Association of history of cerebrovascular disease with severity of COVID-19

Abstract

Objective: To determine whether a history of cerebrovascular disease (CVD) increases risk of severe coronavirus disease 2019 (COVID-19).

Methods: In a retrospective multicenter study, we retrieved individual data from in-patients treated March 1 to April 15, 2020 from COVID-19 registries of three hospitals in Saxony, Germany. We also performed a systematic review and meta-analysis following PRISMA recommendations using PubMed, EMBASE, Cochrane Library databases and bibliographies of identified papers (last search on April 11, 2020) and pooled data with those deriving from our multicenter study. Of 3762 records identified, 11 eligible observational studies of laboratory-confirmed COVID-19 patients were included in quantitative data synthesis. Risk ratios (RR) of severe COVID-19 according to history of CVD were pooled using DerSimonian and Laird random effects model. Between-study heterogeneity was assessed using Cochran's Q and I2-statistics. Severity of COVID-19 according to definitions applied in included studies was the main outcome. Sensitivity analyses were conducted for clusters of studies with equal definitions of severity.

Results: Pooled analysis included data from 1906 laboratory-confirmed COVID-19 patients (43.9% females, median age ranging from 39 to 76 years). Patients with previous CVD had higher risk of severe COVID-19 than those without [RR 2.07, 95% confidence interval (CI) 1.52-2.81; p < 0.0001]. This association was also observed in clusters of studies that defined severe manifestation of the disease by clinical parameters (RR 1.44, 95% CI 1.22-1.71; p < 0.0001), necessity of intensive care (RR 2.79, 95% CI 1.83-4.24; p < 0.0001) and in-hospital death (RR 2.18, 95% CI 1.75-2.7; p < 0.0001).

Conclusion: A history of CVD might constitute an important risk factor of unfavorable clinical course of COVID-19 suggesting a need of tailored infection prevention and clinical management strategies for this population at risk.

Keywords: COVID-19; Cerebrovascular disease; Critical care; Prognosis; Stroke.

Fig. 1

Map of study sites in Germany where individual data on patients with COVID-19 were retrieved. Location of participating sites in Saxony, Germany, with rates of confirmed infections with SARS CoV-2 based on epidemiological data provided by Robert Koch Institute as of April 15, 2020 (www.rki.de/EN/Home/homepage_node.html). Numbers in brackets refer to absolute numbers of patients included in the multicenter cohort

Fig. 2

Flowchart on identification of studies on COVID-19 eligible for quantitative data synthesis. PRISMA flowchart illustrating systematic screening and selection process of published observational studies reporting on laboratory-confirmed COVID-19 patients with data available on disease severity and past history of CVD

Fig. 3

Association of history of cerebrovascular disease and severe clinical manifestation of COVID-19 among included studies. Forest plots illustrating associations of history of CVD and severe clinical manifestation of COVID-19 for composite severity outcome subsuming all definitions of severity as reported by included studies (a) as well as for clusters of studies defining severity by grading of clinical parameters (b), whether patients required intensive care (c), and in-hospital death (d). Composite outcome analysis as well as assessment of each cluster included only studies that have not shown any overlap in study populations during full text evaluation. Individual patient data from German multicenter cohort were evaluated for severity based on the Chinese Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatment

Fig. 4

Assessment of publication bias. Visual inspection of funnel plot is not indicative of publication bias