SARS-CoV-2 uses ACE2, an inhibitor of the Renin-Angiotensin-Aldosterone System (RAAS), for cellular entry. Studies indicate that RAAS imbalance worsens the prognosis in COVID-19. We present a consecutive retrospective COVID-19 cohort with findings of frequent pulmonary thromboembolism (17%), high pulmonary artery pressure (60%) and lung MRI perfusion disturbances. We demonstrate, in swine, that infusing angiotensin II or blocking ACE2 induces increased pulmonary artery pressure, reduces blood oxygenation, increases coagulation, disturbs lung perfusion, induces diffuse alveolar damage, and acute tubular necrosis compared to control animals. We further demonstrate that this imbalanced state can be ameliorated by infusion of an angiotensin receptor blocker and low-molecular-weight heparin. In this work, we show that a pathophysiological state in swine induced by RAAS imbalance shares several features with the clinical COVID-19 presentation. Therefore, we propose that severe COVID-19 could partially be driven by a RAAS imbalance.
PurposeTo follow up the clinical outcome of patients with suspected pulmonary embolism (PE), in those only imaged using unenhanced, free-breathing magnetic resonance imaging (MRI).Methods and materialsFifty-seven patients aged 29–99 years (mean 70, SD 18) that could not undergo Computed Tomography Pulmonary Angiography (CTPA) were offered alternative imaging diagnostics in parallel with ongoing methodological studies validating MRI vs CTPA. Contraindications included renal failure (n = 44), severe iodine contrast allergy (n = 10), pregnancy (n = 2) and radioactive iodine therapy (n = 1). The unenhanced MRI protocol was based on free-breathing, steady-state free precession with no cardiac or respiratory gating. Retrospective review of the electronic medical record (EMR) was made of 0–12 months post-imaging and was collected during 2012–2018.ResultsAll 57 MRIs were of diagnostic quality and 12 pulmonary embolisms were diagnosed. Of the 57 patients, 44 were already on, or had started anticoagulation therapy due to clinical suspicion of PE. Four of the patients were put on anticoagulation after the positive MRI and 13 were taken off anticoagulation after a negative MRI report. Other diagnoses reported (considering dyspnea) were pleural effusion (n = 24), consolidation (n = 12) and pericardial effusion (n = 2). One patient had a deep vein thrombosis (DVT) within three months of our negative MRI result and then had a stroke within one year. Another patient suffered a stroke within three months of being diagnosed (by MRI) with PE and given anticoagulation as treatment.ConclusionsOur method supported or altered clinical decision-making and treatment in this cohort. A diagnostic tool for PE without intravenous contrast agent or radiation is of great benefit for certain patients.
SARS-CoV-2 enters the cell through the ACE2 receptor, which is considered one of the main inhibitors in the Renin-Angiotensin-Aldosterone System (RAAS).1 ,2 The virus has been shown to downregulate the ACE2 receptor, leading to a subsequent increase in the vasopressoragentangiotensinII.3 Evidently,criticalcoronavirusdisease2019(COVID-19)is thought to be due to a dysregulated immune response, causing a cytokine-release syndrome eventually leading to acute respiratory distress syndrome (ARDS).4 ,5 However, several reports on clinical laboratory features and case-descriptions of critically ill patients with COVID-19 show discrepancies compared to typical ARDS. Here, we show that infusing swines with angiotensin II induces a pathophysiological syndrome closely resembling that of patients with RT-PCR-positive COVID-19. By using multimodal clinical imaging of patients, comparing laboratory data and translational histological features, we show that it is highly likely that an increase in RAAS is one, if not the main, pathogenic feature in critical COVID-19. Furthermore, it is plausible that this large animal model can be used to screen for potential new treatments for patients with severe COVID-19 and that MRI lung perfusion can be used to evaluate the outcome of potential treatments targeting the pathophysiological syndrome.
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