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BackgroundIn animal models of pulmonary arterial hypertension (PAH), angiotensin converting enzyme type 2 (ACE2) and Angiotensin 1–7 [Ang-(1–7)] have been shown to have vasodilatory, anti-proliferative, anti-fibrotic and anti-hypertrophic properties. However, the status and role of the ACE2-Ang-(1–7) axis in human PAH is incompletely understood.MethodsWe studied 85 patients with a diagnosis of PAH of distinct etiologies. Fifty-five healthy blood donors paired for age and sex served as controls. Blood samples were obtained from the pulmonary artery in patients with PAH during right heart catheterisation. Peripheral blood was obtained for both groups. Ang-(1–7) and angiotensin II (AngII) were measured by zone capillary electrophoresis. Aldosterone, Angiotensin-(1–9), Angiotensin A, (Ang-A) and ACE2 were measured by ELISA, and ACE2 activity was determined enzymatically.ResultsOf the 85 patients, 47 had idiopathic PAH, 25 had PAH-associated with congenital heart disease, and 13 had PAH-associated with collagen vascular disease. Compared to controls, patients with PAH had a higher concentration of AngII [(1.03(IQR 0.72–1.88) versus 0.19(IQR 0.10–0.37)pmoles·mL−1;p<0.001)] and of aldosterone [(88.7(58.7–132) versus 12.9(9.55–19.9)ng·dL−1;p<0.001)]. Conversely, PAH patients had a lower concentration of Ang-(1–7) than controls [(0.69(0.474–0.91) versus 4.07(2.82–6.73)pmoles·mL−1;p<0.001)], and a lower concentration of Ang-(1–9), and Ang-A. Similarly, the ACE2 concentration was higher than in controls [(8.7(5.35–13.2) versus 4.53(1.47–14.3)ng·mL−1;p=0.011)], whereas the ACE2 activity was significantly reduced [(1.88(1.08–2.81) versus 5.97(3.1–17.8)nmoles·mL−1;p<0.001)]. No significant differences were found among the three different etiologic forms of PAH.ConclusionsThe AngII-ACE2-Ang- (1–7) axis appears to be altered in human PAH and we propose that this imbalance, in favour of AngII, plays a role in the pathogenesis of the severe PAH. Further mechanistic studies are warranted.

In the coronavirus disease 2019 (COVID-19) era, the presence of acute respiratory failure is generally associated with acute respiratory distress syndrome; however, it is essential to consider other differential diagnoses that require different, and urgent, therapeutic approaches. Herein we describe a COVID-19 case complicated with bilateral spontaneous pneumothorax. A previously healthy 45-year-old man was admitted to our emergency department with sudden-onset chest pain and progressive shortness of breath 17 days after diagnosis with uncomplicated COVID-19 infection. He was tachypneic and presented severe hypoxemia (75% percutaneous oxygen saturation). Breath sounds were diminished bilaterally on auscultation. A chest X-ray revealed the presence of a large bilateral pneumothorax. A thoracic computed tomography (CT) scan confirmed the large bilateral pneumothorax, with findings consistent with severe COVID-19 infection. Chest tubes were inserted, with immediate clinical improvement. Follow-up chest CT scan revealed resolution of bilateral pneumothorax, reduction of parenchymal consolidation, and formation of large bilateral pneumatoceles. The patient remained under observation and was then discharged home. Bilateral spontaneous pneumothorax is a very rare, potentially life-threatening complication in patients with COVID-19. This case highlights the importance of recognizing this complication early to prevent potentially fatal consequences.

Background: Information about angiotensin II (Ang II), angiotensin-converting enzyme 2 (ACE2), and Ang-(1–7) levels in patients with COVID-19 is scarce. Objective: To characterize the Ang II–ACE2–Ang-(1–7) axis in patients with SARS-CoV-2 infection to understand its role in pathogenesis and prognosis. Methods: Patients greater than 18 years diagnosed with COVID-19, based on clinical findings and positive RT-PCR test, who required hospitalization and treatment were included. We compared Ang II, aldosterone, Ang-(1–7), and Ang-(1–9) concentrations and ACE2 concentration and activity between COVID-19 patients and historic controls. We compared baseline demographics, laboratory results (enzyme, peptide, and inflammatory marker levels), and outcome (patients who survived versus those who died). Results: Serum from 74 patients [age: 58 (48–67.2) years; 68% men] with moderate (20%) or severe (80%) COVID-19 were analyzed. During 13 (10–21) days of hospitalization, 25 patients died from COVID-19 and 49 patients survived. Compared with controls, Ang II concentration was higher and Ang-(1–7) concentration was lower, despite significantly higher ACE2 activity in patients. Ang II concentration was higher and Ang-(1–7) concentration was lower in patients who died. The Ang II/Ang-(1–7) ratio was significantly higher in patients who died. In multivariate analysis, Ang II/Ang-(1–7) ratio greater than 3.45 (OR = 5.87) and lymphocyte count ⩽0.65 × 103/µl (OR = 8.43) were independent predictors of mortality from COVID-19. Conclusion: In patients with severe SARS-CoV-2 infection, imbalance in the Ang II–ACE2–Ang-(1–7) axis may reflect deleterious effects of Ang II and may indicate a worse outcome.

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