Neurological and (neuro)psychological sequelae in intensive care and general ward <scp>COVID</scp>‐19 survivors

Klinkhammer, Simona; Horn, Janneke; Duits, Annelien; Visser‐Meily, Johanna M. A.; Verwijk, Esmée; Slooter, Arjen J. C.; Postma, Alida A.; Heugten, Caroline van; Aries, Marcel; Bussel, Bas C.T. van; Jansen, Jacobus F.A.; Janssen, Marcus L.F.; Santen, Susanne van; Magdelijns, Fabienne; Posthuma, Rein; David, M; Linden, E. J.; Woude, Meta van der; Dormans, Tom; Otten, Amy; Karakus, Attila; Bronsveld, Inez; Karin,; Kaasjager, A. H.; Galenkamp, Niek; Geurtsen, Gert J.; Brouwer, Matthijs C.; Brinkman, Kees; Kylstra, Wytske A; Koch, Dook W.; Beudel, Martijn

doi:10.1111/ene.15812

Cited by 21 publications

(11 citation statements)

References 38 publications

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“…This study examined the trajectory of cognitive complaints in a sample not selected based on complaint experience, but the results align with studies that recruited patients with persistent complaints ( 31 ). It is crucial to distinguish cognitive complaints from dysfunction, as previous research has demonstrated a discrepancy between self-reported problems and cognitive test performance ( 15 , 32 ). Consistently, we previously observed cognitive complaints exceeding dysfunction in this sample ( 15 ).…”

Section: Discussionmentioning

confidence: 99%

“…It is crucial to distinguish cognitive complaints from dysfunction, as previous research has demonstrated a discrepancy between self-reported problems and cognitive test performance ( 15 , 32 ). Consistently, we previously observed cognitive complaints exceeding dysfunction in this sample ( 15 ). Notably, psychological symptoms, such as depression, are often associated with underestimated cognitive functions ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

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

Klinkhammer,

Duits,

Horn

et al. 2024

JRM

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Klinkhammer,

Duits,

Horn

et al. 2024

JRM

Self Cite

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“…BBB damage may allow neurotoxins to enter the brain and promote neurodegeneration [ 24 ]. Moreover, BBB dysfunction is likely to result in cerebral microbleeds, which were more prevalent in COVID-19 ICU survivors than general ward survivors [ 25 , 26 ]. Given these plausible pathways, anti-inflammatory pharmacologic approaches and psychotropic medications, e.g., systemic corticosteroids [ 27 ], l -arginine [ 28 ], curcumin [ 29 ], vitamins [ 30 ], etc., may be considered to mitigate the long-term symptoms in COVID-19 survivors.…”

Section: Discussionmentioning

confidence: 99%

Blood-brain barrier breakdown in COVID-19 ICU survivors: an MRI pilot study

Shi,

Jiang,

Rando

et al. 2023

NeuroImmune Pharmacology and Therapeutics

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Objectives Coronavirus disease 2019 (COVID-19) results in severe inflammation at the acute stage. Chronic neuroinflammation and abnormal immunological response have been suggested to be the contributors to neuro-long-COVID, but direct evidence has been scarce. This study aims to determine the integrity of the blood-brain barrier (BBB) in COVID-19 intensive care unit (ICU) survivors using a novel MRI technique. Methods COVID-19 ICU survivors (n=7) and age and sex-matched control participants (n=17) were recruited from June 2021 to March 2023. None of the control participants were hospitalized due to COVID-19 infection. The COVID-19 ICU survivors were studied at 98.6 ± 14.9 days after their discharge from ICU. A non-invasive MRI technique was used to assess the BBB permeability to water molecules, in terms of permeability surface area-product (PS) in the units of mL/100 g/min. Results PS was significantly higher in COVID-19 ICU survivors (p=0.038) when compared to the controls, with values of 153.1 ± 20.9 mL/100 g/min and 132.5 ± 20.7 mL/100 g/min, respectively. In contrast, there were no significant differences in whole-brain cerebral blood flow (p=0.649) or brain volume (p=0.471) between the groups. Conclusions There is preliminary evidence of a chronic BBB breakdown in COVID-19 survivors who had a severe acute infection, suggesting a plausible contributor to neurological long-COVID symptoms.

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“…Proposed pathophysiological mechanisms include residual lung damage, direct invasion of CNS tissue, endothelial injury, and immune dysregulation [ 7 , 9 ]. Given that brain imaging typically does not reveal structural lesions in the majority of long-COVID cases, a more subtle CNS involvement is conceivable, potentially contributing to the elevation of neural injury biomarkers, as previously described in other neurological conditions, i.e., in the early stages of dementia and post-anoxic encephalopathies [ 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

A Prospective Study on Neural Biomarkers in Patients with Long-COVID Symptoms

Vrettou,

Vassiliou,

Keskinidou

et al. 2024

JPM

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Background: this prospective observational study aims to assess serum levels of glial fibrillary acidic protein (GFAP), s100b, and total Tau in long-COVID patients, exploring correlations with symptoms, cognitive decline, mental health, and quality of life. Methods: Long-COVID patients visiting our outpatient clinic (February 2021–December 2022) were screened alongside age- and sex-matched controls. GFAP, s100b, and total Tau in serum were measured with ELISA. Cognitive function, depression, anxiety, post-traumatic stress disorder, and quality of life were evaluated using MoCA, HADS (depression and anxiety), IES-R, and SF-36, respectively. Results: Sixty-five long-COVID patients and 20 controls were included. GFAP levels were significantly higher in long-COVID patients (p = 0.031), though not correlating with the presence of long-COVID symptoms. S100b and total Tau showed no significant differences between patients and controls. Nervous system-related symptoms were reported in 47% of patients. High rates of cognitive decline (65.9%), depression (32.2%), anxiety (47.5%), and post-traumatic stress disorder (44.1%) were observed. Over 80% of the study population scored below normative cutoffs for SF-36, indicating a significant impact on quality of life. Conclusions: in this long-COVID cohort with substantial psychological and cognitive symptoms, GFAP levels were elevated compared to controls, though not correlating with the presence of long-COVID symptoms.

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Neurological and (neuro)psychological sequelae in intensive care and general ward COVID‐19 survivors

Cited by 21 publications

References 38 publications

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

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

Blood-brain barrier breakdown in COVID-19 ICU survivors: an MRI pilot study

A Prospective Study on Neural Biomarkers in Patients with Long-COVID Symptoms

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