Phaedra-impact

Currently, it is largely unknown to what extent the heart is involved in COVID-19. The aim of this project is to assess the incidence and consequences of cardiac damage in patients who have experienced COVID-19. How often does COVID-19 lead to myocardial damage? What are the short- and long-term consequences of this damage and what can we do to prevent it from occurring? These are the central questions that will be answered within the DEFENCE consortium. The Research The DEFENCE consortium integrates several national studies initiated at the onset of the COVID-19 pandemic, encompassing diverse patient groups as part of the COPP study, ranging from elite athletes (COMMIT study) and individuals recovering at home (COVID@Heart study) to hospitalized patients (CAPACITY-COVID registry and CAPACITY 2 study) and children with post-infection inflammatory syndromes affecting the heart (MIS-C). By harmonizing these initiatives, a unique cohort spanning the entire spectrum of COVID-19 severity has been established. The ongoing studies are extended at multiple levels within the DEFENCE project. This includes: Standardized Healthcare Pathway Implementation: Implementing and evaluating a standardized healthcare pathway to assess cardiac damage occurrence within 6 months post-hospitalization for COVID-19. Serial Cardiac Magnetic Resonance (CMR) Imaging: Performing serial CMR imaging to determine the prevalence and reversibility of myocardial damage, with all scans assessed in a core lab. Evaluation of Cardiovascular Symptoms: Assessing the incidence of cardiovascular symptoms such as chest pain and palpitations in the post-acute phase through patient questionnaires. Linking Data to National Datasets: Linking study data to national datasets at Statistics Netherlands to analyze long-term cardiovascular morbidity and mortality. To evaluate whether cardiovascular disease is a characteristic feature of COVID-19, a comparison with other respiratory tract infections, including seasonal influenza will be made. Origin This research has is funded by ZonMw, but has been set up through the efforts of WCN, NLHI, NHR, the Dutch Heart Foundation, NVVC, NVIC, Harteraad, and the EuroQol Research Foundation, who collaborate within the Dutch CardioVascular Alliance.

The SARS-CoV-2 pandemic has a high burden of morbidity and mortality due to development of the acute respiratory distress syndrome (ARDS). The reninangiotensin-system (RAS) plays an important role in the development of ARDS, with ACE2 (angiotensin-converting enzyme 2) being a key enzyme within this. The virus's spike protein binds to ACE2, facillitating cellular internalization. Downregulation of ACE2 results in the excessive accumulation of angiotensin II, which in turn increases pulmonary vascular permeability through stimulation of the angiotensin II type 1a receptor (AT1R), thereby exacerbating lung pathology associated with decreased ACE2 activity. Currently available AT1R blockers (ARBs) such as valsartan, have shown potential to block this pathological process mediated by angiotensin II. The Focus The primary aim of the PRAETORIAN-COVID trial is to investigate the effect of the ARB valsartan compared to placebo on the composite end point of admission to an intensive care unit, mechanical ventilation, or death of COVID-19 patients. The Research Participants receiving active treatment are administered valsartan at a dosage titrated to blood pressure, with a maximum of 160 mg twice daily. Participants receiving placebo are provided with a matching placebo. The treatment duration was 14 days or until reaching the primary endpoint, or until hospital discharge, if applicable within 14 days.Two complementary mechanisms underpin the potential efficacy of angiotensin II type 1 receptor blockers (ARBs) in preventing acute respiratory distress syndrome (ARDS) and reducing morbidity and mortality: ARBs block excessive angiotensin-mediated activation of the AT1R. ARBs upregulate ACE2 expression, leading to reduced angiotensin II levels and increased production of the protective vasodilator angiotensin 1–7. Given these mechanisms, ARBs show promise in preventing ARDS development, potentially reducing the need for intensive care unit (ICU) admission and mechanical ventilation, and ultimately lowering mortality rates associated with SARS-CoV-2 infection.