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Neurological complications of COVID-19

Dai et al., QJM: An International Journal of Medicine, doi:10.1093/qjmed/hcac272

Dec 2022

Review of the neurological complications of COVID-19 and their possible pathways and mechanisms. The main pathways of SARS-CoV-2 neuroinvasion include the olfactory nerve, gut-brain axis, vagus nerve, and hematogenous dissemination through disrupting the blood-brain barrier. Mechanisms of neurological damage include direct viral damage, cytokine storm, hypoxemia, and coagulation abnormalities. Authors discuss serious complications including ischemic and hemorrhagic stroke, encephalopathy, encephalitis, neurodegenerative diseases like Alzheimer's, and neuropsychiatric disorders. Authors also review potential methods for preventing neurological complications.

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Dai et al., 9 Dec 2022, peer-reviewed, 8 authors. Contact: hmchyczsl@126.com.

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Neurological complications of COVID-19

X Dai, X Cao, Q Jiang, B Wu, T Lou, Y Shao, Y Hu, Q Lan

QJM: An International Journal of Medicine, doi:10.1093/qjmed/hcac272

Corona Virus Disease 2019 (COVID-19) has caused several pandemic peaks worldwide due to its high variability and infectiousness, and COVID-19 has become a long-standing global public health problem. There is growing evidence that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) frequently causes multi-organ injuries and more severe neurological manifestations. Therefore, increased awareness of possible neurological complications is beneficial in preventing and mitigating the impact of long-term sequelae and improving the prognostic outcome of critically ill patients with COVID-19. Here, we review the main pathways of SARS-CoV-2 neuroinvasion and the potential mechanisms causing neurological damage. We also discuss in detail neurological complications, aiming to provide cutting-edge basis for subsequent related basic research and clinical studies of diagnosis and treatment.

Author contributions Xingliang Dai (Conceptualization, Funding acquisition [

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There is growing evidence that severe acute ' 'respiratory syndrome coronavirus-2 (SARS-CoV-2) frequently causes multi-organ injuries and ' 'more severe neurological manifestations. Therefore, increased awareness of possible ' 'neurological complications is beneficial in preventing and mitigating the impact of long-term ' 'sequelae and improving the prognostic outcome of critically ill patients with COVID-19. Here, ' 'we review the main pathways of SARS-CoV-2 neuroinvasion and the potential mechanisms causing ' 'neurological damage. 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' 'China'}]}, { 'given': 'X', 'family': 'Cao', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Clinical Medicine, The First Clinical College of ' 'Anhui Medical University , Hefei 230032, P. R. China'}]}, { 'given': 'Q', 'family': 'Jiang', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Clinical Medicine, The First Clinical College of ' 'Anhui Medical University , Hefei 230032, P. R. China'}]}, { 'given': 'B', 'family': 'Wu', 'sequence': 'additional', 'affiliation': [ { 'name': 'From the Department of Neurosurgery, The First Affiliated ' 'Hospital of Anhui Medical University , Hefei 230022, P. R. ' 'China'}]}, { 'given': 'T', 'family': 'Lou', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Clinical Medicine, The First Clinical College of ' 'Anhui Medical University , Hefei 230032, P. R. 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COVID19 ' '(Review)', 'volume': '46', 'author': 'Skalny', 'year': '2020', 'journal-title': 'Int J Mol Med'}, { 'key': '2023032720364652300_', 'first-page': '343', 'article-title': 'COVID-19: poor outcomes in patients with zinc deficiency', 'volume': '100', 'author': 'Jothimani', 'year': '2020', 'journal-title': 'Int J Infect Dis'}, { 'key': '2023032720364652300_', 'first-page': '685', 'article-title': 'Combating COVID-19 and building immune resilience: a potential role for ' 'magnesium nutrition?', 'volume': '39', 'author': 'Wallace', 'year': '2020', 'journal-title': 'J Am Coll Nutr'}, { 'key': '2023032720364652300_', 'first-page': '361', 'article-title': 'Melatonin drugs inhibit SARS-CoV-2 entry into the brain and ' 'virus-induced damage of cerebral small vessels', 'volume': '79', 'author': 'Cecon', 'year': '2022', 'journal-title': 'Cell Mol Life Sci'}, { 'key': '2023032720364652300_', 'first-page': '47', 'article-title': 'Role of melatonin on virus-induced neuropathogenesis—a concomitant ' 'therapeutic strategy to understand SARS-CoV-2 infection', 'volume': '10', 'author': 'Wongchitrat', 'year': '2021', 'journal-title': 'Antioxidants (Basel)'}, { 'key': '2023032720364652300_', 'first-page': '110982', 'article-title': 'Early use of non-steroidal anti-inflammatory drugs in COVID-19 might ' 'reverse pathogenesis, prevent complications and improve clinical ' 'outcomes', 'volume': '133', 'author': 'Kelleni', 'year': '2021', 'journal-title': 'Biomed Pharmacother'}, { 'key': '2023032720364652300_', 'first-page': 'e12732', 'article-title': 'Melatonin multifaceted pharmacological actions on melatonin receptors ' 'converging to abrogate COVID-19', 'volume': '71', 'author': 'Reynolds', 'year': '2021', 'journal-title': 'J Pineal Res'}, { 'key': '2023032720364652300_', 'first-page': '153308', 'article-title': 'Prevention and treatment of COVID-19 using Traditional Chinese ' 'Medicine: a review', 'volume': '85', 'author': 'Zhao', 'year': '2021', 'journal-title': 'Phytomedicine'}, { 'key': '2023032720364652300_', 'first-page': 'e343', 'article-title': 'COVID-19 patients upregulate toll-like receptor 4-mediated inflammatory ' 'signaling that mimics bacterial sepsis', 'volume': '35', 'author': 'Sohn', 'year': '2020', 'journal-title': 'J Korean Med Sci'}, { 'key': '2023032720364652300_', 'first-page': '491', 'article-title': 'TLR4 as a therapeutic target for respiratory and neurological ' 'complications of SARS-CoV-2', 'volume': '25', 'author': 'Kaushik', 'year': '2021', 'journal-title': 'Expert Opin Ther Targets'}, { 'key': '2023032720364652300_', 'first-page': '109567', 'article-title': 'TRP channels in COVID-19 disease: potential targets for prevention and ' 'treatment', 'volume': '345', 'author': 'Jaffal', 'year': '2021', 'journal-title': 'Chem Biol Interact'}, { 'key': '2023032720364652300_', 'first-page': '108634', 'article-title': 'COVID-19: a review of therapeutic strategies and vaccine candidates', 'volume': '222', 'author': 'Izda', 'year': '2021', 'journal-title': 'Clin Immunol'}, { 'key': '2023032720364652300_', 'first-page': '134', 'article-title': 'Cathepsin L plays a key role in SARS-CoV-2 infection in humans and ' 'humanized mice and is a promising target for new drug development', 'volume': '6', 'author': 'Zhao', 'year': '2021', 'journal-title': 'Signal Transduct Target Ther'}, { 'key': '2023032720364652300_', 'first-page': '202', 'article-title': 'Comparing COVID-19 vaccines for their characteristics, efficacy and ' 'effectiveness against SARS-CoV-2 and variants of concern: a narrative ' 'review', 'volume': '28', 'author': 'Fiolet', 'year': '2022', 'journal-title': 'Clin Microbiol Infect'}, { 'key': '2023032720364652300_', 'first-page': '1', 'article-title': 'COVID-19 vaccines: the status and perspectives in delivery points of ' 'view', 'volume': '170', 'author': 'Chung', 'year': '2021', 'journal-title': 'Adv Drug Deliv Rev'}, { 'key': '2023032720364652300_', 'first-page': '7020', 'article-title': 'The efficiency and safety of high-dose vitamin C in patients with ' 'COVID-19: a retrospective cohort study', 'volume': '13', 'author': 'Gao', 'year': '2021', 'journal-title': 'Aging (Albany NY)'}, { 'key': '2023032720364652300_', 'first-page': '3104', 'article-title': 'Functional role of dietary intervention to improve the outcome of ' 'COVID-19: a hypothesis of work', 'volume': '21', 'author': 'Messina', 'year': '2020', 'journal-title': 'Int J Mol Sci'}, { 'key': '2023032720364652300_', 'first-page': '653750', 'article-title': 'The role of omega-3 polyunsaturated fatty acids in the treatment of ' 'patients with acute respiratory distress syndrome: a clinical review', 'volume': '2015', 'author': 'Garcia', 'year': '2015', 'journal-title': 'Biomed Res Int'}, { 'key': '2023032720364652300_', 'first-page': '44', 'article-title': 'Can melatonin be a potential “silver bullet” in treating COVID-19 ' 'patients?', 'volume': '8', 'author': 'Cardinali', 'year': '2020', 'journal-title': 'Diseases'}, { 'key': '2023032720364652300_', 'first-page': '1044', 'article-title': 'Hyperactivation of P2X7 receptors as a culprit of COVID-19 ' 'neuropathology', 'volume': '26', 'author': 'Ribeiro', 'year': '2021', 'journal-title': 'Mol Psychiatry'}, { 'key': '2023032720364652300_', 'first-page': '1344', 'article-title': 'Montelukast drug may improve COVID-19 prognosis: a review of evidence', 'volume': '11', 'author': 'Barre', 'year': '2020', 'journal-title': 'Front Pharmacol'}, { 'key': '2023032720364652300_', 'first-page': '173629', 'article-title': 'Can selective serotonin reuptake inhibitors have a neuroprotective ' 'effect during COVID-19?', 'volume': '889', 'author': 'Costa', 'year': '2020', 'journal-title': 'Eur J Pharmacol'}, { 'key': '2023032720364652300_', 'first-page': '194', 'article-title': 'Pathological sequelae of long-haul COVID', 'volume': '23', 'author': 'Mehandru', 'year': '2022', 'journal-title': 'Nat Immunol'}, {'key': '2023032720364652300_', 'author': 'World Health Organization (WHO)'}, {'key': '2023032720364652300_', 'author': 'World Health Organization (WHO)'}, { 'key': '2023032720364652300_', 'first-page': 'e2313', 'article-title': 'Covid-19 vaccines and variants of concern: a review', 'volume': '32', 'author': 'Hadj', 'year': '2022', 'journal-title': 'Rev Med Virol'}], 'container-title': 'QJM: An International Journal of Medicine', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://academic.oup.com/qjmed/advance-article-pdf/doi/10.1093/qjmed/hcac272/48479022/hcac272.pdf', 'content-type': 'application/pdf', 'content-version': 'am', 'intended-application': 'syndication'}, { 'URL': 'https://academic.oup.com/qjmed/article-pdf/116/3/161/49652026/hcac272.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'syndication'}, { 'URL': 'https://academic.oup.com/qjmed/article-pdf/116/3/161/49652026/hcac272.pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 3, 27]], 'date-time': '2023-03-27T20:37:16Z', 'timestamp': 1679949436000}, 'score': 1, 'resource': {'primary': {'URL': 'https://academic.oup.com/qjmed/article/116/3/161/6885454'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2022, 12, 9]]}, 'references-count': 262, 'journal-issue': { 'issue': '3', 'published-online': {'date-parts': [[2022, 12, 9]]}, 'published-print': {'date-parts': [[2023, 3, 27]]}}, 'URL': 'http://dx.doi.org/10.1093/qjmed/hcac272', 'relation': {}, 'ISSN': ['1460-2725', '1460-2393'], 'subject': ['General Medicine'], 'published-other': {'date-parts': [[2023, 3, 1]]}, 'published': {'date-parts': [[2022, 12, 9]]}}

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