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Haider L, Rommer P, Ahmet I, Dena A, Thurnher AP, Tomassino E, Bonderman D, Thalhammer F, Seidel S, Berger T, Thurnher M. No brain MRI abnormalities after mild-to-moderate COVID-19: an observational study. Neuroradiology 2025:10.1007/s00234-025-03586-1. [PMID: 40314790 DOI: 10.1007/s00234-025-03586-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Accepted: 03/05/2025] [Indexed: 05/03/2025]
Abstract
PURPOSE To assess COVID-19-related morphological brain changes in individuals who recovered from mild-to-moderate COVID-19. METHOD This prospective cohort study enrolled 112 consecutive individuals who recovered from mild-to-moderate COVID-19 and underwent an MRI of the brain between September 2020 and March 2022. MR exams were consistently obtained on a clinical 3T MR scanner in all study participants and 50 age-matched matched controls. The following clinical neuroradiological MR imaging findings were analyzed: post- and acute ischemic lesions, cortical signal alterations, microbleeds, perfusion abnormalities, cytotoxic lesions of the corpus callosum, and vascular abnormalities. Additionally, we manually quantified white matter lesion loads and the number of perivascular spaces and performed an automated brain volumetric analysis. RESULTS In 112 consecutive individuals the mean age was 45 years, female: male = 70:42, mean days at MRI after SARS CoV-2 infection: 228 (sd: 140), and hospitalized: non-hospitalized ratio = 30:82. Using general linear regression models, adjusting for age and gender, the frequency of white matter hyperintensities was not significantly different between subjects who recovered from COVID-19 and matched controls: 9.8 (sd: 17.3) vs. 7.6 (sd: 12.7), p = 0.590. Similarly, the number of enlarged perivascular spaces was not significantly different between the two groups: 62.7 (sd: 43.5) vs. 61.3 (sd: 47.2), p = 0.902. A subgroup analysis between those who were hospitalized in the course of the disease, in which no one required intensive care, and those who remained outpatients, also did not reveal any differences in MRI measures. We did not find evidence for perfusion-/diffusion abnormalities, (micro-)hemorrhages, or cortical abnormalities. CONCLUSIONS In the present cohort, there was currently no evidence of COVID-19-related morphological brain changes in individuals who recovered from mild-to-moderate COVID-19.
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Affiliation(s)
- Lukas Haider
- Section of Neuroradiology and Musculoskeletal Radiology, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria
- NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London Institute of Neurology, London, UK
| | - Paulus Rommer
- Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Iscel Ahmet
- Fifth Medical Department with Cardiology, Favoriten Clinic, Vienna, Austria
| | - Alexandra Dena
- Section of Neuroradiology and Musculoskeletal Radiology, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Alexander P Thurnher
- Section of Neuroradiology and Musculoskeletal Radiology, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Emanuele Tomassino
- Section of Neuroradiology and Musculoskeletal Radiology, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria
- Department of Diagnostic Neuroradiology, Hôpital Neurologique - Université Claude Bernard 1, Lyon, France
| | - Diana Bonderman
- Fifth Medical Department with Cardiology, Favoriten Clinic, Vienna, Austria
- Department of Internal Medicine, Division of Cardiology, Medical University of Vienna, Vienna, Austria
| | | | - Stefan Seidel
- Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Thomas Berger
- Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Majda Thurnher
- Section of Neuroradiology and Musculoskeletal Radiology, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria.
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Cardoso CDO, Rodrigues Sandoval ES, de Oliveira Chagas LBM, Badra SJ, Covas DT, Haddad SK, Figueiredo LTM. Neurologic manifestations of COVID-19 and viral test in cerebrospinal fluid. PLoS One 2025; 20:e0312621. [PMID: 40106398 PMCID: PMC11922214 DOI: 10.1371/journal.pone.0312621] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Accepted: 10/09/2024] [Indexed: 03/22/2025] Open
Abstract
BACKGROUND Neurological manifestations are present in about one-third of COVID-19 cases, ranging from mild symptoms, such as anosmia, to more severe forms like demyelinating syndromes. Although direct invasion of the CNS has been demonstrated, the immune- mediated pathway is also described and more accepted. Even in cases where viral detection in CSF is absent, it should not rule out neuroinvasion. There are few prospective studies about neurological manifestations of COVID-19, especially with viral tests in CSF; as well there are still many questions about COVID-19 associated with neurological disease. Thus, we describe clinical and CSF findings of a prospective cohort of patients with nasal positive tests for SARS-CoV-2 and neurological involvement. We also discuss the pathogenic mechanisms related to these manifestations. METHODS AND FINDINGS This is a prospective cohort study; 27 patients were evaluated according to clinical presentation, the time interval between COVID-19 diagnosis and onset of neurological alterations, syndromic diagnosis, imaging and CSF findings. Real time polymerase chain reaction for SARS-CoV-2 genome was performed in all CSF samples. 2 RT-PCR in spinal cord fluid resulted positive in 9 (33.3%) cases, five of them had a positive swab nasal test concomitant to neurologic disease. Respiratory signs were described in 12 out 27 patients, five of them with viral detection in CSF. White cell counts in CSF were normal range in the majority of cases, except for 3 occurrences: two patients had elevated CSF WBC counts and viral detection in CSF (10 and 36 cells/mm3) and one also had elevated CSF WBC count but viral detection in CSF was negative (21cells/mm3). The observed neurological signs encompassed a diverse neurologic spectrum, including seizures, paresis, gait abnormalities, headaches, alteration in consciousness and memory or cognitive impairment. Both imaging and CSF alterations exhibited non-specific characteristics. Syndromic diagnoses included stroke, dementia or cognitive impairments, Guillain-Barré Syndrome, encephalitis, encephalomyelitis, acute flaccid palsy and optical neuritis. CONCLUSIONS The patients in the present study had COVID-19 and neurologic involvement including a wide range of clinical manifestations. SARS-CoV-2 was detected in one-third of CSF samples, regardless of time interval between COVID-19 diagnosis and the onset of neurological signs. These conditions encompass various pathogenic pathways and the neuroinvasion potential of SARS-CoV-2 should be more studied.
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Affiliation(s)
- Carla de Oliveira Cardoso
- Virology Research Center, Department of Internal Medicine, Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Evandra Strazza Rodrigues Sandoval
- Advanced Molecular Biology Laboratory, Blood Center of Ribeirão Preto, Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | | | - Soraya Jabur Badra
- Virology Research Center, Department of Internal Medicine, Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Dimas Tadeu Covas
- Advanced Molecular Biology Laboratory, Blood Center of Ribeirão Preto, Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Simone Kashima Haddad
- Advanced Molecular Biology Laboratory, Blood Center of Ribeirão Preto, Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Luiz Tadeu Moraes Figueiredo
- Virology Research Center, Department of Internal Medicine, Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
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Pawar P, Akolkar K, Saxena V. An integrated bioinformatics approach reveals the potential role of microRNA-30b-5p and let-7a-5p during SARS CoV-2 spike-1 mediated neuroinflammation. Int J Biol Macromol 2024; 277:134329. [PMID: 39098684 DOI: 10.1016/j.ijbiomac.2024.134329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 07/16/2024] [Accepted: 07/23/2024] [Indexed: 08/06/2024]
Abstract
SARS-CoV-2 induced neuroinflammation contributing to neurological sequelae is one of the critical outcomes of long-COVID, however underlying regulatory mechanisms involved therein are poorly understood. We deciphered the profile of dysregulated microRNAs, their targets, associated pathways, protein-protein interactions (PPI), transcription factor-hub genes interaction networks, hub genes-microRNA co-regulatory networks in SARS-CoV-2 Spike-1 (S1) stimulated microglial cells along with candidate drug prediction using RNA-sequencing and multiple bioinformatics approaches. We identified 11 dysregulated microRNAs in the S1-stimulated microglial cells (p < 0.05). KEGG analysis revealed involvement of important neuroinflammatory pathways such as MAPK signalling, PI3K-AKT signalling, Ras signalling and axon guidance. PPI analysis further identified 11 hub genes involved in these pathways. Real time PCR validation confirmed a significant upregulation of microRNA-30b-5p and let-7a-5p; proinflammatory cytokines- IL-6, TNF-α, IL-1β, GM-CSF; and inflammatory genes- PIK3CA and AKT in the S1-stimulated microglial cells, while PTEN and SHIP1 expression was decreased as compared to the non-stimulated cells. Drug prediction analysis further indicated resveratrol, diclofenac and rapamycin as the potential drugs based on their degree of interaction with hub genes. Thus, targeting of these microRNAs and/or their intermediate signalling molecules would be a prospective immunotherapeutic approach in alleviating SARS-CoV-2-S1 mediated neuroinflammation; and needs further investigations.
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Affiliation(s)
- Puja Pawar
- Division of Immunology and Serology, ICMR-National Institute of Translational Virology & AIDS Research (NITVAR), MIDC, Bhosari, Pune, Maharashtra, India
| | - Kadambari Akolkar
- Division of Immunology and Serology, ICMR-National Institute of Translational Virology & AIDS Research (NITVAR), MIDC, Bhosari, Pune, Maharashtra, India
| | - Vandana Saxena
- Division of Immunology and Serology, ICMR-National Institute of Translational Virology & AIDS Research (NITVAR), MIDC, Bhosari, Pune, Maharashtra, India.
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Hashimoto Y, Iwagami M, Yamana H, Ono S, Takeuchi Y, Michihata N, Uemura K, Aihara M, Yasunaga H. Ocular Adverse Events After Influenza Vaccination in Older Adults: Self-Controlled Case Series Using a Large Database in Japan. Ophthalmic Epidemiol 2024; 31:448-453. [PMID: 38085757 DOI: 10.1080/09286586.2023.2289990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Revised: 10/23/2023] [Accepted: 11/25/2023] [Indexed: 09/08/2024]
Abstract
BACKGROUND To clarify the risk of adverse ocular events following influenza vaccination. METHODS This self-controlled case series study used a claims database linked to vaccination records of a large city in Japan between April 2014 and September 2021. Individuals aged ≥ 65 years who developed adverse ocular events during the follow-up period were included. The exposure was influenza vaccination. The primary outcome was defined as the occurrence of at least one of the following five eye diseases: uveitis, scleritis, retinal vein occlusion, retinal artery occlusion, or optic neuritis. Conditional Poisson regression was used to estimate the within-subject incidence rate ratio of ocular adverse events during the risk period (0-56 days after vaccination) compared to the control period. RESULTS A total of 4,527 cases were eligible for the study (median age, 74 years; male, 42%). The incidence rate ratio for the outcome during the risk period was 0.99 (95% confidence interval, 0.87 to 1.14). No increased risk was observed for individual components of the outcome either; the incidence rate ratio was 0.94 (0.78 to 1.13) for uveitis, 1.17 (0.86 to 1.59) for scleritis, 0.98 (0.76 to 1.27) for retinal vein occlusion, 0.89 (0.42 to 1.87) for retinal artery occlusion, and 0.87 (0.44 to 1.70) for optic neuritis. CONCLUSIONS This self-controlled case series showed no apparent increase in the risk of adverse ocular events after influenza vaccination among older adults. These results mitigate the concerns of older adults who may hesitate to receive influenza vaccination for fear of adverse ocular events. ABBREVIATION HR = hazard ratio; CI = confidence interval; RVO = retinal vein occlusion; SCCS = self-controlled case series.
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Affiliation(s)
- Yohei Hashimoto
- Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan
- Save Sight Institute, The University of Sydney, Sydney, NSW, Australia
| | - Masao Iwagami
- Department of Health Services Research, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Hayato Yamana
- Data Science Center, Jichi Medical University, Tochigi, Japan
| | - Sachiko Ono
- Department of Eat-loss Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yoshinori Takeuchi
- Division of Medical Statistics, Department of Social Medicine, Faculty of Medicine, Toho University, Tokyo, Japan
- Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Nobuaki Michihata
- Cancer Prevention Center, Chiba Cancer Center Research Institute, Chiba, Japan
| | - Kohei Uemura
- Department of Biostatistics and Bioinformatics, Interfaculty Initiative in Information Studies, The University of Tokyo, Tokyo, Japan
| | - Makoto Aihara
- Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hideo Yasunaga
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan
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Orhan Varoglu A, Avarisli A, Keskin H, Darici D. The risk factors affecting the persistence of corpus callosum splenium lesions. Acta Radiol 2024; 65:1101-1108. [PMID: 39093607 DOI: 10.1177/02841851241267147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/04/2024]
Abstract
BACKGROUND The most compact portion of the corpus callosum (CC) is the corpus splenium (CS). PURPOSE To evaluate the connection between clinical and demographic features to determine whether neuroimaging findings will be permanent or temporary in CS patients. MATERIAL AND METHODS We enrolled 93 patients (age range = 18-86 years) with CS lesions. Demographic and clinical information were recorded. We examined the lesions depending on the location. Group 1 (n = 20) had lesions limited to the CS (egg-shaped or round); group 2 (n = 15) had "boomerang sign" lesions; and group 3 (n = 58) had splenium involvement in conditions affecting the whole brain (Boomerang sign+ plus). RESULTS Group 1 had a lower mean age, shorter disease duration, and fewer persistent lesions than others (P < 0.01, P < 0.001, and P < 0.001, respectively). The mean disease onset age (in years) in group 1 was higher than that of the other groups (P < 0.045). Group 2 had lower potassium (K) (P < 0.003) and red cell distribution width levels (P < 0.029) than the other groups. Age <41.5 years (P < 0.001), age at illness initiation <48.5 years (P < 0.002), disease duration <5.5 months (P < 0.001), and eosinophil level <0.29 uL (P 0.014) all point to temporary lesions. CONCLUSION Cases with limited CS lesions have younger onset ages, lower disease onset ages, and shorter disease durations. Age, age of disease onset, disease duration, and eosinophil level are risk variables that affect whether CS lesions are permanent or temporary.
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Affiliation(s)
- Asuman Orhan Varoglu
- Department of Neurology, Medical School, Istanbul Medeniyet University, Istanbul, Turkey
| | - Aysenur Avarisli
- Department of Neurology, Medical School, Istanbul Medeniyet University, Istanbul, Turkey
| | - Havva Keskin
- Department of Internal Medicine, Ankara University, Ankara, Turkey
| | - Didem Darici
- Department of Neurology, Medical School, Istanbul Medeniyet University, Istanbul, Turkey
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Khodanovich M, Svetlik M, Kamaeva D, Usova A, Kudabaeva M, Anan’ina T, Vasserlauf I, Pashkevich V, Moshkina M, Obukhovskaya V, Kataeva N, Levina A, Tumentceva Y, Vasilieva S, Schastnyy E, Naumova A. Demyelination in Patients with POST-COVID Depression. J Clin Med 2024; 13:4692. [PMID: 39200834 PMCID: PMC11355865 DOI: 10.3390/jcm13164692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 07/31/2024] [Accepted: 08/06/2024] [Indexed: 09/02/2024] Open
Abstract
Background: Depression is one of the most severe sequelae of COVID-19, with major depressive disorder often characterized by disruption in white matter (WM) connectivity stemming from changes in brain myelination. This study aimed to quantitatively assess brain myelination in clinically diagnosed post-COVID depression (PCD) using the recently proposed MRI method, macromolecular proton fraction (MPF) mapping. Methods: The study involved 63 recovered COVID-19 patients (52 mild, 11 moderate, and 2 severe) at 13.5 ± 10.0 months post-recovery, with matched controls without prior COVID-19 history (n = 19). A post-COVID depression group (PCD, n = 25) was identified based on psychiatric diagnosis, while a comparison group (noPCD, n = 38) included participants with neurological COVID-19 complications, excluding clinical depression. Results: Fast MPF mapping revealed extensive demyelination in PCD patients, particularly in juxtacortical WM (predominantly occipital lobe and medial surface), WM tracts (inferior fronto-occipital fasciculus (IFOF), posterior thalamic radiation, external capsule, sagittal stratum, tapetum), and grey matter (GM) structures (hippocampus, putamen, globus pallidus, and amygdala). The noPCD group also displayed notable demyelination, but with less magnitude and propagation. Multiple regression analysis highlighted IFOF demyelination as the primary predictor of Hamilton scores, PCD presence, and severity. The number of post-COVID symptoms was a significant predictor of PCD presence, while the number of acute symptoms was a significant predictor of PCD severity. Conclusions: This study, for the first time, reveals extensive demyelination in numerous WM and GM structures in PCD, outlining IFOF demyelination as a key biomarker.
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Affiliation(s)
- Marina Khodanovich
- Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36 Lenina Ave., Tomsk 634050, Russia
| | - Mikhail Svetlik
- Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36 Lenina Ave., Tomsk 634050, Russia
| | - Daria Kamaeva
- Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36 Lenina Ave., Tomsk 634050, Russia
- Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk 634014, Russia
| | - Anna Usova
- Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36 Lenina Ave., Tomsk 634050, Russia
- Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 12/1 Savinykh Street, Tomsk 634028, Russia
| | - Marina Kudabaeva
- Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36 Lenina Ave., Tomsk 634050, Russia
| | - Tatyana Anan’ina
- Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36 Lenina Ave., Tomsk 634050, Russia
| | - Irina Vasserlauf
- Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36 Lenina Ave., Tomsk 634050, Russia
| | - Valentina Pashkevich
- Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36 Lenina Ave., Tomsk 634050, Russia
| | - Marina Moshkina
- Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36 Lenina Ave., Tomsk 634050, Russia
| | - Victoria Obukhovskaya
- Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36 Lenina Ave., Tomsk 634050, Russia
- Department of Fundamental Psychology and Behavioral Medicine, Siberian State Medical University, 2 Moskovskiy Trakt, Tomsk 634050, Russia
| | - Nadezhda Kataeva
- Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36 Lenina Ave., Tomsk 634050, Russia
- Department of Neurology and Neurosurgery, Siberian State Medical University, 2 Moskovskiy Trakt, Tomsk 634028, Russia
| | - Anastasia Levina
- Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36 Lenina Ave., Tomsk 634050, Russia
- Medica Diagnostic and Treatment Center, 86 Sovetskaya Street, Tomsk 634510, Russia
| | - Yana Tumentceva
- Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36 Lenina Ave., Tomsk 634050, Russia
| | - Svetlana Vasilieva
- Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk 634014, Russia
| | - Evgeny Schastnyy
- Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk 634014, Russia
| | - Anna Naumova
- Department of Radiology, School of Medicine, South Lake Union Campus, University of Washington, 850 Republican Street, Seattle, WA 98109, USA
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Medavarapu S, Goyal N, Anziska Y. Acute transverse myelitis (ATM) associated with COVID 19 infection and vaccination: A case report and literature review. AIMS Neurosci 2024; 11:178-187. [PMID: 38988884 PMCID: PMC11230862 DOI: 10.3934/neuroscience.2024011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 05/27/2024] [Accepted: 06/03/2024] [Indexed: 07/12/2024] Open
Abstract
Acute transverse myelitis (ATM) is an inflammatory disorder caused by many etiologies, from postinfectious to autoimmune. Rarely, ATM cases have been reported after both COVID-19 infection and COVID-19 vaccination. We described our experience with ATM after COVID-19 infection and conducted a literature review. Case finding Methods We reported a case of longitudinally extensive ATM after COVID 19 infection, who also received convalescent plasma therapy, and present a comprehensive literature review of ATM cases reported after COVID-19 infection and COVID-19 vaccination. The literature search was done using PubMed and Google scholar with keywords and selected peer-reviewed articles. The search included all cases from Jan 2020 to Sept 2022. Results A total of 60 ATM cases reported association with post COVID 19 infection, and 23 ATM cases reported association with post COVID 19 vaccinations. Among post COVID 19 ATM cases, the mean age was 49 years and the youngest reported was 7-month-old. A total of 55% (33) were longitudinally extensive ATM. The most common symptom was lower extremity weakness. One case was reported as necrotizing myelitis on biopsy, and another case overlapped with syndrome of GBS and longitudinal ATM. No cases reported using convalescent plasma therapy after infection. Almost all the ATM cases were treated with steroids, but some cases needed additional treatment since not all responded adequately. Six cases (10%) responded with steroids plus plasmapheresis, and 5 cases (8%) responded with steroids + IVIG, especially in the pediatric age group. One case reported a positive response after treatment with eculizumab, and another with infliximab. Two cases (3%) remained paraparetic. Among post covid-19 vaccine ATM cases, 4 cases (17%) were reported as longitudinally extensive ATM. Five cases (21%) had symptom onset within a week after vaccination. Almost all reported a response to steroids except for one case which reported fatality after the 58th day after vaccination. Conclusion ATM, in the setting of acute COVID-19 infection, has been described in multiple cases and is a rare complication of COVID-19 vaccination.
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Affiliation(s)
- Srinivas Medavarapu
- Department of Neurocritical care, Mount Sinai and and Department of Neurology, State University of New York Downstate, Brooklyn, NY, USA
| | - Nitasha Goyal
- State University of New York Downstate Medical School, Brooklyn, NY, USA
| | - Yaacov Anziska
- Department of Neurology, Neuromuscular Disease, State University of New York Downstate, Brooklyn, NY, USA
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Adamaszek M, Langner S, Mehrholz J, Heiinrich A. Opsoclonus-Myoclonus-Ataxia Syndrome Due to Covid-19. CEREBELLUM (LONDON, ENGLAND) 2024; 23:1245-1248. [PMID: 37814146 DOI: 10.1007/s12311-023-01610-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 09/26/2023] [Indexed: 10/11/2023]
Abstract
Opsoclonus-myoclonus syndrome (OMS) as a rare neurological encephalopathic entity associated with non-specific infections or cancer processes has been repeatedly described in the setting of SARS-CoV-2 infection. We report a case of a 53-year-old man with SARS-CoV-2 infection, who developed clinical features of opsoclonus-myoclonus ataxia syndrome including cognitive impairments with a prolonged course of disease. Of particular note, cerebrospinal fluid (CSF) analysis revealed the production of myelin oligodendrocyte glycoprotein (MOG) antibodies, suggesting an underlying neuroimmunological mechanism associated with infection with the novel SARS-CoV-2 virus.
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Affiliation(s)
- Michael Adamaszek
- Department of Neurological and Neurocognitive Rehabilitation, Klinik Bavaria Kreischa, An der Wolfsschlucht, 1-2 01731, Kreischa, Germany.
| | - Soenke Langner
- Department of Radiology, Rostock University Medical Center, Schillingallee 35, 18057, Rostock, Germany
| | - Jan Mehrholz
- Department of Public Health, Dresden Medical School, Technical University Dresden, Dresden, Germany
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Khodanovich M, Naumova A, Kamaeva D, Obukhovskaya V, Vasilieva S, Schastnyy E, Kataeva N, Levina A, Kudabaeva M, Pashkevich V, Moshkina M, Tumentceva Y, Svetlik M. Neurocognitive Changes in Patients with Post-COVID Depression. J Clin Med 2024; 13:1442. [PMID: 38592295 PMCID: PMC10933987 DOI: 10.3390/jcm13051442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Revised: 02/16/2024] [Accepted: 02/20/2024] [Indexed: 04/10/2024] Open
Abstract
Background: Depression and cognitive impairment are recognized complications of COVID-19. This study aimed to assess cognitive performance in clinically diagnosed post-COVID depression (PCD, n = 25) patients using neuropsychological testing. Methods: The study involved 71 post-COVID patients with matched control groups: recovered COVID-19 individuals without complications (n = 18) and individuals without prior COVID-19 history (n = 19). A post-COVID depression group (PCD, n = 25) was identified based on psychiatric diagnosis, and a comparison group (noPCD, n = 46) included participants with neurological COVID-19 complications, excluding clinical depression. Results: The PCD patients showed gender-dependent significant cognitive impairment in the MoCA, Word Memory Test (WMT), Stroop task (SCWT), and Trail Making Test (TMT) compared to the controls and noPCD patients. Men with PCD showed worse performances on the SCWT, in MoCA attention score, and on the WMT (immediate and delayed word recall), while women with PCD showed a decline in MoCA total score, an increased processing time with less errors on the TMT, and worse immediate recall. No differences between groups in Sniffin's stick test were found. Conclusions: COVID-related direct (post-COVID symptoms) and depression-mediated (depression itself, male sex, and severity of COVID-19) predictors of decline in memory and information processing speed were identified. Our findings may help to personalize the treatment of depression, taking a patient's gender and severity of previous COVID-19 disease into account.
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Affiliation(s)
- Marina Khodanovich
- Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36 Lenina Ave., Tomsk 634050, Russia; (D.K.); (V.O.); (N.K.); (A.L.); (M.K.); (V.P.); (M.M.); (Y.T.); (M.S.)
| | - Anna Naumova
- Department of Radiology, School of Medicine, South Lake Union Campus, University of Washington, 850 Republican Street, Seattle, WA 98109, USA;
| | - Daria Kamaeva
- Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36 Lenina Ave., Tomsk 634050, Russia; (D.K.); (V.O.); (N.K.); (A.L.); (M.K.); (V.P.); (M.M.); (Y.T.); (M.S.)
- Laboratory of Molecular Genetics and Biochemistry, Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 4 Aleutskaya Street, Tomsk 634014, Russia
| | - Victoria Obukhovskaya
- Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36 Lenina Ave., Tomsk 634050, Russia; (D.K.); (V.O.); (N.K.); (A.L.); (M.K.); (V.P.); (M.M.); (Y.T.); (M.S.)
- Department of Fundamental Psychology and Behavioral Medicine, Siberian State Medical University, 2 Moskovskiy Trakt, Tomsk 6340505, Russia
| | - Svetlana Vasilieva
- Department of Affective States, Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 4 Aleutskaya Street, Tomsk 634014, Russia; (S.V.); (E.S.)
| | - Evgeny Schastnyy
- Department of Affective States, Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 4 Aleutskaya Street, Tomsk 634014, Russia; (S.V.); (E.S.)
| | - Nadezhda Kataeva
- Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36 Lenina Ave., Tomsk 634050, Russia; (D.K.); (V.O.); (N.K.); (A.L.); (M.K.); (V.P.); (M.M.); (Y.T.); (M.S.)
- Department of Neurology and Neurosurgery, Siberian State Medical University, 2 Moskovskiy Trakt, Tomsk 6340505, Russia
| | - Anastasia Levina
- Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36 Lenina Ave., Tomsk 634050, Russia; (D.K.); (V.O.); (N.K.); (A.L.); (M.K.); (V.P.); (M.M.); (Y.T.); (M.S.)
- Medica Diagnostic and Treatment Center, 86 Sovetskaya Street, Tomsk 634510, Russia
| | - Marina Kudabaeva
- Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36 Lenina Ave., Tomsk 634050, Russia; (D.K.); (V.O.); (N.K.); (A.L.); (M.K.); (V.P.); (M.M.); (Y.T.); (M.S.)
| | - Valentina Pashkevich
- Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36 Lenina Ave., Tomsk 634050, Russia; (D.K.); (V.O.); (N.K.); (A.L.); (M.K.); (V.P.); (M.M.); (Y.T.); (M.S.)
| | - Marina Moshkina
- Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36 Lenina Ave., Tomsk 634050, Russia; (D.K.); (V.O.); (N.K.); (A.L.); (M.K.); (V.P.); (M.M.); (Y.T.); (M.S.)
| | - Yana Tumentceva
- Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36 Lenina Ave., Tomsk 634050, Russia; (D.K.); (V.O.); (N.K.); (A.L.); (M.K.); (V.P.); (M.M.); (Y.T.); (M.S.)
| | - Mikhail Svetlik
- Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36 Lenina Ave., Tomsk 634050, Russia; (D.K.); (V.O.); (N.K.); (A.L.); (M.K.); (V.P.); (M.M.); (Y.T.); (M.S.)
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10
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Rittmannsberger H, Barth M, Lamprecht B, Malik P, Yazdi-Zorn K. [Interaction of somatic findings and psychiatric symptoms in COVID-19. A scoping review]. NEUROPSYCHIATRIE : KLINIK, DIAGNOSTIK, THERAPIE UND REHABILITATION : ORGAN DER GESELLSCHAFT OSTERREICHISCHER NERVENARZTE UND PSYCHIATER 2024; 38:1-23. [PMID: 38055146 DOI: 10.1007/s40211-023-00487-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 10/24/2023] [Indexed: 12/07/2023]
Abstract
An infection with SARS-CoV‑2 can affect the central nervous system, leading to neurological as well as psychiatric symptoms. In this respect, mechanisms of inflammation seem to be of much greater importance than the virus itself. This paper deals with the possible contributions of organic changes to psychiatric symptomatology and deals especially with delirium, cognitive symptoms, depression, anxiety, posttraumatic stress disorder and psychosis. Processes of neuroinflammation with infection of capillary endothelial cells and activation of microglia and astrocytes releasing high amounts of cytokines seem to be of key importance in all kinds of disturbances. They can lead to damage in grey and white matter, impairment of cerebral metabolism and loss of connectivity. Such neuroimmunological processes have been described as a organic basis for many psychiatric disorders, as affective disorders, psychoses and dementia. As the activation of the glia cells can persist for a long time after the offending agent has been cleared, this can contribute to long term sequalae of the infection.
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Affiliation(s)
- Hans Rittmannsberger
- Abteilung Psychiatrie und psychotherapeutische Medizin, Pyhrn-Eisenwurzen Klinikum Steyr, Steyr, Österreich.
| | - Martin Barth
- Abteilung Psychiatrie und psychotherapeutische Medizin, Pyhrn-Eisenwurzen Klinikum Steyr, Steyr, Österreich
| | - Bernd Lamprecht
- Med Campus III, Universitätsklinik für Innere Medizin mit Schwerpunkt Pneumologie, Kepler Universitätsklinikum GmbH, Linz, Österreich
- Medizinische Fakultät, Johannes Kepler Universität Linz, Linz, Österreich
| | - Peter Malik
- Abteilung Psychiatrie und psychotherapeutische Medizin, Pyhrn-Eisenwurzen Klinikum Steyr, Steyr, Österreich
| | - Kurosch Yazdi-Zorn
- Neuromed Campus, Klinik für Psychiatrie mit Schwerpunkt Suchtmedizin, Kepler Universitätsklinikum GmbH, Linz, Österreich
- Medizinische Fakultät, Johannes Kepler Universität Linz, Linz, Österreich
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11
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Chang H, Chen E, Hu Y, Wu L, Deng L, Ye‐Lehmann S, Mao X, Zhu T, Liu J, Chen C. Extracellular Vesicles: The Invisible Heroes and Villains of COVID-19 Central Neuropathology. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2305554. [PMID: 38143270 PMCID: PMC10933635 DOI: 10.1002/advs.202305554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 11/18/2023] [Indexed: 12/26/2023]
Abstract
Acknowledging the neurological symptoms of COVID-19 and the long-lasting neurological damage even after the epidemic ends are common, necessitating ongoing vigilance. Initial investigations suggest that extracellular vesicles (EVs), which assist in the evasion of the host's immune response and achieve immune evasion in SARS-CoV-2 systemic spreading, contribute to the virus's attack on the central nervous system (CNS). The pro-inflammatory, pro-coagulant, and immunomodulatory properties of EVs contents may directly drive neuroinflammation and cerebral thrombosis in COVID-19. Additionally, EVs have attracted attention as potential candidates for targeted therapy in COVID-19 due to their innate homing properties, low immunogenicity, and ability to cross the blood-brain barrier (BBB) freely. Mesenchymal stromal/stem cell (MSCs) secreted EVs are widely applied and evaluated in patients with COVID-19 for their therapeutic effect, considering the limited antiviral treatment. This review summarizes the involvement of EVs in COVID-19 neuropathology as carriers of SARS-CoV-2 or other pathogenic contents, as predictors of COVID-19 neuropathology by transporting brain-derived substances, and as therapeutic agents by delivering biotherapeutic substances or drugs. Understanding the diverse roles of EVs in the neuropathological aspects of COVID-19 provides a comprehensive framework for developing, treating, and preventing central neuropathology and the severe consequences associated with the disease.
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Affiliation(s)
- Haiqing Chang
- Department of AnesthesiologyWest China HospitalSichuan UniversityLaboratory of Anesthesia and Critical Care MedicineNational‐Local Joint Engineering Research Centre of Translational Medicine of AnesthesiologyWest China HospitalSichuan UniversityChengduSichuan610041China
| | - Erya Chen
- Department of AnesthesiologyWest China HospitalSichuan UniversityLaboratory of Anesthesia and Critical Care MedicineNational‐Local Joint Engineering Research Centre of Translational Medicine of AnesthesiologyWest China HospitalSichuan UniversityChengduSichuan610041China
| | - Yi Hu
- Department of Cardiology, Honghui hospitalXi'an Jiaotong UniversityXi'an710049China
| | - Lining Wu
- Department of AnesthesiologyWest China HospitalSichuan UniversityLaboratory of Anesthesia and Critical Care MedicineNational‐Local Joint Engineering Research Centre of Translational Medicine of AnesthesiologyWest China HospitalSichuan UniversityChengduSichuan610041China
| | - Liyun Deng
- Department of AnesthesiologyWest China HospitalSichuan UniversityLaboratory of Anesthesia and Critical Care MedicineNational‐Local Joint Engineering Research Centre of Translational Medicine of AnesthesiologyWest China HospitalSichuan UniversityChengduSichuan610041China
| | - Shixin Ye‐Lehmann
- Diseases and Hormones of the Nervous System University of Paris‐Scalay Bicêtre Hosptial BâtGrégory Pincus 80 Rue du Gal Leclerc, CedexLe Kremlin Bicêtre94276France
| | - Xiaobo Mao
- Department of NeurologyInstitute of Cell EngineeringSchool of MedicineJohns Hopkins UniversityBaltimoreMD21218USA
| | - Tao Zhu
- Department of AnesthesiologyWest China HospitalSichuan UniversityLaboratory of Anesthesia and Critical Care MedicineNational‐Local Joint Engineering Research Centre of Translational Medicine of AnesthesiologyWest China HospitalSichuan UniversityChengduSichuan610041China
| | - Jin Liu
- Department of AnesthesiologyWest China HospitalSichuan UniversityLaboratory of Anesthesia and Critical Care MedicineNational‐Local Joint Engineering Research Centre of Translational Medicine of AnesthesiologyWest China HospitalSichuan UniversityChengduSichuan610041China
| | - Chan Chen
- Department of AnesthesiologyWest China HospitalSichuan UniversityLaboratory of Anesthesia and Critical Care MedicineNational‐Local Joint Engineering Research Centre of Translational Medicine of AnesthesiologyWest China HospitalSichuan UniversityChengduSichuan610041China
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12
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Rasizadeh R, Aghbash PS, Nahand JS, Entezari-Maleki T, Baghi HB. SARS-CoV-2-associated organs failure and inflammation: a focus on the role of cellular and viral microRNAs. Virol J 2023; 20:179. [PMID: 37559103 PMCID: PMC10413769 DOI: 10.1186/s12985-023-02152-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Accepted: 08/04/2023] [Indexed: 08/11/2023] Open
Abstract
SARS-CoV-2 has been responsible for the recent pandemic all over the world, which has caused many complications. One of the hallmarks of SARS-CoV-2 infection is an induced immune dysregulation, in some cases resulting in cytokine storm syndrome, acute respiratory distress syndrome and many organs such as lungs, brain, and heart that are affected during the SARS-CoV-2 infection. Several physiological parameters are altered as a result of infection and cytokine storm. Among them, microRNAs (miRNAs) might reflect this poor condition since they play a significant role in immune cellular performance including inflammatory responses. Both host and viral-encoded miRNAs are crucial for the successful infection of SARS-CoV-2. For instance, dysregulation of miRNAs that modulate multiple genes expressed in COVID-19 patients with comorbidities (e.g., type 2 diabetes, and cerebrovascular disorders) could affect the severity of the disease. Therefore, altered expression levels of circulating miRNAs might be helpful to diagnose this illness and forecast whether a COVID-19 patient could develop a severe state of the disease. Moreover, a number of miRNAs could inhibit the expression of proteins, such as ACE2, TMPRSS2, spike, and Nsp12, involved in the life cycle of SARS-CoV-2. Accordingly, miRNAs represent potential biomarkers and therapeutic targets for this devastating viral disease. In the current study, we investigated modifications in miRNA expression and their influence on COVID-19 disease recovery, which may be employed as a therapy strategy to minimize COVID-19-related disorders.
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Affiliation(s)
- Reyhaneh Rasizadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Parisa Shiri Aghbash
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Javid Sadri Nahand
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, 5166/15731, Iran
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Taher Entezari-Maleki
- Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hossein Bannazadeh Baghi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, 5166/15731, Iran.
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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13
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Chiba Y, Takahashi Y, Kawakita R, Deguchi K, Masaki T. Cytotoxic Lesions of the Corpus Callosum (CLOCC) Suggesting Exacerbation by Heterogeneous COVID-19 Booster Vaccination. Cureus 2023; 15:e41105. [PMID: 37519563 PMCID: PMC10382211 DOI: 10.7759/cureus.41105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/28/2023] [Indexed: 08/01/2023] Open
Abstract
Cytotoxic lesions of the corpus callosum (CLOCC) is a disease entity associated with reversible lesions of the corpus callosum on magnetic resonance imaging (MRI). CLOCC is caused by a variety of etiologies, but CLOCC after vaccination is extremely rare. Four prior cases of CLOCC after the first dose of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine have been reported; these were localized to the splenium and showed early clinical and neuroradiological recovery. We experienced an unusual case in which a heterogeneous COVID-19 booster vaccination caused rather severe CLOCC damage. A 74-year-old Japanese woman presented with ataxia, high fever, and hearing loss several days after her third vaccination against COVID-19. This booster was an mRNA-1273 while her first and second vaccinations were both BNT162b2 type. SARS-CoV-2 real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis was negative, but serum SARS-CoV-2 S-IgG antibodies were elevated. Her cerebrospinal fluid (CSF) showed an elevated cell count and high levels of protein and interleukin-6 (IL-6). Brain MRI showed CLOCC spreading throughout the body of the corpus callosum. After the exclusion of other potential causes, the diagnosis of vaccination-related CLOCC was made. Six months later, recovery of clinical and MRI findings remained incomplete. It was suggested that the patient's CLOCC might have been caused by the increase in CSF IL-6 due to an enhanced immune response from the heterogeneous vaccination, resulting in more severe damage to the corpus callosum than usual.
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Affiliation(s)
- Yuta Chiba
- Gastroenterology and Neurology, Kagawa University, Kita-gun, JPN
| | | | - Rie Kawakita
- Gastroenterology and Neurology, Kagawa University, Kita-gun, JPN
| | - Kazushi Deguchi
- Gastroenterology and Neurology, Kagawa University, Kita-gun, JPN
| | - Tsutomu Masaki
- Gastroenterology and Neurology, Kagawa University, Kita-gun, JPN
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14
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Norouzi-Barough L, Asgari Khosroshahi A, Gorji A, Zafari F, Shahverdi Shahraki M, Shirian S. COVID-19-Induced Stroke and the Potential of Using Mesenchymal Stem Cells-Derived Extracellular Vesicles in the Regulation of Neuroinflammation. Cell Mol Neurobiol 2023; 43:37-46. [PMID: 35025001 PMCID: PMC8755896 DOI: 10.1007/s10571-021-01169-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 11/09/2021] [Indexed: 02/07/2023]
Abstract
Ischemic stroke (IS) is a known neurological complication of COVID-19 infection, which is associated with high mortality and disability. Following IS, secondary neuroinflammation that occurs can play both harmful and beneficial roles and lead to further injury or repair of damaged neuronal tissue, respectively. Since inflammation plays a pivotal role in the pathogenesis of COVID-19-induced stroke, targeting neuroinflammation could be an effective strategy for modulating the immune responses following ischemic events. Numerous investigations have indicated that the application of mesenchymal stem cells-derived extracellular vesicles (MSC-EVs) improves functional recovery following stroke, mainly through reducing neuroinflammation as well as promoting neurogenesis and angiogenesis. Therefore, MSC-EVs can be applied for the regulation of SARS-CoV-2-mediated inflammation and the management of COVID-19- related ischemic events. In this study, we have first described the advantages and disadvantages of neuroinflammation in the pathological evolution after IS and summarized the characteristics of neuroinflammation in COVID-19-related stroke. Then, we have discussed the potential benefit of MSC-EVs in the regulation of inflammatory responses after COVID-19-induced ischemic events.
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Affiliation(s)
- Leyla Norouzi-Barough
- Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | | | - Ali Gorji
- Epilepsy Research Center, Department of Neurosurgery, Westfälische Wilhelms-Universitat Münster, Munster, Germany
- Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran
| | - Fariba Zafari
- Cellular and Molecular Research Center, Research Institute for Prevention of Non- Communicable Disease, Qazvin University of Medical Sciences, Qazvin, Iran
| | | | - Sadegh Shirian
- Department of Pathology, School of Veterinary Medicine, Shahrekord University, Shahrekord, Iran.
- Shiraz Molecular Pathology Research Center, Dr. Daneshbod Pathol Lab, Shiraz, Iran.
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15
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Yıldırım Z, Timer SM, Çelik D, Karademir F, Kale N. Mild Encephalitis/Encephalopathy with a Reversible Lesion in The Splenium. Noro Psikiyatr Ars 2023; 60:90-96. [PMID: 36911559 PMCID: PMC9999219 DOI: 10.29399/npa.27961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 09/28/2021] [Indexed: 11/07/2022] Open
Abstract
Mild encephalitis/encephalopathy with a reversible lesion in the splenium (MERS) is a clinico-radiological syndrome with mild central nervous system symptoms and a reversible lesion in the splenium of the corpus callosum. It is mainly associated with a number of viral and bacterial infections, including Coronavirus disease 2019 (COVID-19). In this paper, we report four MERS patients. One had a mumps infection, the second had aseptic meningitis, the third had Marchiafava-Bignami disease, and the fourth had atypical pneumonia associated with COVID-19 infection.
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Affiliation(s)
- Zerrin Yıldırım
- İstanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Neuroscience, İstanbul, Turkey.,Bağcılar Training and Research Hospital, Department of Neurology, İstanbul, Turkey
| | | | - Didem Çelik
- Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital, Department of Neurology, İstanbul, Turkey
| | - Fazilet Karademir
- Bağcılar Training and Research Hospital, Department of Neurology, İstanbul, Turkey
| | - Nilüfer Kale
- Bağcılar Training and Research Hospital, Department of Neurology, İstanbul, Turkey
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16
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Exosomes in Cerebral Ischemia-Reperfusion Injury: Current Perspectives and Future Challenges. Brain Sci 2022; 12:brainsci12121657. [PMID: 36552117 PMCID: PMC9776031 DOI: 10.3390/brainsci12121657] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Revised: 11/18/2022] [Accepted: 11/25/2022] [Indexed: 12/12/2022] Open
Abstract
Cerebral ischemia impedes the functional or metabolic demands of the central nervous system (CNS), which subsequently leads to irreversible brain damage. While recanalization of blocked vessels recovers cerebral blood flow, it can also aggravate brain injury, termed as ischemia/reperfusion (I/R) injury. Exosomes, nanometric membrane vesicles, attracted wide attention as carriers of biological macromolecules. In the brain, exosomes can be secreted by almost all types of cells, and their contents can be altered during the pathological and clinical processes of cerebral I/R injury. Herein, we will review the current literature on the possible role of cargos derived from exosomes and exosomes-mediated intercellular communication in cerebral I/R injury. The PubMed and Web of Science databases were searched through January 2015. The studies published in English were identified using search terms including "exosomes", "cerebral ischemia-reperfusion injury", "brain ischemia-reperfusion injury", and "stroke". We will also focus on the potential therapeutic effects of stem cell-derived exosomes and underlying mechanisms in cerebral I/R injury. Meanwhile, with the advantages of low immunogenicity and cytotoxicity, high bioavailability, and the capacity to pass through the blood-brain barrier, exosomes also attract more attention as therapeutic modalities for the treatment of cerebral I/R injury.
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17
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Yepes M. Neurological Complications of SARS-CoV-2 Infection and COVID-19 Vaccines: From Molecular Mechanisms to Clinical Manifestations. Curr Drug Targets 2022; 23:1620-1638. [PMID: 36121081 DOI: 10.2174/1389450123666220919123029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 05/31/2022] [Accepted: 07/26/2022] [Indexed: 01/25/2023]
Abstract
Coronavirus Disease 2019 (COVID-19) is an infectious disease, caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), that reached pandemic proportions in 2020. Despite the fact that it was initially characterized by pneumonia and acute respiratory distress syndrome, it is now clear that the nervous system is also compromised in one third of these patients. Indeed, a significant proportion of COVID-19 patients suffer nervous system damage via a plethora of mechanisms including hypoxia, coagulopathy, immune response to the virus, and the direct effect of SARS-CoV-2 on endothelial cells, neurons, astrocytes, pericytes and microglia. Additionally, a low number of previously healthy individuals develop a variety of neurological complications after receiving COVID-19 vaccines and a large proportion of COVID-19 survivors experience longlasting neuropsychiatric symptoms. In conclusion, COVID-19 is also a neurological disease, and the direct and indirect effects of the virus on the nervous system have a significant impact on the morbidity and mortality of these patients. Here we will use the concept of the neurovascular unit, assembled by endothelial cells, basement membrane, perivascular astrocytes, neurons and microglia, to review the effects of SARS-CoV-2 in the nervous system. We will then use this information to review data published to this date on the neurological manifestations of COVID-19, the post- COVID syndrome and COVID-19 vaccines.
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Affiliation(s)
- Manuel Yepes
- Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Atlanta, GA, USA.,Department of Neurology & Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA, USA.,Department of Neurology, Veterans Affairs Medical Center, Atlanta, GA, USA
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18
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Kubo M, Kubo K, Kobayashi KI, Komiya N. Non-severe COVID-19 complicated by cytotoxic lesions of the corpus callosum (mild encephalitis/encephalopathy with a reversible splenial lesion): a case report and literature review. Int J Infect Dis 2022; 125:1-9. [PMID: 36122669 PMCID: PMC9477791 DOI: 10.1016/j.ijid.2022.09.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 09/07/2022] [Accepted: 09/07/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Coronavirus disease 2019- (COVID-19-) associated cytotoxic lesions of the corpus callosum (CLOCCs) have been reported as a rare neurological abnormality in severe cases. Here, a case of CLOCCs in the early stages of mild COVID-19 infection during the Omicron BA.1 epidemic is reported along with a literature review. CASE REPORT A Japanese woman with COVID-19 presented to the emergency department with altered consciousness and cerebellar symptoms a day after fever onset. Magnetic resonance imaging (MRI) revealed a lesion with restricted diffusion in the corpus callosum. She exhibited no complications of pneumonia, her neurological symptoms resolved after two days, and after 10 days, the brain lesion was not detected on MRI. LITERATURE REVIEW The PubMed database was searched for case reports that met the CLOCC definition proposed by Starkey et al. The search yielded 15 COVID-19-associated cases reported as CLOCCs and 13 cases described under former terms, including mild encephalitis/encephalopathy with a reversible splenial lesion. Adult cases with a documented course were accompanied by pneumonia or hypoxemia, whereas pediatric cases were mostly accompanied by a multisystem inflammatory syndrome. CONCLUSION COVID-19-associated CLOCCs can occur, even at an early, non-severe stage. Therefore, this condition may be underdiagnosed if MRI is not performed.
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Affiliation(s)
- Mayu Kubo
- Department of Emergency Medicine, Japanese Red Cross Wakayama Medical Center, 4–20 Komatsubara-dori, Wakayama, 640-8558, Japan
| | - Kenji Kubo
- Department of Emergency Medicine, Japanese Red Cross Wakayama Medical Center, 4–20 Komatsubara-dori, Wakayama, 640-8558, Japan,Department of Infectious Diseases, Japanese Red Cross Wakayama Medical Center, 4–20 Komatsubara-dori, Wakayama, 640-8558, Japan,Corresponding author
| | - Ken-ichiro Kobayashi
- Department of Infectious Diseases, Japanese Red Cross Wakayama Medical Center, 4–20 Komatsubara-dori, Wakayama, 640-8558, Japan
| | - Nobuhiro Komiya
- Department of Infectious Diseases, Japanese Red Cross Wakayama Medical Center, 4–20 Komatsubara-dori, Wakayama, 640-8558, Japan
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19
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Role of Demyelination in the Persistence of Neurological and Mental Impairments after COVID-19. Int J Mol Sci 2022; 23:ijms231911291. [PMID: 36232592 PMCID: PMC9569975 DOI: 10.3390/ijms231911291] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 09/16/2022] [Accepted: 09/21/2022] [Indexed: 11/16/2022] Open
Abstract
Long-term neurological and mental complications of COVID-19, the so-called post-COVID syndrome or long COVID, affect the quality of life. The most persistent manifestations of long COVID include fatigue, anosmia/hyposmia, insomnia, depression/anxiety, and memory/attention deficits. The physiological basis of neurological and psychiatric disorders is still poorly understood. This review summarizes the current knowledge of neurological sequelae in post-COVID patients and discusses brain demyelination as a possible mechanism of these complications with a focus on neuroimaging findings. Numerous reviews, experimental and theoretical studies consider brain demyelination as one of the mechanisms of the central neural system impairment. Several factors might cause demyelination, such as inflammation, direct effect of the virus on oligodendrocytes, and cerebrovascular disorders, inducing myelin damage. There is a contradiction between the solid fundamental basis underlying demyelination as the mechanism of the neurological injuries and relatively little published clinical evidence related to demyelination in COVID-19 patients. The reason for this probably lies in the fact that most clinical studies used conventional MRI techniques, which can detect only large, clearly visible demyelinating lesions. A very limited number of studies use specific methods for myelin quantification detected changes in the white matter tracts 3 and 10 months after the acute phase of COVID-19. Future research applying quantitative MRI assessment of myelin in combination with neurological and psychological studies will help in understanding the mechanisms of post-COVID complications associated with demyelination.
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20
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Freitas FEDA, Batista MAC, Braga DCDA, de Oliveira LB, Antunes VR, Cardoso LM. The gut-brain axis and sodium appetite: Can inflammation-related signaling influence the control of sodium intake? Appetite 2022; 175:106050. [PMID: 35447164 DOI: 10.1016/j.appet.2022.106050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 04/11/2022] [Accepted: 04/12/2022] [Indexed: 11/29/2022]
Abstract
Sodium is the main cation present in the extracellular fluid. Sodium and water content in the body are responsible for volume and osmotic homeostasis through mechanisms involving sodium and water excretion and intake. When body sodium content decreases below the homeostatic threshold, a condition termed sodium deficiency, highly motivated sodium seeking, and intake occurs. This is termed sodium appetite. Classically, sodium and water intakes are controlled by a number of neuroendocrine mechanisms that include signaling molecules from the renin-angiotensin-aldosterone system acting in the central nervous system (CNS). However, recent findings have shown that sodium and water intakes can also be influenced by inflammatory agents and mediators acting in the CNS. For instance, central infusion of IL-1β or TNF-α can directly affect sodium and water consumption in animal models. Some dietary conditions, such as high salt intake, have been shown to change the intestinal microbiome composition, stimulating the immune branch of the gut-brain axis through the production of inflammatory cytokines, such as IL-17, which can stimulate the brain immune system. In this review, we address the latest findings supporting the hypothesis that immune signaling in the brain could produce a reduction in thirst and sodium appetite and, therefore, contribute to sodium intake control.
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Affiliation(s)
| | | | | | | | - Vagner Roberto Antunes
- Dept. of Physiology and Biophysics - ICB, University of São Paulo, São Paulo, SP, Brazil
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21
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Özdemir Ö, Arslan Z. Issues related to post-COVID-19 syndrome. World J Methodol 2022; 12:224-234. [PMID: 36159103 PMCID: PMC9350724 DOI: 10.5662/wjm.v12.i4.224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 04/20/2022] [Accepted: 06/27/2022] [Indexed: 02/06/2023] Open
Abstract
The pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 2019-2022 leads to a multisystem illness that results in damage to numerous organ systems. In this review, our goal was to assess current research on long-term respiratory, cardiac, neurological, digestive, rheumatological, urogenital, and dermatological system complications of coronavirus disease 2019 (COVID-19). Bibliographic searches were conducted in December 2021 using PubMed and Google Scholar, retrospectively, covering all COVID-19 literature to determine the consequences of the disease. This review may help to determine the prospects for new studies and predict the upcoming aspects requiring assessment in post-COVID-19 syndrome.
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Affiliation(s)
- Öner Özdemir
- Division of Pediatric Allergy and Immunology, Sakarya University Medical Faculty, Sakarya 54100, Turkey
| | - Zeynep Arslan
- Department of Pediatrics, Sakarya University Research and Training Hospital, Sakarya 54100, Turkey
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22
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de Mello AJ, Moretti M, Rodrigues ALS. SARS-CoV-2 consequences for mental health: Neuroinflammatory pathways linking COVID-19 to anxiety and depression. World J Psychiatry 2022; 12:874-883. [PMID: 36051596 PMCID: PMC9331446 DOI: 10.5498/wjp.v12.i7.874] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 05/03/2022] [Accepted: 06/17/2022] [Indexed: 02/06/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has been linked to an increased prevalence of mental health disorders, particularly anxiety and depression. Moreover, the COVID-19 pandemic has caused stress in people worldwide due to several factors, including fear of infection; social isolation; difficulty in adapting to new routines; lack of coping methods; high exposure to social media, misinformation, and fake reports; economic impact of the measures implemented to slow the contagion and concerns regarding the disease pathogenesis. COVID-19 patients have elevated levels of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, and other inflammation-related factors. Furthermore, invasion of the central nervous system by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may potentially contribute to neuroinflammatory alterations in infected individuals. Neuroinflammation, a consequence of psychological stress due to the COVID-19 pandemic, may also play a role in the development of anxiety and depressive symptoms in the general population. Considering that neuroinflammation plays a significant role in the pathophysiology of depression and anxiety, this study investigated the effects of SARS-CoV-2 on mental health and focused on the impact of the COVID-19 pandemic on the neuroinflammatory pathways.
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Affiliation(s)
- Anna Julie de Mello
- Department of Biochemistry, Universidade Federal de Santa Catarina, Florianópolis 88040-200, Brazil
| | - Morgana Moretti
- Department of Biochemistry, Universidade Federal de Santa Catarina, Florianópolis 88040-200, Brazil
| | - Ana Lúcia S Rodrigues
- Department of Biochemistry, Universidade Federal de Santa Catarina, Florianópolis 88040-200, Brazil
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23
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Lozano-Iraguen P, Arribas-Del Campo J, Castro-Pesce A, Morales-García C, Chiang-Odeh F, Pelayo-Varela C. [Acute disseminated encephalomyelitis associated with SARS-CoV-2 infection without respiratory compromise]. Rev Neurol 2022; 75:45-48. [PMID: 35822571 PMCID: PMC10186722 DOI: 10.33588/rn.7502.2021335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Indexed: 05/21/2023]
Abstract
INTRODUCTION COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to grow all over the world since december of 2019. Although the main clinical manifestation is pulmonary disease, neurological manifestations are a prominent and increasingly recognized feature of the disease. The Acute Disseminated Encephalomyelitis (ADEM) is a rare autoimmune disorder, most commonly triggered by a viral infection. There are a few case reports of ADEM associated with COVID-19, almost all of them associated pulmonary disease. We report the case of a young patient with diagnosis of ADEM with SARS-CoV-2 infection without clinical respiratory symptoms. CASE REPORT A 20-year-old woman with no relevant medical history was brought to the emergency department with a progressive confusional state lasted for 7 days. Family reported the development of smell and taste deficit since two weeks before the onset of neurological symptoms. There were no complaints of pulmonary symptoms. At admission, she was drowsy and disoriented. Left homonymous hemianopsia and an ipsilateral Babinski sign was identified. A brain magnetic resonance image was done showing multiple hyperintense bilateral, asymmetric patchy and poorly marginated lesions with gadolinium enhancement. She was SARS-CoV-2 PCR positive on nasopharyngeal swab. Intravenous high-dose glucocorticoids were administered with marked clinical improvement. CONCLUSION ADEM is an extremely uncommon complication of SARS-CoV-2infection. Acute disseminated encephalomyelitis should be considered a potentially treatable cause of encephalopathy or multifocal neurological deficits in COVID-19 patients, even in the absence of respiratory symptoms.
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Affiliation(s)
- P Lozano-Iraguen
- Clínica Dávila, Santiago de Chile, Chile
- Universidad de los Andes, Santiago de Chile, Chile
| | - J Arribas-Del Campo
- Clínica Dávila, Santiago de Chile, Chile
- Universidad de los Andes, Santiago de Chile, Chile
| | - A Castro-Pesce
- Clínica Dávila, Santiago de Chile, Chile
- Universidad de los Andes, Santiago de Chile, Chile
| | - C Morales-García
- Clínica Dávila, Santiago de Chile, Chile
- Universidad de los Andes, Santiago de Chile, Chile
| | - F Chiang-Odeh
- Clínica Dávila, Santiago de Chile, Chile
- Universidad de los Andes, Santiago de Chile, Chile
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24
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Vidal E, López-Figueroa C, Rodon J, Pérez M, Brustolin M, Cantero G, Guallar V, Izquierdo-Useros N, Carrillo J, Blanco J, Clotet B, Vergara-Alert J, Segalés J. Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice. Vet Pathol 2022; 59:613-626. [PMID: 34955064 PMCID: PMC9207990 DOI: 10.1177/03009858211066841] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disease, but it can also affect other organs including the central nervous system. Several animal models have been developed to address different key questions related to Coronavirus Disease 2019 (COVID-19). Wild-type mice are minimally susceptible to certain SARS-CoV-2 lineages (beta and gamma variants), whereas hACE2-transgenic mice succumb to SARS-CoV-2 and develop a fatal neurological disease. In this article, we aimed to chronologically characterize SARS-CoV-2 neuroinvasion and neuropathology. Necropsies were performed at different time points, and the brain and olfactory mucosa were processed for histopathological analysis. SARS-CoV-2 virological assays including immunohistochemistry were performed along with a panel of antibodies to assess neuroinflammation. At 6 to 7 days post inoculation (dpi), brain lesions were characterized by nonsuppurative meningoencephalitis and diffuse astrogliosis and microgliosis. Vasculitis and thrombosis were also present and associated with occasional microhemorrhages and spongiosis. Moreover, there was vacuolar degeneration of virus-infected neurons. At 2 dpi, SARS-CoV-2 immunolabeling was only found in the olfactory mucosa, but at 4 dpi intraneuronal virus immunolabeling had already reached most of the brain areas. Maximal distribution of the virus was observed throughout the brain at 6 to 7 dpi except for the cerebellum, which was mostly spared. Our results suggest an early entry of the virus through the olfactory mucosa and a rapid interneuronal spread of the virus leading to acute encephalitis and neuronal damage in this mouse model.
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Affiliation(s)
- Enric Vidal
- IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus UAB, Bellaterra, Barcelona, Catalonia, Spain
| | - Carlos López-Figueroa
- IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus UAB, Bellaterra, Barcelona, Catalonia, Spain
| | - Jordi Rodon
- IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus UAB, Bellaterra, Barcelona, Catalonia, Spain
| | - Mónica Pérez
- IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus UAB, Bellaterra, Barcelona, Catalonia, Spain
| | - Marco Brustolin
- IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus UAB, Bellaterra, Barcelona, Catalonia, Spain
| | - Guillermo Cantero
- IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus UAB, Bellaterra, Barcelona, Catalonia, Spain
| | - Víctor Guallar
- Barcelona Supercomputing Center (BSC), Jordi Girona, Barcelona, Spain
- Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain
| | - Nuria Izquierdo-Useros
- IrsiCaixa AIDS Research Institute, Badalona, Spain
- Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, Badalona, Spain
| | | | - Julià Blanco
- IrsiCaixa AIDS Research Institute, Badalona, Spain
- Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, Badalona, Spain
- University of Vic-Central University of Catalonia (UVic-UCC), Vic, Spain
| | - Bonaventura Clotet
- IrsiCaixa AIDS Research Institute, Badalona, Spain
- Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, Badalona, Spain
- University of Vic-Central University of Catalonia (UVic-UCC), Vic, Spain
| | - Júlia Vergara-Alert
- IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus UAB, Bellaterra, Barcelona, Catalonia, Spain
| | - Joaquim Segalés
- Departament de Sanitat i Anatomia Animals, Facultat de Veterinària de la UAB, Campus UAB, Bellaterra, Barcelona, Catalonia, Spain
- UAB, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus UAB, Bellaterra, Barcelona, Catalonia, Spain
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25
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Qi P, Huang M, Li T. Screening the Potential Biomarkers of COVID-19-Related Thrombosis Through Bioinformatics Analysis. Front Genet 2022; 13:889348. [PMID: 35692833 PMCID: PMC9174658 DOI: 10.3389/fgene.2022.889348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 05/09/2022] [Indexed: 11/30/2022] Open
Abstract
A high proportion of critically ill patients with coronavirus disease 2019 (COVID-19) experience thrombosis, and there is a strong correlation between anticoagulant therapy and the COVID-19 survival rate, indicating that common COVID-19 and thrombosis targets have potential therapeutic value for severe COVID-19.Gene expression profiling data were downloaded from Gene Expression Omnibus (GEO), and common differentially expressed genes (co-DEGs) were identified. The potential biological functions of these co-DEGs were explored by functional enrichment analysis, and protein–protein interaction (PPI) networks were constructed to elucidate the molecular mechanisms of the co-DEGs. Finally, hub genes in the co-DEG network were identified, and correlation analysis was performed.We identified 8320 upregulated genes and 7651 downregulated genes from blood samples of COVID-19 patients and 368 upregulated genes and 240 downregulated genes from blood samples of thrombosis patients. The enriched cellular component terms were mainly related to cytosolic ribosomes and ribosomal subunits. The enriched molecular function terms were mainly related to structural constituents of ribosomes and electron transfer activity. Construction of the PPI network and identification of hub genes ultimately confirmed that RPS7, IGF1R, DICER1, ERH, MCTS1, and TNPO1 were jointly upregulated hub genes, and FLNA and PXN were jointly downregulated hub genes.The identification of novel potential biomarkers provides new options for treating COVID-19-related thrombosis and reducing the rate of severe COVID-19.
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Affiliation(s)
- Peng Qi
- Department of Emergency, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Mengjie Huang
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Tanshi Li
- Department of Emergency, First Medical Center of Chinese PLA General Hospital, Beijing, China
- *Correspondence: Tanshi Li,
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26
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Dunai C, Collie C, Michael BD. Immune-Mediated Mechanisms of COVID-19 Neuropathology. Front Neurol 2022; 13:882905. [PMID: 35665037 PMCID: PMC9160362 DOI: 10.3389/fneur.2022.882905] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 03/29/2022] [Indexed: 12/15/2022] Open
Abstract
Although SARS-CoV-2 causes a respiratory viral infection, there is a large incidence of neurological complications occurring in COVID-19 patients. These range from headaches and loss of smell to encephalitis and strokes. Little is known about the likely diverse mechanisms causing these pathologies and there is a dire need to understand how to prevent and treat them. This review explores recent research from the perspective of investigating how the immune system could play a role in neurological complications, including cytokines, blood biomarkers, immune cells, and autoantibodies. We also discuss lessons learnt from animal models. Overall, we highlight two key points that have emerged from increasing evidence: (1) SARS-CoV-2 does not invade the brain in the majority of cases and so the associated neurological complications might arise from indirect effects, such as immune activation (2) although the immune system plays a critical role in controlling the virus, its dysregulation can cause pathology.
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Affiliation(s)
- Cordelia Dunai
- Department of Clinical Infection Microbiology and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
- NIHR HPRU for Emerging and Zoonotic Infection, Liverpool, United Kingdom
| | - Ceryce Collie
- Department of Clinical Infection Microbiology and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
| | - Benedict D. Michael
- Department of Clinical Infection Microbiology and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
- NIHR HPRU for Emerging and Zoonotic Infection, Liverpool, United Kingdom
- The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom
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27
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Bensaidane MR, Picher-Martel V, Émond F, De Serres G, Dupré N, Beauchemin P. Case Report: Acute Necrotizing Encephalopathy Following COVID-19 Vaccine. Front Neurol 2022; 13:872734. [PMID: 35572945 PMCID: PMC9099242 DOI: 10.3389/fneur.2022.872734] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 03/28/2022] [Indexed: 11/29/2022] Open
Abstract
Objectives Acute necrotizing encephalopathy (ANE) is a rare neurological disorder arising from a para- or post-infectious "cytokine storm. "It has recently been reported in association with coronavirus disease 2019 (COVID-19) infection. Methods A 56-year-old male with a diagnosis of ANE 48 h following the first dose of ChAdOx1 nCoV-19 vaccination was investigated. Cytokine analyses on serum and cerebrospinal fluid (CSF) were performed. The patient was treated with high-dose corticosteroids and followed clinically and radiologically. Results Favorable clinical and radiological outcomes were noted. There was an upregulation in serum levels of CXCL5, CXCL1, Il-8, IL-15, CCL2, TGF-B, and EGF, and up-regulation in CSF levels of CXCL5, IL-2, IL-3, and IL-8. Discussion As COVID-19 infection has been previously reported as a possible rare cause of ANE, we speculate on an aberrant immune response mechanism that was brought about by the vaccine. To increase our understanding of the pathogenesis of ANE in the context of COVID-19 vaccination and to better define its clinical features and outcomes, clinicians and scientists should continue reporting convincing cases of such entities.
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Affiliation(s)
- Mohamed Reda Bensaidane
- Department of Medicine, Faculty of Medicine, Centre Hospitalier Universitaire de Québec—Université Laval, Quebec, QC, Canada
| | - Vincent Picher-Martel
- Department of Medicine, Faculty of Medicine, Centre Hospitalier Universitaire de Québec—Université Laval, Quebec, QC, Canada
- Department of Psychiatry and Neuroscience, Faculty of Medicine, CERVO Brain Research Centre, Quebec, QC, Canada
| | - François Émond
- Department of Medicine, Faculty of Medicine, Centre Hospitalier Universitaire de Québec—Université Laval, Quebec, QC, Canada
| | - Gaston De Serres
- Institut National de Santé Publique du Québec, Quebec, QC, Canada
| | - Nicolas Dupré
- Department of Medicine, Faculty of Medicine, Centre Hospitalier Universitaire de Québec—Université Laval, Quebec, QC, Canada
| | - Philippe Beauchemin
- Department of Medicine, Faculty of Medicine, Centre Hospitalier Universitaire de Québec—Université Laval, Quebec, QC, Canada
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28
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MacDougall M, El-Hajj Sleiman J, Beauchemin P, Rangachari M. SARS-CoV-2 and Multiple Sclerosis: Potential for Disease Exacerbation. Front Immunol 2022; 13:871276. [PMID: 35572514 PMCID: PMC9102605 DOI: 10.3389/fimmu.2022.871276] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Accepted: 03/21/2022] [Indexed: 12/15/2022] Open
Abstract
While the respiratory tract is the primary route of entry for SARS-CoV-2, evidence shows that the virus also impacts the central nervous system. Intriguingly, case reports have documented SARS-CoV-2 patients presenting with demyelinating lesions in the brain, spinal cord, and optic nerve, suggesting possible implications in neuroimmune disorders such as multiple sclerosis (MS) and other related neuroimmune disorders. However, the cellular mechanisms underpinning these observations remain poorly defined. The goal of this paper was to review the literature to date regarding possible links between SARS-CoV-2 infection and neuroimmune demyelinating diseases such as MS and its related disorders, with the aim of positing a hypothesis for disease exacerbation. The literature suggests that SARS-CoV, SARS-CoV-2, and orthologous murine coronaviruses invade the CNS via the olfactory bulb, spreading to connected structures via retrograde transport. We hypothesize that a glial inflammatory response may contribute to damaged oligodendrocytes and blood brain barrier (BBB) breakdown, allowing a second route for CNS invasion and lymphocyte infiltration. Potential for molecular mimicry and the stimulation of autoreactive T cells against myelin is also described. It is imperative that further studies on SARS-CoV-2 neuroinvasion address the adverse effects of the virus on myelin and exacerbation of MS symptoms, as nearly 3 million people suffer from MS worldwide.
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Affiliation(s)
- Madison MacDougall
- Department of Biological Sciences, Salisbury University, Salisbury, MD, United States
- Department of Psychology, Salisbury University, Salisbury, MD, United States
| | - Jad El-Hajj Sleiman
- Division of Neurology, Department of Medicine, CHU de Québec – Université Laval, Quebec City, QC, Canada
| | - Philippe Beauchemin
- Division of Neurology, Department of Medicine, CHU de Québec – Université Laval, Quebec City, QC, Canada
| | - Manu Rangachari
- Axe Neurosciences, Centre de Recherche du CHU de Québec – Université Laval, Quebec City, QC, Canada
- Department of Molecular Medicine, Faculty of Medicine, Université Laval, Quebec City, QC, Canada
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29
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Ide T, Kawanami T, Eriguchi M, Hara H. SARS-CoV-2-related Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease: A Case Report and Literature Review. Intern Med 2022; 61:1253-1258. [PMID: 35135920 PMCID: PMC9107978 DOI: 10.2169/internalmedicine.8709-21] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
We herein report a case of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A 24-year-old woman developed unilateral optic neuritis 3 weeks after contracting coronavirus disease 2019 (COVID-19), followed by intracranial demyelinating lesions and myelitis. Since serum anti-MOG antibody was positive, we diagnosed MOG antibody-associated disease. Immunotherapy with steroids resulted in the rapid improvement of neurological symptoms. This is a suggestive case, as there are no reports of MOG antibody-associated disease with multiple neurological lesions occurring after COVID-19. The response to immunotherapy was favorable. This case suggests that it is important to measure anti-MOG antibodies in patients who develop inflammatory neurological disease after COVID-19.
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Affiliation(s)
- Toshihiro Ide
- Division of Neurology, Department of Internal Medicine, Saga University Faculty of Medicine, Japan
| | - Takeru Kawanami
- Division of Neurology, Department of Internal Medicine, Saga University Faculty of Medicine, Japan
| | - Makoto Eriguchi
- Division of Neurology, Department of Internal Medicine, Saga University Faculty of Medicine, Japan
| | - Hideo Hara
- Division of Neurology, Department of Internal Medicine, Saga University Faculty of Medicine, Japan
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30
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Wang Y, Wang Y, Huo L, Li Q, Chen J, Wang H. SARS-CoV-2-associated acute disseminated encephalomyelitis: a systematic review of the literature. J Neurol 2022; 269:1071-1092. [PMID: 34459986 PMCID: PMC8403692 DOI: 10.1007/s00415-021-10771-8] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 08/22/2021] [Accepted: 08/23/2021] [Indexed: 12/15/2022]
Abstract
The literature on cases of acute disseminated encephalomyelitis (ADEM) associated with SARS-CoV-2 infection has been rapidly increasing. However, the specific clinical features of ADEM associated with SARS-CoV-2 (SARS-CoV-2-ADEM) have not been previously evaluated. We screened all articles resulting from a search of PubMed and Web of Science databases looking for reports of ADEM published between December 01, 2019, and June 5, 2021. Of the 48 ADEM cases identified from 37 studies, 34 (71%) had ADEM while 14 (29%) were of AHLE. RT-PCR for SARS-CoV-2 was positive in 83% (n = 19) of patients. 26 patients (54%) were male, and 18 patients (38%) were female, with a male to female sex ratio of 1.4:1; median age was 44 (1.4-71) years. 9 patients (19%, 9/48) were children. Of the 9 children patients, their median age was 9 years (range 1.4-13 years), 6 patients (67%) were female, and 2 patients (22%) were male, with a female to male sex ratio of 3:1.39 patients (81%) was performed CSF analysis. PCR for SARS-CoV-2 tested positive in 3 patients (14%, 3/22) on CSF sample. 31 (64%) of patients had a poor outcome on discharge from hospital. Five (10%) patients died in hospital. Compared to classic ADEM, SARS-CoV-2-ADEM have a more longer duration between the onset of the antecedent infective symptoms and the start of ADEM symptoms, the older age distribution of the patients, relatively poor outcome, a lower full recovery rate, a more frequently brain lesions involved the periventricular white matter and corpus callosum, and less frequently affected the deep gray matter. Taken together, the present comprehensive review reveals that although rare, ADEM can be associated with SARS-CoV-2 infection. SARS-CoV-2-ADEM seems to share most features of classic ADEM, with moderate discrepancies from the classical ADEM.
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Affiliation(s)
- Yumin Wang
- Department of Respiratory and Critical Care Medicine, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, 100049, People's Republic of China
| | - Yanchao Wang
- Department of Neurology, The Affiliated Hospital of Chifeng University, Chifeng, 024005, People's Republic of China
| | - Liang Huo
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, 110004, China
| | - Qiang Li
- Department of Neurology, The Affiliated Hospital of Chifeng University, Chifeng, 024005, People's Republic of China
| | - Jichao Chen
- Department of Respiratory and Critical Care Medicine, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, 100049, People's Republic of China
| | - Hongquan Wang
- Department of Neurology, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, 100049, People's Republic of China.
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31
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Letter: Spectrum of hospitalized NeuroCOVID diagnoses from a tertiary care neurology centre in Eastern India. J Clin Neurosci 2022; 96:227-228. [PMID: 35000765 PMCID: PMC8733856 DOI: 10.1016/j.jocn.2021.12.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 12/25/2021] [Indexed: 11/24/2022]
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32
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Rothstein A, Favilla C, Sloane K, Witsch J. Perspective: COVID-19 and Its Neurologic Sequelae. TRANSLATIONAL PERIOPERATIVE AND PAIN MEDICINE 2022; 9:478-481. [PMID: 36381996 PMCID: PMC9645563 DOI: 10.31480/2330-4871/162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
COVID-19 led to a catastrophic, international, public health crisis after its first detection in 2019 [1]. Though it is primarily a respiratory virus, it impacts the central and peripheral nervous systems leading to further COVID-19-associated disability [2]. This Perspective reviews our current understanding of the neurological sequelae of COVID-19 and the gaps in our understanding of their treatment and epidemiology.
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Affiliation(s)
- Aaron Rothstein
- Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Christopher Favilla
- Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Kelly Sloane
- Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Jens Witsch
- Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
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van Campen C(LMC, Rowe PC, Visser FC. Orthostatic Symptoms and Reductions in Cerebral Blood Flow in Long-Haul COVID-19 Patients: Similarities with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. MEDICINA (KAUNAS, LITHUANIA) 2021; 58:medicina58010028. [PMID: 35056336 PMCID: PMC8778312 DOI: 10.3390/medicina58010028] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 12/18/2021] [Accepted: 12/21/2021] [Indexed: 12/12/2022]
Abstract
Background and Objectives: Symptoms and hemodynamic findings during orthostatic stress have been reported in both long-haul COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but little work has directly compared patients from these two groups. To investigate the overlap in these clinical phenotypes, we compared orthostatic symptoms in daily life and during head-up tilt, heart rate and blood pressure responses to tilt, and reductions in cerebral blood flow in response to orthostatic stress in long-haul COVID-19 patients, ME/CFS controls, and healthy controls. Materials and Methods: We compared 10 consecutive long-haul COVID-19 cases with 20 age- and gender-matched ME/CFS controls with postural tachycardia syndrome (POTS) during head-up tilt, 20 age- and gender-matched ME/CFS controls with a normal heart rate and blood pressure response to head-up tilt, and 10 age- and gender-matched healthy controls. Identical symptom questionnaires and tilt test procedures were used for all groups, including measurement of cerebral blood flow and cardiac index during the orthostatic stress. Results: There were no significant differences in ME/CFS symptom prevalence between the long-haul COVID-19 patients and the ME/CFS patients. All long-haul COVID-19 patients developed POTS during tilt. Cerebral blood flow and cardiac index were more significantly reduced in the three patient groups compared with the healthy controls. Cardiac index reduction was not different between the three patient groups. The cerebral blood flow reduction was larger in the long-haul COVID-19 patients compared with the ME/CFS patients with a normal heart rate and blood pressure response. Conclusions: The symptoms of long-haul COVID-19 are similar to those of ME/CFS patients, as is the response to tilt testing. Cerebral blood flow and cardiac index reductions during tilt were more severely impaired than in many patients with ME/CFS. The finding of early-onset orthostatic intolerance symptoms, and the high pre-illness physical activity level of the long-haul COVID-19 patients, makes it unlikely that POTS in this group is due to deconditioning. These data suggest that similar to SARS-CoV-1, SARS-CoV-2 infection acts as a trigger for the development of ME/CFS.
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Affiliation(s)
| | - Peter C. Rowe
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA;
| | - Frans C. Visser
- Stichting CardioZorg, Planetenweg 5, 2132 HN Hoofddorp, The Netherlands;
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Dams L, Kraemer M, Becker J. MOG-antibody-associated longitudinal extensive myelitis after ChAdOx1 nCoV-19 vaccination. Mult Scler 2021; 28:1159-1162. [PMID: 34931927 DOI: 10.1177/13524585211057512] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
This case report describes a 59-year-old man with myelin oligodendrocyte glycoprotein (MOG)-positive longitudinal extensive transverse myelitis (LETM) after being vaccinated with the COVID-19 vaccine ChAdOx1 nCoV-19. He presented with urinary retention, gait disturbance, hypoesthesia and brisk reflexes in his lower extremities without paresis. Due to the ineffectiveness of high-dose intravenous methylprednisolone, therapeutic plasma exchange was performed, gradually improving the patient's condition. Vaccination as a trigger for an excessive immunological response seems plausible, though unspecific for the ChAdOx1 nCoV-19 vaccine.
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Affiliation(s)
| | - Markus Kraemer
- Alfried Krupp Hospital, Essen, Germany; Heinrich-Heine-University of Düsseldorf, Düsseldorf, Germany
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Rodríguez-Hernández YA, Villamizar-Gómez FJ, Mantilla-Pardo JC, Robledo-Arias JS, Rahman S, Lozada-Martinez ID, Bin Razzak KS. Post-COVID 19 neurological syndrome: The need to define a cut-off score between the acute and post-COVID 19 phases. Ann Med Surg (Lond) 2021; 71:102983. [PMID: 34745603 PMCID: PMC8557944 DOI: 10.1016/j.amsu.2021.102983] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Accepted: 10/28/2021] [Indexed: 12/26/2022] Open
Affiliation(s)
| | | | | | | | - Sabrina Rahman
- Department of Public Health, Independent University- Bangladesh, Dhaka, Bangladesh
| | - Ivan David Lozada-Martinez
- Colombian Clinical Research Group in Neurocritical Care, Latin American Council of Neurocritical Care, Cartagena, Colombia
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Berrichi S, Bouayed Z, Berrajaa S, Bahouh C, Oulalite AM, Douqchi B, Bella I, Bkiyar H, Housni B. Acute Disseminated Encephalomyelitis: A rare form of COVID-19's neurotropism. Ann Med Surg (Lond) 2021; 71:102940. [PMID: 34659750 PMCID: PMC8504072 DOI: 10.1016/j.amsu.2021.102940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 10/09/2021] [Accepted: 10/09/2021] [Indexed: 11/30/2022] Open
Abstract
Introduction the COVID-19 pandemic still accounts for thousands of cases every day. It's neurological involvement has been well documented most likely due to auto-immune mechanisms than the virus itself. Case report we report the case of a 38 years old women who developed an Acute Disseminated Encephalomyelitis following a COVID-19 infection, with a favorable outcome after immunosuppressive therapy. Discussion In this chapter, we discuss ADEM's pathogenesis as well as its clinical and radiological features before detailing its relationship with infectious and vaccination episodes. We also discuss how our patient disease evolved. Conclusion Acute Disseminated Encephalomyelitis is an immune-mediated disorder in which the widespread inflammation of the brain and spinal cord is responsible for a variety of symptoms. The novel COVID-19 virus and its vaccine are both a newly incriminated etiologies of this demyelinating disorder.
COVID-19 neurotropism has been well established and its neurological manifestations are varied. Demyelinating disorders are immune-induced disease most likely due to an antigenic analogy between the virus and myelin constituents. COVID-19 induced ADEM is extremely rare, only a dozen cases have been reported worldwide, and ours is the only case reported in our country.
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Affiliation(s)
- Samia Berrichi
- Department of Anesthesiology, Intensive Care Medicine and Resuscitation, MOHAMMED VI University Hospital Center, Oujda, Morocco
- Corresponding author. Department of Anesthesiology, Intensive Care Medicine and Resuscitation, MOHAMMED VI University Hospital Center, Oujda, Morocco.
| | - Zakaria Bouayed
- Department of Anesthesiology, Intensive Care Medicine and Resuscitation, MOHAMMED VI University Hospital Center, Oujda, Morocco
- Corresponding author. Department of Anesthesiology, Intensive Care Medicine and Resuscitation, MOHAMMED VI University Hospital Center, Oujda, Morocco.
| | - Sara Berrajaa
- Department of Anesthesiology, Intensive Care Medicine and Resuscitation, MOHAMMED VI University Hospital Center, Oujda, Morocco
| | - Choukri Bahouh
- Department of Anesthesiology, Intensive Care Medicine and Resuscitation, MOHAMMED VI University Hospital Center, Oujda, Morocco
| | - Amine Mohammed Oulalite
- Department of Anesthesiology, Intensive Care Medicine and Resuscitation, MOHAMMED VI University Hospital Center, Oujda, Morocco
| | - Badie Douqchi
- Department of Anesthesiology, Intensive Care Medicine and Resuscitation, MOHAMMED VI University Hospital Center, Oujda, Morocco
| | - Islam Bella
- Department of Anesthesiology, Intensive Care Medicine and Resuscitation, MOHAMMED VI University Hospital Center, Oujda, Morocco
| | - Houssam Bkiyar
- Department of Anesthesiology, Intensive Care Medicine and Resuscitation, MOHAMMED VI University Hospital Center, Oujda, Morocco
| | - Brahim Housni
- Department of Anesthesiology, Intensive Care Medicine and Resuscitation, MOHAMMED VI University Hospital Center, Oujda, Morocco
- Simulation Center, Faculty of Medicine and Pharmacy, Oujda, Morocco
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microRNA Heterogeneity, Innate-Immune Defense and the Efficacy of SARS-CoV-2 Infection-A Commentary. Noncoding RNA 2021; 7:ncrna7020037. [PMID: 34207055 PMCID: PMC8293307 DOI: 10.3390/ncrna7020037] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 06/07/2021] [Accepted: 06/13/2021] [Indexed: 12/12/2022] Open
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a member of the genus Betacoronavirus in the family Coronaviridae, possesses an unusually large single-stranded viral RNA (ssvRNA) genome of about ~29,811 nucleotides (nt) that causes severe and acute respiratory distress and a highly lethal viral pneumonia known as COVID-19. COVID-19 also presents with multiple ancillary systemic diseases and often involves cardiovascular, inflammatory, and/or neurological complications. Pathological viral genomes consisting of ssvRNA, like cellular messenger RNA (mRNA), are susceptible to attack, destruction, neutralization, and/or modulation by naturally occurring small non-coding RNAs (sncRNAs) within the host cell, some of which are known as microRNAs (miRNAs). This paper proposes that the actions of the 2650 known human miRNAs and other sncRNAs form the basis for an under-recognized and unappreciated innate-immune regulator of ssvRNA viral genome activities and have implications for the efficiency of SARS-CoV-2 invasion, infection, and replication. Recent research indicates that both miRNA and mRNA abundance, speciation, and complexity varies widely amongst human individuals, and this may: (i) In part explain the variability in the innate-immune immunological and pathophysiological response of different human individuals to the initiation and progression of SARS-CoV-2 infection in multiple tissue types; and (ii) further support our understanding of human biochemical and genetic individuality and the variable resistance of individuals to ssvRNA-mediated viral infection and disease. This commentary will briefly address current findings and concepts in this fascinating research area of non-coding RNA and innate-immunity with special reference to natural host miRNAs, SARS-CoV-2, and the current COVID-19 pandemic.
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