Effects of Simulated COVID-19 Cytokine Storm on Stent Thrombogenicity

Abstract

Background: Cytokine storm-related hypercoagulation may be important in the pathogenesis of stent thrombosis in patients with SARS-CoV-2. Whether stent polymers behave differently under such conditions has never been explored.

Methods: Fluorinated polymer-nanocoated and uncoated COBRA stents (CeloNova), BioLinx-polymer-coated Resolute Onyx stents (Medtronic), and Synergy stents (Boston Scientific), which are abluminally coated with a bioabsorbable polymer, were exposed to human blood from healthy donors which was supplemented with 400 pg/mL IL-6 and 100 pg/mL TNF-α, similar to what is seen in cytokine storm caused by SARS-CoV-2. Platelet adhesion and neutrophil activation, assessed by immunofluorescence, were compared under cytokine storm and control conditions (untreated blood) (n = 4 experimental runs).

Results: Platelet adhesion values, defined as %platelet-covered area x staining intensity, were significantly lower in coated and uncoated COBRA and in Resolute Onyx than in Synergy under control conditions (1.28 × 10⁷ ± 0.43 × 10⁷ vs. 2.92 × 10⁷ ± 0.49 × 10⁷ vs. 3.57 × 10⁷ ± 0.73 × 10⁷ vs. 9.94 × 10⁷ ± 0.99 × 10⁷; p ≤0.0001). In cytokine storm, platelet adhesion values remained low in coated COBRA-PzF (1.78 × 10⁷ ± 0.38 × 10⁷) compared to all other devices (uncoated COBRA: 5.92 × 10⁷ ± 0.96 × 10⁷; Resolute Onyx: 7.27 × 10⁷ ± 1.82 × 10⁷; Synergy: 11.28 × 10⁷ ± 1.08 × 10⁷; p ≤ 0.0001). Although cytokine storm conditions significantly increased neutrophil activation in all stents, it was significantly less in coated and uncoated COBRA, and in Resolute Onyx than in Synergy.

Conclusions: Blood-biomaterials interactions may determine the thrombogenic potential of stents. Under simulated cytokine storm conditions, fluoropolymer-coated stents showed the most favorable anti-thrombogenic and anti-inflammatory properties.

Keywords: COVID-19; Cytokine storm; Myocardial infarction; Neutrophils; Platelets; Stent thrombosis.