Prevalence and trajectories of neuropsychological post-COVID-19 symptoms in initially hospitalized patients

Authors

  • Simona Klinkhammer School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands; Limburg Brain Injury Center, Maastricht University, Maastricht, the Netherlands
  • Annelien A. Duits School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands; Department of Medical Psychology, Maastricht University Medical Center, Maastricht, the Netherlands; Department of Medical Psychology, Radboud University Medical Center, Nijmegen, the Netherlands
  • Janneke Horn Department of Intensive Care, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Neuroscience, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
  • Arjen J.C. Slooter UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Department of Neurology, UZ Brussel and Vrije Universiteit Brussel, Brussels Health Campus, Jette, Belgium
  • Esmée Verwijk Amsterdam Neuroscience, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Department of Medical Psychology, Amsterdam University Medical Center, Amsterdam, the Netherlands; Department of Psychology, Brain and Cognition, University of Amsterdam, Amsterdam, the Netherlands
  • Susanne van Santen Department of Intensive Care Medicine, Maastricht University Medical Center, Maastricht, the Netherlands
  • Johanna M.A. Visser-Meily Department of Rehabilitation, Physical Therapy Science & Sports, University Medical Center Utrecht, Utrecht, the Netherlands; Center of Excellence for Rehabilitation Medicine and De Hoogstraat Rehabilitation, University Medical Center Utrecht, Utrecht, the Netherlands
  • Caroline van Heugten School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands; Limburg Brain Injury Center, Maastricht University, Maastricht, the Netherlands; Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands

DOI:

https://doi.org/10.2340/jrm.v56.25315

Keywords:

SARS-CoV-2, Long COVID, post-COVID, PASC, fatigue, cognitive complaints, post-infection

Abstract

Objective: To investigate the prevalence and trajectories of post-COVID-19 neuropsychological symptoms.

Design: Prospective longitudinal multicentre cohort study.

Subjects: A total of 205 patients initially hospitalized with SARS-CoV-2 (COVID-19).

Methods: Validated questionnaires were administered at 9 months (T1) and 15 months (T2) post-hospital discharge to assess fatigue, cognitive complaints, insomnia, anxiety, depression, and post-traumatic stress symptoms.

Results: Analyses included 184 out of 205 patients. Approximately 50% experienced high cognitive complaints at T1 and T2, while severe fatigue affected 52.5% at T1 and 55.6% at T2. Clinically relevant insomnia scores were observed in 25% of patients at both time-points. Clinically relevant anxiety scores were present in 18.3% at T1 and 16.7% at T2, depression in 15.0% at T1 and 18.9% at T2, and PTSD in 12.4% at T1 and 11.8% at T2. Most symptoms remained stable, with 59.2% of patients experiencing at least 1 persistent symptom. In addition, 31.5% of patients developed delayed-onset symptoms.

Conclusion: Post-COVID-19 cognitive complaints and fatigue are highly prevalent and often persist. A subgroup develops delayed symptoms. Emotional distress is limited. Screening can help identify most patients experiencing long-term problems. Future research should determine risk factors for persistent and delayed onset symptoms.

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References

Fernández-de-Las-Peñas C, Palacios-Ceña D, Gómez-Mayordomo V, Florencio LL, Cuadrado ML, Plaza-Manzano G, et al. Prevalence of post-COVID-19 symptoms in hospitalized and non-hospitalized COVID-19 survivors: a systematic review and meta-analysis. Eur J Intern Med 2021; 92: 55–70.

https://doi.org/10.1016/j.ejim.2021.06.009 DOI: https://doi.org/10.1016/j.ejim.2021.06.009

Kohn L, Dauvrin M, Detollenaere J, Primus-de Jong C, Maertens de Noordhout C, Castanares-Zapatero D, et al. Long COVID and return to work: a quali-tative study. Occup Med 2024; 74: 29–36.

https://doi.org/10.1093/occmed/kqac119 DOI: https://doi.org/10.1093/occmed/kqac119

Barker-Collo S, Jones K, Theadom A, Starkey N, Dowell A, McPherson K, et al. Neuropsychological outcome and its correlates in the first year after adult mild traumatic brain injury: a population-based New Zealand study. Brain Inj 2015; 29: 1604–1616.

https://doi.org/10.3109/02699052.2015.1075143 DOI: https://doi.org/10.3109/02699052.2015.1075143

Van Rijsbergen MW, Mark RE, Kop WJ, De Kort PL, Sitskoorn MM. Course and predictors of subjective cognitive complaints during the first 12 months after stroke. J Stroke Cerebrovasc Dis 2020; 29: 104588. DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2019.104588

https://doi.org/10.1016/ j.jstrokecerebrovasdis.2019.104588

Bailey Jr DE, Barroso J, Muir AJ, Sloane R, Richmond J, McHutchison J, et al. Patients with chronic hepatitis C undergoing watchful waiting: Exploring trajectories of illness uncertainty and fatigue. Res Nurs Health 2010; 33: 465–473.

https://doi.org/10.1002/nur.20397 DOI: https://doi.org/10.1002/nur.20397

Pence BW, Barroso J, Harmon JL, Leserman J, Salahuddin N, Hammill BG. Chronicity and remission of fatigue in patients with established HIV infec-tion. AIDS Patient Care STDS 2009; 23: 239–244.

https://doi.org/10.1089/apc.2008.0175 DOI: https://doi.org/10.1089/apc.2008.0175

Lam MH-B, Wing Y-K, Yu MW-M, Leung C-M, Ma RC, Kong AP, et al. Mental morbidities and chronic fatigue in severe acute respiratory syndrome sur-vivors: long-term follow-up. Arch Intern Med 2009; 169: 2142–2147.

https://doi.org/10.1001/archinternmed.2009.384 DOI: https://doi.org/10.1001/archinternmed.2009.384

Schepers VP, Visser-Meily AM, Ketelaar M, Lindeman E. Poststroke fatigue: course and its relation to personal and stroke-related factors. Arch Phys Med Rehabil 2006; 87: 184–188.

https://doi.org/10.1016/j.apmr.2005.10.005 DOI: https://doi.org/10.1016/j.apmr.2005.10.005

Mazza MG, Palladini M, Villa G, De Lorenzo R, Querini PR, Benedetti F. Prevalence, trajectory over time, and risk factor of post-COVID-19 fatigue. J Psychiatr Res 2022; 155: 112–119.

https://doi.org/10.1016/j.jpsychires.2022.08.008 DOI: https://doi.org/10.1016/j.jpsychires.2022.08.008

Huang L, Yao Q, Gu X, Wang Q, Ren L, Wang Y, et al. 1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study. The lancet 2021; 398: 747–758.

https://doi.org/10.1016/S0140-6736(21)01755-4 DOI: https://doi.org/10.1016/S0140-6736(21)01755-4

Frontera JA, Yang D, Medicherla C, Baskharoun S, Bauman K, Bell L, et al. Trajectories of neurologic recovery 12 months after hospitalization for COVID-19: a prospective longitudinal study. Neurology 2022; 99: e33–e45. DOI: https://doi.org/10.1212/WNL.0000000000201680

https://doi.org/10.1212/WNL.0000000000200356 DOI: https://doi.org/10.1212/WNL.0000000000200356

Fernández-de-Las-Peñas C, Martín-Guerrero JD, Cancela-Cilleruelo I, Moro-López-Menchero P, Rodríguez-Jiménez J, Pellicer-Valero OJ. Trajectory curves of post-COVID anxiety/depressive symptoms and sleep quality in previously hospitalized COVID-19 survivors: the LONG-COVID-EXP-CM multicenter study. Psychol Med 2023; 53: 4298–4299.

https://doi.org/10.1017/S003329172200006X DOI: https://doi.org/10.1017/S003329172200006X

Han Q, Zheng B, Daines L, Sheikh A. Long-term sequelae of COVID-19: a systematic review and meta-analysis of one-year follow-up studies on post-COVID symptoms. Pathogens 2022; 11: 269.

https://doi.org/10.3390/pathogens11020269 DOI: https://doi.org/10.3390/pathogens11020269

Klinkhammer S, Horn J, Visser-Meily JM, Verwijk E, Duits A, Slooter AJ, et al. Dutch multicentre, prospective follow-up, cohort study comparing the neurological and neuropsychological sequelae of hospitalised non-ICU-and ICU-treated COVID-19 survivors: a study protocol. BMJ open 2021; 11: e054901.

https://doi.org/10.1136/bmjopen-2021-054901 DOI: https://doi.org/10.1136/bmjopen-2021-054901

Klinkhammer S, Horn J, Duits AA, Visser-Meily JM, Verwijk E, Slooter AJ, et al. Neurological and (neuro) psychological sequelae in intensive care and general ward COVID-19 survivors. Eur J Neurol 2023; 30: 1880–1890.

https://doi.org/http://dx.doi.org/10.1111/ene.15812 DOI: https://doi.org/10.1111/ene.15812

van Rijsbergen MW, Mark RE, de Kort PL, Sitskoorn MM. Prevalence and profile of poststroke subjective cognitive complaints. J Stroke Cerebrovasc Dis 2015; 24: 1823–1831.

https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.04.017 DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.04.017

Lambert NJ, Corps S. COVID-19 “long hauler” symptoms survey report. 2020.

Heesakkers H, van der Hoeven JG, Corsten S, Janssen I, Ewalds E, Simons KS, et al. Clinical outcomes among patients with 1-year survival following intensive care unit treatment for COVID-19. JAMA 2022; 327: 559–565.

https://doi.org/10.1001/jama.2022.0040. DOI: https://doi.org/10.1001/jama.2022.0040

Bouwman V, Adriaanse MC, van’t Riet E, Snoek FJ, Dekker JM, Nijpels G. Depression, anxiety and glucose metabolism in the general dutch population: the new Hoorn study. PLoS One 2010; 5: e9971.

https://doi.org/10.1371/journal.pone.0009971 DOI: https://doi.org/10.1371/journal.pone.0009971

Ahmed H, Patel K, Greenwood DC, Halpin S, Lewthwaite P, Salawu A, et al. Long-term clinical outcomes in survivors of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome coronavirus (MERS) outbreaks after hospitalisation or ICU admission: a systematic review and meta-analysis. J Rehabil Med 2020; 52: 1–11.

https://doi.org/10.2340/16501977-2694 DOI: https://doi.org/10.2340/16501977-2694

Zeng L-N, Zong Q-Q, Yang Y, Zhang L, Xiang Y-F, Ng CH, et al. Gender difference in the prevalence of insomnia: a meta-analysis of observational studies. Frontiers in Psychiatry 2020; 11: 577429.

https://doi.org/10.3389/fpsyt.2020.577429 DOI: https://doi.org/10.3389/fpsyt.2020.577429

Fernández-de-Las-Peñas C, Martín-Guerrero JD, Cancela-Cilleruelo I, Moro-López-Menchero P, Pellicer-Valero OJ. Exploring the recovery curve for long-term post-COVID dyspnea and fatigue. Eur J Intern Med 2022; 101: 120–123.

https://doi.org/10.1016/j.ejim.2022.03.036 DOI: https://doi.org/10.1016/j.ejim.2022.03.036

O’Brien K, Townsend L, Dowds J, Bannan C, Nadarajan P, Kent B, et al. 1-year quality of life and health-outcomes in patients hospitalised with COVID-19: a longitudinal cohort study. Respir Res 2022; 23: 1–11.

https://doi.org/10.1186/s12931-022-02032-7 DOI: https://doi.org/10.1186/s12931-022-02032-7

Seeßle J, Waterboer T, Hippchen T, Simon J, Kirchner M, Lim A, et al. Persistent symptoms in adult patients 1 year after coronavirus disease 2019 (COVID-19): a prospective cohort study. Clin Infect Dis 2022; 74: 1191–1198.

https://doi.org/10.1093/cid/ciab611 DOI: https://doi.org/10.1093/cid/ciab611

Boynton PM, Greenhalgh T. Selecting, designing, and developing your questionnaire. BMJ 2004; 328: 1312–1315.

https://doi.org/10.1136/bmj.328.7451.1312 DOI: https://doi.org/10.1136/bmj.328.7451.1312

Campos MC, Nery T, Starke AC, de Bem Alves AC, Speck AE, Junior ASA. Post-viral fatigue in COVID-19: A review of symptom assessment methods, mental, cognitive, and physical impairment. Neurosci Biobehav Rev 2022; 142: 104902.

https://doi.org/10.1016/j.neubiorev.2022.104902 DOI: https://doi.org/10.1016/j.neubiorev.2022.104902

Mangot-Sala L, Smidt N, Liefbroer AC. Changes in anxiety and depression symptoms during the Covid-19 lockdown in the Netherlands. The moderating role of pre-existing mental health, employment situation and alcohol consumption. Soc Psychiatry Psychiatr Epidemiol 2023; 58: 1561–1571.

https://doi.org/10.1007/s00127-023-02480-6 DOI: https://doi.org/10.1007/s00127-023-02480-6

Ori AP, Wieling M, van Loo HM, Initiative LCR. Longitudinal analyses of depression, anxiety, and suicidal ideation highlight greater prevalence in the northern Dutch population during the COVID-19 lockdowns. J Affect Disord 2023; 323: 62–70.

https://doi.org/10.1016/j.jad.2022.11.040 DOI: https://doi.org/10.1016/j.jad.2022.11.040

Halsøy Ø, Johnson SU, Hoffart A, Ebrahimi OV. Insomnia symptoms in the general population during the COVID-19 pandemic. Front Psychiatr 2021; 12: 762799.

https://doi.org/10.3389/fpsyt.2021.762799 DOI: https://doi.org/10.3389/fpsyt.2021.762799

AlRasheed MM, Fekih-Romdhane F, Jahrami H, Pires GN, Saif Z, Alenezi AF, et al. The prevalence and severity of insomnia symptoms during COVID-19: a global systematic review and individual participant data meta-analysis. Sleep Med 2022 ; 100: 7–23.

https://doi.org/10.1016/j.sleep.2022.06.020 DOI: https://doi.org/10.1016/j.sleep.2022.06.020

Schild A-K, Scharfenberg D, Kirchner L, Klein K, Regorius A, Goereci Y, et al. Subjective and objective cognitive deficits in patients with post-COVID syndrome. Zeitschrift für Neuropsychologie 2023; https://doi.org/10.1024/1016-264X/a000374.

https://doi.org/10.1024/1016-264X/a000374 DOI: https://doi.org/10.1024/1016-264X/a000374

Vos L, Williams MW, Poritz JM, Ngan E, Leon-Novelo L, Sherer M. The discrepancy between cognitive complaints and neuropsychological test findings in persons with traumatic brain injury. J Head Trauma Rehabil 2020; 35: E382–E392.

https://doi.org/10.1097/HTR.0000000000000557 DOI: https://doi.org/10.1097/HTR.0000000000000557

Bonanno GA. Loss, trauma, and human resilience: have we underestimated the human capacity to thrive after extremely aversive events? Am Psychol 2004; 59: 20–28.

https://doi.org/10.1037/0003-066X.59.1.20 DOI: https://doi.org/10.1037/0003-066X.59.1.20

van Mierlo M, van Heugten C, Post MW, Hoekstra T, Visser-Meily A. Trajectories of health-related quality of life after stroke: results from a one-year prospective cohort study. Disabil Rehabil 2018; 40: 997–1006.

https://doi.org/10.1080/09638288.2017.1292320 DOI: https://doi.org/10.1080/09638288.2017.1292320

Kimhi S, Eshel Y, Marciano H, Adini B, Bonanno GA. Trajectories of depression and anxiety during COVID-19 associations with religion, income, and economic difficulties. J Psychiatr Res 2021; 144: 389–396. DOI: https://doi.org/10.1016/j.jpsychires.2021.10.043

https://doi.org/10.1016/ j.jpsychires.2021.10.043 DOI: https://doi.org/10.1055/s-0041-1725992

Grefkes C, Fink GR. Recovery from stroke: current concepts and future perspectives. Neurological research and practice 2020; 2: 1–10.

https://doi.org/10.1186/s42466-020-00060-6. DOI: https://doi.org/10.1186/s42466-020-00060-6

Davis MC, Zautra AJ, Younger J, Motivala SJ, Attrep J, Irwin MR. Chronic stress and regulation of cellular markers of inflammation in rheumatoid arthri-tis: implications for fatigue. Brain Behav Immun 2008; 22: 24-32

https://doi.org/10.1016/j.bbi.2007.06.013 DOI: https://doi.org/10.1016/j.bbi.2007.06.013

Nesselroade JR, Ram N. Studying intraindividual variability: what we have learned that will help us understand lives in context. Res Hum Dev 2004; 1: 9–29. DOI: https://doi.org/10.1207/s15427617rhd0101&2_3

https://doi.org/10.1080/15427609.2004.9683328 DOI: https://doi.org/10.1080/15427609.2004.9683328

Kuut TA, Müller F, Csorba I, Braamse A, Aldenkamp A, Appelman B, et al. Efficacy of cognitive behavioral therapy targeting severe fatigue following COVID-19: results of a randomized controlled trial. Clin Infect Dis 2023; 77: 687–695.

https://doi.org/10.1093/cid/ciad257 DOI: https://doi.org/10.1093/cid/ciad257

Bonanno GA, Westphal M, Mancini AD. Resilience to loss and potential trauma. Annu Rev Clin Psychol 2011; 7: 511-535

https://doi.org/10.1146/annurev-clinpsy-032210-104526 DOI: https://doi.org/10.1146/annurev-clinpsy-032210-104526

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2024-03-12

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Klinkhammer, S., Duits, A. A., Horn, J., Slooter, A. J., Verwijk, E., van Santen, S., … van Heugten, C. (2024). Prevalence and trajectories of neuropsychological post-COVID-19 symptoms in initially hospitalized patients. Journal of Rehabilitation Medicine, 56, jrm25315. https://doi.org/10.2340/jrm.v56.25315

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Vol. 56 (2024)

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Copyright (c) 2024 Simona Klinkhammer, Annelien A. Duits, Janneke Horn, Arjen J.C. Slooter, Esmée Verwijk, Susanne van Santen, Johanna M.A. Visser-Meily, Caroline van Heugten

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