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 × 10 7 ± 0.43 × 10 7 vs. 2.92 × 10 7 ± 0.49 × 10 7 vs. 3.57 × 10 7 ± 0.73 × 10 7 vs. 9.94 × 10 7 ± 0.99 × 10 7 ; p ≤0.0001). In cytokine storm, platelet adhesion values remained low in coated COBRA-PzF (1.78 × 10 7 ± 0.38 × 10 7 ) compared to all other devices (uncoated COBRA: 5.92 × 10 7 ± 0.96 × 10 7 ; Resolute Onyx: 7.27 × 10 7 ± 1.82 × 10 7 ; Synergy: 11.28 × 10 7 ± 1.08 × 10 7 ; 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.

Caspase-4/11 exacerbates disease severity in SARS–CoV-2 infection by promoting inflammation and immunothrombosis

“…SARS–CoV-2 infection is accompanied by long-term sequelae mediated in part by vascular damage and thrombosis ( 28 ). Given that we noted decreased neutrophil gene signatures in Casp11 −/− lungs upon infection and since tissue infiltration by neutrophils can activate blood clotting cascades and thrombosis ( 29 , 30 ), we examined whether the production of VWF, a marker for endothelial damage, which is essential to thrombus formation, is regulated by CASP11. Using RNAscope ISH technology, we found significantly more blood vessels expressing VWF messenger RNA (mRNA) in the lung vascular architecture of SARS–CoV-2–infected WT mice when compared to Casp11 −/− lungs at day 4 after infection ( Fig.…”

2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19 in Adults: Myocarditis and Other Myocardial Involvement, Post-Acute Sequelae of SARS-CoV-2 Infection, and Return to Play

“…Myocardial injury with COVID-19 has been extensively reported, with rates widely varying depending upon the population studied. 4 The underlying causes are numerous and include but are not limited to myocarditis, 22 acute coronary syndrome (myocardial infarction type 1), 17 demand ischemia (myocardial infarction type 2), 25 , 32 , 33 , 34 , 35 multisystem inflammatory syndrome in children (MIS-C) and multisystem inflammatory syndrome in adults (MIS-A), 20 , 21 , 24 takotsubo/stress cardiomyopathy, 36 , 37 cytokine storm, 34 acute cor pulmonale resulting from macropulmonary or micropulmonary emboli, 23 , 25 myocardial injury from chronic conditions like pre-existing heart failure, 38 , 39 , 40 , 41 and acute viral infection unmasking subclinical heart disease. 38 Because 1 or more of these etiologies may coexist, it can sometimes be challenging to identify a specific underlying cause.…”

The interplay between inflammation and thrombosis in COVID-19: Mechanisms, therapeutic strategies, and challenges

“…This internalization leads to programmed cell death of platelets and release of prothrombotic intracellular contents, as well as generation of microvesicles [ 61 ]. In addition, inflammatory cytokines, such as IL-1β, IL-6 and TNFα, can hyperactive platelets, leading to pronounced adhesion, morphological changes, and aggregation [ 62 , 63 ]. Upon activation, platelets also release many inflammatory mediators, such as IL-1β, PF4, and express the surface molecules P-selectin and CD40L, facilitating their interactions with endothelial cells and leukocytes.…”