Potential Neurologic Manifestations of COVID-19

Nordvig, Anna S.; Fong, Kathryn T.; Willey, Joshua Z.; Thakur, Kiran T.; Boehme, Amelia K; Vargas, Wendy; Smith, Craig J.; Elkind, Mitchell S.V.

doi:10.1212/cpj.0000000000000897

Cited by 77 publications

(83 citation statements)

References 37 publications

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“…Long-term health problems, including neurological symptoms such as headache, fatigue, dizziness, memory loss, confusion, and difficulty focusing, are associated with post-COVID-19 infection [ 10 ]. Over 30% of post-COVID-19 individuals complained of memory loss [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Characterization and Biomarker Analyses of Post-COVID-19 Complications and Neurological Manifestations

Sun

Tang

Peluso

et al. 2021

Cells

161

146

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As the SARS-CoV-2 pandemic continues, reports have demonstrated neurologic sequelae following COVID-19 recovery. Mechanisms to explain long-term neurological sequelae are unknown and need to be identified. Plasma from 24 individuals recovering from COVID-19 at 1 to 3 months after initial infection were collected for cytokine and antibody levels and neuronal-enriched extracellular vesicle (nEV) protein cargo analyses. Plasma cytokine IL-4 was increased in all COVID-19 participants. Volunteers with self-reported neurological problems (nCoV, n = 8) had a positive correlation of IL6 with age or severity of the sequalae, at least one co-morbidity and increased SARS-CoV-2 antibody compared to those COVID-19 individuals without neurological issues (CoV, n = 16). Protein markers of neuronal dysfunction including amyloid beta, neurofilament light, neurogranin, total tau, and p-T181-tau were all significantly increased in the nEVs of all participants recovering from COVID-19 compared to historic controls. This study suggests ongoing peripheral and neuroinflammation after COVID-19 infection that may influence neurological sequelae by altering nEV proteins. Individuals recovering from COVID-19 may have occult neural damage while those with demonstrative neurological symptoms additionally had more severe infection. Longitudinal studies to monitor plasma biomarkers and nEV cargo are warranted to assess persistent neurodegeneration and systemic effects.

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Section: Introductionmentioning

confidence: 99%

Characterization and Biomarker Analyses of Post-COVID-19 Complications and Neurological Manifestations

Sun

Tang

Peluso

et al. 2021

Cells

161

146

View full text Add to dashboard Cite

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“…In adults, the occurrence of this type of event has been described in different critical conditions, including viral infections (23). The physiopathology proposed for cerebrovascular accidents secondary to COVID-19 is the hyperin ammatory process, associated vasculitis, and coagulopathic states (22,24). It is unclear whether the same pathophysiology explains these events in pediatric patients.…”

Section: Discussionmentioning

confidence: 99%

High incidence of stroke and mortality in pediatric critical care patients with COVID-19 in Peru

Coronado

Tasayco-Muñoz²,

Morales³

et al. 2020

Preprint

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Introduction: Pediatric critical care patients with COVID-19 treated in Peru have higher mortality than those previously reported from other countries. Pediatric providers have reported a high number of patients without comorbidities presenting with hemorrhagic strokes associated with COVID-19. We present a study analyzing the factors associated with mortality in this setting.Methods: Prospective case-control study that included patients < 17 years old admitted to a pediatric critical care unit with a positive test confirming COVID-19. The primary outcome was mortality, and secondary outcomes were laboratory results and length of stay. Fisher’s exact test and the Mann-Whitney U test were used for the analysis.Results: Forty-seven patients were admitted to critical care. The mortality of our study is 21.3%. The mortality of patients with neurological presentation was 45.5%, which was significantly higher than the mortality of acute COVID-19 (26.7%) and MIS-C (4.8%), p 0.18. Other risk factors for mortality in our cohort were strokes and comorbidities. Only one patient presenting with hemorrhagic stroke had an undiagnosed comorbidity.Conclusion: Cerebrovascular events associated with COVID-19 in pediatric patients, including infants, must be recognized as one of the more severe presentations of this infection in pediatric patients.

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“…Experimental evidence showed two types of neurological manifestations referring to the CNS and peripheral nervous system (PNS). Of the PNS, there are various neurological associations such as hypogeusia, hyposmia, impaired eye movement, trigeminal neuropathy, Miller-Fisher syndrome, polyneuritis cranialis, rhabdomyolysis, Guillain-Barré Syndrome, and olfactory dysfunction ( Ahmad and Rathore, 2020 ; de Freitas Ferreira et al, 2020 ; Mochan and Modi, 2020 ; Nordvig et al, 2020 ; Pascual-Goñi et al, 2020 ; Yavarpour-Bali and Ghasemi-Kasman, 2020 ). COVID-19 also causes CNS impairment such as cerebrovascular disorders, acute ischemic stroke (1–3%), intracranial haemorrhage (0.5%), encephalitis (brain inflammation), demyelination, meningitis, polyneuritis cranialis, vasculitis, and skeletal muscular damage ( Li et al, 2016 ; Dorche et al, 2020 ; Filatov et al, 2020 ; Mao et al, 2020 ; Moriguchi et al, 2020 ; Zhou et al, 2020 ).…”

Section: Neuronal Manifestations Of Coronavirusesmentioning

confidence: 99%

Targeting Neurological Manifestations of Coronaviruses by Candidate Phytochemicals: A Mechanistic Approach

et al. 2021

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The novel coronavirus 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a wide range of manifestations. In this regard, growing evidence is focusing on COVID-19 neurological associations; however, there is a lack of established pathophysiological mechanisms and related treatments. Accordingly, a comprehensive review was conducted, using electronic databases, including PubMed, Scopus, Web of Science, and Cochrane, along with the author’s expertize in COVID-19 associated neuronal signaling pathways. Besides, potential phytochemicals have been provided against neurological signs of COVID-19. Considering a high homology among SARS-CoV, Middle East Respiratory Syndrome and SARS-CoV-2, revealing their precise pathophysiological mechanisms seems to pave the road for the treatment of COVID-19 neural manifestations. There is a complex pathophysiological mechanism behind central manifestations of COVID-19, including pain, hypo/anosmia, delirium, impaired consciousness, pyramidal signs, and ischemic stroke. Among those dysregulated neuronal mechanisms, neuroinflammation, angiotensin-converting enzyme 2 (ACE2)/spike proteins, RNA-dependent RNA polymerase and protease are of special attention. So, employing multi-target therapeutic agents with considerable safety and efficacy seems to show a bright future in fighting COVID-19 neurological manifestations. Nowadays, natural secondary metabolites are highlighted as potential multi-target phytochemicals in combating several complications of COVID-19. In this review, central pathophysiological mechanisms and therapeutic targets of SARS-CoV-2 has been provided. Besides, in terms of pharmacological mechanisms, phytochemicals have been introduced as potential multi-target agents in combating COVID-19 central nervous system complications.

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Potential Neurologic Manifestations of COVID-19

Cited by 77 publications

References 37 publications

Characterization and Biomarker Analyses of Post-COVID-19 Complications and Neurological Manifestations

Characterization and Biomarker Analyses of Post-COVID-19 Complications and Neurological Manifestations

High incidence of stroke and mortality in pediatric critical care patients with COVID-19 in Peru

Targeting Neurological Manifestations of Coronaviruses by Candidate Phytochemicals: A Mechanistic Approach

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