SARS-CoV-2 infection predicts larger infarct volume in patients with acute ischemic stroke

Abstract

Background and purpose: Acute ischemic stroke (AIS) is a fearful complication of Coronavirus Disease-2019 (COVID-19). Aims of this study were to compare clinical/radiological characteristics, endothelial and coagulation dysfunction between acute ischemic stroke (AIS) patients with and without COVID-19 and to investigate if and how the SARS-CoV-2 spike protein (SP) was implicated in triggering platelet activation.

Methods: We enrolled AIS patients with COVID-19 within 12 h from onset and compared them with an age- and sex-matched cohort of AIS controls without COVID-19. Neuroimaging studies were performed within 24 h. Blood samples were collected in a subset of 10 patients.

Results: Of 39 AIS patients, 22 had COVID-19 and 17 did not. Admission levels of Factor VIII and von Willebrand factor antigen were significantly higher in COVID-19 patients and positively correlated with the infarct volume. In multivariate linear regression analyses, COVID-19 was an independent predictor of infarct volume (B 20.318, Beta 0.576, 95%CI 6.077-34.559; p = 0.011). SP was found in serum of 2 of the 10 examined COVID-19 patients. Platelets from healthy donors showed a similar degree of procoagulant activation induced by COVID-19 and non-COVID-19 patients' sera. The anti-SP and anti-FcγRIIA blocking antibodies had no effect in modulating platelet activity in both groups.

Conclusions: SARS-CoV-2 infection seems to play a major role in endothelium activation and infarct volume extension during AIS.

Keywords: COVID-19; SARS-CoV-2; coagulation; endothelium activation; platelet activation; stroke; thrombosis.

Figure 1

Fibrinogen, FVIII and VWF:Ag circulating levels are significantly higher in COVID-19 acute ischemic stroke patients than in the non-COVID-19 acute ischemic stroke patients. The graphs show the differences (Mann-Whitney U test) in coagulation parameters between acute ischemic stroke (AIS) patients with COVID-19 and without COVID-19: (A) Fibrinogen (without COVID-19, n = 14 vs. with COVID-19, n = 20); (B) Factor VIII (FVIII) (without COVID-19, n = 10 vs. with COVID-19, n = 8); (C) von Willebrand Factor Antigen (vWF:Ag) (without COVID-19, n = 9 vs. with COVID-19, n = 8).

Figure 2

Sera from AIS patients, with or without COVID-19, induce activation of platelets from healthy controls. Flow cytometric analysis of (A, C) integrin activation (shown as median fluorescence intensity, MFI, of PAC1-FITC) and of (B, D) phosphatidylserine exposure, i.e., platelet pro-coagulant activity (shown as MFI of Annexin V-PE) of washed healthy platelets (of n = 3 healthy donors combined) incubated with sera from acute ischemic stroke (AIS, n = 10) patients, with or without COVID-19, or of healthy controls (HC, n = 6), in the presence or absence of blocking antibodies for the spike protein subunit 1 protein (α-S1) or the FcγRIIA (α-FcγRIIA) [Kruskal Wallis test for (A, B); two-way ANOVA for (C, D)]. ^*p < 0.05, ^**p < 0.01, ^***p < 0.001.