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1.
Eur J Neurol ; 28(10): 3360-3368, 2021 10.
Article in English | MEDLINE | ID: covidwho-1606972

ABSTRACT

BACKGROUND AND PURPOSE: COVID-19-related acute neurological phenotypes are being increasingly recognised, with neurological complications reported in more than 30% of hospitalised patients. However, multicentric studies providing a population-based perspective are lacking. METHODS: We conducted a retrospective multicentric study at five hospitals in Northern Portugal, representing 45.1% of all hospitalised patients in this region, between 1 March and 30 June 2020. RESULTS: Among 1261 hospitalised COVID-19 patients, 457 (36.2%) presented neurological manifestations, corresponding to a rate of 357 per 1000 in the North Region. Patients with neurologic manifestations were younger (68.0 vs. 71.2 years, p = 0.002), and the most frequent neurological symptoms were headache (13.4%), delirium (10.1%), and impairment of consciousness (9.7%). Acute well-defined central nervous system (CNS) involvement was found in 19.1% of patients, corresponding to a rate of 217 per 1000 hospitalised patients in the whole region. Assuming that all patients with severe neurological events were hospitalised, we extrapolated our results to all COVID-19 patients in the region, estimating that 116 will have a severe neurological event, corresponding to a rate of nine per 1000 (95% CI = 7-11). Overall case fatality in patients presenting neurological manifestations was 19.8%, increasing to 32.6% among those with acute well-defined CNS involvement. CONCLUSIONS: We characterised the population of hospitalised COVID-19 patients in Northern Portugal and found that neurological symptoms are common and associated with a high degree of disability at discharge. CNS involvement with criteria for in-hospital admission was observed in a significant proportion of patients. This knowledge provides the tools for adequate health planning and for improving COVID-19 multidisciplinary patient care.


Subject(s)
COVID-19 , Nervous System Diseases , Humans , Nervous System Diseases/epidemiology , Portugal/epidemiology , Retrospective Studies , SARS-CoV-2
2.
Eur J Neurol ; 28(10): 3245-3253, 2021 10.
Article in English | MEDLINE | ID: covidwho-1604031

ABSTRACT

BACKGROUND AND PURPOSE: Neurological complications of SARS-CoV-2 infection are noticed among critically ill patients soon after disease onset. Information on delayed neurological sequelae of SARS-CoV-2 infection is nil. Following a longitudinal study design, the occurrence of cognitive decline among individuals with a history of mild symptomatic SARS-CoV-2 infection was assessed. METHODS: Stroke- and seizure-free Atahualpa residents aged ≥40 years, who had pre-pandemic cognitive assessments as well as normal brain magnetic resonance imaging and electroencephalogram recordings, underwent repeated evaluations 6 months after a SARS-CoV-2 outbreak infection in Atahualpa. Patients requiring oxygen therapy, hospitalization, and those who had initial neurological manifestations were excluded. Cognitive decline was defined as a reduction in the Montreal Cognitive Assessment (MoCA) score between the post-pandemic and pre-pandemic assessments that was ≥4 points greater than the reduction observed between two pre-pandemic MoCAs. The relationship between SARS-CoV-2 infection and cognitive decline was assessed by fitting logistic mixed models for longitudinal data as well as exposure-effect models. RESULTS: Of 93 included individuals (mean age 62.6 ± 11 years), 52 (56%) had a history of mild symptomatic SARS-CoV-2 infection. Post-pandemic MoCA decay was worse in seropositive individuals. Cognitive decline was recognized in 11/52 (21%) seropositive and 1/41 (2%) seronegative individuals. In multivariate analyses, the odds for developing cognitive decline were 18.1 times higher among SARS-CoV-2 seropositive individuals (95% confidence interval 1.75-188; p = 0.015). Exposure-effect models confirmed this association (ß = 0.24; 95% confidence interval 0.07-0.41; p = 0.006). CONCLUSIONS: This study provides evidence of cognitive decline among individuals with mild symptomatic SARS-CoV-2 infection. The pathogenesis of this complication remains unknown.


Subject(s)
COVID-19 , Cognitive Dysfunction , Aged , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/etiology , Humans , Longitudinal Studies , Middle Aged , Prospective Studies , SARS-CoV-2
3.
Emerg Infect Dis ; 27(8): 2179-2182, 2021 08.
Article in English | MEDLINE | ID: covidwho-1403444

ABSTRACT

We report 3 confirmed autochthonous tick-borne encephalitis cases in Belgium diagnosed during summer 2020. Clinicians should include this viral infection in the differential diagnosis for patients with etiologically unexplained neurologic manifestations, even for persons without recent travel history.


Subject(s)
Encephalitis Viruses, Tick-Borne , Encephalitis, Tick-Borne , Belgium/epidemiology , Encephalitis, Tick-Borne/diagnosis , Encephalitis, Tick-Borne/epidemiology , Humans , Travel
4.
Childs Nerv Syst ; 37(7): 2305-2312, 2021 07.
Article in English | MEDLINE | ID: covidwho-1384405

ABSTRACT

PURPOSE: To describe the temporal association of specific acute neurological symptoms in pediatric patients with confirmed SARS-CoV-2 infection between May and August 2020. METHODS: We performed a recollection of all the clinical and laboratory data of patients having acute neurological symptoms temporally associated with SARS-CoV-2 infection at a third-level referral hospital in Mexico City (Instituto Nacional de Pediatría). Patients in an age group of 0-17 years with acute neurological signs (including ascending weakness with areflexia, diminished visual acuity, encephalopathy, ataxia, stroke, or weakness with plasma creatinine kinase (CK) elevation) were evaluated. RESULTS: Out of 23 patients with neurological manifestations, 10 (43%) had a confirmed SARS-CoV-2 infection. Among the infected patients, 5 (50%) were males aged 2-16 years old (median age 11.8 years old). Four (40%) patients confirmed a close contact with a relative positive for SARS-CoV-2, while 6 (60%) cases had a history of SARS-CoV-2-related symptoms over the previous 2 weeks. The following diagnoses were established: 3 cases of GBS, 2 of ON, 2 of AIS, one of myositis with rhabdomyolysis, one ACA, and one of anti-NMDA-R encephalitis. CONCLUSIONS: Neurological manifestations temporally associated with SARS-CoV-2 infection were noticed in the pediatric population even without respiratory symptoms. In this study, 2 of 6 symptomatic patients had mild respiratory symptoms and 4 had unspecific symptoms. During this pandemic, SARS-CoV-2 infection should be considered as etiology in patients with acute neurological symptoms, with or without previous respiratory manifestations, particularly in teenagers.


Subject(s)
COVID-19 , Stroke , Adolescent , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Male , Mexico/epidemiology , Pandemics , SARS-CoV-2
5.
Front Immunol ; 11: 565521, 2020.
Article in English | MEDLINE | ID: covidwho-1389164

ABSTRACT

Neurological disorders caused by neuroviral infections are an obvious pathogenic manifestation. However, non-neurotropic viruses or peripheral viral infections pose a considerable challenge as their neuropathological manifestations do not emerge because of primary infection. Their secondary or bystander pathologies develop much later, like a syndrome, during and after the recovery of patients from the primary disease. Massive inflammation caused by peripheral viral infections can trigger multiple neurological anomalies. These neurological damages may range from a general cognitive and motor dysfunction up to a wide spectrum of CNS anomalies, such as Acute Necrotizing Hemorrhagic Encephalopathy, Guillain-Barré syndrome, Encephalitis, Meningitis, anxiety, and other audio-visual disabilities. Peripheral viruses like Measles virus, Enteroviruses, Influenza viruses (HIN1 series), SARS-CoV-1, MERS-CoV, and, recently, SARS-CoV-2 are reported to cause various neurological manifestations in patients and are proven to be neuropathogenic even in cellular and animal model systems. This review presents a comprehensive picture of CNS susceptibilities toward these peripheral viral infections and explains some common underlying themes of their neuropathology in the human brain.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/complications , Coronavirus Infections/immunology , Middle East Respiratory Syndrome Coronavirus/immunology , Neurogenic Inflammation/complications , Neurogenic Inflammation/immunology , Pneumonia, Viral/complications , Pneumonia, Viral/immunology , SARS Virus/immunology , Severe Acute Respiratory Syndrome/complications , Animals , Blood-Brain Barrier/immunology , Blood-Brain Barrier/virology , COVID-19 , Coronavirus Infections/virology , Cytokines/blood , Disease Models, Animal , Humans , Microglia/immunology , Microglia/virology , Neurogenic Inflammation/virology , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/virology
6.
Neurol Clin Pract ; 11(2): e64-e72, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1304433

ABSTRACT

BACKGROUND: An increasing number of neurologic problems are being described in coronavirus disease 2019 (COVID-19) disease, but their frequency and type have not been defined. In this study, we sought to determine the extent of neurologic manifestations of COVID-19 in a prospective series of unselected patients admitted to the general medicine wards of our hospitals due to COVID-19 and who were examined by a team of neurologists. METHODS: Eight neurologists provided medical attention to patients hospitalized for COVID-19 to provide medical support to other hospital units tasked with the care of an increasingly larger influx of patients with COVID-19. A series of 100 consecutive, unselected patients were evaluated systematically, including a questionnaire that collected medical information derived from the initial examination and the medical history. RESULTS: Eighty-eight percent of the patients had 1 neurologic manifestation associated with COVID-19 during hospitalization. Most common were anosmia-dysgeusia and headache (44% each), myalgias (43%), and dizziness (36%). Less frequent were encephalopathy (8%), syncope (7%), seizures (2%), and ischemic stroke during the period of hospitalization (2%). Anosmia and headache associated with younger patients with less severe disease, and both were associated with each other and with serum inflammatory markers. Encephalopathy was associated with fever and syncope and with markers of inflammation. CONCLUSIONS: Neurologic disturbances are common in patients with COVID-19, particularly if patients are evaluated by neurologists. There is a wide variety of neurologic conditions, some of them severe, in the spectrum of COVID-19 disease that will benefit from an evaluation by practicing neurologists.

7.
Sci Rep ; 11(1): 12888, 2021 06 18.
Article in English | MEDLINE | ID: covidwho-1275957

ABSTRACT

The first systematic review and meta-analysis to help clinician to identify early signs and symptoms of neurological manifestation in COVID-19 positive patients which will further help in early management of patients. Present systematic review and meta-analysis aimed to discuss the prevalence of neurological involvement of the 2019-nCoV patients and assess the symptomatic trend of events as compared to the 2002 "SARS" and 2012 "MERS" pandemics. The articles were systematically screened through several search engine and databases. The articles published or in preprint were included in the study till 15th May 2020. The systematic review done as per the published literatures which included 31 cross sectional, observational studies and case reports which revealed neurological signs and symptoms in SARS-COV-2 disease. For meta-analysis, we included 09 observational and cross-sectional studies which included COVID-19 positive patients and assessed the predominance of various neurological signs and symptoms in COVID-19 patients with relation to SARS-2002 and MERS-2012. Data was analyzed by using the "MedCalc" Statistical Software version 19.2.6 and reported as pooled prevalence. Standard I2 test was used to analyze the heterogeneity. We have collected and screened about a total 2615articles, finally we have included 31articles for the systematic review and 09 for meta-analysis as per the inclusion/exclusion criteria. The analysis was made as per the prevalence rate of neurological symptoms in COVID-19 positive patients. The cumulative neurological outcome of SARS-2002 and MERS-2012 was assessed to get the trends which was further tried to correlate the events with the current pandemic. During the analysis severity and outcome of neurological manifestations range from simple headache to vague non-focal complaints to severe neurologic impairment associated with seizure or meningitis. Central and peripheral nervous system (CNS/PNS) manifestations were seen during the SARS-2002, MERS-2012 and COVID-19. However, none of the publication had primary or secondary objectives of searching neurological manifestations in the COVID-19 patients and the pathogenic mechanism which will subsequently strengthen the importance to start more prospective clinical trials. The prevalence of neurological signs and symptoms were taken as primary objective. Thereafter, the prevalence of each CNS/PNS symptoms was categorized and their prevalence studied. The selection of Bagheri et al., 2020 may be discussed because they have done the cross-sectional study with the neurological finding and correlated the data with prevalence of the COVID-19 positive patients. The proportion of patients presenting with neurological outcome and clinical/PCR positivity were done. We had searched and followed all the possible online/web source, still the data collection process may remain a limitation of work due to addition of several publications on COVID-19 every day. Due to lack of data of SARS-CoV and MERS-CoV, we have included the case reports, MERS and COVID-19 in CNS/PNS manifestations.


Subject(s)
COVID-19/epidemiology , Coronavirus Infections/epidemiology , Nervous System Diseases/virology , Pandemics/statistics & numerical data , Severe Acute Respiratory Syndrome/epidemiology , Comorbidity , Humans , Nervous System Diseases/epidemiology , Prevalence
8.
CNS Neurosci Ther ; 27(10): 1127-1135, 2021 10.
Article in English | MEDLINE | ID: covidwho-1270830

ABSTRACT

AIMS: To determine if neurologic symptoms at admission can predict adverse outcomes in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Electronic medical records of 1053 consecutively hospitalized patients with laboratory-confirmed infection of SARS-CoV-2 from one large medical center in the USA were retrospectively analyzed. Univariable and multivariable Cox regression analyses were performed with the calculation of areas under the curve (AUC) and concordance index (C-index). Patients were stratified into subgroups based on the presence of encephalopathy and its severity using survival statistics. In sensitivity analyses, patients with mild/moderate and severe encephalopathy (defined as coma) were separately considered. RESULTS: Of 1053 patients (mean age 52.4 years, 48.0% men [n = 505]), 35.1% (n = 370) had neurologic manifestations at admission, including 10.3% (n = 108) with encephalopathy. Encephalopathy was an independent predictor for death (hazard ratio [HR] 2.617, 95% confidence interval [CI] 1.481-4.625) in multivariable Cox regression. The addition of encephalopathy to multivariable models comprising other predictors for adverse outcomes increased AUCs (mortality: 0.84-0.86, ventilation/ intensive care unit [ICU]: 0.76-0.78) and C-index (mortality: 0.78 to 0.81, ventilation/ICU: 0.85-0.86). In sensitivity analyses, risk stratification survival curves for mortality and ventilation/ICU based on severe encephalopathy (n = 15) versus mild/moderate encephalopathy (n = 93) versus no encephalopathy (n = 945) at admission were discriminative (p < 0.001). CONCLUSIONS: Encephalopathy at admission predicts later progression to death in SARS-CoV-2 infection, which may have important implications for risk stratification in clinical practice.


Subject(s)
Brain Diseases/diagnosis , Brain Diseases/mortality , COVID-19/diagnosis , COVID-19/mortality , Patient Admission/trends , Adult , Aged , Brain Diseases/therapy , COVID-19/therapy , Cohort Studies , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies
9.
Curr Neurol Neurosci Rep ; 21(8): 41, 2021 Jun 14.
Article in English | MEDLINE | ID: covidwho-1267512

ABSTRACT

PURPOSE OF REVIEW: In recent years, the spectrum of neurological manifestations of antiphospholipid syndrome (APS) has been growing. We provide a critical review of the literature with special emphasis on presentation, proposed mechanisms of disease, and treatment of neurological involvement in APS. RECENT FINDINGS: Although stroke is the most common cause of neurological manifestations in patients with APS, other neurological disorders have been increasingly associated with the disease, including cognitive dysfunction, headache, and epilepsy. Direct oral anticoagulants have failed to show non-inferiority compared to vitamin K antagonists for the prevention of major thrombotic events. Antiphospholipid antibodies are often found in patients with acute COVID-19 but clear evidence supporting an association between these antibodies and the risk of thrombotic events, including stroke and cerebral venous thrombosis, is still lacking. APS patients may present with several distinct neurological manifestations. New criteria will facilitate the classification of patients presenting with increasingly recognized non-criteria neurological manifestations.


Subject(s)
Antiphospholipid Syndrome , COVID-19 , Antibodies, Antiphospholipid , Anticoagulants , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/diagnosis , Antiphospholipid Syndrome/drug therapy , Humans , SARS-CoV-2
10.
J Neurol ; 269(1): 12-18, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1258215

ABSTRACT

BACKGROUND: Altered mental status (AMS) is a common neurological manifestation of COVID-19 infection in hospitalized patients. The principal causes of AMS have yet to be determined. We aimed to identify the common causes of AMS in patients with COVID-19 presenting to the emergency department with AMS on arrival. METHODS: We conducted a retrospective observational study of patients presenting with AMS to three New York hospitals, from March 1 to April 16, 2020. Underlying causes of AMS on arrival to the emergency department (ED) were categorized as (1) neurological causes (stroke, seizure, encephalitis); (2) metabolic encephalopathy; (3) indeterminant. Multivariable analysis was used to assess independent predictors. RESULTS: Overall, 166 patients presented to the ED with AMS. Metabolic encephalopathy was diagnosed as the cause in 154 (92.8%), with 118 (71.1%) categorized as multifactorial ME and 36 (21.7%) with single-cause ME. Hypoxia 103 (62.0%) and renal failure 75 (45.2%) were the most common underlying mechanisms. Neurological causes of AMS occurred in a total 20 patients (12%) and as the sole factor in 5 (3.0%); 10 (6.0%) cases were seizure related and 10 (6.0%) were cerebrovascular events. Of the 7 patients with indeterminant causes, only 1 was suspicious for encephalitis (0.6%). Age, pre-existing dementia and cerebrovascular disease, and impaired renal function were independent predictors of AMS. CONCLUSION: In patients with COVID-19, AMS on presentation to the ED is most frequently caused by metabolic encephalopathy (delirium). Seizures and cerebrovascular events contribute to a lesser degree; encephalitis appears rare.


Subject(s)
COVID-19 , Mental Disorders , Emergency Service, Hospital , Humans , Mental Disorders/epidemiology , Mental Disorders/etiology , SARS-CoV-2 , Seizures/epidemiology , Seizures/etiology
11.
Microb Pathog ; 158: 105023, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1253397

ABSTRACT

BACKGROUND: Long period of SARS-CoV-2 infection has been associated with psychiatric and cognitive disorders in adolescents and children. SARS-CoV-2 remains dormant in the CNS leading to neurological complications. The wide expression of ACE2 in the brain raises concern for its involvement in SARS-CoV-2 infection. Though, the mechanistic insights about blood-brain barriers (BBB) crossing by SARS-CoV-2 and further brain infection are still not clear. Moreover, the mechanism behind dormant SARS-CoV-2 infections leading to chronic neurological disorders needs to be unveiled. There is an urgent need to find out the risk factor involved in COVID-19-associated neurological disease. Therefore, the role of immune-associated genes in the pathogenesis of COVID-19 associated neurological diseases is presented which could contribute to finding associated genetic risk factors. METHOD: The search utilizing multiple databases, specifically, EMBASE, PubMed (Medline), and Google Scholar was performed. Moreover, the literature survey on the involvement of COVID-19, neuropathogenesis, and its consequences was done. DESCRIPTION: Persistent inflammatory stimuli may promote the progression of neurodegenerative diseases. An increased expression level of cytokine, chemokine, and decreased expression level of immune cells has been associated with the COVID-19 patient. Cytokine storm was observed in severe COVID-19 patients. The nature of SARS-CoV-2 infection can be neuroinflammatory. Genes of immune response could be associated with neurodegenerative diseases. CONCLUSION: The present review will provide a useful framework and help in understanding COVID-19-associated neuropathogenesis. Experimental studies on immune-associated genes in COVID-19 patients with neurological manifestations could be helpful to establish its neuropathogenesis.


Subject(s)
COVID-19 , Neurodegenerative Diseases , Adolescent , Brain , Cytokines , Humans , SARS-CoV-2
12.
Egypt J Neurol Psychiatr Neurosurg ; 57(1): 68, 2021.
Article in English | MEDLINE | ID: covidwho-1255980

ABSTRACT

BACKGROUND: The COVID-19 pandemic has drastically affected everyone in a hit or miss manner. Since it began, evidence of the neuro-invasive potential of the virus has been intensifying significantly. Several pathways have been hypothesized to elucidate the neurotropic nature of SARS-CoV2. It is the need of the hour to collect vital information. OBJECTIVE: To evaluate and correlate the neuro-radiological and neurological manifestations in patients diagnosed with SARS-CoV2.To identify neuro-invasive pathways of COVID infection. METHODS: Relevant studies were identified through four databases-the Cochrane Library, PubMed, Science Direct, and Web of Science. These were searched using relevant keywords-"COVID-19," "SARS-CoV2," "neurological manifestations," "neuroimaging," "CT," and "MRI." Relevant articles were screened according to a pre-defined inclusion and exclusion criteria from December 2019 to August 2020. RESULTS: Our review included a total of 63 full text publications with 584 patients, composed mainly of observational studies, case reports, and case series. The most common neurological manifestations associated with COVID-19 were altered mental status, stroke, and paralysis. About 17.85% patients who underwent neuroimaging were found to be having ischemic changes suggestive of a stroke. This was followed by hemorrhagic changes as the second most common finding. The most commonly involved vessel was the Middle Cerebral Artery. Besides stroke, we found that SARS-CoV2 could be the cause for new-onset seizures, Guillain-Barre Syndrome, encephalitis, and many other severe neurological diseases. CONCLUSION: The information that we have obtained so far will prove dynamic to healthcare providers working against the COVID-19 pandemic. It is necessary to be aware of these atypical neurological findings for the early diagnosis and treatment of COVID-19 infected patients. However, to completely understand the connection between SARS-CoV2 and the nervous system, further research is necessary.

13.
Ital J Pediatr ; 47(1): 123, 2021 Jun 02.
Article in English | MEDLINE | ID: covidwho-1255951

ABSTRACT

OBJECTIVES: To describe clinical characteristics, laboratory tests, radiological data and outcome of pediatric cases with SARS-CoV-2 infection complicated by neurological involvement. STUDY DESIGN: A computerized search was conducted using PubMed. An article was considered eligible if it reported data on pediatric patient(s) with neurological involvement related to SARS-CoV-2 infection. We also described a case of an acute disseminated encephalomyelitis (ADEM) in a 5-year-old girl with SARS-CoV-2 infection: this case was also included in the systematic review. RESULTS: Forty-four articles reporting 59 cases of neurological manifestations in pediatric patients were included in our review. Most (32/59) cases occurred in the course of a multisystem inflammatory syndrome in children (MIS-C). Neurological disorders secondary to cerebrovascular involvement were reported in 10 cases: 4 children with an ischemic stroke, 3 with intracerebral hemorrhage, 1 with a cerebral sinus venous thrombosis, 1 with a subarachnoid hemorrhage, 1 with multiple diffuse microhemorrhages. Reversible splenial lesions were recognized in 9 cases, benign intracranial hypertension in 4 patients, meningoencephalitis in 4 cases, autoimmune encephalitis in 1 girl, cranial nerves impairment in 2 patients and transverse myelitis in 1 case. Five cases had Guillain-Barré syndrome (GBS) and two, including ours, had ADEM. Radiological investigations were performed in almost all cases (45/60): the most recurrent radiological finding was a signal change in the splenium of the corpus callosum. The presence of SARS-CoV-2 viral nucleic acid in the cerebrospinal fluid was proved only in 2 cases. The outcome was favorable in almost all, except in 5 cases. CONCLUSIONS: Our research highlights the large range of neurological manifestations and their presumed pathogenic pathways associated with SARS-CoV-2 infection in children. Nervous system involvement could be isolated, developing during COVID-19 or after its recovery, or arise in the context of a MIS-C. The most reported neurological manifestations are cerebrovascular accidents, reversible splenial lesions, GBS, benign intracranial hypertension, meningoencephalitis; ADEM is also a possible complication, as we observed in our patient. Further studies are required to investigate all the neurological complications of SARS-CoV-2 infection and their underlying pathogenic mechanism.


Subject(s)
COVID-19/complications , Nervous System Diseases/virology , Pneumonia, Viral/complications , Child , Humans , Pneumonia, Viral/virology , SARS-CoV-2
14.
BMC Infect Dis ; 21(1): 515, 2021 Jun 02.
Article in English | MEDLINE | ID: covidwho-1255907

ABSTRACT

BACKGROUND: SARS-CoV-2 can affect the human brain and other neurological structures. An increasing number of publications report neurological manifestations in patients with COVID-19. However, no studies have comprehensively reviewed the clinical and paraclinical characteristics of the central and peripheral nervous system's involvement in these patients. This study aimed to describe the features of the central and peripheral nervous system involvement by COVID-19 in terms of pathophysiology, clinical manifestations, neuropathology, neuroimaging, electrophysiology, and cerebrospinal fluid findings. METHODS: We conducted a comprehensive systematic review of all the original studies reporting patients with neurological involvement by COVID-19, from December 2019 to June 2020, without language restriction. We excluded studies with animal subjects, studies not related to the nervous system, and opinion articles. Data analysis combined descriptive measures, frequency measures, central tendency measures, and dispersion measures for all studies reporting neurological conditions and abnormal ancillary tests in patients with confirmed COVID-19. RESULTS: A total of 143 observational and descriptive studies reported central and peripheral nervous system involvement by COVID-19 in 10,723 patients. Fifty-one studies described pathophysiologic mechanisms of neurological involvement by COVID-19, 119 focused on clinical manifestations, 4 described neuropathology findings, 62 described neuroimaging findings, 28 electrophysiology findings, and 60 studies reported cerebrospinal fluid results. The reviewed studies reflect a significant prevalence of the nervous system's involvement in patients with COVID-19, ranging from 22.5 to 36.4% among different studies, without mortality rates explicitly associated with neurological involvement by SARS-CoV-2. We thoroughly describe the clinical and paraclinical characteristics of neurological involvement in these patients. CONCLUSIONS: Our evidence synthesis led to a categorical analysis of the central and peripheral neurological involvement by COVID-19 and provided a comprehensive explanation of the reported pathophysiological mechanisms by which SARS-CoV-2 infection may cause neurological impairment. International collaborative efforts and exhaustive neurological registries will enhance the translational knowledge of COVID-19's central and peripheral neurological involvement and generate therapeutic decision-making strategies. REGISTRATION: This review was registered in PROSPERO 2020 CRD42020193140 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020193140.


Subject(s)
COVID-19/complications , Nervous System Diseases/virology , Peripheral Nervous System/physiopathology , Peripheral Nervous System/virology , Brain , COVID-19/cerebrospinal fluid , Electrophysiological Phenomena , Humans , Nervous System Diseases/cerebrospinal fluid , Neuroimaging
16.
Arch Acad Emerg Med ; 9(1): e34, 2021.
Article in English | MEDLINE | ID: covidwho-1241364

ABSTRACT

INTRODUCTION: COVID-19 might present with other seemingly unrelated manifestations; for instance, neurological symptoms. This study aimed to evaluate the neurologic manifestations and their correlated factors in COVID-19 patients. METHODS: This retrospective observational study was conducted from March 17, 2020 to June 20, 2020 in a tertiary hospital in Iran. The study population consisted of adult patients with a positive result for COVID-19 real-time reverse transcriptase polymerase chain reaction (RT-PCR) using nasopharyngeal swabs. Both written and electronic data regarding baseline characteristic, laboratory findings, and neurological manifestations were evaluated and reported. RESULTS: 727 COVID-19 patients with the mean age of 49.94 ± 17.49 years were studied (56.9% male). At least one neurological symptom was observed in 403 (55.4%) cases. Headache (29.0%), and smell (22.3%) and taste (22.0%) impairment were the most prevalent neurological symptoms, while seizure (1.1%) and stroke (2.3%) were the least common ones. Patients with neurological manifestations were significantly older (p = 0.04), had greater body mass index (BMI) (p = 0.02), longer first symptom to admission duration (p < 0.001) and were more frequently opium users (p = 0.03) compared to COVID-19 patients without neurological symptoms. O2 saturation was significantly lower in patients with neurological manifestations (p = 0.04). In addition, medians of neutrophil count (p = 0.006), neutrophil-lymphocyte ratio (NLR) (p = 0.02) and c-reactive protein (CRP) (p = 0.001) were significantly higher and the median of lymphocyte count (p = 0.03) was significantly lower in patients with neurological manifestations. CONCLUSION: The prevalence of neurological manifestations in the studied cases was high (55.4%). This prevalence was significantly higher in older age, grated BMI, longer lasting disease, and opium usage.

17.
J Infect Public Health ; 14(6): 734-739, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1237766

ABSTRACT

Coronavirus is known to cause various systemic infections both in human and animal which are mostly mild in nature. However, recent years have seen major pandemics caused by coronavirus which are very invasive and virulent in nature. The recent SARS-CoV2 is a new addition to this list of coronavirus pandemics. So the present study was done to systematically review the CNS involvement and its manifestations in SARS-CoV2 positive patients. Systemic review of article published between 1st Dec 2019 to 31st July 2020 searched through web-based database of MEDLINE (Pubmed) and Google scholar using following keywords "COVID -19" OR "CORONAVIRUS" OR "SARS-CoV2" AND "NEUROLOGICAL" OR "CNS" OR "BRAIN". Using the steps of systemic review eight article were selected for qualitative analysis. Majority of these article were reporting neurological symptoms among patients admitted in different wards along with others general symptoms. None of the study was specifically devoted to study the neurological manifestations and complications in SARS-CoV2 positive patients. The present study concludes that there is a scarcity of good quality research which attempts to establish the role of SARS-CoV2 infection in CNS and its manifestations. However, there are evidences that CNS involvement is present in majority of the patients. Proper documentation of theses involvement and indentification of these into mild, moderate and severe infection will help in early identification and treatment of these patients.


Subject(s)
COVID-19 , RNA, Viral , Animals , Brain , Humans , Pandemics , SARS-CoV-2
18.
Brain Behav Immun ; 97: 13-21, 2021 10.
Article in English | MEDLINE | ID: covidwho-1233366

ABSTRACT

SARS-Cov-2 infection is frequently associated with Nervous System manifestations. However, it is not clear how SARS-CoV-2 can cause neurological dysfunctions and which molecular processes are affected in the brain. In this work, we examined the frontal cortex tissue of patients who died of COVID-19 for the presence of SARS-CoV-2, comparing qRT-PCR with ddPCR. We also investigated the transcriptomic profile of frontal cortex from COVID-19 patients and matched controls by RNA-seq analysis to characterize the transcriptional signature. Our data showed that SARS-CoV-2 could be detected by ddPCR in 8 (88%) of 9 examined samples while by qRT-PCR in one case only (11%). Transcriptomic analysis revealed that 11 genes (10 mRNAs and 1 lncRNA) were differential expressed when frontal cortex of COVID-19 patients were compared to controls. These genes fall into categories including hypoxia, hemoglobin-stabilizing protein, hydrogen peroxide processes. This work demonstrated that the quantity of viral RNA in frontal cortex is minimal and it can be detected only with a very sensitive method (ddPCR). Thus, it is likely that SARS-CoV-2 does not actively infect and replicate in the brain; its topography within encephalic structures remains uncertain. Moreover, COVID-19 may have a role on brain gene expression, since we observed an important downregulation of genes associated to hypoxia inducting factor system (HIF) that may inhibit the capacity of defense system during infection and oxigen deprivation, showing that hypoxia, well known multi organ condition associated to COVID-19, also marked the brain.


Subject(s)
COVID-19 , SARS-CoV-2 , Frontal Lobe , Humans , Transcriptome , Whole Exome Sequencing
19.
J Neurol ; 268(12): 4448-4478, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1233263

ABSTRACT

BACKGROUND: The literature on neurological manifestations in COVID-19 patients has been rapidly increasing with the pandemic. However, data on CNS inflammatory disorders in COVID-19 are still evolving. We performed a literature review of CNS inflammatory disorders associated with coronavirus disease-2019 (COVID-19). METHODS: We screened all articles resulting from a search of PubMed, Google Scholar and Scopus, using the keywords; "SARS-CoV-2 and neurological complication", "SARS-CoV-2 and CNS Complication" looking for reports of transverse myelitis, longitudinally extensive transverse myelitis, neuromyelitis optica, myelitis, Myelin Oligodendrocyte Glycoprotein Antibody Disorder (MOGAD), Acute Disseminated Encephalomyelitis (ADEM), Acute Hemorrhagic Necrotizing Encephalitis/Acute Hemorrhagic Leukoencephalitis (AHNE/AHLE), Cytotoxic lesion of the Corpus Callosum/Mild Encephalopathy Reversible Splenium Lesion(CLOCC/MERS) and Optic neuritis published between December 01, 2019 and March 15, 2021. RESULTS: Our literature search revealed 43 patients meeting the diagnosis of myelitis, including Transverse Myelitis, ADEM, AHNE/AHLE or CLOCC/MERS and Optic neuritis. Acute myelitis was most commonly associated with non-severe COVID-19 and all reported cases of AHNE/AHLE had severe COVID-19 infection. Based on IDSA/ATS criteria of either requiring vasopressor for septic shock or mechanical ventilation, 49% (n = 18) patients were considered to have a severe COVID infection. There were 7 (n = 19%) fatalities. CONCLUSION: To our knowledge, this is among the first reviews that includes the clinical features, neuroimaging, CSF findings and outcomes in COVID-19-associated CNS inflammatory disorders. Our observational review study reveals that although rare, myelitis, ADEM, AHNE and CLOCC can be associated with COVID-19 infection. Further studies using MRI imaging and CSF analysis in early diagnosis and intervention of these disorders are warranted.


Subject(s)
COVID-19 , Central Nervous System Diseases/virology , Myelitis, Transverse , COVID-19/cerebrospinal fluid , COVID-19/diagnostic imaging , Central Nervous System Diseases/cerebrospinal fluid , Humans , Myelin-Oligodendrocyte Glycoprotein , Myelitis, Transverse/diagnostic imaging , Myelitis, Transverse/virology , Neuroimaging , Observational Studies as Topic
20.
Front Neurol ; 12: 644848, 2021.
Article in English | MEDLINE | ID: covidwho-1231359

ABSTRACT

Along with the propagation of COVID-19, emerging evidence reveals significant neurological manifestations in severely infected COVID-19 patients. Among these patients admitted to the intensive care unit (ICU), behavioral unresponsiveness may occur frequently, yet, there are still only a few cases reported and with rare descriptions of their motor behavior after pathological awakening. Several hypotheses regarding central lesions in these patients are conceivable. Here, we describe two acute SARS-CoV-2- infected patients who developed neurological symptoms evoking the condition of clinical cognitive motor dissociation (CMD). This diagnosis could be confirmed first by clinical observation of a dissociation between preserved cognitive abilities and lack of initial motor interaction and second, by performing 18F- FDG PET imaging. Accurate diagnosis led to an appropriate neuro-rehabilitation regimen with long-term neuro-rehabilitation leading to an improved outcome for both patients.

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