Post-COVID-19 Syndrome is Rarely Associated with Damage of the Nervous System: Findings from a Prospective Observational Cohort Study in 171 Patients

Fleischer, Michael; Szepanowski, Fabian; Tovar, Muriel; Herchert, Klaas; Dinse, Hannah; Schweda, Adam; Mausberg, Anne K.; Holle-Lee, Dagny; Köhrmann, Martin; Stögbauer, Julia; Jokisch, Daniel; Jokisch, Martha; Deuschl, Cornelius; Skoda, Eva-Maria; Teufel, Martin; Stettner, Mark; Kleinschnitz, Christoph

doi:10.1007/s40120-022-00395-z

Cited by 46 publications

(44 citation statements)

References 69 publications

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“…Brain stem dysfunction [36], a reduced cerebral blood flow [31,82] and the involvement of the ANS [25,26,30,31,[37][38][39] are discussed with respect to long COVID. Recently, preinfection psychological distress was discussed as risk factor for long COVID, too [75,83]. This is in line with the self-reported stress prior to acute infection regarding the patients of the present study.…”

Section: Neurophysiological Considerations With Respect To the Reacti...supporting

confidence: 88%

The Adaptive Force as potential biomechanical parameter in the recovery process of patients with long COVID

Schaefer¹,

Bittmann²

2022

Preprint

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Neuromuscular symptoms in long COVID patients are common. Since adequate diagnostics are still missing, investigating muscle function might be beneficial. The holding capacity (maximal isometric Adaptive Force; AFisomax) was previously suggested to be especially vulnerable for impairments. This longitudinal, non-clinical study aimed to investigate the AF in long COVID patients in recovery process. AF parameters of elbow/hip flexors were assessed in 17 patients at three timepoints (pre: long COVID state, post: immediately after first treatment, end: recovery) by an objectified manual muscle test. The tester applied an increasing force on the limb of the patient, who had to resist isometrically for as long as possible. The intensity of 13 common symptoms were queried. At pre, patients started to lengthen their muscles at ~50% of the maximal AF (AFmax), which was then reached during eccentric motion, indicating unstable adaptation. At post and end, AFisomax increased significantly to ~99% and 100% of AFmax, respectively, reflecting stable adaptation. AFmax was statistically similar for all three timepoints. Symptoms intensity decreased significantly from pre to end. In conclusion, maximal holding capacity seems to be impaired in long COVID patients and increases with substantial health improvement. AFisomax might be a suitable sensitive functional parameter to assess long COVID patients and to support therapy process.

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Section: Neurophysiological Considerations With Respect To the Reacti...supporting

confidence: 88%

The Adaptive Force as potential biomechanical parameter in the recovery process of patients with long COVID

Schaefer¹,

Bittmann²

2022

Preprint

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“…Moreover, despite several studies detecting changes in brain microstructure of people with post-COVID-19 with structural MRI (Colonna et al 2020 ; Freeman et al 2021 ; Hixon et al 2021 ; Nuzzo et al 2021 ; Cecchini et al 2022 ) and DTI (Liu et al 2019 ; Tian et al 2020 ; Qin et al 2021 ), no correlations with fatigue symptoms have been reported. Other recent studies found that post-COVID-19 symptoms were rarely associated with damage of the central or peripheral nervous system (Fleischer et al 2022 ) or alterations in regional cerebral glucose metabolism (Dressing et al 2022 ). Moreover, the Fleischer and colleagues concluded that psychosomatic mechanisms, such as somato-sensoric amplification may play a role in the pathogenesis of post-COVID-19 symptoms (Fleischer et al 2022 ).…”

Section: Discussionmentioning

confidence: 99%

“…Other recent studies found that post-COVID-19 symptoms were rarely associated with damage of the central or peripheral nervous system (Fleischer et al 2022 ) or alterations in regional cerebral glucose metabolism (Dressing et al 2022 ). Moreover, the Fleischer and colleagues concluded that psychosomatic mechanisms, such as somato-sensoric amplification may play a role in the pathogenesis of post-COVID-19 symptoms (Fleischer et al 2022 ).…”

Section: Discussionmentioning

confidence: 99%

“…Functional neuroimaging techniques to study fatigue, such as positron emission tomography with the glucose analog 18 F-fluorodeoxyglucose (FDG-PET), may provide more information about the underlying mechanisms of post-COVID-19 fatigue symptoms. A review by Rudroff et al (Rudroff et al 2021 ) summarized studies in people with post-COVID-19 that showed FDG-PET hypo-metabolism in a variety of brain regions and associations with symptoms (Fleischer et al 2022 ). For example, Guedj et al (Guedj et al 2021 ) found hypo-metabolism in the bilateral rectal/orbital gyrus (including the olfactory gyrus), hippocampus, temporal lobe (including the amygdala), bilateral pons/medulla brainstem, thalamus, and the bilateral cerebellum using FDG-PET in people with post-COVID-19 symptoms (Guedj et al 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, Guedj et al ( 2021 ) demonstrated that bilateral hypo-metabolism in various brain regions was significantly associated with post-COVID-19 symptoms, including cognitive impairment, pain, and insomnia (Guedj et al 2021 ). On the other hand, other studies found that neurological deficits or significant MRI abnormalities were rarely objectified in people with post-COVID-19 and, if present, could be attributed to other neurological disorders in most cases (Fleischer et al 2022 ; Kachaner et al 2022 ). In line with this, Dressing et al ( 2022 ) demonstrated no significant changes in cerebral glucose metabolism in post-COVID-19 subjects with self-reported cognitive impairment and fatigue (Dressing et al 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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Fatigue and perceived fatigability, not objective fatigability, are prevalent in people with post-COVID-19

2022

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Persistent symptoms after acute COVID-19 infection, termed post-COVID-19 fatigue, occur in 44–70% of patients. Characterizing fatigue in this population is vital to determine the etiology of post-COVID-19 fatigue symptoms and to assess the effectiveness of potential interventions. The purpose of this study was to assess differences in perceived and objective fatigability between people with post-COVID-19 symptoms ( N = 29, 20 females) and people who had COVID-19 but are not experiencing persistent symptoms ( N = 20, 12 females). Perceived fatigability, fatigue, pain, and quality of life were assessed with the Fatigue Severity Scale (FSS), Fatigue Assessment Scale (FAS), Visual Analog Scale for Pain (VAS), and the EQ-5D-5L, respectively. Objective fatigability was evaluated with torque and work fatigue indices (FI-T and FI-W), calculated via an isokinetic fatigue task. The results revealed that, the subjects with post-COVID-19 symptoms had significantly higher FAS ( p < 0.01), FSS ( p < 0.01), VAS ( p < 0.01), and EQ-5D-5L VAS ( p < 0.01) scores compared to subjects without post-COVID-19 symptoms, indicating greater fatigue and perceived fatigability, increased pain, and worse quality of life. However, there were no differences between the two groups for the FI-Ts (all p ≥ 0.07) or FI-W (all p ≥ 0.08), indicating no differences in objective fatigability. This study found that people with post-COVID-19 symptoms have increased fatigue and perceived fatigability, but not objective fatigability, compared to subjects without post-COVID-19 symptoms.

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Measurement Properties of the Patient Health Questionnaire–15 and Somatic Symptom Scale–8

Hybelius,

Kosic,

Salomonsson

et al. 2024

JAMA Netw Open

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ImportanceThe subjective experience of somatic symptoms is a key concern throughout the health care system. Valid and clinically useful instruments are needed.ObjectiveTo evaluate the measurement properties of 2 widespread patient-reported outcomes: the Patient Health Questionnaire–15 (PHQ-15) and Somatic Symptom Scale–8 (SSS-8).Data SourcesMedline, PsycINFO, and Web of Science were last searched February 1, 2024.Study SelectionEnglish-language studies reporting estimates pertaining to factor analysis, taxometric analysis, internal consistency, construct validity, mean scores in relevant groups, cutoffs, areas under the receiver operating characteristic curves (AUROCs), minimal clinically important difference, test-retest reliability, or sensitivity to change.Data Extraction and SynthesisSearch hits were reviewed by independent raters. Cronbach α, Pearson r, means, and between-group effect sizes indicative of sensitivity to change were pooled in random-effects meta-analysis. Study quality was assessed using 3 instruments. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 reporting guideline.Main Outcomes and MeasuresComprehensive overview of evidence pertaining to the measurement properties of the PHQ-15 and SSS-8.ResultsA total of 305 studies with 361 243 participants were included. Most concerned routine care (178 studies) and the general population (27 studies). In factor analyses, both scales reflected a combination of domain-specific factors (cardiopulmonary, fatigue, gastrointestinal, pain) and a general symptom burden factor. The pooled PHQ-15 α was 0.81 (95% CI, 0.80-0.82), but with low item-total correlations for items concerning menstrual problems, fainting spells, and sexual problems (item-total correlations &lt;0.40), and the SSS-8 α was 0.80 (0.77-0.83). Pooled correlations with other measures of somatic symptom burden were 0.71 (95% CI, 0.64-0.78) for the PHQ-15 and 0.82 (95% CI, 0.72-0.92) for the SSS-8. Reported AUROCs for identification of somatoform disorders ranged from 0.63 (95% CI, 0.50-0.76) to 0.79 (95% CI, 0.73-0.85) for the PHQ-15 and from 0.71 (95% CI, 0.66-0.77) to 0.73 (95% CI, 0.69-0.76) for the SSS-8. The minimal clinically important difference on both scales was 3 points. Test-retest reliability could not be pooled and was inconsistent for the PHQ-15 (PHQ-15: r = 0.65-0.93; ICC, 0.87; SSS-8: r = 0.996, ICC = 0.89). The PHQ-15 showed tentative sensitivity to change (g = 0.32; 95% CI, 0.08-0.56), but data for the SSS-8 were lacking.Conclusions and RelevanceIn this systematic review and meta-analysis, findings supported use of the PHQ-15 and SSS-8 for the assessment of symptom burden, but users should be aware of the complex, multifactorial structures of these scales. More evidence is needed concerning longitudinal measurement properties.

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Post-COVID-19 Syndrome is Rarely Associated with Damage of the Nervous System: Findings from a Prospective Observational Cohort Study in 171 Patients

Cited by 46 publications

References 69 publications

The Adaptive Force as potential biomechanical parameter in the recovery process of patients with long COVID

The Adaptive Force as potential biomechanical parameter in the recovery process of patients with long COVID

Fatigue and perceived fatigability, not objective fatigability, are prevalent in people with post-COVID-19

Measurement Properties of the Patient Health Questionnaire–15 and Somatic Symptom Scale–8

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