key: cord-0706657-i0p29hha
authors: Dmytriw, Adam A.; Dibas, Mahmoud; Schirmer, Clemens M.; Settecase, Fabio; Heran, Manraj K. S.; Efendizade, Aslan; Kühn, Anna Luisa; Puri, Ajit S.; Ospel, Johanna; Menon, Bijoy; Sivakumar, Sanjeev; Mowla, Ashkan; Vela‐Duarte, Daniel; Linfante, Italo; Dabus, Guilherme; Regenhardt, Robert W.; Patel, Aman B.; Leslie‐Mazwi, Thabele; D’Amato, Salvatore; Rosenthal, Joseph; Zha, Alicia; Talukder, Nafee; Sheth, Sunil; Cooke, Daniel; Leung, Lester Y.; Malek, Adel; Voetsch, Barbara; Sehgal, Siddharth; Wakhloo, Ajay K.; Wu, Hannah; Cohen, Jake; Turkel‐Parella, David; Xavier, Andrew; Tiwari, Ambooj
title: Age and Acute Ischemic Stroke Outcome in North American Patients With COVID‐19
date: 2021-07-03
journal: J Am Heart Assoc
DOI: 10.1161/jaha.121.021046
sha: d3f4598630b782f0d074db076c077fd69e1f42ac
doc_id: 706657
cord_uid: i0p29hha

BACKGROUND: Acute ischemic stroke (AIS) in the context of COVID‐19 has received considerable attention for its propensity to affect patients of all ages. We aimed to evaluate the effect of age on functional outcome and mortality following an acute ischemic event. METHODS AND RESULTS: A prospectively maintained database from comprehensive stroke centers in Canada and the United States was analyzed for patients with AIS from March 14 to September 30, 2020 who tested positive for SARS‐CoV‐2. The primary outcome was Modified Rankin Scale score at discharge, and the secondary outcome was mortality. Baseline characteristics, laboratory values, imaging, and thrombectomy workflow process times were assessed. Among all 126 patients with COVID‐19 who were diagnosed with AIS, the median age was 63 years (range, 27–94). There were 35 (27.8%) patients with AIS in the aged ≤55 years group, 47 (37.3%) in the aged 56 to 70 group, and 44 (34.9%) in the aged >70 group. Intravenous tissue plasminogen activator and thrombectomy rates were comparable across these groups, (P=0.331 and 0.212, respectively). There was a significantly lower rate of mortality between each group favoring younger age (21.9% versus 45.0% versus 48.8%, P=0.047). After multivariable adjustment for possible confounders, a 1‐year increase in age was significantly associated with fewer instances of a favorable outcome of Modified Rankin Scale 0 to 2 (odds ratio [OR], 0.95; 95 CI%, 0.90–0.99; P=0.048) and higher mortality (OR, 1.06; 95 CI%, 1.02–1.10; P=0.007). CONCLUSIONS: AIS in the context of COVID‐19 affects young patients at much greater rates than pre‐pandemic controls. Nevertheless, instances of poor functional outcome and mortality are closely tied to increasing age.

T he COVID-19 epidemic emerged in Wuhan, China in December 2019, and was associated with an unpreceded healthcare crisis. 1, 2 The intersection of acute ischemic stroke and COVID-19-related disease represents a public health crisis that requires urgent communication to the medical community. 3, 4 AIS in those without traditional risk factors is an emerging hallmark of COVID-19, unprecedented in the modern era of previous viral pandemics, and a distinguishing characteristic compared with other coronavirus infections. Of late, concerns have been raised about acute ischemic stroke After adjusting for hypertension and National Institutes of Health Stroke Scale in the multivariable model (Tables 2 and 3) , a 1-year increase in age was significantly associated with fewer instances of favorable outcome (odds ratio [OR], 0.95; 95% CI, 0.90-0.99; P=0.048). Furthermore, on mortality modeling and after adjusting for diabetes mellitus and National Institutes of Health Stroke Scale (Table S1 ), we observed significantly higher rates of mortality with each 1-year increase in age (OR, 1.06; 95% CI, 1.02-1.10; P=0.007).

AIS is known historically to be a disease of older patients, and our results suggest that patients still fare poorly as age increases in the context of COVID-19. Recently, it has been shown that patients with AIS infected with COVID-19 were more likely to be younger and have higher rates of large vessel occlusions compared with historical controls. 7 Similarly, in this study, there were 35 patients (27.8%) aged <56 years. As a virus which targets angiotensin-converting enzyme 2 receptors, it's suggested that direct endothelial damage may be at least partly to blame for the unprecedented burden upon the young and those without traditional risk factors. 8 AIS is known historically to be a disease of older patients, and our results suggest that patients still fare poorly as age increases in the context of COVID-19.

It is still uncertain what the exact mechanisms are that predispose this population to AIS, however, we corroborate early observations of better outcomes and lower rates of mortality in younger patients. 9 There are 2 major age-related discoveries that differentiate these findings from pre-COVID era AIS. The first is that the proportion of young patients experiencing AIS and particularly large vessel occlusions is vastly more than that before the pandemic. This is a crucial finding, and likely relates to hypercoagulability in the absence of traditional risk factors. Not only does this imply different pathophysiology in these patients, but seemingly also from other coronavirus pandemics.

The other surprising difference is that the risk of poor outcomes increases with every year of age. We believe this is crucial information to disseminate as although attention to the young is important, there is potential to ignore the fact that older patients fare worse to a degree at this also not precedented before the pandemic. In this case, there is reason to believe that there is an interaction between COVID-associated stroke, respiratory disease, and age. These associations with age merit further study. This is a large study that was conducted through several centers in North America. Despite that, this study has some limitations. Principally, some variables that might affect the outcomes including socioeconomic status, local healthcare infrastructure, resources, and personal social support networks may also be at play. Furthermore, this study was done in healthcare centers and thus these patients have more All variables that had a P≤0.05 in the univariate model in Table S1 were included with age in the multivariable model. mRS indicates Modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; and OR, odds ratio.

Clinical course and outcome of 107 patients infected with the novel coronavirus, SARS-CoV-2, discharged from two hospitals in Wuhan

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Etiologic subtypes of ischemic stroke in SARS-CoV-2 patients in a cohort of New York City hospitals

Ischaemic stroke associated with COVID-19 and racial outcome disparity in North America

Large-vessel stroke as a presenting feature of Covid-19 in the young

Incidence, characteristics and outcomes of large vessel stroke in COVID-19 cohort: an international multicenter study. Neurosurgery. 2021. Epub ahead of print

SARS-CoV-2 and stroke in a New York healthcare system

Risk of stroke in hospitalized SARS-CoV-2 infected patients: a multinational study

Cerebrovascular events and outcomes in hospitalized patients with COVID-19: the SVIN COVID-19 multinational registry

We would like to acknowledge Dr Kevin Phan MD, PhD, MSc, MPhil for statistical expertise and guidance. All North American Neurovascular COVID-19 (NAN-C) Consortium members are named on the title page without exception.Author contributions: Dmytriw, Tiwari were responsible for statistical analysis, manuscript drafting, and critical revision. The remaining authors were responsible for data curation and critical manuscript revision.

None.

None. Table S1 SUPPLEMENTAL MATERIAL