Head-to-head comparison of four COVID-19 vaccines on platelet activation, coagulation and inflammation. The TREASURE study.

INTRODUCTION: Studies exploring alterations in blood coagulation and platelet activation induced by COVID-19 vaccines are not concordant. We aimed to assess the impact of four COVID-19 vaccines on platelet activation, coagulation, and inflammation considering also the immunization dose and the history of SARS-CoV-2 infection. METHODS: TREASURE study enrolled 368 consecutive subjects (161 receiving viral vector vaccines -ChAdOx1-S/Vaxzevria or Janssen- and 207 receiving mRNA vaccines -Comirnaty/Pfizer-BioNTech or Spikevax/Moderna). Blood was collected the day before and 8 ± 2 days after the vaccination. Platelet activation markers (P-selectin, aGPIIbIIIa and Tissue Factor expression; number of platelet-monocyte and -granulocyte aggregates) and microvesicle release were analyzed by flow cytometry. Platelet thrombin generation (TG) capacity was measured using the Calibrated Automated Thrombogram. Plasma coagulation and inflammation markers and immune response were evaluated by ELISA. RESULTS: Vaccination did not induce platelet activation and microvesicle release. IL-6 and CRP levels (+30%), D-dimer, fibrinogen and F1+2 (+13%, +3.7%, +4.3%, respectively) but not TAT levels significantly increased upon immunization with all four vaccines, with no difference among them and between first and second dose. An overall minor post-vaccination reduction of aPC, TM and TFPI, all possibly related to endothelial function, was observed. No anti-PF4 seroconversion was observed. CONCLUSION: This study showed that the four COVID-19 vaccines administered to a large population sample induce a transient inflammatory response, with no onset of platelet activation. The minor changes in clotting activation and endothelial function might be potentially involved at a population level in explaining the very rare venous thromboembolic complications of COVID-19 vaccination.

Outcomes and mechanical complications of acute myocardial infarction during the second wave pandemic in a Milan HUB center for cardiac emergencies.

Aims: COVID-19 has dramatically impacted the healthcare system. Evidence from previous studies suggests a decline in in-hospital admissions for acute myocardial infarction (AMI) during the pandemic. However, the effect of the pandemic on mechanical complications (MC) in acute ST-segment elevation myocardial infarction (STEMI) has not been comprehensively investigated. Therefore, we evaluated the impact of the pandemic on MC and in-hospital outcomes in STEMI during the second wave, in which there was a huge SARS-CoV-2 diffusion in Italy. Methods and results: Based on a single center cohort of AMI patients admitted with STEMI between February 1, 2019, and February 28, 2021, we compared the characteristics and outcomes of STEMI patients treated during the pandemic vs. those treated before the pandemic. In total, 479 STEMI patients were included, of which 64.5% were during the pandemic. Relative to before the pandemic, primary percutaneous coronary intervention (PCI) declined (87.7 vs. 94.7%, p = 0.014) during the pandemic. Compared to those admitted before the pandemic (10/2019 to 2/2020), STEMI patients admitted during the second wave (10/2020 to 2/2021) presented with a symptom onset-to-door time greater than 24 h (26.1 vs. 10.3%, p = 0.009) and a reduction of primary PCI (85.2 vs. 97.1%, p = 0.009). MC occurred more often in patients admitted during the second wave of the pandemic than in those admitted before the pandemic (7.0 vs. 0.0%, p = 0.032). In-hospital mortality increased during the second wave (10.6 vs. 2.9%, p = 0.058). Conclusion: Although the experience gained during the first wave and a more advanced hub-and-spoke system for cardiovascular emergencies persists, late hospitalizations and a high incidence of mechanical complications in STEMI were observed even in the second wave.

The Impact of COVID-19 Pandemic on Scientific Research: an Upcoming New Wave?

The coronavirus disease (COVID)-19 pandemic continues to have an impact on health care. A potential new wave can be foreseen concerning the impact of the pandemic on medical research and literature. We focused our attention on journals belonging to "Medicine, General and Internal" Clarivate™ category and "Q1" journal impact factor quartile. We found that since January 2020, 9621 papers regarding COVID-19 have been published in these journals. This occurred at the expense of non-COVID-19-related scientific papers as most journals did not increase the total number of their published articles. Thus, our analysis may outlook a new potential scientific wave related to COVID-19, in addition to the clinical ones, possibly delaying the improvement in the quality of care for other diseases in the next years.

Cardiac Care of Non-COVID-19 Patients During the SARS-CoV-2 Pandemic: The Pivotal Role of CCTA.

Aim: The aim of this study is to evaluate the potential use of coronary CT angiography (CCTA) as the sole available non-invasive diagnostic technique for suspected coronary artery disease (CAD) during the coronavirus disease 2019 (COVID-19) pandemic causing limited access to the hospital facilities. Methods and Results: A consecutive cohort of patients with suspected stable CAD and clinical indication to non-invasive test was enrolled in a hub hospital in Milan, Italy, from March 9 to April 30, 2020. Outcome measures were obtained as follows: cardiac death, ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina. All the changes in medical therapy following the result of CCTA were annotated. A total of 58 patients with a mean age of 64 ± 11 years (36 men and 22 women) were enrolled. CCTA showed no CAD in 14 patients (24.1%), non-obstructive CAD in 30 (51.7%) patients, and obstructive CAD in 14 (24.1%) patients. Invasive coronary angiography (ICA) was considered deferrable in 48 (82.8%) patients. No clinical events were recorded after a mean follow-up of 376.4 ± 32.1 days. Changes in the medical therapy were significantly more prevalent in patients with vs. those without CAD at CCTA. Conclusion: The results of the study confirm the capability of CCTA to safely defer ICA in the majority of symptomatic patients and to correctly identify those with critical coronary stenoses necessitating coronary revascularization. This characteristic could be really helpful especially when the hospital resources are limited.

Acute Myocardial Infarction During the COVID-19 Pandemic: An Update on Clinical Characteristics and Outcomes

The outbreak of coronavirus disease 2019 (COVID-19) has rapidly become a worldwide pandemic. On top of respiratory complications, COVID-19 is associated with major direct and indirect cardiovascular consequences, with the latter probably being even more relevant, especially in the setting of time-dependent cardiovascular emergencies. A growing amount of data suggests a dramatic decline in hospital admissions for acute myocardial infarction (AMI) worldwide during the COVID-19 pandemic, mostly since patients did not activate emergency medical systems because hospitals were perceived as dangerous places regarding the infection risk. Moreover, during the COVID-19 pandemic, patients with AMI had a significantly higher in-hospital mortality compared to those admitted before COVID-19, potentially due to late arrival to the hospital. Finally, no consensus has been reached regarding the most adequate healthcare management pathway for AMI and shared guidance on how to handle patients with AMI during the pandemic is still needed. In this review, we will provide an update on epidemiology, clinical characteristics, and outcomes of patients with AMI during the COVID-19 pandemic, with a special focus on its collateral cardiac impact.

Platelet and Endothelial Activation as Potential Mechanisms Behind the Thrombotic Complications of COVID-19 Patients.

The authors hypothesized that the cytokine storm described in COVID-19 patients may lead to consistent cell-based tissue factor (TF)-mediated activation of coagulation, procoagulant microvesicles (MVs) release, and massive platelet activation. COVID-19 patients have higher levels of TF+ platelets, TF+ granulocytes, and TF+ MVs than healthy subjects and coronary artery disease patients. Plasma MV-associated thrombin generation is present in prophylactic anticoagulated patients. A sustained platelet activation in terms of P-selectin expression and platelet-leukocyte aggregate formation, and altered nitric oxide/prostacyclin synthesis are also observed. COVID-19 plasma, added to the blood of healthy subjects, induces platelet activation similar to that observed in vivo. This effect was blunted by pre-incubation with tocilizumab, aspirin, or a P2Y12 inhibitor.

Extent of lung involvement over severity of cardiac disease for the prediction of adverse outcome in COVID-19 patients with cardiovascular disease.

BACKGROUND: Aim of the present study was to assess if the presence of high cardiovascular risk, left ventricle systolic dysfunction or elevated BNP or Troponin are able to independently predict the outcome of patients with known cardiac disease and COVID-19 pneumonia. METHODS AND RESULTS: From March 7th to April 28th, forty consecutive patients with known cardiac disease (chronic coronary artery disease, n=38; atrial fibrillation, n = 7; valvular disease, n = 13) referred to our emergency department for symptoms of suspected COVID-19, laboratory diagnosis of COVID-19 and typical signs of viral pneumonia at chest CT were enrolled in the study. The only predictor of the composite end-point (all cause of death + invasive ventilation + thromboembolic event) was the lung involvement % at chest CT (OR: 1.06; 95%CI: 1.01-1.11, P = 0.02). In the multivariate analysis, the lung involvement % at chest CT was the only independent predictor of the composite end-point (OR: 1.06; 95%CI: 1.01-1.11, P = 0.034). CONCLUSIONS: The extent of lung involvement by COVID-19 is the only independent predictor of adverse outcome of patients and is predominant over the severity of cardiac disease.

An In-hospital Pathway for Acute Coronary Syndrome Patients During the COVID-19 Outbreak: Initial Experience Under Real-World Suboptimal Conditions.

Owing to the COVID-19 outbreak in Lombardy, Italy) there is an urgent need to manage cardiovascular emergencies, including acute coronary syndrome (ACS), with appropriate standards of care and dedicated preventive measures and pathways against the risk of SARS-CoV-2 infection. For this reason, the Government of Lombardy decided to centralize the treatment of ACS patients in a limited number of centers, including our university cardiology institute, which in the past 4 weeks became a cardiovascular emergency referral center in a regional hub-and-spoke system. Therefore, we rapidly developed a customized pathway to allocate patients to the appropriate hospital ward, and treat them according to ACS severity and risk of suspected SARS-CoV-2 infection. We present here the protocol dedicated to ACS patients adopted in our center since March 13, 2020, and our initial experience in the management of ACS patients during the first 4 weeks of its use. Certainly, the protocol has room for further improvement as everyone's experience grows, but we hope that it could be a starting point, adaptable to different realities and local resources.