Risk of thrombotic complications in influenza versus COVID-19 hospitalized patients.

Background: Whereas accumulating studies on patients with coronavirus disease 2019 (COVID-19) report high incidences of thrombotic complications, large studies on clinically relevant thrombosis in patients with other respiratory tract infections are lacking. How this high risk in COVID-19 patients compares to those observed in hospitalized patients with other viral pneumonias such as influenza is unknown. Objectives: To assess the incidence of venous and arterial thrombotic complications in hospitalized patients with influenza as opposed to that observed in hospitalized patients with COVID-19. Methods: This was a retrospective cohort study; we used data from Statistics Netherlands (study period: 2018) on thrombotic complications in hospitalized patients with influenza. In parallel, we assessed the cumulative incidence of thrombotic complications-adjusted for competing risk of death-in patients with COVID-19 in three Dutch hospitals (February 24 to April 26, 2020). Results: Of the 13 217 hospitalized patients with influenza, 437 (3.3%) were diagnosed with thrombotic complications, versus 66 (11%) of the 579 hospitalized patients with COVID-19. The 30-day cumulative incidence of any thrombotic complication in influenza was 11% (95% confidence interval [CI], 9.4-12) versus 25% (95% CI, 18-32) in COVID-19. For venous thrombotic (VTC) complications and arterial thrombotic complications alone, these numbers were, respectively, 3.6% (95% CI, 2.7-4.6) and 7.5% (95% CI, 6.3-8.8) in influenza versus 23% (95% CI, 16-29) and 4.4% (95% CI, 1.9-8.8) in COVID-19. Conclusions: The incidence of thrombotic complications in hospitalized patients with influenza was lower than in hospitalized patients with COVID-19. This difference was mainly driven by a high risk of VTC complications in the patients with COVID-19 admitted to the Intensive Care Unit. Remarkably, patients with influenza were more often diagnosed with arterial thrombotic complications.

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.

Lung ultrasound and computed tomography to monitor COVID-19 pneumonia in critically ill patients: a two-center prospective cohort study.

BACKGROUND: Lung ultrasound can adequately monitor disease severity in pneumonia and acute respiratory distress syndrome. We hypothesize lung ultrasound can adequately monitor COVID-19 pneumonia in critically ill patients. METHODS: Adult patients with COVID-19 pneumonia admitted to the intensive care unit of two academic hospitals who underwent a 12-zone lung ultrasound and a chest CT examination were included. Baseline characteristics, and outcomes including composite endpoint death or ICU stay > 30 days were recorded. Lung ultrasound and CT images were quantified as a lung ultrasound score involvement index (LUSI) and CT severity involvement index (CTSI). Primary outcome was the correlation, agreement, and concordance between LUSI and CTSI. Secondary outcome was the association of LUSI and CTSI with the composite endpoints. RESULTS: We included 55 ultrasound examinations in 34 patients, which were 88% were male, with a mean age of 63 years and mean P/F ratio of 151. The correlation between LUSI and CTSI was strong (r = 0.795), with an overall 15% bias, and limits of agreement ranging - 40 to 9.7. Concordance between changes in sequentially measured LUSI and CTSI was 81%. In the univariate model, high involvement on LUSI and CTSI were associated with a composite endpoint. In the multivariate model, LUSI was the only remaining independent predictor. CONCLUSIONS: Lung ultrasound can be used as an alternative for chest CT in monitoring COVID-19 pneumonia in critically ill patients as it can quantify pulmonary involvement, register changes over the course of the disease, and predict death or ICU stay > 30 days. TRIAL REGISTRATION: NTR, NL8584. Registered 01 May 2020-retrospectively registered, https://www.trialregister.nl/trial/8584.