Risk of Ischemic Stroke in Patients With Coronavirus Disease 2019 (COVID-19) vs Patients With Influenza

Merkler, Alexander E; Parikh, Neal S; Mir, Saad; Gupta, Ajay; Kamel, Hooman; Lin, Eaton; Lantos, Joshua; Schenck, Edward J.; Goyal, Parag; Bruce, Samuel S.; Kahan, Joshua; Lansdale, Kelsey N; LeMoss, Natalie M.; Murthy, Santosh B.; Stieg, Philip E.; Fink, Matthew E.; Iadecola, Costantino; Segal, Alan Z.; Cusick, Marika; Campion, Thomas R.; Díaz, Iván; Zhang, Cenai; Navi, Babak B.

doi:10.1001/jamaneurol.2020.2730

Cited by 523 publications

(572 citation statements)

References 27 publications

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“…Cerebrovascular diseases were among the most commonly reported complications, including ischemic stroke, and cerebral hemorrhages. 41,[54][55][56][57][58][59] . Studies from China, Spain and the US report that 1-1.6% of hospitalized patients were affected by cerebrovascular disease.…”

Section: Neurological Complicationsmentioning

confidence: 99%

“…Studies from China, Spain and the US report that 1-1.6% of hospitalized patients were affected by cerebrovascular disease. 41,54,55,57,59 Yet, cardiovascular risk factors were pre-existent in many of the ª 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association stroke patients.…”

Section: Neurological Complicationsmentioning

confidence: 99%

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Neurological manifestations of coronavirus infections – a systematic review

Almqvist

Granberg

Tzortzakakis

et al. 2020

Ann Clin Transl Neurol

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To optimize diagnostic workup of the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, we systematically reviewed neurological and neuroradiological manifestations of SARS-CoV-2 and all other known human coronavirus species (HCoV). Which lessons can we learn? We identified relevant publications (until 26 July 2020) using systematic searches in PubMed, Web of Science, and Ovid EMBASE with predefined search strings. A total of 4571 unique publications were retrieved, out of which 378 publications were selected for in-depth analysis by two raters, including a total of 17549 (out of which were 14418 SARS-CoV-2) patients. Neurological complications and associated neuroradiological manifestations are prevalent for all HCoVs (HCoV-229E, HKU1, NL63, OC43, Middle East respiratory syndrome (MERS)-CoV, SARS-CoV-1, and SARS-CoV-2). Moreover there are similarities in symptomatology across different HCoVs, particularly between SARS-CoV-1 and SARS-CoV-2. Common neurological manifestations include fatigue, headache, and smell/taste disorders. Additionally, clinicians need to be attentive for at least five classes of neurological complications: (1) Cerebrovascular disorders including ischemic stroke and macro/micro-hemorrhages, (2) encephalopathies, (3) para-/postinfectious immune-mediated complications such as Guillain-Barr e syndrome and acute disseminated encephalomyelitis, (4) (meningo-)encephalitis, potentially with concomitant seizures, and (5) neuropsychiatric complications such as psychosis and mood disorders. Our systematic review highlights the need for vigilance regarding neurological complications in patients infected by SARS-CoV-2 and other HCoVs, especially since some complications may result in chronic disability. Neuroimaging protocols should be designed to specifically screen for these complications. Therefore, we propose practical imaging guidelines to facilitate the diagnostic workup and monitoring of patients infected with HCoVs. additional HCoV species (HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43) cause disease in humans, albeit typically with milder clinical courses. 3 While coronaviruses primarily target the human respiratory system, 4 they can also enter the central nervous system (CNS). This is evident from pre-clinical research, where murine coronaviruses have been used to model human encephalitis for decades. 5 HCoVs also show neurotropism. SARS-CoV-1 6 and SARS-CoV-2 7 both use the cell membrane-bound human angiotensin-converting enzyme 2 for cellular entry, which is, among other tissues, expressed on vascular endothelial cells in the brain. 8 Yet, SARS-CoV-2 seems to have an even higher affinity to bind to this receptor compared to SARS-CoV-1. 9 SARS-CoV-1 and SARS-CoV-2 are also most related genetically, with 79% genome homology. 10 Therefore, it is not surprising that several studies have described neurological symptomatology in both SARS-CoV-1 and SARS-CoV-2 infections. 3,11 Neurological complications have also been described in other HCoVs. 12 The aim of this study ...

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Section: Neurological Complicationsmentioning

confidence: 99%

Section: Neurological Complicationsmentioning

confidence: 99%

Neurological manifestations of coronavirus infections – a systematic review

Almqvist

Granberg

Tzortzakakis

et al. 2020

Ann Clin Transl Neurol

View full text Add to dashboard Cite

show abstract

“…This prothrombotic state added another dimension to the AKI that we saw and which led us to change our approach to anticoagulation in patients with COVID‐19 and venous thromboembolic (VTE) prophylaxis. It also explains the increased incidence of ischaemic stroke associated with severe COVID‐19 pneumonia 11 …”

Section: Coagulation Systemmentioning

confidence: 98%

Learnings from critical care on COVID‐19

Pittard

2020

Trends Urol & Men's Health

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“…More serious neurological symptoms experienced by COVID-19 patients range from encephalitis, encephalopathies, acute disseminated encephalomyelitis and myelitis, cerebrovascular disease and seizures, ischaemic strokes, intracerebral haemorrhages, and altered mental health status [ 63 ]. Recently, there is an unusual increase in cerebral venous thrombosis in both young and old COVID-19 patients whereby thrombotic occlusions cause a high risk of acute ischaemic strokes [ 64 , 65 , 66 ].…”

Section: Sars-cov-2 Infectivity Symptoms and Complicationsmentioning

confidence: 99%

Targeting the SphK-S1P-SIPR Pathway as a Potential Therapeutic Approach for COVID-19

McGowan

Haddadi

Nassif

et al. 2020

IJMS

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The world is currently experiencing the worst health pandemic since the Spanish flu in 1918—the COVID-19 pandemic—caused by the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic is the world’s third wake-up call this century. In 2003 and 2012, the world experienced two major coronavirus outbreaks, SARS-CoV-1 and Middle East Respiratory syndrome coronavirus (MERS-CoV), causing major respiratory tract infections. At present, there is neither a vaccine nor a cure for COVID-19. The severe COVID-19 symptoms of hyperinflammation, catastrophic damage to the vascular endothelium, thrombotic complications, septic shock, brain damage, acute disseminated encephalomyelitis (ADEM), and acute neurological and psychiatric complications are unprecedented. Many COVID-19 deaths result from the aftermath of hyperinflammatory complications, also referred to as the “cytokine storm syndrome”, endotheliitus and blood clotting, all with the potential to cause multiorgan dysfunction. The sphingolipid rheostat plays integral roles in viral replication, activation/modulation of the immune response, and importantly in maintaining vasculature integrity, with sphingosine 1 phosphate (S1P) and its cognate receptors (SIPRs: G-protein-coupled receptors) being key factors in vascular protection against endotheliitus. Hence, modulation of sphingosine kinase (SphK), S1P, and the S1P receptor pathway may provide significant beneficial effects towards counteracting the life-threatening, acute, and chronic complications associated with SARS-CoV-2 infection. This review provides a comprehensive overview of SARS-CoV-2 infection and disease, prospective vaccines, and current treatments. We then discuss the evidence supporting the targeting of SphK/S1P and S1P receptors in the repertoire of COVID-19 therapies to control viral replication and alleviate the known and emerging acute and chronic symptoms of COVID-19. Three clinical trials using FDA-approved sphingolipid-based drugs being repurposed and evaluated to help in alleviating COVID-19 symptoms are discussed.

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Risk of Ischemic Stroke in Patients With Coronavirus Disease 2019 (COVID-19) vs Patients With Influenza

Cited by 523 publications

References 27 publications

Neurological manifestations of coronavirus infections – a systematic review

Neurological manifestations of coronavirus infections – a systematic review

Learnings from critical care on COVID‐19

Targeting the SphK-S1P-SIPR Pathway as a Potential Therapeutic Approach for COVID-19

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