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

Abstract

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 5 stroke cases in COVID-19. We complied with the PRISMA guidelines, and used the Newcastle–Ottawa 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.

COVID-19 and thrombosis: From bench to bedside

“…While the data on VTE are quite robust, evidence is evolving on the risk of arterial thromboembolism with COVID-19 infection. The frequency of acute ischemic stroke and myocardial infarction appears to be much smaller than the risk of VTE, although not inconsequential [ 85 , 86 ]. At this time, there are no guidelines supporting the use of aspirin for prophylaxis of arterial thromboembolism in patients with COVID-19 [87] although studies with antiplatelets are planned or ongoing (clinicaltrials.gov NCT04365309 ).…”

Risk, clinical course and outcome of ischemic stroke in patients hospitalized with COVID-19: a multicenter cohort study

“…First, most studies were performed in Asia and North America, with only a few European cohorts. [3][4][5]7 Geographical variation may explain some of the heterogeneity, with a higher incidence reported in Asia than in North America and Europe. 3 In addition, regional differences in COVID-19 surges may have resulted in a higher threshold for seeking medical attention in some pandemic areas, especially for patients with mild symptoms of stroke.…”

“…[3][4][5]7 Geographical variation may explain some of the heterogeneity, with a higher incidence reported in Asia than in North America and Europe. 3 In addition, regional differences in COVID-19 surges may have resulted in a higher threshold for seeking medical attention in some pandemic areas, especially for patients with mild symptoms of stroke. Second, in most studies ischemic stroke was recorded as one of various cardiovascular events, with case-ascertainment often not performed by neurologists or stroke physicians.…”

“…The occurrence of ischemic stroke varied greatly, ranging from 0.01% to 6.9%. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] This may be explained in part by differences in study design, size, case-findings methods, and settings.…”

“…2 Several studies have found that patients with COVID-19 who had acute ischemic stroke were more likely to die. [3][4][5] It remains unclear whether this association with an increased mortality is driven by disease severity and the prothrombotic state triggered by COVID-19. Alternatively, other confounding factors, such as impeded functional recovery due to fever and infection and withdrawal of care in patients with COVID-19 and ischemic stroke, may also play a role.…”