Fatigue and cognitive impairment after COVID-19: A prospective multicentre study

Tim J Hartung; Christian Neumann; Thomas Bahmer; Irina Chaplinskaya-Sobol; Matthias Endres; Johanna Geritz; Karl Georg Haeusler; Peter U Heuschmann; Hanna Hildesheim; Andreas Hinz; Sina Hopff; Anna Horn; Michael Krawczak; Lilian Krist; Jennifer Kudelka; Wolfgang Lieb; Corina Maetzler; Anja Mehnert-Theuerkauf; Felipe A Montellano; Caroline Morbach; Sein Schmidt; Stefan Schreiber; Flo Steigerwald; Stefan Störk; Walter Maetzler; Carsten Finke

doi:10.1016/j.eclinm.2022.101651

Fatigue and cognitive impairment after COVID-19: A prospective multicentre study

EClinicalMedicine. 2022 Sep 17:53:101651. doi: 10.1016/j.eclinm.2022.101651. eCollection 2022 Nov.

Authors

Tim J Hartung^{1

2}, Christian Neumann³, Thomas Bahmer^{4

5}, Irina Chaplinskaya-Sobol⁶, Matthias Endres^{1

7

8

9

10}, Johanna Geritz³, Karl Georg Haeusler¹¹, Peter U Heuschmann^{12

13}, Hanna Hildesheim³, Andreas Hinz², Sina Hopff¹⁴, Anna Horn¹², Michael Krawczak¹⁵, Lilian Krist¹⁶, Jennifer Kudelka³, Wolfgang Lieb¹⁷, Corina Maetzler³, Anja Mehnert-Theuerkauf², Felipe A Montellano^{12

11

18}, Caroline Morbach¹⁹, Sein Schmidt²⁰, Stefan Schreiber²¹, Flo Steigerwald¹, Stefan Störk^{22

23}, Walter Maetzler³, Carsten Finke¹

Affiliations

¹ Klinik und Hochschulambulanz für Neurologie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
² Department of Medical Psychology and Medical Sociology, University Medical Center Leipzig, Leipzig, Germany.
³ Neurology Department, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany.
⁴ Internal Medicine Department I, University Hospital Schleswig Holstein, Campus Kiel, Kiel, Germany.
⁵ Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany.
⁶ Department of Medical Informatics, University Medical Center Göttingen, Göttingen, Germany.
⁷ Center for Stroke Research Berlin, Berlin, Germany.
⁸ Excellence Cluster NeuroCure, Berlin, Germany.
⁹ German Center for Neurodegenerative Diseases (DZNE), Partner Site Berlin, Germany.
¹⁰ German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Germany.
¹¹ Department of Neurology, Universitätsklinikum Würzburg, Würzburg, Germany.
¹² Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany.
¹³ Clinical Trial Center, University Hospital Würzburg, Würzburg, Germany.
¹⁴ University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne, Duesseldorf, Germany.
¹⁵ Institute of Medical Informatics and Statistics, Kiel University, University Medical Center Schleswig-Holstein Campus Kiel, Kiel, Germany.
¹⁶ Institute of Social Medicine, Epidemiology and Health Economics, Charité-Universitätsmedizin Berlin, Berlin, Germany.
¹⁷ Institute of Epidemiology, Kiel University, Kiel, Germany.
¹⁸ Comprehensive Heart Failure Center, University and University Hospital Würzburg, Würzburg, Germany.
¹⁹ University Hospital Würzburg, Department for Medicine I and Comprehensive Heart Failure Center, Würzburg, Germany.
²⁰ Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Clinical Study Center, Berlin, Germany.
²¹ Universitätsklinikum Schleswig-Holstein, Christian-Albrechts-Universität zu Kiel, Klinik für Innere Medizin I, Kiel, Germany.
²² Department of Clinical Research & Epidemiology, Comprehensive Heart Failure Center, University Hospital Würzburg, Würzburg, Germany.
²³ Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany.

Abstract

Background: Reliable estimates of frequency, severity and associated factors of both fatigue and cognitive impairment after COVID-19 are needed. Also, it is not clear whether the two are distinct sequelae of COVID-19 or part of the same syndrome."

Methods: In this prospective multicentre study, frequency of post-COVID fatigue and cognitive impairment were assessed in n = 969 patients (535 [55%] female) ≥6 months after SARS-CoV-2 infection with the FACIT-Fatigue scale (cut-off ≤30) and Montreal Cognitive Assessment (≤25 mild, ≤17 moderate impairment) between November 15, 2020 and September 29, 2021 at University Medical Center Schleswig-Holstein, Campus Kiel and University Hospital Würzburg in Germany. 969 matched non-COVID controls were drawn from a pre-pandemic, randomised, Germany-wide population survey which also included the FACIT-Fatigue scale. Associated sociodemographic, comorbid, clinical, psychosocial factors and laboratory markers were identified with univariate and multivariable linear regression models.

Findings: On average 9 months after infection, 19% of patients had clinically relevant fatigue, compared to 8% of matched non-COVID controls (p < 0.001). Factors associated with fatigue were female gender, younger age, history of depression and the number of acute COVID symptoms. Among acute COVID symptoms, altered consciousness, dizziness and myalgia were most strongly associated with long-term fatigue. Moreover, 26% of patients had mild and 1% had moderate cognitive impairment. Factors associated with cognitive impairment were older age, male gender, shorter education and a history of neuropsychiatric disease. There was no significant correlation between fatigue and cognitive impairment and only 5% of patients suffered from both conditions.

Interpretation: Fatigue and cognitive impairment are two common, but distinct sequelae of COVID-19 with potentially separate pathophysiological pathways.

Funding: German Federal Ministry of Education and Research (BMBF).

Keywords: CI, confidence interval; COVID-19; COVID-19, Coronavirus Disease 2019; CRP, C-reactive protein; CSF, cerebrospinal fluid; Cognitive dysfunction; Fatigue; GAD-7, 7-item anxiety screening questionnaire; MoCA, Montreal Cognitive Assessment; NAPKON, National Pandemic Cohort Network; PCR, polymerase chain reaction; PHQ-8, 8-item depression module of the Patient Health Questionnaire; PSQI, Pittsburgh Sleep Quality Index; Post-acute COVID-19 syndrome; SARS-CoV-2; SARS-CoV-2, Severe Acute Respiratory Distress Syndrome caused by Corona Virus 2; VIF, variance inflation factor.