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1.
Neurol Neuroimmunol Neuroinflamm ; 9(1)2022 01.
Article in English | MEDLINE | ID: covidwho-1596607

ABSTRACT

BACKGROUND AND OBJECTIVES: To investigate whether children receiving immunosuppressive therapies for neuroimmunologic disorders had (1) increased susceptibility to SARS-CoV2 infection or to develop more severe forms of COVID-19; (2) increased relapses or autoimmune complications if infected; and (3) changes in health care delivery during the pandemic. METHODS: Patients with and without immunosuppressive treatment were recruited to participate in a retrospective survey evaluating the period from March 14, 2020, to March 30, 2021. Demographics, clinical features, type of immunosuppressive treatment, suspected or confirmed COVID-19 in the patients or cohabitants, and changes in care delivery were recorded. RESULTS: One hundred fifty-three children were included: 84 (55%) female, median age 13 years (interquartile range [8-16] years), 79 (52%) on immunosuppressive treatment. COVID-19 was suspected or confirmed in 17 (11%) (all mild), with a frequency similar in patients with and without immunosuppressive treatment (11/79 [14%] vs 6/74 [8%], p = 0.3085). The frequency of neurologic relapses was similar in patients with (18%) and without (21%) COVID-19. Factors associated with COVID-19 included having cohabitants with COVID-19 (p < 0.001) and lower blood levels of vitamin D (p = 0.039). Return to face-to-face schooling or mask type did not influence the risk of infection, although 43(28%) children had contact with a classmate with COVID-19. Clinic visits changed from face to face to remote for 120 (79%) patients; 110 (92%) were satisfied with the change. DISCUSSION: In this cohort of children with neuroimmunologic disorders, the frequency of COVID-19 was low and not affected by immunosuppressive therapies. The main risk factors for developing COVID-19 were having cohabitants with COVID-19 and low vitamin D levels.


Subject(s)
COVID-19/complications , COVID-19/immunology , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Nervous System Diseases/complications , Nervous System Diseases/immunology , SARS-CoV-2/immunology , Adolescent , COVID-19/prevention & control , COVID-19/virology , Child , Delivery of Health Care/organization & administration , Delivery of Health Care/statistics & numerical data , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Masks/statistics & numerical data , Masks/virology , Nervous System Diseases/virology , Pandemics , Recurrence , Retrospective Studies , Vitamin D/blood
2.
Curr Opin Pediatr ; 33(6): 580-590, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1546081

ABSTRACT

PURPOSE OF REVIEW: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has overwhelmed the global community, negatively impacting patient health and research efforts; associated neurological manifestations are a significant cause of morbidity. This review outlines the worldwide epidemiology of neurologic manifestations of different SARS-CoV-2 clinical pediatric phenotypes, including acute coronavirus disease 2019 (COVID-19), multisystem inflammatory syndrome in children (MIS-C) and postacute sequelae of COVID-19 (PASC). We discuss strategies to develop adaptive global research platforms for future investigation into emerging pediatric neurologic conditions. RECENT FINDINGS: Multicenter, multinational studies show that neurological manifestations of acute COVID-19, such as smell/taste disorders, headache, and stroke, are common in hospitalized adults (82%) and children (22%), associated with increased mortality in adults. Neurological manifestations of MIS-C are reported in up to 20% of children, including headache, irritability, and encephalopathy. Data on PASC are emerging and include fatigue, cognitive changes, and headache. Reports of neurological manifestations in each phenotype are limited by lack of pediatric-informed case definitions, common data elements, and resources. SUMMARY: Coordinated, well resourced, multinational investigation into SARS-CoV-2-related neurological manifestations in children is critical to rapid identification of global and region-specific risk factors, and developing treatment and mitigation strategies for the current pandemic and future health neurologic emergencies.


Subject(s)
COVID-19 , Nervous System Diseases/virology , Systemic Inflammatory Response Syndrome , COVID-19/complications , Child , Humans , Multicenter Studies as Topic , Pandemics
3.
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
4.
Viruses ; 13(7)2021 07 15.
Article in English | MEDLINE | ID: covidwho-1448933

ABSTRACT

Virus-induced infections of the central nervous system (CNS) are among the most serious problems in public health and can be associated with high rates of morbidity and mortality, mainly in low- and middle-income countries, where these manifestations have been neglected. Typically, herpes simplex virus 1 and 2, varicella-zoster, and enterovirus are responsible for a high number of cases in immunocompetent hosts, whereas other herpesviruses (for example, cytomegalovirus) are the most common in immunocompromised individuals. Arboviruses have also been associated with outbreaks with a high burden of neurological disorders, such as the Zika virus epidemic in Brazil. There is a current lack of understanding in Brazil about the most common viruses involved in CNS infections. In this review, we briefly summarize the most recent studies and findings associated with the CNS, in addition to epidemiological data that provide extensive information on the circulation and diversity of the most common neuro-invasive viruses in Brazil. We also highlight important aspects of the prion-associated diseases. This review provides readers with better knowledge of virus-associated CNS infections. A deeper understanding of these infections will support the improvement of the current surveillance strategies to allow the timely monitoring of the emergence/re-emergence of neurotropic viruses.


Subject(s)
Central Nervous System Diseases/virology , Central Nervous System Infections/epidemiology , Prion Diseases/epidemiology , Alphavirus/pathogenicity , Brazil/epidemiology , Central Nervous System/virology , Central Nervous System Diseases/metabolism , Central Nervous System Diseases/physiopathology , Central Nervous System Infections/virology , Central Nervous System Viral Diseases/physiopathology , Central Nervous System Viral Diseases/virology , Enterovirus/pathogenicity , Flavivirus/pathogenicity , Herpesviridae/pathogenicity , Humans , Nervous System Diseases/epidemiology , Nervous System Diseases/virology , Prion Diseases/physiopathology , Prions/metabolism , Prions/pathogenicity , Simplexvirus/pathogenicity , Virus Diseases/virology , Viruses/pathogenicity , Zika Virus/pathogenicity
5.
Front Immunol ; 12: 711741, 2021.
Article in English | MEDLINE | ID: covidwho-1430696

ABSTRACT

COVID-19 is widespread worldwide and seriously affects the daily life and health of humans. Countries around the world are taking necessary measures to curb the spread. However, COVID-19 patients often have at least one organ complication and sequelae in addition to respiratory symptoms. Controlling the epidemic is only a phased victory, and the complication and sequelae of COVID-19 will need more attention in the post-epidemic era. We collected general information from over 1000 articles published in 2020 after the COVID-19 outbreak and systematically analyzed the complication and sequelae associated with eight major systems in COVID-19 patients caused by ACE2 intervention in the RAS regulatory axis. The autoimmune response induced by 2019-nCoV attacks and damages the normal tissues and organs of the body. Our research will help medical workers worldwide address COVID-19 complication and sequelae.


Subject(s)
COVID-19/pathology , Cardiovascular Diseases/pathology , Endocrine System Diseases/pathology , Gastrointestinal Diseases/pathology , Nervous System Diseases/pathology , Urologic Diseases/pathology , COVID-19/complications , Cardiovascular Diseases/virology , Disease Outbreaks , Disease Progression , Endocrine System Diseases/virology , Gastrointestinal Diseases/virology , Humans , Nervous System Diseases/virology , SARS-CoV-2 , Urologic Diseases/virology
6.
Ital J Pediatr ; 47(1): 191, 2021 Sep 18.
Article in English | MEDLINE | ID: covidwho-1413462

ABSTRACT

BACKGROUND: Presently, it is known that, even if less frequently than in adults, children can develop a severe new coronavirus disease 2019 (COVID-19). Children with the SARS-CoV-2 infection can have neurological signs and symptoms of disease more frequently than previously thought, revealing the involvement of the central nervous system, the peripheral nervous system, or both. Aim of this manuscript is to highlight the neurologic complications associated with SARS-CoV-2 among pediatric patients with COVID-19, suggesting when to monitor carefully neurologic development. MAIN FINDINGS: Children with a severe chronic underlying disease, infants and toddlers and those who develop the so-called multisystem inflammatory syndrome (MIS-C) are those with the highest incidence of neurological complications. Fortunately, in most of the cases, neurological manifestations, mainly represented by headache and anosmia, are mild and transient and do not significantly complicate the COVID-19 course. However, in some cases, very severe clinical problems associated with relevant alterations of neuroimaging, electroencephalography, nerve conduction studies and electromyography findings can develop. Generally, almost all the children with COVID-19 and neurological manifestations till now described have made a complete recovery, although in some cases this has occurred after several weeks of treatment. Moreover, COVID-19 infection during pregnancy has been found associated with an increased risk of obstetric complications that can lead to neurological acute and long-term manifestations in neonates. CONCLUSIONS: Based on data showing the neurologic impact of COVID-19 in pediatric age, we suggest monitoring neurological development a few months after healing in pediatric patients who have presented MIS-C, seizures or other neurological manifestations and in children of pregnant women with COVID-19 in order to detect overt and subtle deficits.


Subject(s)
COVID-19/complications , Nervous System Diseases/virology , Pregnancy Complications, Infectious/virology , Systemic Inflammatory Response Syndrome/virology , COVID-19/diagnosis , COVID-19/virology , Child , Child, Preschool , Comorbidity , Female , Humans , Infant , Infant, Newborn , Male , Nervous System Diseases/diagnosis , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Risk Factors , SARS-CoV-2 , Seizures/virology , Systemic Inflammatory Response Syndrome/diagnosis
7.
Am J Pathol ; 191(11): 1946-1954, 2021 11.
Article in English | MEDLINE | ID: covidwho-1397147

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was originally identified as an outbreak in Wuhan, China, toward the end of 2019 and quickly became a global pandemic, with a large death toll. Originally identified as a respiratory disease, similar to previously discovered SARS and Middle East respiratory syndrome (MERS), concern has since been raised about the effects of SARS-CoV-2 infection on the vasculature. This viral-vascular involvement is of particular concern with regards to the small vessels present in the brain, with mounting evidence demonstrating that SARS-CoV-2 is capable of crossing the blood-brain barrier. Severe symptoms, termed coronavirus disease 2019 (COVID-19), often result in neurologic complications, regardless of patient age. These neurologic complications range from mild to severe across all demographics; however, the long-term repercussions of neurologic involvement on patient health are still unknown.


Subject(s)
Blood Vessels/virology , Blood-Brain Barrier/virology , COVID-19/complications , Nervous System Diseases/virology , Humans , SARS-CoV-2
8.
Front Immunol ; 12: 730088, 2021.
Article in English | MEDLINE | ID: covidwho-1394763

ABSTRACT

In December 2019, a new viral disease emerged and quickly spread all around the world. In March 2020, the COVID-19 outbreak was classified as a global pandemic and by June 2021, the number of infected people grew to over 170 million. Along with the patients' mild-to-severe respiratory symptoms, reports on probable central nervous system (CNS) effects appeared shortly, raising concerns about the possible long-term detrimental effects on human cognition. It remains unresolved whether the neurological symptoms are caused directly by the SARS-CoV-2 infiltration in the brain, indirectly by secondary immune effects of a cytokine storm and antibody overproduction, or as a consequence of systemic hypoxia-mediated microglia activation. In severe COVID-19 cases with impaired lung capacity, hypoxia is an anticipated subsidiary event that can cause progressive and irreversible damage to neurons. To resolve this problem, intensive research is currently ongoing, which seeks to evaluate the SARS-CoV-2 virus' neuroinvasive potential and the examination of the antibody and autoantibody generation upon infection, as well as the effects of prolonged systemic hypoxia on the CNS. In this review, we summarize the current research on the possible interplay of the SARS-CoV-2 effects on the lung, especially on alveolar macrophages and direct and indirect effects on the brain, with special emphasis on microglia, as a possible culprit of neurological manifestation during COVID-19.


Subject(s)
COVID-19/complications , Central Nervous System Infections/complications , Central Nervous System Infections/virology , Lung/virology , SARS-CoV-2/pathogenicity , COVID-19/immunology , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/immunology , Humans , Lung/immunology , Microglia/immunology , Microglia/pathology , Microglia/virology , Nervous System Diseases/virology , SARS-CoV-2/immunology
9.
Cells ; 10(9)2021 08 31.
Article in English | MEDLINE | ID: covidwho-1390541

ABSTRACT

COVID-19 presents with a wide range of clinical neurological manifestations. It has been recognized that SARS-CoV-2 infection affects both the central and peripheral nervous system, leading to smell and taste disturbances; acute ischemic and hemorrhagic cerebrovascular disease; encephalopathies and seizures; and causes most surviving patients to have long lasting neurological symptoms. Despite this, typical neuropathological features associated with the infection have still not been identified. Studies of post-mortem examinations of the cerebral cortex are obtained with difficulty due to laboratory safety concerns. In addition, they represent cases with different neurological symptoms, age or comorbidities, thus a larger number of brain autoptic data from multiple institutions would be crucial. Histopathological findings described here are aimed to increase the current knowledge on neuropathology of COVID-19 patients. We report post-mortem neuropathological findings of ten COVID-19 patients. A wide range of neuropathological lesions were seen. The cerebral cortex of all patients showed vascular changes, hyperemia of the meninges and perivascular inflammation in the cerebral parenchyma with hypoxic neuronal injury. Perivascular lymphocytic inflammation of predominantly CD8-positive T cells mixed with CD68-positive macrophages, targeting the disrupted vascular wall in the cerebral cortex, cerebellum and pons were seen. Our findings support recent reports highlighting a role of microvascular injury in COVID-19 neurological manifestations.


Subject(s)
COVID-19/pathology , Cerebral Cortex/pathology , Aged , Aged, 80 and over , Autopsy , Brain/pathology , Brain/virology , Brain Diseases/pathology , Brain Diseases/virology , CD8-Positive T-Lymphocytes/pathology , Cerebral Cortex/virology , Female , Humans , Inflammation , Macrophages/pathology , Male , Microvessels/pathology , Microvessels/virology , Middle Aged , Nervous System Diseases/pathology , Nervous System Diseases/virology , SARS-CoV-2/pathogenicity
11.
BMJ Case Rep ; 14(4)2021 Apr 15.
Article in English | MEDLINE | ID: covidwho-1388472

ABSTRACT

Neurological complications of SARS-CoV-2 continue to be recognised. In children, neurological phenomenon has been reported generally in the acute infectious period. It is possible that SARS-CoV-2 could trigger an immune-mediated post-infectious phenomenon. Here, we present a unique case of post-infectious marantic cardiac lesion causing cerebrovascular accident in a patient with Down syndrome.


Subject(s)
COVID-19/complications , Down Syndrome , Nervous System Diseases/virology , Stroke/virology , Child , Down Syndrome/complications , Down Syndrome/virology , Humans , Inflammation/complications , Inflammation/virology
14.
J Neurovirol ; 27(5): 782-786, 2021 10.
Article in English | MEDLINE | ID: covidwho-1375851

ABSTRACT

Neurological symptoms in COVID-19 patients can also be found in the pediatric population, but they are usually described as mild symptoms. Herein, we described a case series of four pediatric patients with severe and highly heterogeneous central and peripheral nervous system manifestations. The objective was to report neurological manifestations of COVID-19 in children and adolescents. The design is case series. The participants are four children and adolescents with confirmed COVID-19. The main outcome and measures are as follows: Clinical data were gathered from electronic medical records, and data of all neurologic symptoms were checked by a trained neurologist. We reported four pediatric patients with COVID-19 and different neurologic symptoms. Case 1 was a 16-year-old girl with a sensory and motor polyradiculopathy with RT-qPCR for COVID-19 and dengue both detected in CSF that improved after appropriate treatment. Case 2 was a 15-year-old boy with Guillain-Barre syndrome and had good response after using human immunoglobulin. Case 3 was a 5-year-old girl with acute intracranial hypertension that improved after going through lumbar puncture and using acetazolamide. Case 4 was a 2-month-old male infant with focal epileptic seizures that recovered after antiepileptic treatment. We highlight the need to consider different neurologic manifestations as part of the COVID-19 clinical spectrum.


Subject(s)
COVID-19/complications , Nervous System Diseases/virology , Adolescent , Child, Preschool , Female , Humans , Infant , Male , SARS-CoV-2
15.
Am J Phys Med Rehabil ; 100(8): 725-729, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1367090

ABSTRACT

ABSTRACT: The coronavirus disease 2019 has been reported to cause various serious neurological sequelae. However, there is little information available about the impact of the disease and its complications on patients' functional status and their postacute needs. Hence, this study was performed to address the current gap in knowledge about the function and postacute needs of those with neurological complications of coronavirus disease 2019. A prospective chart review was completed for 319 patients admitted with coronavirus disease 2019 between March 4 and May 1, 2020. Primary outcomes included rate of new functional decline, discharge location, need for outpatient physical/occupational/speech therapy, need for durable medical equipment at discharge, and presence of dysphagia at discharge. Patients with neurological complications were compared with patients without neurological complications. Two hundred ninety-six cases were included in the final analysis, and 81 (27.4%) of these patients experienced neurological complications. Results indicated that hospitalized coronavirus disease 2019 patients with neurological complications exhibit a significantly longer length of stay, higher frequency of functional decline, higher mortality rate, and more frequent discharge to a subacute rehabilitation facility (all P < 0.0001). The findings of this study are expected to better prepare patients, providers, and health systems for the postacute needs of those with coronavirus disease 2019 and neurological complications.


Subject(s)
COVID-19/complications , Nervous System Diseases/rehabilitation , Nervous System Diseases/virology , Adult , Aged , Female , Hospitalization , Humans , Male , Middle Aged , Pandemics , Patient Discharge , Prospective Studies , Recovery of Function , SARS-CoV-2 , Subacute Care
16.
Brain Pathol ; 31(6): e13013, 2021 11.
Article in English | MEDLINE | ID: covidwho-1354468

ABSTRACT

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the new coronavirus responsible for the pandemic disease in the last year, is able to affect the central nervous system (CNS). Compared with its well-known pulmonary tropism and respiratory complications, little has been studied about SARS-CoV-2 neurotropism and pathogenesis of its neurological manifestations, but also about postmortem histopathological findings in the CNS of patients who died from COVID-19 (coronavirus disease 2019). We present a systematic review, carried out according to the Preferred Reporting Items for Systematic Review standards, of the neuropathological features of COVID-19. We found 21 scientific papers, the majority of which refer to postmortem examinations; the total amount of cases is 197. Hypoxic changes are the most frequently reported alteration of brain tissue, followed by ischemic and hemorrhagic lesions and reactive astrogliosis and microgliosis. These findings do not seem to be specific to SARS-CoV-2 infection, they are more likely because of systemic inflammation and coagulopathy caused by COVID-19. More studies are needed to confirm this hypothesis and to detect other possible alterations of neural tissue. Brain examination of patients dead from COVID-19 should be included in a protocol of standardized criteria to perform autopsies on these subjects.


Subject(s)
Brain/physiology , Brain/virology , COVID-19/pathology , Nervous System Diseases/virology , SARS-CoV-2/metabolism , Brain/physiopathology , COVID-19/metabolism , COVID-19/virology , Central Nervous System/physiology , Central Nervous System/virology , Humans , Inflammation/pathology , Inflammation/virology , Nervous System Diseases/etiology , Nervous System Diseases/pathology , Pandemics
17.
Immunol Res ; 69(6): 553-557, 2021 12.
Article in English | MEDLINE | ID: covidwho-1345196

ABSTRACT

The persistence of neurological symptoms after SARS-CoV-2 infection, as well as the presence of late axonal damage, is still unknown. We performed extensive systemic and neurological follow-up evaluations in 107 out of 193 consecutive patients admitted to the COVID-19 medical unit, University Hospital of Verona, Italy between March and June 2020. We analysed serum neurofilament light chain (NfL) levels in all cases including a subgroup (n = 29) of patients with available onset samples. Comparisons between clinical and biomarker data were then performed. Neurological symptoms were still present in a significant number (n = 49) of patients over the follow-up. The most common reported symptoms were hyposmia (n = 11), fatigue (n = 28), myalgia (n = 14), and impaired memory (n = 11) and were more common in cases with severe acute COVID-19. Follow-up serum NfL values (15.2 pg/mL, range 2.4-62.4) were within normal range in all except 5 patients and did not differentiate patients with vs without persistent neurological symptoms. In patients with available onset and follow-up samples, a significant (p < 0.001) decrease of NfL levels was observed and was more evident in patients with a severe acute disease. Despite the common persistence of neurological symptoms, COVID-19 survivors do not show active axonal damage, which seems a peculiar feature of acute SARS-CoV-2 infection.


Subject(s)
Axons/pathology , COVID-19/pathology , Nervous System Diseases/pathology , Adult , Aged , Aged, 80 and over , Ageusia/pathology , Ageusia/virology , Anosmia/pathology , Anosmia/virology , Axons/virology , Disease Progression , Fatigue/pathology , Fatigue/virology , Female , Humans , Italy , Male , Memory Disorders/pathology , Memory Disorders/virology , Middle Aged , Myalgia/pathology , Myalgia/virology , Nervous System Diseases/virology , Neurofilament Proteins/blood , SARS-CoV-2
18.
Med Clin (Barc) ; 157(3): 141-143, 2021 08 13.
Article in English, Spanish | MEDLINE | ID: covidwho-1340761

ABSTRACT

INTRODUCTION: In the context of the global COVID-19 pandemic, the different clinical manifestations of this infection pose a challenge for healthcare professionals. Respiratory involvement, the main symptom of SARS-CoV-2 infection, means that other manifestations, such as neurological, take a back seat, with the consequent delay in diagnosis and treatment. MATERIAL AND METHODS: All COVID-19 patients admitted with neurological symptoms or diagnosed with encephalitis since March 2020 in a tertiary hospital in Zaragoza, Spain. RESULTS: Two patients with COVID-19 infection confirmed by nasopharyngeal PCR and whose clinical picture consisted of neurological alterations compatible with encephalitis. Cerebrospinal fluid (CSF) microbiology was negative for bacteria and viruses, including SARS-CoV-2 but, given the clinical suspicion of encephalitis due to the latter, antiviral treatment with immunoglobulins and plasmapheresis was started early. Despite this, the evolution was not satisfactory. CONCLUSIONS: COVID-19 encephalitis is a recently described clinical entity, whose pathophysiology is still unknown and no treatment with clinical evidence is available to date.


Subject(s)
COVID-19 , Encephalitis , Nervous System Diseases , COVID-19/complications , Encephalitis/diagnosis , Encephalitis/virology , Humans , Nervous System Diseases/diagnosis , Nervous System Diseases/virology , Pandemics , Spain
19.
Fluids Barriers CNS ; 18(1): 32, 2021 Jul 14.
Article in English | MEDLINE | ID: covidwho-1311251

ABSTRACT

BACKGROUND: SARS-CoV-2, a coronavirus (CoV), is known to cause acute respiratory distress syndrome, and a number of non-respiratory complications, particularly in older male patients with prior health conditions, such as obesity, diabetes and hypertension. These prior health conditions are associated with vascular dysfunction, and the CoV disease 2019 (COVID-19) complications include multiorgan failure and neurological problems. While the main route of entry into the body is inhalation, this virus has been found in many tissues, including the choroid plexus and meningeal vessels, and in neurons and CSF. MAIN BODY: We reviewed SARS-CoV-2/COVID-19, ACE2 distribution and beneficial effects, the CNS vascular barriers, possible mechanisms by which the virus enters the brain, outlined prior health conditions (obesity, hypertension and diabetes), neurological COVID-19 manifestation and the aging cerebrovascualture. The overall aim is to provide the general reader with a breadth of information on this type of virus and the wide distribution of its main receptor so as to better understand the significance of neurological complications, uniqueness of the brain, and the pre-existing medical conditions that affect brain. The main issue is that there is no sound evidence for large flux of SARS-CoV-2 into brain, at present, compared to its invasion of the inhalation pathways. CONCLUSIONS: While SARS-CoV-2 is detected in brains from severely infected patients, it is unclear on how it gets there. There is no sound evidence of SARS-CoV-2 flux into brain to significantly contribute to the overall outcomes once the respiratory system is invaded by the virus. The consensus, based on the normal route of infection and presence of SARS-CoV-2 in severely infected patients, is that the olfactory mucosa is a possible route into brain. Studies are needed to demonstrate flux of SARS-CoV-2 into brain, and its replication in the parenchyma to demonstrate neuroinvasion. It is possible that the neurological manifestations of COVID-19 are a consequence of mainly cardio-respiratory distress and multiorgan failure. Understanding potential SARS-CoV-2 neuroinvasion pathways could help to better define the non-respiratory neurological manifestation of COVID-19.


Subject(s)
COVID-19/virology , Nervous System Diseases/virology , COVID-19/complications , COVID-19/pathology , Humans , Nervous System Diseases/etiology , Nervous System Diseases/pathology , Prognosis , Risk Factors
20.
J Neurosci ; 41(25): 5338-5349, 2021 06 23.
Article in English | MEDLINE | ID: covidwho-1282334

ABSTRACT

Clinical reports suggest that the coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome (SARS)-coronavirus-2 (CoV-2) has not only taken millions of lives, but has also created a major crisis of neurologic complications that persist even after recovery from the disease. Autopsies of patients confirm the presence of the coronaviruses in the CNS, especially in the brain. The invasion and transmission of SARS-CoV-2 in the CNS is not clearly defined, but, because the endocytic pathway has become an important target for the development of therapeutic strategies for COVID-19, it is necessary to understand endocytic processes in the CNS. In addition, mitochondria and mechanistic target of rapamycin (mTOR) signaling pathways play a critical role in the antiviral immune response, and may also be critical for endocytic activity. Furthermore, dysfunctions of mitochondria and mTOR signaling pathways have been associated with some high-risk conditions such as diabetes and immunodeficiency for developing severe complications observed in COVID-19 patients. However, the role of these pathways in SARS-CoV-2 infection and spread are largely unknown. In this review, we discuss the potential mechanisms of SARS-CoV-2 entry into the CNS and how mitochondria and mTOR pathways might regulate endocytic vesicle-mitochondria interactions and dynamics during SARS-CoV-2 infection. The mechanisms that plausibly account for severe neurologic complications with COVID-19 and potential treatments with Food and Drug Administration-approved drugs targeting mitochondria and the mTOR pathways are also addressed.


Subject(s)
COVID-19/complications , Nervous System Diseases/virology , Neurons/virology , Animals , COVID-19/drug therapy , COVID-19/metabolism , COVID-19/pathology , COVID-19/virology , Humans , Mitochondria/metabolism , Mitochondria/virology , Nervous System Diseases/drug therapy , Nervous System Diseases/metabolism , Nervous System Diseases/pathology , Neurons/metabolism , SARS-CoV-2/pathogenicity , TOR Serine-Threonine Kinases/metabolism
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