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 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 cerebrovascular diseases 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-effect model.

Summary of review: Of 2277 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 hemorrhage was less common (11.6%). Patients with COVID-19 developing acute cerebrovascular diseases, 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 cerebrovascular diseases are not uncommon in patients with 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 suggests that cerebral thrombosis and/or thromboembolism could be possible causative pathways for the disease.

Keywords: COVID-19; SARS-CoV-2; Stroke; acute cerebrovascular disease; hemorrhagic stroke.

Figure 1.

Pooled analysis of the proportion of COVID-19 patients developing acute CVD, presented for continents.

Figure 2.

Risk factors for acute CVD in COVID-19 patients, showing the distributions of female sex, hypertension, diabetes, coronary artery disease, and severe COVID-19 in infected patients with and without stroke. Stroke characteristics of patients with and without COVID-19 are also showed, presenting the distribution of AIS from large vessel occlusion, the rates of acute stroke treatments, and of in-hospital deaths between the two groups.

Figure 3.

Overview on the possible stroke mechanisms in COVID-19 patients. This figure was created using Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0 Unported License; https://smart.servier.com.