroscience. 2022; 6(2):9. https://doi.org/10.3390/ctn6020009
Chicago/Turabian StyleVoruz, Philippe, Gilles Allali, Lamyae Benzakour, Anthony Nuber-Champier, Marine Thomasson, Isabele Jacot de Alcântara, Jordan Pierce, Patrice H. Lalive, Karl-Olof Lövblad, Olivia Braillard, and et al. 2022. "Long COVID Neuropsychological Deficits after Severe, Moderate, or Mild Infection" Clinical and Translational Neuroscience 6, no. 2: 9. https://doi.org/10.3390/ctn6020009