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1.
J Infect Dis ; 225(6): 965-970, 2022 03 15.
Article in English | MEDLINE | ID: covidwho-1740882

ABSTRACT

Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in serum and cerebrospinal fluid (CSF) samples from 16 patients with coronavirus disease 2019 and neurological symptoms were assessed using 2 independent methods. Immunoglobulin G (IgG) specific for the virus spike protein was found in 81% of patients in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in 2 patients with negative serological findings. Levels of IgG in both serum and CSF were associated with disease severity (P < .05). All patients with elevated markers of central nervous system damage in CSF also had CSF antibodies (P = .002), and CSF antibodies had the highest predictive value for neuronal damage markers of all tested clinical variables.


Subject(s)
Antibodies, Viral/blood , COVID-19/diagnosis , Immunoglobulin G/blood , Nervous System Diseases/blood , Nervous System Diseases/cerebrospinal fluid , SARS-CoV-2/isolation & purification , Aged , Antibodies, Neutralizing/blood , Antibody Formation , Biomarkers/blood , Biomarkers/cerebrospinal fluid , COVID-19/blood , COVID-19/cerebrospinal fluid , COVID-19/complications , Female , Humans , Male , Middle Aged , Nervous System Diseases/diagnosis , Nervous System Diseases/etiology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus
2.
J Med Life ; 14(2): 216-224, 2021.
Article in English | MEDLINE | ID: covidwho-1262737

ABSTRACT

With the exponential growth of COVID-19 cases, the neurological complications reported during or after the infection became more common. There is limited knowledge regarding the pathophysiological mechanisms that are responsible for these complications. Recent data provides compelling evidence for the neurotropic nature of SARS-CoV-2, based on neurological manifestations reported during the current pandemic, as well as on previous experience with other coronaviruses. We present the case of a patient who developed headaches, motor deficit and dysphasia after respiratory COVID-19. Imaging tests showed heterogeneous central nervous system lesions (multiple subarachnoid hemorrhages and two ischemic strokes). Given the plethora of atypical neurological complications of COVID-19 described in the current literature, establishing a positive diagnosis and deciding on a treatment plan proved to be particularly challenging. We set to discuss some of the possible pathologies, hypothesized to be associated with COVID-19, that could lead to concomitant neurological lesions, similar to those noticed in our patient.


Subject(s)
COVID-19/complications , Nervous System Diseases/diagnosis , Nervous System Diseases/virology , Antibodies, Viral/blood , COVID-19/blood , COVID-19/diagnostic imaging , COVID-19/virology , Computed Tomography Angiography , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Nervous System Diseases/blood , Nervous System Diseases/diagnostic imaging , Pandemics , SARS-CoV-2/physiology , Thorax/diagnostic imaging , Tomography, X-Ray Computed
3.
Eur Arch Psychiatry Clin Neurosci ; 272(1): 41-52, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1130771

ABSTRACT

The objective is to investigate coronavirus disease 2019 (COVID-19)-associated neurological and psychiatric effects and explore possible pathogenic mechanisms. This study included 77 patients with laboratory-confirmed COVID-19 in Wuhan, China. Neurological manifestations were evaluated by well-trained neurologists, psychologists, psychiatric presentations and biochemical changes were evaluated using the Generalized Anxiety Disorder 7-item scale, Patient Health Questionnaire-9, Brief Psychiatric Rating Scale, and electronic medical records. Eighteen (23.4%) patients presented with neurological symptoms. Patients with neurological presentations had higher urea nitrogen, cystatin C, and high-sensitivity C-reactive protein levels and lower basophil counts. Among them, patients with muscle involvement had higher urea nitrogen and cystatin C levels but lower basophil counts. In addition, patients with psychiatric presentations were older and had higher interleukin (IL)-6 and IL-10 levels and higher alkaline phosphatase, R-glutamate transferase, and urea nitrogen levels. Moreover, patients with anxiety had higher IL-6 and IL-10 levels than those without, and patients with moderate depression had higher CD8 + T cell counts and lower CD4 + /CD8 + ratios than other patients. This study indicates that the central nervous system may be influenced in patients with COVID-19, and the pathological mechanisms may be related to direct virus invasion of the central nervous system, infection-mediated overreaction of the immune system, and aberrant serum pro-inflammatory factors. In addition, basophils and cystatin C may also play important roles during these pathological processes. Our findings suggest that neurological and psychiatric presentations should be evaluated and managed in patients with COVID-19. Further studies are needed to investigate the underlying mechanisms.


Subject(s)
COVID-19 , Mental Disorders , Nervous System Diseases , C-Reactive Protein/analysis , COVID-19/physiopathology , COVID-19/psychology , China/epidemiology , Cystatin C/blood , Humans , Interleukin-10/blood , Mental Disorders/blood , Mental Disorders/epidemiology , Nervous System Diseases/blood , Nervous System Diseases/epidemiology , Urea/blood
4.
Ann Neurol ; 89(5): 1041-1045, 2021 05.
Article in English | MEDLINE | ID: covidwho-1100843

ABSTRACT

Patients with coronavirus disease 2019 (COVID-19) can present with distinct neurological manifestations. This study shows that inflammatory neurological diseases were associated with increased levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, chemokine (C-X-C motif) ligand 8 (CXCL8), and CXCL10 in the cerebrospinal fluid. Conversely, encephalopathy was associated with high serum levels of IL-6, CXCL8, and active tumor growth factor ß1. Inflammatory syndromes of the central nervous system in COVID-19 can appear early, as a parainfectious process without significant systemic involvement, or without direct evidence of severe acute respiratory syndrome coronavirus 2 neuroinvasion. At the same time, encephalopathy is mainly influenced by peripheral events, including inflammatory cytokines. ANN NEUROL 2021;89:1041-1045.


Subject(s)
COVID-19/blood , COVID-19/cerebrospinal fluid , Inflammation Mediators/blood , Inflammation Mediators/cerebrospinal fluid , Nervous System Diseases/blood , Nervous System Diseases/cerebrospinal fluid , Biomarkers/blood , Biomarkers/cerebrospinal fluid , COVID-19/epidemiology , Cytokines/blood , Cytokines/cerebrospinal fluid , Humans , Nervous System Diseases/epidemiology
5.
Cells ; 10(2)2021 02 13.
Article in English | MEDLINE | ID: covidwho-1085116

ABSTRACT

As the SARS-CoV-2 pandemic continues, reports have demonstrated neurologic sequelae following COVID-19 recovery. Mechanisms to explain long-term neurological sequelae are unknown and need to be identified. Plasma from 24 individuals recovering from COVID-19 at 1 to 3 months after initial infection were collected for cytokine and antibody levels and neuronal-enriched extracellular vesicle (nEV) protein cargo analyses. Plasma cytokine IL-4 was increased in all COVID-19 participants. Volunteers with self-reported neurological problems (nCoV, n = 8) had a positive correlation of IL6 with age or severity of the sequalae, at least one co-morbidity and increased SARS-CoV-2 antibody compared to those COVID-19 individuals without neurological issues (CoV, n = 16). Protein markers of neuronal dysfunction including amyloid beta, neurofilament light, neurogranin, total tau, and p-T181-tau were all significantly increased in the nEVs of all participants recovering from COVID-19 compared to historic controls. This study suggests ongoing peripheral and neuroinflammation after COVID-19 infection that may influence neurological sequelae by altering nEV proteins. Individuals recovering from COVID-19 may have occult neural damage while those with demonstrative neurological symptoms additionally had more severe infection. Longitudinal studies to monitor plasma biomarkers and nEV cargo are warranted to assess persistent neurodegeneration and systemic effects.


Subject(s)
COVID-19/complications , Extracellular Vesicles/pathology , Nervous System Diseases/etiology , Adult , Aged , Amyloid beta-Peptides/analysis , Biomarkers/analysis , Biomarkers/blood , COVID-19/blood , COVID-19/pathology , Female , Humans , Immunoglobulin G/blood , Interleukin-4/blood , Interleukin-6/blood , Male , Middle Aged , Nervous System Diseases/blood , Nervous System Diseases/pathology , Neurofilament Proteins/analysis , Neurogranin/analysis , Neurons/pathology , tau Proteins/analysis
6.
J Neurotrauma ; 38(1): 1-43, 2021 01 01.
Article in English | MEDLINE | ID: covidwho-1066221

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus attacks multiple organs of coronavirus disease 2019 (COVID-19) patients, including the brain. There are worldwide descriptions of neurological deficits in COVID-19 patients. Central nervous system (CNS) symptoms can be present early in the course of the disease. As many as 55% of hospitalized COVID-19 patients have been reported to have neurological disturbances three months after infection by SARS-CoV-2. The mutability of the SARS-COV-2 virus and its potential to directly affect the CNS highlight the urgency of developing technology to diagnose, manage, and treat brain injury in COVID-19 patients. The pathobiology of CNS infection by SARS-CoV-2 and the associated neurological sequelae of this infection remain poorly understood. In this review, we outline the rationale for the use of blood biomarkers (BBs) for diagnosis of brain injury in COVID-19 patients, the research needed to incorporate their use into clinical practice, and the improvements in patient management and outcomes that can result. BBs of brain injury could potentially provide tools for detection of brain injury in COVID-19 patients. Elevations of BBs have been reported in cerebrospinal fluid (CSF) and blood of COVID-19 patients. BB proteins have been analyzed in CSF to detect CNS involvement in patients with infectious diseases, including human immunodeficiency virus and tuberculous meningitis. BBs are approved by the U.S. Food and Drug Administration for diagnosis of mild versus moderate traumatic brain injury and have identified brain injury after stroke, cardiac arrest, hypoxia, and epilepsy. BBs, integrated with other diagnostic tools, could enhance understanding of viral mechanisms of brain injury, predict severity of neurological deficits, guide triage of patients and assignment to appropriate medical pathways, and assess efficacy of therapeutic interventions in COVID-19 patients.


Subject(s)
Brain Injuries/blood , Brain Injuries/diagnosis , Brain/metabolism , COVID-19/blood , COVID-19/diagnosis , Biomarkers/blood , Brain/pathology , Brain Injuries/etiology , COVID-19/complications , Humans , Nervous System Diseases/blood , Nervous System Diseases/diagnosis , Nervous System Diseases/etiology , Prospective Studies , Retrospective Studies
8.
Neurol Sci ; 41(11): 3031-3038, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-758040

ABSTRACT

BACKGROUND: COVID-19 disease affects the nervous system and led to an increase in neurological consults for patients at admission and through the period of hospitalization during the peak of the pandemic. METHODS: Patients with clinical and laboratory diagnosis of COVID-19 that required a neurologic consultation or those who presented with neurological problems on admission that led to a diagnosis of SARS-CoV-2 infection during a 2-month period at the peak of the pandemic were included in this study. Demographic and clinical variables were analyzed. RESULTS: Thirty-five patients were included. The presenting neurologic manifestations on admission led to the diagnosis of COVID-19 in 14 patients (40%). The most common reasons for consultation during the hospitalization period were stroke (11), encephalopathy (7), seizures (6), and neuropathies (5) followed by a miscellaneous of syncope (2), migraine (1), anosmia (1), critical illness myopathy (1), and exacerbation of residual dysarthria (1). The most common neurological disturbances were associated with severe disease except for neuropathies. Patients with encephalopathies and seizures had markedly increased D-dimer and ferritin values, even higher than stroke patients. RT-PCR was performed in 8 CSF samples and was negative in all of them. CONCLUSION: Neurological disturbances represent a significant and severe burden in COVID-19 patients, and they can be the presenting condition that leads to the diagnosis of the viral infection in a high percentage of patients. Evidence of direct viral mechanisms was scarce, but the pathogenesis of the diverse manifestations remains enigmatic.


Subject(s)
Coronavirus Infections/complications , Nervous System Diseases/epidemiology , Nervous System Diseases/virology , Pneumonia, Viral/complications , Adult , Aged , Aged, 80 and over , Betacoronavirus , Biomarkers/blood , C-Reactive Protein/analysis , COVID-19 , Coronavirus Infections/blood , Cross-Sectional Studies , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Hospitalization , Humans , Incidence , Male , Middle Aged , Nervous System Diseases/blood , Pandemics , Pneumonia, Viral/blood , Referral and Consultation , SARS-CoV-2 , Young Adult
10.
J Neurol ; 267(9): 2485-2489, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-378307

ABSTRACT

Coronavirus disease 2019 (COVID-19) has become a pandemic disease globally. While it mostly presents with respiratory symptoms, it has already been found that it could manifest with a series of neurological symptoms as well, either at presentation or during the course of the disease. Symptoms vary from non-specific such as headache or dizziness to more specific such as convulsions and cerebrovascular disease (CVD). This study aims to give an overview of the neurological manifestations of COVID-19 and discuss the potential pathogenetic mechanisms of central nervous system (CNS) involvement. Clinicians and especially internists, neurologists, and infectious disease specialists should be aware of these symptoms and able to recognize them early. Prompt diagnosis and immediate management of the neurological manifestations of the novel coronavirus will not only improve the prognosis of COVID-19 patients but will also prevent the dissemination of the disease due to misdiagnosed cases.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Nervous System Diseases/epidemiology , Nervous System Diseases/physiopathology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , Brain Diseases/blood , Brain Diseases/epidemiology , Brain Diseases/physiopathology , COVID-19 , Cerebrovascular Disorders/blood , Cerebrovascular Disorders/epidemiology , Cerebrovascular Disorders/physiopathology , Coronavirus Infections/blood , Humans , Nervous System Diseases/blood , Pandemics , Pneumonia, Viral/blood , SARS-CoV-2
11.
JAMA Neurol ; 77(6): 683-690, 2020 06 01.
Article in English | MEDLINE | ID: covidwho-46613

ABSTRACT

Importance: The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, is serious and has the potential to become an epidemic worldwide. Several studies have described typical clinical manifestations including fever, cough, diarrhea, and fatigue. However, to our knowledge, it has not been reported that patients with COVID-19 had any neurologic manifestations. Objective: To study the neurologic manifestations of patients with COVID-19. Design, Setting, and Participants: This is a retrospective, observational case series. Data were collected from January 16, 2020, to February 19, 2020, at 3 designated special care centers for COVID-19 (Main District, West Branch, and Tumor Center) of the Union Hospital of Huazhong University of Science and Technology in Wuhan, China. The study included 214 consecutive hospitalized patients with laboratory-confirmed diagnosis of severe acute respiratory syndrome coronavirus 2 infection. Main Outcomes and Measures: Clinical data were extracted from electronic medical records, and data of all neurologic symptoms were checked by 2 trained neurologists. Neurologic manifestations fell into 3 categories: central nervous system manifestations (dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, and seizure), peripheral nervous system manifestations (taste impairment, smell impairment, vision impairment, and nerve pain), and skeletal muscular injury manifestations. Results: Of 214 patients (mean [SD] age, 52.7 [15.5] years; 87 men [40.7%]) with COVID-19, 126 patients (58.9%) had nonsevere infection and 88 patients (41.1%) had severe infection according to their respiratory status. Overall, 78 patients (36.4%) had neurologic manifestations. Compared with patients with nonsevere infection, patients with severe infection were older, had more underlying disorders, especially hypertension, and showed fewer typical symptoms of COVID-19, such as fever and cough. Patients with more severe infection had neurologic manifestations, such as acute cerebrovascular diseases (5 [5.7%] vs 1 [0.8%]), impaired consciousness (13 [14.8%] vs 3 [2.4%]), and skeletal muscle injury (17 [19.3%] vs 6 [4.8%]). Conclusions and Relevance: Patients with COVID-19 commonly have neurologic manifestations. During the epidemic period of COVID-19, when seeing patients with neurologic manifestations, clinicians should suspect severe acute respiratory syndrome coronavirus 2 infection as a differential diagnosis to avoid delayed diagnosis or misdiagnosis and lose the chance to treat and prevent further transmission.


Subject(s)
Betacoronavirus , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Hospitalization/trends , Nervous System Diseases/diagnosis , Nervous System Diseases/epidemiology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Adult , Aged , COVID-19 , China/epidemiology , Coronavirus Infections/blood , Female , Humans , Male , Middle Aged , Nervous System Diseases/blood , Pandemics , Pneumonia, Viral/blood , Retrospective Studies , SARS-CoV-2
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