Tag: long covid neurology

Central hypersomnia and chronic insomnia: expanding the spectrum of sleep disorders in long COVID syndrome – a prospective cohort study

Abstract:

Introduction: Long-onset COVID syndrome has been described in patients with COVID-19 infection with persistence of symptoms or development of sequelae beyond 4 weeks after the onset of acute symptoms, a medium- and long-term consequence of COVID-19. This syndrome can affect up to 32% of affected individuals, with symptoms of fatigue, dyspnea, chest pain, cognitive disorders, insomnia, and psychiatric disorders. The present study aimed to characterize and evaluate the prevalence of sleep symptoms in patients with long COVID syndrome.

Methodology: A total of 207 patients with post-COVID symptoms were evaluated through clinical evaluation with a neurologist and specific exams in the subgroup complaining of excessive sleepiness.

Results: Among 189 patients included in the long COVID sample, 48 (25.3%) had sleep-related symptoms. Insomnia was reported by 42 patients (22.2%), and excessive sleepiness (ES) was reported by 6 patients (3.17%). Four patients with ES were evaluated with polysomnography and test, multiple sleep latencies test, and actigraphic data. Two patients had a diagnosis of central hypersomnia, and one had narcolepsy. A history of steroid use was related to sleep complaints (insomnia and excessive sleepiness), whereas depression was related to excessive sleepiness. We observed a high prevalence of cognitive complaints in these patients.

Conclusion: Complaints related to sleep, such as insomnia and excessive sleepiness, seem to be part of the clinical post-acute syndrome (long COVID syndrome), composing part of its clinical spectrum, relating to some clinical data.

Source: Moura AEF, Oliveira DN, Torres DM, Tavares-Júnior JWL, Nóbrega PR, Braga-Neto P, Sobreira-Neto MA. Central hypersomnia and chronic insomnia: expanding the spectrum of sleep disorders in long COVID syndrome – a prospective cohort study. BMC Neurol. 2022 Nov 9;22(1):417. doi: 10.1186/s12883-022-02940-7. PMID: 36352367; PMCID: PMC9643986. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9643986/ (Full text)

Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study

Abstract:

Growing evidence links COVID-19 with acute and long-term neurological dysfunction. However, the pathophysiological mechanisms resulting in central nervous system involvement remain unclear, posing both diagnostic and therapeutic challenges. Here we show outcomes of a cross-sectional clinical study (NCT04472013) including clinical and imaging data and corresponding multidimensional characterization of immune mediators in the cerebrospinal fluid (CSF) and plasma of patients belonging to different Neuro-COVID severity classes.

The most prominent signs of severe Neuro-COVID are blood-brain barrier (BBB) impairment, elevated microglia activation markers and a polyclonal B cell response targeting self-antigens and non-self-antigens. COVID-19 patients show decreased regional brain volumes associating with specific CSF parameters, however, COVID-19 patients characterized by plasma cytokine storm are presenting with a non-inflammatory CSF profile. Post-acute COVID-19 syndrome strongly associates with a distinctive set of CSF and plasma mediators. Collectively, we identify several potentially actionable targets to prevent or intervene with the neurological consequences of SARS-CoV-2 infection.

Source: Etter MM, Martins TA, Kulsvehagen L, Pössnecker E, Duchemin W, Hogan S, Sanabria-Diaz G, Müller J, Chiappini A, Rychen J, Eberhard N, Guzman R, Mariani L, Melie-Garcia L, Keller E, Jelcic I, Pargger H, Siegemund M, Kuhle J, Oechtering J, Eich C, Tzankov A, Matter MS, Uzun S, Yaldizli Ö, Lieb JM, Psychogios MN, Leuzinger K, Hirsch HH, Granziera C, Pröbstel AK, Hutter G. Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study. Nat Commun. 2022 Nov 9;13(1):6777. doi: 10.1038/s41467-022-34068-0. PMID: 36351919; PMCID: PMC9645766.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9645766/ (Full text)

Dysautonomia in Children with Post-Acute Sequelae of Coronavirus 2019 Disease and/or Vaccination

Abstract:

Long-term health problems such as fatigue, palpitations, syncope, and dizziness are well-known in patients after COVID-19 (post-acute sequelae of coronavirus (PASC)). More recently, comparable problems have been noticed after the SARS-CoV-2 vaccination (post-VAC). The pathophysiology of these problems is not well-understood.

Methods: In 38 children and young adults, we tested if these health problems were related to dysautonomia in an active standing test (Group 1: 19 patients after COVID-19; Group 2: 12 patients with a breakthrough infection despite a vaccination; and Group 3: 7 patients after a vaccination without COVID-19). The data were compared with a control group of 47 healthy age-matched patients, as recently published.

Results: All patients had a normal left ventricular function as measured by echocardiography. Significantly elevated diastolic blood pressure in all patient groups indicated a regulatory cardiovascular problem. Compared with the healthy control group, the patient groups showed significantly elevated heart rates whilst lying and standing, with significantly higher heart rate increases. The stress index was significantly enhanced in all patient groups whilst lying and standing. Significantly decreased pNN20 values, mostly whilst standing, indicated a lower vagus activity in all patient groups. The respiratory rates were significantly elevated in Groups 1 and 2.

Conclusion: The uniform increase in the heart rates and stress indices, together with low pNN20 values, indicated dysautonomia in children with health problems after COVID-19 disease and/or vaccination. A total of 8 patients fulfilled the criteria of postural orthostatic tachycardia syndrome and 9 patients of an inappropriate sinus tachycardia, who were successfully treated with omega-3 fatty acid supplementation and pharmacotherapy.

Source: Buchhorn R. Dysautonomia in Children with Post-Acute Sequelae of Coronavirus 2019 Disease and/or Vaccination. Vaccines (Basel). 2022 Oct 9;10(10):1686. doi: 10.3390/vaccines10101686. PMID: 36298551; PMCID: PMC9607162. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9607162/ (Full text)

SARS-CoV-2 promotes microglial synapse elimination in human brain organoids

Abstract:

Neuropsychiatric manifestations are common in both the acute and post-acute phase of SARS-CoV-2 infection, but the mechanisms of these effects are unknown. In a newly established brain organoid model with innately developing microglia, we demonstrate that SARS-CoV-2 infection initiate neuronal cell death and cause a loss of post-synaptic termini. Despite limited neurotropism and a decelerating viral replication, we observe a threefold increase in microglial engulfment of postsynaptic termini after SARS-CoV-2 exposure.

We define the microglial responses to SARS-CoV-2 infection by single cell transcriptomic profiling and observe an upregulation of interferon-responsive genes as well as genes promoting migration and synapse engulfment. To a large extent, SARS-CoV-2 exposed microglia adopt a transcriptomic profile overlapping with neurodegenerative disorders that display an early synapse loss as well as an increased incident risk after a SARS-CoV-2 infection. Our results reveal that brain organoids infected with SARS-CoV-2 display disruption in circuit integrity via microglia-mediated synapse elimination and identifies a potential novel mechanism contributing to cognitive impairments in patients recovering from COVID-19.

Source: Samudyata, Oliveira AO, Malwade S, Rufino de Sousa N, Goparaju SK, Gracias J, Orhan F, Steponaviciute L, Schalling M, Sheridan SD, Perlis RH, Rothfuchs AG, Sellgren CM. SARS-CoV-2 promotes microglial synapse elimination in human brain organoids. Mol Psychiatry. 2022 Oct 5:1–12. doi: 10.1038/s41380-022-01786-2. Epub ahead of print. PMID: 36198765; PMCID: PMC9533278.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9533278/ (Full text)

The Psychiatric Consequences of Long-COVID: A Scoping Review

Abstract:

The COVID-19 pandemic has represented a new form of traumatic event, affecting the general population worldwide and causing severe disruption of daily routine. A new urgent concern is related to the burden associated with COVID-19 symptoms that persist beyond the onset of infection, the so-called long-COVID syndrome.
The present paper aims to: (1) describe the most frequent psychiatric symptoms reported by patients affected by long-COVID syndrome; (2) evaluate methodological discrepancies among the available studies; (3) inform clinicians and policy-makers on the possible strategies to be promoted in order to manage the psychiatric consequences of long-COVID syndrome.
Twenty-one papers have been included in the present review, mostly with a cross-sectional or cohort design. Significant heterogeneity of long-COVID syndrome definitions was found. The presence of psychiatric symptoms was evaluated with very different assessment tools.
The most common psychiatric symptoms of the long-COVID syndrome included fatigue, cognitive disturbances/impairment, depression, and anxiety symptoms. The rate of fatigue varied from 93.2–82.3% to 11.5%, cognitive impairment/cognitive dysfunction from 61.4% to 23.5% and depressive-anxiety symptoms from 23.5%to 9.5%
Source: Sampogna G, Di Vincenzo M, Giallonardo V, Perris F, Volpicelli A, Del Vecchio V, Luciano M, Fiorillo A. The Psychiatric Consequences of Long-COVID: A Scoping Review. Journal of Personalized Medicine. 2022; 12(11):1767. https://doi.org/10.3390/jpm12111767  https://www.mdpi.com/2075-4426/12/11/1767/htm (Full text)

Psychiatric and neurological complications of long COVID

Abstract:

COVID-19 was primarily considered a pulmonary disease with extrapulmonary manifestations. As the pandemic spread, there has been growing evidence that the disease affects various organs/systems, including the central and peripheral nervous systems. Accumulation of clinical data demonstrates that in a large population of survivors impairments in the function of one or more organs may persist for a long time, a phenomenon commonly known as post COVID or long COVID.

Fatigue and cognitive dysfunction, such as concentration problems, short-term memory deficits, general memory loss, a specific decline in attention, language and praxis abilities, encoding and verbal fluency, impairment of executive functions, and psychomotor coordination, are amongst the most common and debilitating features of neuropsychatric symptoms of post COVID syndrome. Several patients also suffer from compromised sleep, depression, anxiety and post-traumatic stress disorder. Patients with long COVID may demonstrate brain hypometabolism, hypoperfusion of the cerebral cortex and changes in the brain structure and functional connectivity.

Children and adolescents represent a minority of COVID-19 cases, so not surprisingly data on the long-term sequelae after SARS-CoV-2 infections in these age groups are scarce. Although the pathogenesis, clinical characteristics, epidemiology, and risk factors of the acute phase of COVID-19 have been largely explained, these areas are yet to be explored in long COVID. This review aims to provide an update on what is currently known about long COVID effects on mental health.

Source: Zawilska JB, Kuczyńska K. Psychiatric and neurological complications of long COVID. J Psychiatr Res. 2022 Oct 20;156:349-360. doi: 10.1016/j.jpsychires.2022.10.045. Epub ahead of print. PMID: 36326545; PMCID: PMC9582925. https://www.sciencedirect.com/science/article/pii/S0022395622005982 (Full text)

Brain 18F-FDG PET imaging in outpatients with post-COVID-19 conditions: findings and associations with clinical characteristics

Abstract:

Background: Brain 18F-FDG PET imaging has the potential to provide an objective assessment of brain involvement in post-COVID-19 conditions but previous studies of heterogeneous patient series yield inconsistent results. The current study aimed to investigate brain 18F-FDG PET findings in a homogeneous series of outpatients with post-COVID-19 conditions and to identify associations with clinical patient characteristics.

Methods: We retrospectively included 28 consecutive outpatients who presented with post-COVID-19 conditions between September 2020 and May 2022 and who satisfied the WHO definition, and had a brain 18F-FDG PET for suspected brain involvement but had not been hospitalized for COVID-19. A voxel-based group comparison with 28 age- and sex-matched healthy controls was performed (p-voxel at 0.005 uncorrected, p-cluster at 0.05 FWE corrected) and identified clusters were correlated with clinical characteristics.

Results: Outpatients with post-COVID-19 conditions exhibited diffuse hypometabolism predominantly involving right frontal and temporal lobes including the orbito-frontal cortex and internal temporal areas. Metabolism in these clusters was inversely correlated with the number of symptoms during the initial infection (r = – 0.44, p = 0.02) and with the duration of symptoms (r = – 0.39, p = 0.04). Asthenia and cardiovascular, digestive, and neurological disorders during the acute phase and asthenia and language disorders during the chronic phase (p ≤ 0.04) were associated with these hypometabolic clusters.

Conclusion: Outpatients with post-COVID-19 conditions exhibited extensive hypometabolic right fronto-temporal clusters. Patients with more numerous symptoms during the initial phase and with a longer duration of symptoms were at higher risk of persistent brain involvement.

Source: Goehringer F, Bruyere A, Doyen M, Bevilacqua S, Charmillon A, Heyer S, Verger A. Brain 18F-FDG PET imaging in outpatients with post-COVID-19 conditions: findings and associations with clinical characteristics. Eur J Nucl Med Mol Imaging. 2022 Nov 2. doi: 10.1007/s00259-022-06013-2. Epub ahead of print. PMID: 36322190. https://link.springer.com/article/10.1007/s00259-022-06013-2 (Full text)

Negative correlation between ACE2 gene expression levels and loss of taste in a cohort of COVID-19 hospitalized patients: New clues to long-term cognitive disorders

Abstract:

In early 2020, one of the most prevalent symptoms of SARS-CoV-2 infection was the loss of smell (anosmia), found in 60-70% of all cases. Anosmia used to occur early, concomitantly with other symptoms, and often persisted after recovery for an extended period, sometimes for months. In addition to smell disturbance, COVID-19 has also been associated with loss of taste (ageusia). The latest research suggests that SARS-CoV-2 could spread from the respiratory system to the brain through receptors in sustentacular cells localized to the olfactory epithelium. The virus invades human cells via the obligatory receptor, angiotensin-converting enzyme II (ACE2), and a priming protease, TMPRSS2, facilitating viral penetration. There is an abundant expression of both ACE2 and TMPRSS2 in sustentacular cells.

In this study, we evaluated 102 COVID-19 hospitalized patients, of which 17.60% presented anosmia and 9.80% ageusia. ACE1, ACE2, and TMPRSS2 gene expression levels in nasopharyngeal tissue were obtained by RT-qPCR and measured using ΔCT analysis. ACE1 Alu287bp association was also evaluated. Logistic regression models were generated to estimate the effects of variables on ageusia and anosmia.

Association of ACE2 expression levels with ageusia. was observed (OR: 1.35; 95% CI: 1.098-1.775); however, no association was observed between TMPRSS2 and ACE1 expression levels and ageusia. No association was observed among the three genes and anosmia, and the Alu287bp polymorphism was not associated with any of the outcomes.

Lastly, we discuss whetherthere is a bridge linking these initial symptoms, including molecular factors, to long-term COVID-19 health consequences such as cognitive dysfunctions.

Source: Braga-Paz I, Ferreira de Araújo JL, Alves HJ, de Ávila RE, Resende GG, Teixeira MM, de Aguiar RS, de Souza RP, Bahia D. Negative correlation between ACE2 gene expression levels and loss of taste in a cohort of COVID-19 hospitalized patients: New clues to long-term cognitive disorders. Front Cell Infect Microbiol. 2022 Sep 29;12:905757. doi: 10.3389/fcimb.2022.905757. PMID: 36250059; PMCID: PMC9556632. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9556632/ (Full text)

Headaches and Dizziness as Disabling, Persistent Symptoms in Patients with Long COVID-A National Multicentre Study

Abstract:

Background: Currently, about 15% of coronavirus disease-19 (COVID-19) patients are affected by Long COVID worldwide; however, this condition has not yet been sufficiently studied. The aim of this study was to identify the impact of symptom persistence as well as clinical and socio-demographic variables in a cohort of people with Long COVID.

Methods: We conducted a descriptive cross-sectional study of a sample of adult patients from different Spanish regions presenting with Long COVID. Data collection was conducted between April and July 2021. Functional status and dependency were assessed.

Results: A multivariate linear regression was performed, and the model was statistically significant (F (7; 114) = 8.79; p < 0.001), according to the overall ALDQ score. The variables with a statistically significant effect on the degree of dependence were age (p = 0.014), time since diagnosis (p = 0.02), headaches (p = 0.031), and dizziness (p = 0.039). Functional status post-COVID showed a positive and significant relationship with the percentage of dependence (p < 0.001).

Conclusions: People affected by Long COVID showed moderate dependency status and limitations in functionality. Those with neurological symptoms, such as dizziness and headaches, as well as older age, showed a higher degree of dependency. Improvements in dependency status occurred with increasing time since diagnosis.

Source: Rodríguez-Pérez MP, Sánchez-Herrera-Baeza P, Rodríguez-Ledo P, Serrada-Tejeda S, García-Bravo C, Pérez-de-Heredia-Torres M. Headaches and Dizziness as Disabling, Persistent Symptoms in Patients with Long COVID-A National Multicentre Study. J Clin Med. 2022 Oct 6;11(19):5904. doi: 10.3390/jcm11195904. PMID: 36233769; PMCID: PMC9572453. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9572453/ (Full text)

SARS-CoV-2, long COVID, prion disease and neurodegeneration

Introduction:

On the last day of the year 2019 a novel Betacoronavirus (2019-nCov), now known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and causing the highly transmissible and lethal pneumonia COVID-19 was first reported in Wuhan, Hubei Province in Central China (Huang et al., ; Fu et al., ; Lu and Sun, ). Since then ongoing research and long-term studies of the sequelae of SARS-CoV-2 infection have indicated that post-infection, recovery from COVID-19 and/or COVID-19 aftermath is associated with long-term physiological and neurological deficits known generically as “long COVID” (Roy et al., ; Ahmad et al., ; Baazaoui and Iqbal, ). Multiple independent epidemiological and clinical studies further indicate that SARS-CoV-2 infection and “long COVID” strongly correlate with the onset of progressive neurological disturbances that include Alzheimer’s disease (AD), prion disease (PrD) and other neurodegenerative disorders. These are apparent: (i) especially in aged and/or senile COVID-19 patients; (ii) in patients experiencing overlapping or inter-current illnesses that include heart disease, diabetes, hypertension, neuropsychiatric and other age-related neurological disorders; and (iii) in those COVID-19 patients who have experienced a particularly virulent and/or a near fatal episode of SARS-CoV-2 infection (Farheen et al., ; Flud et al., ; Fu et al., ). Conversely, increasing numbers of epidemiological studies suggest that elderly people with neurological deficits commonly observed in AD are highly vulnerable to SARS-CoV-2 infection, and especially the development of more severe forms of COVID-19 disease (Chiricosta et al., ; Hsu et al., ; Fu et al., ). The recent finding that the SARS-CoV-2 “S1” spike protein essential for viral infectivity contains prion-like domains associated with immune-evasion and the promotion of protein aggregation and aggregate “seeding” is particularly intriguing (Baazaoui and Iqbal, ; Bernardini et al., ; Tetz and Tetz, ). Based on these and other very recent findings this “Opinion” paper will: (i) address our current understanding of the emerging role of SARS-CoV-2 infection with “long COVID” with special reference to AD and PrD; (ii) will review the latest findings of the SARS-CoV-2 “S1” spike protein and its preferred interaction with the ubiquitous angiotensin converting enzyme-2 (ACE2) receptor (ACE2R); and (iii) will highlight the interplay of the molecular biology and neuropathology of SARS-CoV-2 with the unusual and immune-evasive character of prion neurobiology, AD and PrD.

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Source: Zhao Y, Jaber VR, Lukiw WJ. SARS-CoV-2, long COVID, prion disease and neurodegeneration. Front Neurosci. 2022 Sep 27;16:1002770. doi: 10.3389/fnins.2022.1002770. PMID: 36238082; PMCID: PMC9551214.  Zhao Y, Jaber VR, Lukiw WJ. SARS-CoV-2, long COVID, prion disease and neurodegeneration. Front Neurosci. 2022 Sep 27;16:1002770. doi: 10.3389/fnins.2022.1002770. PMID: 36238082; PMCID: PMC9551214. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9551214/ (Full text)