key: cord-1001039-fpxd0ont
authors: Fifi, Johanna T; Mocco, J
title: COVID-19 related stroke in young individuals
date: 2020-08-18
journal: Lancet Neurol
DOI: 10.1016/s1474-4422(20)30272-6
sha: 971f9b9277eb011f47ce379d3a0bd821814a0e6f
doc_id: 1001039
cord_uid: fpxd0ont

nan

Evidence is mounting on the diverse neurological pre sen tations associated with COVID19. In a Rapid Review in The Lancet Neurology, Mark Ellul and col leagues 1 nicely cover these findings, but we would like to emphasise the risk of associated stroke. As des cribed in this Rapid Review, severe acute respiratory syn drome coronavirus 2 (SARSCoV2) might be more likely to cause throm botic vascular events, including stroke, than other coronavirus and seasonal infectious diseases. In fact, a 7·6fold increase in the odds of stroke with COVID19 compared with influenza was recently reported. 2 The reported incidence of cerebrovascular dis ease in patients testing positive for SARSCoV2 ranges from 1% to 6%, poten tially equating to large numbers of individuals as the pandemic progresses in some countries. 1, 3 The proposed mechanisms for these cerebrovascular events include a hypercoagulable state from sys temic inflam mation and cytokine storm; 1 postinfectious immunemediated responses; 1 and direct viralinduced endotheliitis or endotheliopathy, potentially leading to angio pathic thrombosis, with viral particles having been isolated from the endothelium of various tissue, including brain tissue. 4, 5 Multiple regions with high COVID19 prevalence have reported stable or increased incidence of large vessel stroke and increased incidence of cryptogenic stroke (patients with no found typical cause of stroke), despite observing a decrease in mild See Rapid Review page 767 stroke that is possibly secondary to quarantine and selfisolation. 6 This quarantine effect is supported by a nationwide analysis in the USA of automated stroke imaging processing software showing decreased imag ing evaluation for stroke during the pandemic. 7 Our group observed that five patients younger than 50 years who tested positive for SARSCoV2, some with no vascular risk factors, were admitted with large vessel stroke to our hospitals during a 2week period (March 23 to April 7, 2020) during the height of the pandemic in New York City (NY, USA). 8 This was a 7fold increase in the rate of large vessel stroke in young people compared with the previous year, and the patients had laboratory findings that suggested a hypercoagulable state, leading to the postulation that stroke was probably related to the presence of SARSCoV2 in these young patients. 9 Since then, this observation of COVID19 related stroke in young patients has been supported by additional data from other centres worldwide. The mean patient age in several thrombectomy case series of COVID19 (mean age of 52·8 years in a series from New York City [NY, USA], 10 mean age of 59·5 years in a series from Paris [France], 11 and mean age of 59·5 years in a combined series from New York City and Philadelphia [PA, USA] 12 ) is younger than the typical population having this procedure. Furthermore, in patients presenting with large vessel stroke during the pandemic, data from the Mount Sinai Health System in New York City confirm that patients who tested positive for SARSCoV2 were significantly younger, with a mean age of 59 years (SD 13), than patients who tested negative for SARSCoV2, who had a mean age of 74 years (SD 17), 13 mirroring the findings of the Paris group. 11 Patients with COVID19 who had imaging confirmed stroke and were admitted to another large New York City medical centre were again found to be younger, with a mean age of 63 years (SD 17), than a control group of patients with stroke who tested negative for SARSCoV2 and had a mean age of 70 years (SD 18). 3 A casecontrol analysis of acute stroke protocol imaging from late March to early April, 2020, across a large New York City health system showed that, after adjusting for age, sex, and vascular risk factors, SASCoV2 positi vity was independently associated with stroke.

Many reports have documented an increased thrombo sis risk early in COVID19 and coagulation abnormalities in Ddimer and fibrinogen can be found in patients with mild symptoms. There are many reports of early COVID19 presenting with thrombotic events, which has led to the consensus to start anticoagulation therapy early in the COVID19 disease course before any thrombotic event. There are reports in the literature specifically addressing macrothrombosis in the internal carotid artery in patients with mild respiratory symptoms of COVID19 14, 15 and stroke as a presenting symptom of the disease. 12 A multi centre series of 26 patients with COVID19 and either ischaemic or haemorrhagic events reported that 27% were younger than 50 years. 16 Additionally, the report stated that two of 15 patients with large vessel stroke were younger than 50 years and without previous stroke risk factors. In this study, consistent with other case series, patients with COVID19 fare worse in terms of clinical outcomes than patients with stroke who do not have COVID19. 6, 12 This is probably related, in part, to the COVID19 disease process.

In conclusion, data supporting an association between COVID19 and stroke in young populations with out typical vascular risk factors, at times with only mild respira tory symptoms, are increasing. Future pros pec tive registries to study this association further, as well as studies of anticoagulation to prevent these poten tially life devastat ing events, are underway. 1 We believe that, in otherwise healthy, young patients who present with stroke dur ing the pan demic, the diagnosis of COVID19 should be thoroughly investigated. Conversely, in patients with mild COVID19 respiratory symptoms, a low threshold for investigation for stroke should be main tained if they present with new neurological symptoms.

We declare no competing interests.

See Online for appendix

The COVID19 pandemic has led to unprecedented challenges. In particular, the impact of COVID19 on neurological services and patients has been immense, as highlighted in a recent Editorial. 1 Despite the heightened burden felt by neurologists, the dedication of our authors and reviewers is not waning. Submissions to The Lancet Neurology between Jan 1 and June 14, 2020, increased by around 70% compared with the same period last year. Unabated expert advice from our clinical and statistical reviewers from around the world is ensuring the con tinued publication of the highest quality research and reviews for our readers.

The journal continues to strive towards the goal of the Lancet group of disseminating the best science for better lives. Our achievement is reflected by the continued place ment of The Lancet Neurology as the leading clinical neurology journal, according to the 2019 Journal Citation Report. The names of everyone who reviewed papers for the journal throughout 2019 are listed in the appendix; those who reviewed five papers, or more, are marked with an asterisk. We extend our warmest gratitude to all these reviewers.

Neurological associations of COVID19

Risk of ischemic stroke in patients with coronavirus disease 2019 (COVID19) vs patients with influenza

SARSCoV2 and stroke in a New York healthcare system

Endothelial cell infection and endotheliitis in COVID19

Central nervous system involvement by severe acute respiratory syndrome coronavirus2 (SARSCoV2)

Falling stroke rates during COVID19 pandemic at a Comprehensive Stroke Center: cover title: falling stroke rates during COVID19

Collateral effect of COVID19 on stroke evaluation in the United States

UK 1 The neurological impact of COVID19

Largevessel stroke as a presenting feature of COVID19 in the young

COVID19 is an independent risk factor for acute ischemic stroke

Stroke and mechanical thrombectomy in patients with COVID19: technical observations and patient characteristics

Treatment of acute ischemic stroke due to large vessel occlusion with COVID19: experience from Paris

Cerebral ischemic and hemorrhagic complications of coronavirus disease 2019

Emergent large vessel occlusion stroke during New York City's COVID19 outbreak: clinical characteristics and paraclinical findings

Macrothrombosis and stroke in patients with mild Covid19 infection

Intraluminal carotid artery thrombus in COVID19: another danger of cytokine storm?

Outcomes and spectrum of major neurovascular events among COVID19 patients: a 3center experience