A low aldosterone/renin ratio and high soluble ACE2 associate with COVID-19 severity.

BACKGROUND: The severity of COVID-19 after SARS-CoV-2 infection is unpredictable. Angiotensin-converting enzyme-2 (ACE2) is the receptor responsible for coronavirus binding, while subsequent cell entry relies on priming by the serine protease TMPRSS2 (transmembrane protease, serine 2). Although renin-angiotensin-aldosterone-system (RAAS) blockers have been suggested to upregulate ACE2, their use in COVID-19 patients is now considered well tolerated. The aim of our study was to investigate parameters that determine COVID-19 severity, focusing on RAAS-components and variation in the genes encoding for ACE2 and TMPRSS2. METHODS: Adult patients hospitalized due to SARS-CoV-2 infection between May 2020 and October 2020 in the Haga Teaching Hospital were included, and soluble ACE2 (sACE2), renin, aldosterone (in heparin plasma) and polymorphisms in the ACE2 and TMPRSS2 genes (in DNA obtained from EDTA blood) were determined. MEASUREMENTS AND MAIN RESULTS: Out of the 188 patients who were included, 60 were defined as severe COVID-19 (ICU and/or death). These patients more often used antidiabetic drugs, were older, had higher renin and sACE2 levels, lower aldosterone levels and a lower aldosterone/renin ratio. In addition, they displayed the TMPRSS2-rs2070788 AA genotype less frequently. No ACE2 polymorphism-related differences were observed. Multivariate regression analysis revealed independent significance for age, sACE2, the aldosterone/renin ratio, and the TMPRSS2 rs2070788 non-AA genotype as predictors of COVID-19 severity, together yielding a C-index of 0.79. Findings were independent of the use of RAAS blockers. CONCLUSION: High sACE2, a low aldosterone/renin ratio and having the TMPRSS2 rs2070788 non-AA genotype are novel independent determinants that may help to predict COVID-19 disease severity. TRIAL REGISTRATION: retrospectively registered.

New onset asthma during pregnancy: two case reports.

INTRODUCTION: Asthma is the most common chronic respiratory disease during pregnancy. However, reports of new onset asthma during pregnancy are lacking. We report two cases of new onset asthma during pregnancy following respiratory tract infection, subsequently one case with M. pneumoniae infection and the other case with a combined infection with respiratory syncytial virus and rhinovirus.   Case presentation:   Both patients presented with the clinical features of an acute asthma exacerbation during pregnancy without a medical history of asthma. During follow up the diagnosis of asthma was supported by spirometry showing significant reversibility and elevated fractional exhaled nitric oxide (FeNO). Patients were hospitalized and received supplemental oxygen, treatment for an acute asthma exacerbation with systemic corticosteroids, high dose inhalation therapy. These therapeutic interventions subsequently led to a good outcome for the mother and newborn in both cases.   Conclusions:  New onset asthma should be part of the differential diagnosis in pregnant patients with respiratory symptoms, particularly in case of mycoplasma infection.  Diagnosing asthma during pregnancy can be challenging. In these circumstances, additional diagnostic tests (like inflammatory biomarkers FeNO and blood eosinophils) can be helpful to support the diagnosis.