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1.
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
2.
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
3.
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
4.
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
5.
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
6.
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
7.
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
8.
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
9.
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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