Anti-platelet factor 4 antibodies causing VITT do not cross-react with SARS-CoV-2 spike protein.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe adverse effect of ChAdOx1 nCoV-19 COVID-19 vaccine (Vaxzevria) and Janssen Ad26.COV2.S COVID-19 vaccine, and it is associated with unusual thrombosis. VITT is caused by anti-platelet factor 4 (PF4) antibodies activating platelets through their FcγRIIa receptors. Antibodies that activate platelets through FcγRIIa receptors have also been identified in patients with COVID-19. These findings raise concern that vaccination-induced antibodies against anti-SARS-CoV-2 spike protein cause thrombosis by cross-reacting with PF4. Immunogenic epitopes of PF4 and SARS-CoV-2 spike protein were compared using in silico prediction tools and 3D modeling. The SARS-CoV-2 spike protein and PF4 share at least 1 similar epitope. Reactivity of purified anti-PF4 antibodies from patients with VITT was tested against recombinant SARS-CoV-2 spike protein. However, none of the affinity-purified anti-PF4 antibodies from 14 patients with VITT cross-reacted with SARS-CoV-2 spike protein. Sera from 222 polymerase chain reaction-confirmed patients with COVID-19 from 5 European centers were tested by PF4-heparin enzyme-linked immunosorbent assays and PF4-dependent platelet activation assays. We found anti-PF4 antibodies in sera from 19 (8.6%) of 222 patients with COVID-19. However, only 4 showed weak to moderate platelet activation in the presence of PF4, and none of those patients developed thrombotic complications. Among 10 (4.5%) of 222 patients who had COVID-19 with thrombosis, none showed PF4-dependent platelet-activating antibodies. In conclusion, antibodies against PF4 induced by vaccination do not cross-react with the SARS-CoV-2 spike protein, indicating that the intended vaccine-induced immune response against SARS-CoV-2 spike protein is not the trigger of VITT. PF4-reactive antibodies found in patients with COVID-19 in this study were not associated with thrombotic complications.

Recovery of systemic hyperinflammation in patients with severe SARS-CoV-2 infection.

INTRODUCTION: Patients with cardiovascular disease (CVD) and acute SARS-CoV-2 infection might show an altered immune response during COVID-19. MATERIAL AND METHODS: Twenty-three patients with CVD and SARS-CoV-2 infection were prospectively enrolled and received a cardiological assessment at study entry and during follow-up visit. Inclusion criteria of our study were age older than 18 years, presence of CVD, and acute SARS-CoV-2 infection. The median age of the patient cohort was 69 (IQR 55-79) years. 12 (52.2%) patients were men. Peripheral monocytes and chemokine/cytokine profiles were analysed. RESULTS: Numbers of classical and non-classical monocytes were significantly decreased during acute SARS-CoV-2 infection compared to 3-month recovery. While classical monocytes reached the expected level in peripheral blood after 3 months, the number of non-classical monocytes remained significantly reduced. DISCUSSION: All three monocyte subsets exhibited changes of established adhesion and activation markers. Interestingly, they also expressed higher levels of pro-inflammatory cytokines like macrophage migration inhibitory factor (MIF) at the time of recovery, although MIF was only slightly increased during the acute phase. CONCLUSION: Changes of monocyte phenotypes and increased MIF expression after 3-month recovery from acute SARS-CoV-2 infection may indicate persistent, possibly long-lasting, pro-inflammatory monocyte function in CVD patients.

Platelet Activation and Plasma Levels of Furin Are Associated With Prognosis of Patients With Coronary Artery Disease and COVID-19.

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Myocardial Abscess After Myocarditis: Advantages of Multimodal Imaging Detecting the Rare Case of Fungal Abscess.

We discuss the rare case of a myocardial abscess of the left ventricle in a 42-year-old man on immunosuppressive therapy after fulminant myocarditis. Multimodal imaging detected the myocardial abscess along with other septic emboli caused by infection with aspergillus fumigatus, which could be treated effectively with antimycotic strategies. (Level of Difficulty: Intermediate.).

"Mind the Gap": An 85-Year-Old Man with Severe Tricuspid Valve Regurgitation Who Underwent Percutaneous Edge-to-Edge Valve Leaflet Plication Using the New and Advanced MitraClip XTR System.

BACKGROUND Severe tricuspid valve regurgitation (TR) is associated with high cardiovascular mortality. Safe and feasible interventional approaches to treat severe TR are of clinical relevance. The MitraClip is a device that has been approved by the US Food and Drug Administration (FDA) for the repair of mitral valve lesions. Percutaneous femoral venous access with fluoroscopic and echocardiographic guidance is used to deliver a cobalt-chromium clip to secure the mitral valve leaflets. We report on an 85-year-old man with tricuspid valve regurgitation who underwent percutaneous edge-to-edge tricuspid valve leaflet plication with the new, advanced MitraClip XTR System. CASE REPORT An 85-year-old man with severe TR due to annulus dilation of the right ventricle and short septal leaflet presented repeatedly at our hospital with severe right heart failure symptoms. Transesophageal echocardiography revealed severe TR with a large coaptation gap size of 10.6 mm. Percutaneous edge-to-edge valve repair with the new-generation MitraClip System XTR with wider clip arms could overcome the large coaptation gap. We achieved a strong reduction of TR after deploying 2 MitraClips XTR. The patient recovered quickly and has not been admitted to hospital due to heart failure symptoms since the intervention for more than 6 months. CONCLUSIONS Previous studies have shown the safety and effectiveness of the MitraClip device and supported FDA approval for tricuspid valve repair. This report of a patient with complex tricuspid regurgitation demonstrated the feasible use of the new MitraClip XTR System, which improved edge-to-edge tricuspid valve repair due to its increased span and improved grip.

Numbers and phenotype of non-classical CD14dimCD16+ monocytes are predictors of adverse clinical outcome in patients with coronary artery disease and severe SARS-CoV-2 infection.

AIMS: To elucidate the prognostic role of monocytes in the immune response of patients with coronary artery disease (CAD) at risk for life-threatening heart and lung injury as major complications of SARS-CoV-2 infection. METHODS AND RESULTS: From February to April 2020, we prospectively studied a cohort of 96 participants comprising 47 consecutive patients with CAD and acute SARS-CoV-2 infection (CAD + SARS-CoV-2), 19 CAD patients without infections, and 30 healthy controls. Clinical assessment included blood sampling, echocardiography, and electrocardiography within 12 h of admission. Respiratory failure was stratified by the Horovitz Index (HI) as moderately/severely impaired when HI ≤200 mmHg. The clinical endpoint (EP) was defined as HI ≤200 mmHg with subsequent mechanical ventilation within a follow-up of 30 days. The numbers of CD14dimCD16+ non-classical monocytes in peripheral blood were remarkably low in CAD + SARS-CoV-2 compared with CAD patients without infection and healthy controls (P < 0.0001). Moreover, these CD14dimCD16 monocytes showed decreased expression of established markers of adhesion, migration, and T-cell activation (CD54, CD62L, CX3CR1, CD80, and HLA-DR). Decreased numbers of CD14dimCD16+ monocytes were associated with the occurrence of EP. Kaplan-Meier curves illustrate that CAD + SARS-CoV-2 patients with numbers below the median of CD14dimCD16+ monocytes (median 1443 cells/mL) reached EP significantly more often compared to patients with numbers above the median (log-rank 5.03, P = 0.025). CONCLUSION: Decreased numbers of CD14dimCD16+ monocytes are associated with rapidly progressive respiratory failure in CAD + SARS-CoV-2 patients. Intensified risk assessments comprising monocyte sub- and phenotypes may help to identify patients at risk for respiratory failure.

Thrombolysis is an appropriate treatment in lead-associated infective endocarditis with giant vegetations located on the right atrial lead.

CD endocarditis is a potentially lethal complication after implantation of permanent pacemakers or implantable cardioverter-defibrillators. Complete extraction of the hardware along with antibiotic treatment is the standard therapy. However, there is no standard procedure in the treatment of lead-associated infective endocarditis with large thrombotic vegetations. The authors present the case of a 60-year-old patient with a large vegetation located on the right atrial lead. Due to a high surgical and thrombembolic risk, especially of acute massive pulmonary embolism, the patient received recombinant tissue plasminogen activator to dissolve the thrombus under echocardiographic monitoring. The thrombotic masses were substantially reduced after thrombolysis. Therefore, standard transvenous extraction of the leads could be performed and high risk cardiac re-operation could be avoided.