Acute Ischemic Stroke in COVID-19: A Case-Based Systematic Review

Wijeratne, Tissa; Sales, Carmela; Karimi, Leila

doi:10.3389/fneur.2020.01031

Cited by 34 publications

(31 citation statements)

References 131 publications

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“…We found a similar rate of stroke incidence in COVID-19 compared to previous reports, but included a higher number of cohort studies. 34,35 We provide a comprehensive picture of the clinical, biochemical, and radiological features of stroke in COVID-19; in comparison to other reviews, 36,37 this was done after excluding case reports and small case series (which may be biased through focusing on particularly unusual cases), thus strengthening the solidity of our results. Core novelties of our investigation are synthesis of evidence on the topic of risk factors for stroke in people with COVID-19 as well as the comparison of stroke characteristics between infected and non-infected patients, both of which are vital to on-going clinical care and management during the current pandemic.…”

Section: Discussionmentioning

confidence: 76%

Stroke in COVID-19: A systematic review and meta-analysis

Nannoni

Groot

Bell

et al. 2020

International Journal of Stroke

475

496

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Background: Coronavirus disease 2019 (COVID-19) has become a global pandemic, affecting millions of people. However, the relationship between COVID-19 and acute cerebrovascular diseases (CVD) is unclear. Aims: We aimed to characterize the incidence, risk factors, clinical-radiological manifestations and outcome of COVID-19-associated stroke. Methods: Three medical databases were systematically reviewed for published articles on acute CVD in COVID-19 (December 2019-September 2020). The review protocol was previously registered (PROSPERO ID=CRD42020185476). Data were extracted from articles reporting ï³5 stroke cases in COVID-19. We complied with the PRISMA guidelines, and used the NewcastleâOttawa Scale to assess data quality. Data were pooled using a random-effects model. Summary of review: Of 2,277 initially identified articles, 61 (2.7%) were entered in the meta-analysis. Out of 108,571 patients with COVID-19, acute CVD occurred in 1.4% (95%CI: 1.0-1.9). The most common manifestation was acute ischemic stroke (87.4%); intracerebral haemorrhage was less common (11.6%). Patients with COVID-19 developing acute CVD, compared to those who did not, were older (pooled median difference=4.8 years; 95%CI:1.7-22.4), more likely to have hypertension (OR=7.35; 95%CI:1.94-27.87), diabetes mellitus (OR=5.56; 95%CI:3.34-9.24), coronary artery disease (OR=3.12; 95%CI:1.61-6.02), and severe infection (OR=5.10; 95%CI:2.72-9.54). Compared to individuals who experienced a stroke without the infection, patients with COVID-19 and stroke were younger (pooled median difference=-6.0 years; 95%CI:-12.3 to -1.4), had higher NIHSS (pooled median difference=5; 95%CI:3-9), higher frequency of large vessel occlusion (OR=2.73; 95%CI:1.63-4.57), and higher in-hospital mortality rate (OR=5.21; 95% CI:3.43-7.90). Conclusions: Acute CVD is not uncommon in COVID-19, especially in those whom are severely infected and have pre-existing vascular risk factors. The pattern of large vessel occlusion and multi-territory infarcts suggest that cerebral thrombosis and/or thromboembolism could be possible causative pathways for the disease.

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Section: Discussionmentioning

confidence: 76%

Stroke in COVID-19: A systematic review and meta-analysis

Nannoni

Groot

Bell

et al. 2020

International Journal of Stroke

475

496

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“…In a prospective cohort study involving patients with concomitant COVID-19 and ischemic stroke, 9 of the 10 patients have elevated NLR (85). Similarly, the majority of AIS patients presented recently (86,87) and in various COVID-19 and AIS case series has reported increased NLR values (72,(88)(89)(90)(91). A significant degree of lymphopenia coupled with viralinduced neutrophilia and the migration of the neutrophils to the ischemic core may explain the elevated NLR among patients with ischemic stroke (92).…”

Section: The Role Of Peripheral Biomarkers To Covid-19 That Are Also Characteristic Of Ischemic Strokementioning

confidence: 99%

COVID-19 Pathophysiology Predicts That Ischemic Stroke Occurrence Is an Expectation, Not an Exception—A Systematic Review

2021

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Clinical reports of neurological manifestations associated with severe coronavirus disease 2019 (COVID-19), such as acute ischemic stroke (AIS), encephalopathy, seizures, headaches, acute necrotizing encephalitis, cerebral microbleeds, posterior reversible leukoencephalopathy syndrome, hemophagocytic lymphohistiocytosis, peripheral neuropathy, cranial nerve palsies, transverse myelitis, and demyelinating disorders, are increasing rapidly. However, there are comparatively few studies investigating the potential impact of immunological responses secondary to hypoxia, oxidative stress, and excessive platelet-induced aggregation on the brain. This scoping review has focused on the pathophysiological mechanisms associated with peripheral and consequential neural (central) inflammation leading to COVID-19-related ischemic strokes. It also highlights the common biological processes shared between AIS and COVID-19 infection and the importance of the recognition that severe respiratory dysfunction and neurological impairments associated with COVID and chronic inflammation [post-COVID-19 neurological syndrome (PCNS)] may significantly impact recovery and ability to benefit from neurorehabilitation. This study provides a comprehensive review of the pathobiology of COVID-19 and ischemic stroke. It also affirms that the immunological contribution to the pathophysiology of COVID-19 is predictive of the neurological sequelae particularly ischemic stroke, which makes it the expectation rather than the exception. This work is of fundamental significance to the neurorehabilitation community given the increasing number of COVID-related ischemic strokes, the current limited knowledge regarding the risk of reinfection, and recent reports of a PCNS. It further highlights the need for global collaboration and research into new pathobiology-based neurorehabilitation treatment strategies and more integrated evidence-based care.

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“…and adaptive immunity, respectively (15). NLR and systemic immune-inflammatory response (SII) provide an excellent biomarker of the innate and adaptive immune response in AIS just as in the case of COVID-19 (16)(17)(18). As a cost-effective (19) and easy to perform test in routine practice, the neutrophil-to-lymphocyte ratio (NLR) has been previously validated as a prognostic indicator in other conditionscancer, cardiac disease, sepsis, coronary artery disease and metabolic syndrome (20).…”

Section: Neutrophils and Lymphocytes Are Common Markers Of Inflammatimentioning

confidence: 99%

“…Low-grade systemic inflammation connects metabolic syndrome, cardiovascular diseases such as AIS and aging (45). AIS occurs in the context of a compromised vascular system very much akin to COVID-19 related neurological issues (18,(46)(47)(48)(49)(50)(51)(52)(53). The evidence is overwhelming that activation of innate immunity before and after the AIS and COVID-19 with adaptive immunity implications after the index events of AIS and COVID-19 share similar pathobiology and trajectory.…”

Section: Nlr and Its Role In Predisposition To Acute Ischemic Strokementioning

confidence: 99%

Universally Available Innate and Adaptive Immune Cell Counts in Acute Ischemic Stroke (AIS) in the Context of Shared Pathobiology with COVID-19; Scoping Review

Wijeratne¹,

Sales²,

Menon³

et al. 2021

Preprint

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Stroke is one of the leading cause of adult disability and the second leading cause of death worldwide. The immune system actively participates in the pathobiological process of AIS, during the index event and during the repair process despite the limited attention drawn to this aspect in the existing stroke guidelines globally. The similar clinical course and similar circulating innate and adaptive immune cell counts in AIS and COVID-19 has created a renewed interest in these easily available biomarkers innate and adaptive immunological changes in AIS with potential diagnostic, prognostic, and therapeutic implications. The current scoping review aimed to assess the significance of circulating neutrophil and lymphocyte counts and their ratio (NLR) in AIS and explore their association with post-stroke recovery trajectory. The Arksey and O'Malley methodological framework was employed to review the published papers on the neutrophil-lymphocyte ratio (NLR) and AIS in late November 2020. Only studies published in English from 2000-2020 were included in this scoping review. Fifty-three published papers were reviewed. This review's key finding is that a canonical inflammatory response occurs in AIS just as in the case of COVID-19 and neurological involvements well described in the recent literature. An excessive circulating innate immune cells (neutrophils) and reduced circulating adaptive immune cells (lymphocytes ) are associated with poorer outcomes during the acute interventions ( reperfusion therapies) as well as the recovery trajectory. Main representatives of innate and adaptive immunity follow a canonical course in AIS and COVID-19. Exaggerated circulating innate ( elevated neutrophils and elevated NLR) and reduced adaptive immune response (lymphopenia) correlate with the worse outcome in AIS and COVID-19. This scoping review's findings make the strongest case for a systems biology-based approach to the standard operating procedures in stroke care urgently.

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Acute Ischemic Stroke in COVID-19: A Case-Based Systematic Review

Cited by 34 publications

References 131 publications

Stroke in COVID-19: A systematic review and meta-analysis

Stroke in COVID-19: A systematic review and meta-analysis

COVID-19 Pathophysiology Predicts That Ischemic Stroke Occurrence Is an Expectation, Not an Exception—A Systematic Review

Universally Available Innate and Adaptive Immune Cell Counts in Acute Ischemic Stroke (AIS) in the Context of Shared Pathobiology with COVID-19; Scoping Review

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