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1.
Front Immunol ; 13: 833548, 2022.
Article in English | MEDLINE | ID: covidwho-1771039

ABSTRACT

The direct impact and sequelae of infections in children and adults result in significant morbidity and mortality especially when they involve the central (CNS) or peripheral nervous system (PNS). The historical understanding of the pathophysiology has been mostly focused on the direct impact of the various pathogens through neural tissue invasion. However, with the better understanding of neuroimmunology, there is a rapidly growing realization of the contribution of the innate and adaptive host immune responses in the pathogenesis of many CNS and PNS diseases. The balance between the protective and pathologic sequelae of immunity is fragile and can easily be tipped towards harm for the host. The matter of immune privilege and surveillance of the CNS/PNS compartments and the role of the blood-brain barrier (BBB) and blood nerve barrier (BNB) makes this even more complex. Our understanding of the pathogenesis of many post-infectious manifestations of various microbial agents remains elusive, especially in the diverse African setting. Our exploration and better understanding of the neuroimmunology of some of the infectious diseases that we encounter in the continent will go a long way into helping us to improve their management and therefore lessen the burden. Africa is diverse and uniquely poised because of the mix of the classic, well described, autoimmune disease entities and the specifically "tropical" conditions. This review explores the current understanding of some of the para- and post-infectious autoimmune manifestations of CNS and PNS diseases in the African context. We highlight the clinical presentations, diagnosis and treatment of these neurological disorders and underscore the knowledge gaps and perspectives for future research using disease models of conditions that we see in the continent, some of which are not uniquely African and, where relevant, include discussion of the proposed mechanisms underlying pathogen-induced autoimmunity. This review covers the following conditions as models and highlight those in which a relationship with COVID-19 infection has been reported: a) Acute Necrotizing Encephalopathy; b) Measles-associated encephalopathies; c) Human Immunodeficiency Virus (HIV) neuroimmune disorders, and particularly the difficulties associated with classical post-infectious autoimmune disorders such as the Guillain-Barré syndrome in the context of HIV and other infections. Finally, we describe NMDA-R encephalitis, which can be post-HSV encephalitis, summarise other antibody-mediated CNS diseases and describe myasthenia gravis as the classic antibody-mediated disease but with special features in Africa.


Subject(s)
Brain Diseases , COVID-19 , Central Nervous System Diseases , Communicable Diseases , Encephalitis , Peripheral Nervous System Diseases , Adult , Autoimmunity , Central Nervous System , Child , Humans , Peripheral Nervous System
2.
Adv Exp Med Biol ; 1353: 197-215, 2021.
Article in English | MEDLINE | ID: covidwho-1680585

ABSTRACT

INTRODUCTION: Although respiratory symptoms predominate in the disease caused by the SARS-Cov-2, the new coronavirus, the related neurological implications increase with numbers of new infected, requiring new tools and sufficient medical apparatus to improve the patients' prognosis. The purpose of this publication is based on the need to clarify the pathophysiological process of COVID-19 from a neurological perspective. The present study aims to review and describe the main neurological aspects associated with SARS-CoV-2, in addition to presenting proposals for conducting and managing these issues. METHODS: The MEDLINE (through PubMed) and Scopus databases were used for systematic research on the correlation between COVID-19 and the nervous system. The reference period were publications between May 2005 and July 2020. The temporal delimitation was based on the objective of elucidating the pathophysiology of neurological involvement seen in the current pandemic. Thus, in 2005, we found articles that reported different etiologies and mechanisms of action of the antiphospholipid syndrome, which helped to understand its current association with COVID-19. Other articles from years prior to the current one contributed, in the same sense of linking, with description of associated processes, in articles from 2020, the SARS-CoV-2 infection. The processes described in times before 2020 and currently correlated with cerebral dysfunction of COVID-19 were distribution of angiotensin II receptors in the brain, inflammation associated with the blood-brain barrier imbalance, and brain barrier function. "SARS-CoV-2 and complications," "neurology," "pathogeny of COVID-19," "stroke," and "encephalopathy" were terms included in the research. The relevance of the articles found was based on congruence with the search terms and on availability of the full text. RESULTS: Recent articles published reported mild neurological symptoms, with, for example, headache and anosmia as part of the set of common symptoms of COVID-19, highlighting the causal link between the disease and neurological complications that may exist during its evolution. It is still unknown whether the neurological clinical expression concomitant with the new coronavirus infection is a consequence or a coincidence. In order to properly treat and monitor these patients from the neurological point of view, it is essential, in times of pandemics, to suspect primary infection by SARS-Cov-2 and diagnose it to proceed with isolation and clinical support. CONCLUSION: The neurological implications of COVID-19 range from initial symptoms, such as headache, to serious complications, such as ischemic stroke. Although the pathogenesis of neurological phenomena requires further studies, targeted management of the patient is feasible, considering agility in recognizing the infection. Therefore, medical precaution and clinical reasoning are emphasized when providing services to the patient.


Subject(s)
COVID-19 , Nervous System Diseases , Stroke , Humans , Pandemics , Peripheral Nervous System , SARS-CoV-2
3.
J Peripher Nerv Syst ; 27(1): 4-30, 2022 03.
Article in English | MEDLINE | ID: covidwho-1673194

ABSTRACT

Increasing literature has linked COVID-19 to peripheral nervous system (PNS) diseases. In addition, as we move from the pandemic to the vaccination era, literature interest is shifting towards the potential association between COVID-19 vaccines and PNS manifestations. We reviewed published literature on COVID-19, COVID-19 vaccines and PNS manifestations between 1 January 2020 and 1 December 2021. For Guillain-Barré syndrome (GBS), isolated cranial neuropathy (ICN) and myositis associated with COVID-19, the demographic, clinical, laboratory, electrophysiological and imaging features were included in a narrative synthesis. We identified 169 studies on COVID-19-associated complications, including 63 papers (92 patients) on GBS, 29 papers (37 patients) on ICN and 11 papers (18 patients) on myositis. Additional clinical phenotypes included chronic inflammatory demyelinating polyneuropathy, vasculitic neuropathies, neuralgic amyotrophy, critical care-related complications, and myasthenia gravis. PNS complications secondary to COVID-19 vaccines have been reported during randomized clinical trials, in real-world case reports, and during large-scale surveillance programs. These mainly include cases of GBS, Bell's palsy, and cases of neuralgic amyotrophy. Based on our extensive review of the literature, any conclusion about a pathophysiological correlation between COVID-19 and PNS disorders remains premature, and solely supported by their temporal association, while epidemiological and pathological data are insufficient. The occurrence of PNS complications after COVID-19 vaccines seems limited to a possible higher risk of facial nerve palsy and GBS, to a degree that widespread access to the ongoing vaccination campaign should not be discouraged, while awaiting for more definitive data from large-scale surveillance studies.


Subject(s)
COVID-19 , Guillain-Barre Syndrome , COVID-19/complications , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Guillain-Barre Syndrome/epidemiology , Guillain-Barre Syndrome/etiology , Humans , Pandemics , Peripheral Nervous System
4.
J. Hum. Growth Dev. (Impr.) ; 31(3): 465-469, Sep.-Dec. 2021. ilus
Article in English | WHO COVID, LILACS (Americas) | ID: covidwho-1592641

ABSTRACT

BACKGROUND: the involvement of the peripheral nervous system (PNS) in COVID-19 is rare and, to date, morphological aspects from muscle and nerve biopsies have not been reported. Here, we describe a case of Guillain-Barré Syndrome (GBS) related to COVID-19 and demonstrate findings from peripheral nerve and skeletal muscle biopsies. A 79-year-old man presented with progressive weakness in both legs over one-week, evolving to both arms and urinary retention within 6 days. Four days earlier, he had a cough, febrile sensation and mild respiratory discomfort. On admission, his was afebrile, and without respiratory distress. A neurological examination disclosed asymmetric proximal weakness, diminished reflexes and no sensitive abnormalities. Three days later, the patient presented with bilateral facial weakness and proximal muscle strength worsened. Deep tendon reflexes and plantar responses were absent. Both superficial and profound sensitivity were decreased. From this point, oxygen saturation worsened, and the patient was placed on mechanical ventilation. CSF testing revealed one cell and protein 185 mg/dl. A chest CT showed the presence of ground-glass opacities and RT-PCR for SARS-CoV-2 was positive. The muscle biopsy revealed moderate neuromyopathic findings with positive expression for MHC-class I, C5b9, CD8 and CD68. The nerve biopsy showed inflammatory infiltrates predominantly with endoneurial compound formed by CD45 and CD68. The patient was treated with Oseltamivir for 9 days followed by IVIG for 5 days and died three days later of septic shock. DISCUSSION: this is the first documented case of GBS associated with COVID-19 with a muscle and nerve anatomopathological study. A systematic review about neurological complications caused by COVID-19 described 11 patients with GBS. The morphological features reported in our patient showed signs of involvement of the immune system, suggesting that direct viral invasion could have played a role in the pathogenesis of peripheral nerve injury. Hereafter, further research will be necessary to understand the triggers for these cells migrating into the peripheral nerve.


INTRODUÇÃO: O envolvimento do sistema nervoso periférico (SNP) na COVID-19 é raro e, até o momento, os aspectos morfológicos de biópsias de músculo e nervo não foram relatados. Descrevemos um caso de Síndrome de Guillain-Barré (SGB) na vigência de COVID-19 destacando os achados na biopsia de músculo e nervo. Um homem de 79 anos apresentou fraqueza progressiva em ambas as pernas ao longo de uma semana, evoluindo para ambos os braços e retenção urinária em 6 dias. Quatro dias antes, apresentou tosse, sensação febril e leve desconforto respiratório. Na admissão, apresentava-se afebril e sem alteração respiratória. O exame neurológico mostrou fraqueza proximal assimétrica, reflexos diminuídos e sensibilidade preservada. Três dias após, o paciente evoluiu com fraqueza facial bilateral e piora da força muscular proximal. Reflexos tendinosos profundos e cutâneo plantar ausentes bilateralmente. A sensibilidade superficial e profunda estavam diminuídas. Evoluiu com piora na saturação de oxigênio sendo colocado sob ventilação mecânica. O exame de liquor revelou uma célula e aumento de proteína (185 mg / dl). A TC de tórax revelou a presença de opacidades em vidro fosco e o RT-PCR para SARS-CoV-2 foi positivo. A biópsia muscular mostrou achados neuromiopáticos moderados com imunoexpressão positiva para MHC classe I, C5b9, CD8 e CD68. A biópsia de nervo revelou infiltrado inflamatório inflamatórios predominantemente endoneural composto por CD45 e CD68. O paciente foi tratado com Oseltamivir por 9 dias seguido de IVIG por 5 dias indo a óbito após três dias por choque séptico. DISCUSSÃO: Este é o primeiro caso documentado de SGB associada a COVID-19 com estudo anatomopatológico de músculo e nervo. Uma revisão sistemática de complicações neurológicas associadas à COVID-19 descreveu 11 pacientes com SGB. As características morfológicas em nosso paciente mostrando sinais de envolvimento do sistema imunológico sugere que a invasão viral direta pode ter colaborado no processo patogênico da lesão neuromuscular. A partir daí, mais pesquisas serão necessárias para entender os gatilhos para essas células migrarem para o nervo periférico.


Subject(s)
Biopsy , Peripheral Nervous System , Guillain-Barre Syndrome , COVID-19
5.
Curr Opin Pediatr ; 33(6): 591-596, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1546082

ABSTRACT

PURPOSE OF REVIEW: Acute central and peripheral nervous system injury may occur in association with coronavirus disease 2019 (COVID-19) caused by infection with the severe acute respiratory syndrome coronavirus 2 virus. This review will assist readers to recognize neurologic manifestations associated with COVID-19 including common and life-threatening symptoms and diagnostic testing. We will also review current recommendations for treatment of neurologic injury associated with COVID-19 infection in children. RECENT FINDINGS: Data from systematic reviews and prospectively collected cohorts of children with COVID-19 are beginning to characterize the breadth of neurologic manifestations associated with COVID-19 in the acute infectious and postinfectious periods. Among hospitalized children in particular, neurologic symptoms are common. Life threatening conditions including encephalitis, myelitis, stroke, and demyelinating syndromes have been reported. Within the pediatric population, age, and preexisting neurologic conditions appear to be important factors in determining likely phenotypes. Treatment at this time is based on careful neuromonitoring, supportive care, and neuromodulatory therapies as indicated. SUMMARY: Neurologic symptoms are common in children with COVID-19 and may be life threatening. The pathophysiology, therapeutic options, and long-term outcomes from COVID-19 associated neurologic injury are currently being investigated.


Subject(s)
COVID-19 , Nervous System Diseases , Stroke , Child , Humans , Peripheral Nervous System , SARS-CoV-2
6.
Trop Biomed ; 38(3): 435-445, 2021 Sep 01.
Article in English | MEDLINE | ID: covidwho-1451066

ABSTRACT

Ever since the first reported case series on SARS-CoV-2-induced neurological manifestation in Wuhan, China in April 2020, various studies reporting similar as well as diverse symptoms of COVID-19 infection relating to the nervous system were published. Since then, scientists started to uncover the mechanism as well as pathophysiological impacts it has on the current understanding of the disease. SARS-CoV-2 binds to the ACE2 receptor which is present in certain parts of the body which are responsible for regulating blood pressure and inflammation in a healthy system. Presence of the receptor in the nasal and oral cavity, brain, and blood allows entry of the virus into the body and cause neurological complications. The peripheral and central nervous system could also be invaded directly in the neurogenic or hematogenous pathways, or indirectly through overstimulation of the immune system by cytokines which may lead to autoimmune diseases. Other neurological implications such as hypoxia, anosmia, dysgeusia, meningitis, encephalitis, and seizures are important symptoms presented clinically in COVID-19 patients with or without the common symptoms of the disease. Further, patients with higher severity of the SARS-CoV-2 infection are also at risk of retaining some neurological complications in the long-run. Treatment of such severe hyperinflammatory conditions will also be discussed, as well as the risks they may pose to the progression of the disease. For this review, articles pertaining information on the neurological manifestation of SARS-CoV-2 infection were gathered from PubMed and Google Scholar using the search keywords "SARS-CoV-2", "COVID-19", and "neurological dysfunction". The findings of the search were filtered, and relevant information were included.


Subject(s)
COVID-19/pathology , Central Nervous System/pathology , Nervous System Diseases/virology , Peripheral Nervous System/pathology , Angiotensin-Converting Enzyme 2/metabolism , Anosmia/virology , Central Nervous System/virology , Dysgeusia/virology , Encephalitis, Viral/virology , Humans , Meningitis, Viral/virology , Nervous System Diseases/pathology , Peripheral Nervous System/virology , SARS-CoV-2 , Seizures/virology
7.
J Med Virol ; 93(9): 5432-5437, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1363681

ABSTRACT

This case series describes three patients affected by severe acute respiratory syndrome coronavirus 2, who developed polyradiculoneuritis as a probable neurological complication of coronavirus disease 2019 (COVID-19). A diagnosis of Guillain Barré syndrome was made on the basis of clinical symptoms, cerebrospinal fluid analysis, and electroneurography. In all of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 gr/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases, a significant decrease in amplitude of compound motor action potential cMAP. Due to the potential role of inflammation on symptoms development and prognosis, interleukin-6 (IL-6) and IL-8 levels were measured in serum and cerebrospinal fluid during the acute phase, while only serum was tested after recovery. Both IL-6 and IL-8 were found increased during the acute phase, both in the serum and cerebrospinal fluid, whereas 4 months after admission (at complete recovery), only IL-8 remained elevated in the serum. These results confirm the inflammatory response that might be linked to peripheral nervous system complications and encourage the use of IL-6 and IL-8 as prognostic biomarkers in COVID-19.


Subject(s)
COVID-19/complications , Guillain-Barre Syndrome/complications , Interleukin-6/cerebrospinal fluid , Interleukin-8/cerebrospinal fluid , Respiratory Insufficiency/complications , SARS-CoV-2/pathogenicity , Action Potentials/drug effects , Acute Disease , Aged , Anti-Bacterial Agents/therapeutic use , Biomarkers/blood , Biomarkers/cerebrospinal fluid , COVID-19/cerebrospinal fluid , COVID-19/drug therapy , COVID-19/virology , Convalescence , Darunavir/therapeutic use , Drug Combinations , Guillain-Barre Syndrome/cerebrospinal fluid , Guillain-Barre Syndrome/drug therapy , Guillain-Barre Syndrome/virology , Humans , Hydroxychloroquine/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Interleukin-6/blood , Interleukin-8/blood , Lopinavir/therapeutic use , Male , Neural Conduction/drug effects , Peripheral Nervous System/drug effects , Peripheral Nervous System/pathology , Peripheral Nervous System/virology , Prognosis , Respiratory Insufficiency/cerebrospinal fluid , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/virology , Ritonavir/therapeutic use , SARS-CoV-2/drug effects
9.
Neurotox Res ; 39(5): 1613-1629, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1281337

ABSTRACT

Aside from the respiratory distress as the predominant clinical presentation of SARS-CoV-2 infection, various neurological complications have been reported with the infection during the ongoing pandemic, some of which cause serious morbidity and mortality. Herein, we gather the latest anatomical evidence of the virus's presence within the central nervous system. We then delve into the possible SARS-CoV-2 entry routes into the neurological tissues, with the hematogenous and the neuronal routes as the two utmost passage routes into the nervous system. We then give a comprehensive review of the neurological manifestations of the SARS-CoV-2 invasion in both the central and peripheral nervous system and its underlying pathophysiology via investigating large studies in the field and case reports in cases of study scarcity.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , Nervous System Diseases/etiology , Nervous System Diseases/physiopathology , COVID-19/virology , Central Nervous System/virology , Humans , Nervous System Diseases/virology , Peripheral Nervous System/virology
10.
J Med Virol ; 93(9): 5432-5437, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1258081

ABSTRACT

This case series describes three patients affected by severe acute respiratory syndrome coronavirus 2, who developed polyradiculoneuritis as a probable neurological complication of coronavirus disease 2019 (COVID-19). A diagnosis of Guillain Barré syndrome was made on the basis of clinical symptoms, cerebrospinal fluid analysis, and electroneurography. In all of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 gr/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases, a significant decrease in amplitude of compound motor action potential cMAP. Due to the potential role of inflammation on symptoms development and prognosis, interleukin-6 (IL-6) and IL-8 levels were measured in serum and cerebrospinal fluid during the acute phase, while only serum was tested after recovery. Both IL-6 and IL-8 were found increased during the acute phase, both in the serum and cerebrospinal fluid, whereas 4 months after admission (at complete recovery), only IL-8 remained elevated in the serum. These results confirm the inflammatory response that might be linked to peripheral nervous system complications and encourage the use of IL-6 and IL-8 as prognostic biomarkers in COVID-19.


Subject(s)
COVID-19/complications , Guillain-Barre Syndrome/complications , Interleukin-6/cerebrospinal fluid , Interleukin-8/cerebrospinal fluid , Respiratory Insufficiency/complications , SARS-CoV-2/pathogenicity , Action Potentials/drug effects , Acute Disease , Aged , Anti-Bacterial Agents/therapeutic use , Biomarkers/blood , Biomarkers/cerebrospinal fluid , COVID-19/cerebrospinal fluid , COVID-19/drug therapy , COVID-19/virology , Convalescence , Darunavir/therapeutic use , Drug Combinations , Guillain-Barre Syndrome/cerebrospinal fluid , Guillain-Barre Syndrome/drug therapy , Guillain-Barre Syndrome/virology , Humans , Hydroxychloroquine/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Interleukin-6/blood , Interleukin-8/blood , Lopinavir/therapeutic use , Male , Neural Conduction/drug effects , Peripheral Nervous System/drug effects , Peripheral Nervous System/pathology , Peripheral Nervous System/virology , Prognosis , Respiratory Insufficiency/cerebrospinal fluid , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/virology , Ritonavir/therapeutic use , SARS-CoV-2/drug effects
11.
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
12.
Pathologe ; 42(2): 172-182, 2021 Mar.
Article in German | MEDLINE | ID: covidwho-1235732

ABSTRACT

The health effects of coronavirus disease 2019 (COVID-19) caused by the infection of SARS-CoV­2 (severe acute respiratory syndrome coronavirus 2) are becoming increasingly clear as the pandemic spreads. In addition to the lungs, other organs are also affected, which can significantly influence morbidity and mortality. In particular, neurological symptoms involving the central nervous system can lead to acute or long-term consequences. The mechanisms of this neuropathogenesis of SARS-CoV­2 infection and its relation to acute and chronic neurological symptoms are the subject of current studies investigating a potential direct and indirect viral infection of the nervous system. The following review summarizes the current status of neuropathological manifestations, molecular pathogenesis, possible infection pathways in the nervous system, and systemic effects. In addition, an overview of the Germany-wide CNS-COVID19 registry and collaborations is presented, which should contribute to a better understanding of the neurological symptoms of COVID-19.


Subject(s)
COVID-19 , Germany , Humans , Pandemics , Peripheral Nervous System , SARS-CoV-2
14.
Curr Neurol Neurosci Rep ; 21(3): 9, 2021 02 14.
Article in English | MEDLINE | ID: covidwho-1080528

ABSTRACT

PURPOSE OF REVIEW: The present review discusses the peripheral nervous system (PNS) manifestations associated with coronavirus disease 2019 (COVID-19). RECENT FINDINGS: Nerve pain and skeletal muscle injury, Guillain-Barré syndrome, cranial polyneuritis, neuromuscular junction disorders, neuro-ophthalmological disorders, neurosensory hearing loss, and dysautonomia have been reported as PNS manifestations in patients with COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19. COVID-19 has shown syndromic complexity. Not only does SARS-CoV-2 affect the central nervous system but also it involves the PNS. The PNS involvement may be due to dysregulation of the immune system attributable to COVID-19. Here we review the broad spectrum of PNS involvement of COVID-19.


Subject(s)
COVID-19 , Guillain-Barre Syndrome , Nervous System Diseases , Central Nervous System , Humans , Peripheral Nervous System , SARS-CoV-2
15.
J Neurol ; 268(9): 3086-3104, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1029550

ABSTRACT

OBJECTIVE: To systematically describe central (CNS) and peripheral (PNS) nervous system complications in hospitalized COVID-19 patients. METHODS: We conducted a prospective, consecutive, observational study of adult patients from a tertiary referral center with confirmed COVID-19. All patients were screened daily for neurological and neuropsychiatric symptoms during admission and discharge. Three-month follow-up data were collected using electronic health records. We classified complications as caused by SARS-CoV-2 neurotropism, immune-mediated or critical illness-related. RESULTS: From April to September 2020, we enrolled 61 consecutively admitted COVID-19 patients, 35 (57%) of whom required intensive care (ICU) management for respiratory failure. Forty-one CNS/PNS complications were identified in 28 of 61 (45.9%) patients and were more frequent in ICU compared to non-ICU patients. The most common CNS complication was encephalopathy (n = 19, 31.1%), which was severe in 13 patients (GCS ≤ 12), including 8 with akinetic mutism. Length of ICU admission was independently associated with encephalopathy (OR = 1.22). Other CNS complications included ischemic stroke, a biopsy-proven acute necrotizing encephalitis, and transverse myelitis. The most common PNS complication was critical illness polyneuromyopathy (13.1%), with prolonged ICU stay as independent predictor (OR = 1.14). Treatment-related PNS complications included meralgia paresthetica. Of 41 complications in total, 3 were para/post-infectious, 34 were secondary to critical illness or other causes, and 4 remained unresolved. Cerebrospinal fluid was negative for SARS-CoV-2 RNA in all 5 patients investigated. CONCLUSION: CNS and PNS complications were common in hospitalized COVID-19 patients, particularly in the ICU, and often attributable to critical illness. When COVID-19 was the primary cause for neurological disease, no signs of viral neurotropism were detected, but laboratory changes suggested autoimmune-mediated mechanisms.


Subject(s)
COVID-19 , Stroke , Adult , Follow-Up Studies , Humans , Peripheral Nervous System , Prospective Studies , RNA, Viral , SARS-CoV-2
16.
Cytokine ; 138: 155404, 2021 02.
Article in English | MEDLINE | ID: covidwho-996816

ABSTRACT

The new coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can trigger a hyperinflammatory state characterized by elevated cytokine levels known as hypercytokinemia or cytokine storm, observed most often in severe patients. Though COVID-19 is known to be a primarily respiratory disease, neurological complications affecting both the central and peripheral nervous systems have also been reported. This review discusses potential routes of SARS-CoV-2 neuroinvasion and pathogenesis, summarizes reported neurological sequelae of COVID-19, and examines how aberrant cytokine levels may precipitate these complications. Clarification of the pathogenic mechanisms of SARS-CoV-2 is needed to encourage prompt diagnosis and optimized care. In particular, identifying the presence of cytokine storm in patients with neurological COVID-19 manifestations will facilitate avenues for treatment. Future investigations into aberrant cytokine levels in COVID-19 patients with neurological symptoms as well as the efficacy of cytokine storm-targeting treatments will be critical in elucidating the pathogenic mechanisms and effective treatments of COVID-19.


Subject(s)
COVID-19/pathology , Cerebrovascular Disorders/pathology , Cytokine Release Syndrome/pathology , Cytokines/blood , Nervous System Diseases/pathology , COVID-19/therapy , Central Nervous System/pathology , Cerebrovascular Disorders/virology , Cytokine Release Syndrome/therapy , Humans , Nervous System Diseases/virology , Peripheral Nervous System/pathology , SARS-CoV-2
17.
J Neurosci Res ; 99(3): 750-777, 2021 03.
Article in English | MEDLINE | ID: covidwho-938490

ABSTRACT

Without protective and/or therapeutic agents the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection known as coronavirus disease 2019 is quickly spreading worldwide. It has surprising transmissibility potential, since it could infect all ages, gender, and human sectors. It attacks respiratory, gastrointestinal, urinary, hepatic, and endovascular systems and can reach the peripheral nervous system (PNS) and central nervous system (CNS) through known and unknown mechanisms. The reports on the neurological manifestations and complications of the SARS-CoV-2 infection are increasing exponentially. Herein, we enumerate seven candidate routes, which the mature or immature SARS-CoV-2 components could use to reach the CNS and PNS, utilizing the within-body cross talk between organs. The majority of SARS-CoV-2-infected patients suffer from some neurological manifestations (e.g., confusion, anosmia, and ageusia). It seems that although the mature virus did not reach the CNS or PNS of the majority of patients, its unassembled components and/or the accompanying immune-mediated responses may be responsible for the observed neurological symptoms. The viral particles and/or its components have been specifically documented in endothelial cells of lung, kidney, skin, and CNS. This means that the blood-endothelial barrier may be considered as the main route for SARS-CoV-2 entry into the nervous system, with the barrier disruption being more logical than barrier permeability, as evidenced by postmortem analyses.


Subject(s)
COVID-19/complications , COVID-19/metabolism , Central Nervous System/metabolism , Nervous System Diseases/etiology , Nervous System Diseases/metabolism , Peripheral Nervous System/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Animals , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/virology , COVID-19/transmission , Central Nervous System/virology , Humans , Nervous System Diseases/virology , Olfactory Nerve/metabolism , Olfactory Nerve/virology , Peripheral Nervous System/virology
18.
Neuromuscul Disord ; 30(10): 859-861, 2020 10.
Article in English | MEDLINE | ID: covidwho-759207

ABSTRACT

In recent months, the new beta-coronavirus has caused a pandemic with symptoms affecting mainly the respiratory system. It is established that the virus may play a neurotropic role and in recent months several cases of Guillain-Barré-Strohl syndrome (GBS) have been reported in patients infected with COVID-19. We report the case of a 54-year-old patient with acute demyelinating polyneuropathy during infection by SARS-CoV-2 who progressed clinically to require assisted ventilation. After several weeks of specific symptomatic treatment, the patient had a favorable outcome. In conclusion, despite being a rare complication, we think it is important to consider the possibility of diffuse involvement of the peripheral nervous system in patients with COVID-19 to adjust clinical monitoring and treatment in these cases.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/therapy , Coronavirus Infections/virology , Guillain-Barre Syndrome/therapy , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Guillain-Barre Syndrome/complications , Guillain-Barre Syndrome/diagnosis , Humans , Male , Middle Aged , Pandemics , Peripheral Nervous System/virology , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , SARS-CoV-2
19.
Indian J Med Res ; 152(1 & 2): 41-47, 2020.
Article in English | MEDLINE | ID: covidwho-732738

ABSTRACT

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been predominantly a respiratory manifestation. Currently, with evolving literature, neurological signs are being increasingly recognized. Studies have reported that SARS-CoV-2 affects all aspects of the nervous system including the central nervous system (CNS), peripheral nervous system (PNS) and the muscular system as well. Not all patients have reverse transcription-polymerase chain reaction positive for the virus in the cerebrospinal fluid, and diagnosing the association of the virus with the myriad of neurological manifestations can be a challenge. It is important that clinicians have a high-index of suspicion for COVID-19 in patients presenting with new-onset neurological symptoms. This will lead to early diagnosis and specific management. Further studies are desired to unravel the varied neurological manifestations, treatment, outcome and long-term sequel in COVID-19 patients.


Subject(s)
Central Nervous System/pathology , Coronavirus Infections/epidemiology , Nervous System Diseases/epidemiology , Peripheral Nervous System/pathology , Pneumonia, Viral/epidemiology , Betacoronavirus/pathogenicity , COVID-19 , Central Nervous System/virology , Coronavirus Infections/complications , Coronavirus Infections/pathology , Coronavirus Infections/virology , Humans , Muscle, Skeletal/pathology , Muscle, Skeletal/virology , Nervous System Diseases/complications , Nervous System Diseases/pathology , Nervous System Diseases/virology , Pandemics , Peripheral Nervous System/virology , Pneumonia, Viral/complications , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , SARS-CoV-2
20.
Life Sci ; 257: 118063, 2020 Sep 15.
Article in English | MEDLINE | ID: covidwho-640510

ABSTRACT

Novel coronavirus (severe acute respiratory syndrome coronavirus-2: SARS-CoV-2) has a high homology with other cousin of coronaviruses such as SARS and Middle East respiratory syndrome-related coronavirus (MERS). After outbreak of the SARS-CoV-2 in China, it has spread so fast around the world. The main complication of coronavirus disease 2019 (COVID-19) is respiratory failure, but several patients have also been admitted to the hospital with neurological symptoms. Direct invasion, hematogenic rout, retrograde and anterograde transport along peripheral nerves are considered as main neuroinvasion mechanisms of SARS-CoV-2. In the present study, we describe the possible routes for entering of SARS-CoV-2 into the nervous system. Then, the neurological manifestations of the SARS-CoV-2 infection in the central nervous system (CNS) and peripheral nervous system (PNS) are reviewed. Furthermore, the neuropathology of the virus and its impacts on other neurological disorders are discussed.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Nervous System Diseases/virology , Pneumonia, Viral/immunology , Betacoronavirus/pathogenicity , COVID-19 , Central Nervous System/virology , China/epidemiology , Coronavirus/immunology , Coronavirus/pathogenicity , Coronavirus Infections/epidemiology , Coronavirus Infections/pathology , Cytokines/immunology , Cytokines/metabolism , Humans , Nervous System Diseases/epidemiology , Pandemics , Peripheral Nervous System/virology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/pathology , SARS-CoV-2 , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/virology
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