Tag: long covid neurology

Electroencephalographic Abnormalities in a Patient Suffering from Long-Term Neuropsychological Complications following SARS-CoV-2 Infection

Abstract:

Introduction: Emotional apathy has recently been identified as a common symptom of long COVID. While recent meta-analyses have demonstrated generalized EEG slowing with the emergence of delta rhythms in patients hospitalized for severe SARS-CoV-2 infection, no EEG study or dopamine transporter scintigraphy (DaTSCAN) has been performed in patients with long COVID presenting with apathy. The objective of this case report was to explore the pathophysiology of neuropsychological symptoms in long COVID.

Case presentation: A 47-year-old patient who developed a long COVID with prominent apathy following an initially clinically mild SARS-CoV-2 infection underwent neuropsychological assessment, cerebral MRI, DaTSCAN, and resting-state high-density EEG 7 months after SARS-CoV-2 infection. The EEG data were compared to those of 21 healthy participants. The patient presented with apathy, cognitive difficulties with dysexecutive syndrome, moderate attentional and verbal episodic memory disturbances, and resolution of premorbid mild gaming disorder, mild mood disturbances, and sleep disturbances. His MRI and DaTSCAN were unremarkable. EEG revealed a complex pattern of oscillatory abnormalities compared to the control group, with a strong increase in whole-scalp delta and beta band activity, as well as a decrease in alpha band activity. Overall, these effects were more prominent in the frontal-central-temporal region.

Conclusion: These results suggest widespread changes in EEG oscillatory patterns in a patient with long COVID characterized by neuropsychological complications with prominent apathy. Despite the inherent limitations of a case report, these results suggest dysfunction in the cortical networks involved in motivation and emotion.

Source: Benis D, Voruz P, Chiuve SC, Garibotto V, Assal F, Krack P, Péron J, Fleury V. Electroencephalographic Abnormalities in a Patient Suffering from Long-Term Neuropsychological Complications following SARS-CoV-2 Infection. Case Rep Neurol. 2023 Dec 5;16(1):6-17. doi: 10.1159/000535241. PMID: 38179211; PMCID: PMC10764086. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10764086/ (Full text)

Post-COVID cognitive deficits at one year are global and associated with elevated brain injury markers and grey matter volume reduction: national prospective study

Abstract:

The spectrum, pathophysiology, and recovery trajectory of persistent post-COVID-19 cognitive deficits are unknown, limiting our ability to develop prevention and treatment strategies. We report the one-year cognitive, serum biomarker, and neuroimaging findings from a prospective, national longitudinal study of cognition in 351 COVID-19 patients who had required hospitalisation, compared to 2,927 normative matched controls.

Cognitive deficits were global and associated with elevated brain injury markers and reduced anterior cingulate cortex volume one year after admission. The severity of the initial infective insult, post-acute psychiatric symptoms, and a history of encephalopathy were associated with greatest deficits. There was strong concordance between subjective and objective cognitive deficits. Treatment with corticosteroids during the acute phase appeared protective against cognitive deficits. Together, these findings support the hypothesis that brain injury in moderate to severe COVID-19 is immune-mediated, and should guide the development of therapeutic strategies.

Source: Benedict Michael, Greta Wood, Brendan Sargent et al. Post-COVID cognitive deficits at one year are global and associated with elevated brain injury markers and grey matter volume reduction: national prospective study, 05 January 2024, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-3818580/v1] https://www.researchsquare.com/article/rs-3818580/v1 (Full text)

Large scale phenotyping of long COVID inflammation reveals mechanistic subtypes of disease after COVID-19 hospitalisation

Abstract:

One in ten SARS-CoV-2 infections result in prolonged symptoms termed long COVID, yet disease phenotypes and mechanisms are poorly understood. We studied the blood proteome of 719 previously hospitalised adults with long COVID grouped by symptoms. Elevated markers of myeloid inflammation and complement activation were associated with long COVID; elevated IL1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue, and anxiety/depression, while MATN2 and DPP10 were elevated in gastrointestinal (GI) symptoms, and C1QA in cognitive impairment.
Proteins suggestive of neurodegeneration were elevated in cognitive impairment, whilst SCG3 (indicative of brain-gut axis disturbance) was specific to GI symptoms. Nasal inflammation was apparent after COVID-19 but did not associate with symptoms. Although SARS-CoV-2 specific IgG was elevated with some long COVID symptoms, virus was not detected from sputum. Thus, systemic inflammation is evident in long COVID and could be targeted in therapeutic trials tailored to pathophysiological differences between symptom groups.

Source: Peter Openshaw, Felicity Liew, Claudia Efstathiou et al. Large scale phenotyping of long COVID inflammation reveals mechanistic subtypes of disease after COVID-19 hospitalisation, 04 December 2023, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-3427282/v1] https://www.researchsquare.com/article/rs-3427282/v1 (Full text)

Long-term neurological dysfunction associated with COVID-19: Lessons from influenza and inflammatory diseases?

Abstract:

As the COVID-19 pandemic persists, SARS-CoV-2 infection is increasingly associated with long-term neurological side effects including cognitive impairment, fatigue, depression, and anxiety, colloquially known as “long-COVID.” While the full extent of long-COVID neuropathology across years or even decades is not yet known, we can perhaps take direction from long-standing research into other respiratory diseases, such as influenza, that can present with similar long-term neurological consequences.

In this review, we highlight commonalities in the neurological impacts of influenza and COVID-19. We first focus on the common potential mechanisms underlying neurological sequelae of long-COVID and influenza, namely (1) viral neurotropism and (2) dysregulated peripheral inflammation. The latter, namely heightened peripheral inflammation leading to central nervous system dysfunction, is emerging as a shared mechanism in various peripheral inflammatory or inflammation-associated diseases and conditions.

We then discuss historical and modern examples of influenza- and COVID-19-associated cognitive impairment, depression, anxiety, and fatigue, revealing key similarities in their neurological sequelae. Although we are learning that the effects of influenza and COVID differ somewhat in terms of their influence on the brain, as the impacts of long-COVID grow, such comparisons will likely prove valuable in guiding ongoing research into long-COVID, and perhaps foreshadow what could be in store for individuals with COVID-19 and their brain health.

Source: Volk P, Rahmani Manesh M, Warren ME, Besko K, Gonçalves de Andrade E, Wicki-Stordeur LE, Swayne LA. Long-term neurological dysfunction associated with COVID-19: Lessons from influenza and inflammatory diseases? J Neurochem. 2023 Nov 28. doi: 10.1111/jnc.16016. Epub ahead of print. PMID: 38014645. https://onlinelibrary.wiley.com/doi/10.1111/jnc.16016 (Full text)

Drawing the Line Between Postacute Sequelae of COVID-19 and Functional Neurologic Disorders A Daunting Clinical Overlap or Irrelevant Conundrum?

Abstract:

Coronavirus disease 2019 (COVID-19) is an acute infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in its multiple variants that classically presents with cough, fatigue, fever, headache, myalgias, and diarrhea. As vaccination becomes widely available and infection rates facilitate herd immunity across the globe, more attention has been given to long-term symptoms that may persist after the index infection, which include impairments in concentration, executive dysfunction, sensory disturbances, depression, anxiety, fatigue, and cough, among other symptoms classified under the umbrella term of postacute sequelae of SARS-CoV-2 infection (PASC).

Functional neurologic disorder (FND), also known as conversion disorder and functional neurologic symptom disorder, refers to the presence of one or more symptoms of altered voluntary motor or sensory function that are incompatible with and not better explained by a known neurological or medical condition that causes significant distress and functional impairment. Although the diagnosis of FND may not require the identification of an underlying psychological stressor, being diagnosed with an FND can worsen stigma and shift attention and resources away from other medical concerns that should be concomitantly addressed.

This review summarizes the literature on the overlapping nature and discrimination of PASC from FND in COVID-19 survivors. Based on this, we develop a treatment framework that targets unique domains of these complex overlapping presentations, following a multidisciplinary approach with an individualized treatment plan inclusive of physical and psychological interventions focused on functional rehabilitation.

Source: Sales, Paulo M.G. MD, MS∗; Greenfield, Melissa J. PsyD∗; Pinkhasov, Aaron MD†; Viswanathan, Ramaswamy MD, DrMedSc‡; Saunders, Ramotse MD§; Huremović, Damir MD, MPP∥. Drawing the Line Between Postacute Sequelae of COVID-19 and Functional Neurologic Disorders: A Daunting Clinical Overlap or Irrelevant Conundrum?. The Journal of Nervous and Mental Disease 211(12):p 882-889, December 2023. | DOI: 10.1097/NMD.0000000000001643 https://journals.lww.com/jonmd/abstract/2023/12000/drawing_the_line_between_postacute_sequelae_of.2.aspx

Role of Tau protein in long COVID and potential therapeutic targets

Abstract:

Introduction: Long COVID is an emerging public health burden and has been defined as a syndrome with common symptoms of fatigue, shortness of breath, cognitive dysfunction, and others impacting day-to-day life, fluctuating or relapsing over, occurring for at least two months in patients with a history of probable or confirmed SARS CoV-2 infection; usually three months from the onset of illness and cannot be explained by an alternate diagnosis. The actual prevalence of long-term COVID-19 is unknown, but it is believed that more than 17 million patients in Europe may have suffered from it during pandemic.

Pathophysiology: Currently, there is limited understanding of the pathophysiology of this syndrome, and multiple hypotheses have been proposed. Our literature review has shown studies reporting tau deposits in tissue samples of the brain from autopsies of COVID-19 patients compared to the control group, and the in-vitro human brain organoid model has shown aberrant phosphorylation of tau protein in response to SARS-CoV-2 infection. Tauopathies, a group of neurodegenerative disorders with the salient features of tau deposits, can manifest different symptoms based on the anatomical region of brain involvement and have been shown to affect the peripheral nervous system as well and explained even in rat model studies.

Long COVID has more than 203 symptoms, with predominant symptoms of fatigue, dyspnea, and cognitive dysfunction, which tauopathy-induced CNS and peripheral nervous system dysfunction can explain. There have been no studies up till now to reveal the pathophysiology of long COVID. Based on our literature review, aberrant tau phosphorylation is a promising hypothesis that can be explored in future studies.

Therapeutic approaches for tauopathies have multidimensional aspects, including targeting post-translational modifications, tau aggregation, and tau clearance through the autophagy process with the help of lysosomes, which can be potential targets for developing therapeutic interventions for the long COVID. In addition, future studies can attempt to find the tau proteins in CSF and use those as biomarkers for the long COVID.

Source: Marwaha B. Role of Tau protein in long COVID and potential therapeutic targets. Front Cell Infect Microbiol. 2023 Oct 25;13:1280600. doi: 10.3389/fcimb.2023.1280600. PMID: 37953801; PMCID: PMC10634420. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634420/ (Full text)

Autonomic Manifestations of Long-COVID Syndrome

Abstract:

Purpose of review: Long-COVID is a novel condition emerging from the COVID-19 pandemic. Long-COVID is characterized by symptoms commonly seen in autonomic disorders including fatigue, brain fog, light-headedness, and palpitations. This article will critically evaluate recent findings and studies on Long-COVID and its physiological autonomic manifestations.

Recent findings: Studies have reported on the prevalence of different symptoms and autonomic disorders in Long-COVID cohorts. Autonomic nervous system function, including both the parasympathetic and sympathetic limbs, has been studied using different testing techniques in Long-COVID patients. While numerous mechanisms may contribute to Long-COVID autonomic pathophysiology, it is currently unclear which ones lead to a Long-COVID presentation. To date, studies have not tested treatment options for autonomic disorders in Long-COVID patients. Long-COVID is associated with autonomic abnormalities. There is a high prevalence of clinical autonomic disorders among Long-COVID patients, with limited knowledge of the underlying mechanisms and the effectiveness of treatment options.

Source: Hira R, Karalasingham K, Baker JR, Raj SR. Autonomic Manifestations of Long-COVID Syndrome. Curr Neurol Neurosci Rep. 2023 Nov 10. doi: 10.1007/s11910-023-01320-z. Epub ahead of print. PMID: 37947962. https://pubmed.ncbi.nlm.nih.gov/37947962/

Analysis of the correlation between heart rate variability and palpitation symptoms in female patients with long COVID

Abstract:

Objectives: To analyze the correlation between heart rate variability (HRV) and palpitation symptoms in female patients with long COVID.

Methods: A total of 272 female healthcare workers who were infected with SARS-CoV-2 for the first time in December 2022 at Fuzhou First Hospital affiliated with Fujian Medical University, were selected as study subjects. These subjects were divided into three groups based on their symptoms: a group with palpitations (70 cases), a group without palpitations but with other symptoms (124 cases), and a group consisting of asymptomatic cases (78 cases). The study compared the general information, COMPASS-31 scores, quality of life scores, and HRV parameters among the three groups. Furthermore, it analyzed the factors influencing palpitation symptoms in female patients with long COVID.

Results: Compared to the other two groups, the HRV parameters SDNN, HRVIndex, LF, and TP were significantly reduced in the group with palpitations (p < 0.05). Multivariate analysis revealed that HRVIndex (p = 0.016; OR: 0.966, 95% CI: 0.940∼0.994) had a significant impact on palpitation symptoms in female patients with long COVID.

Conclusions: The symptoms of palpitations in female patients with long COVID were found to be related to HRV parameters. Autonomic dysfunction may be connected to the occurrence of palpitation symptoms in long COVID.

Source: Jiang Yu, Cheng Yan, Xiao Jingwen, Wang Yicheng, Chen Geng, Zhang Yan. Analysis of the correlation between heart rate variability and palpitation symptoms in female patients with long COVID. Frontiers in Cardiovascular Medicine, 10, 2023 DOI=10.3389/fcvm.2023.1273156 ISSN=2297-055X  https://www.frontiersin.org/articles/10.3389/fcvm.2023.1273156 (Full text)

Similar Patterns of Dysautonomia in Myalgic Encephalomyelitis/Chronic Fatigue and Post-COVID-19 Syndromes

Abstract:

Background There is a considerable overlap between clinical presentation of post-COVID-19 condition (PCC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) . Many of their common symptoms can be linked to dysregulation of the autonomic nervous system (dysautonomia). This study aimed to objectively assess autonomic function in patients with PCC and in patients with ME/CFS whose disease was not related to COVID-19.

Methods Synchronous recordings of an electrocardiogram, continuous dynamics of blood pressure in the digital artery using the Penaz method and ultrasound pneumotachography with the spirography function were obtained with spiroarteriocardiorhythmography method in 34 patients diagnosed with ME/CFS, in whom the onset of the disease was not associated with COVID-19, 29 patients meeting PCC definition and 32 healthy controls. Heart rate variability (HRV), systolic and diastolic blood pressure variability (RV), respiration variability were assessed at rest and in tests with fixed respiratory rates. At rest, indicators of baroreflex regulation were additionally determined (baroreflex effectiveness index and baroreflex sensitivity).

Results The total power, power of very low frequency, low-frequency and high-frequency of RR interval variability at rest as well as baroreflex effectiveness index in up-ramps of arterial blood pressure and baroreflex sensitivity were significantly lower both in PCC and ME/CFS patients compared to HC. Several diagnostic prediction models for ME/CFS were developed based on HRV parameters. During slow breathing HRV parameters return to normal in PCC, but not in ME/CFS. Correlation analysis revealed a close relationship of HRV, RV parameters and baroreflex sensitivity with fatigue, but not with HADS depressive/anxiety symptoms in ME/CFS and PCC.

Conclusion A similar pattern of HRV and baroreflex failure with signs of a pathological acceleration of age-dependent dysautonomia was identified in ME/CFS and PCC. The clinical, diagnostic and therapeutic implications of these findings are discussed, in light of previously described relationship between inflammation, vascular pathology, atherosclerotic cardiovascular disease and autonomic dysfunction.

Source: Ryabkova, V.A.; Rubinskiy, A.V.; Marchenko, V.N.; Trofimov, V.I.; Churilov, L.P. Similar Patterns of Dysautonomia in Myalgic Encephalomyelitis/Chronic Fatigue and Post-COVID-19 Syndromes. Preprints 2023, 2023111228. https://doi.org/10.20944/preprints202311.1228.v1 https://www.preprints.org/manuscript/202311.1228/v1 (Full text available as PDF file)