Key Points Question Does androgen suppression improve clinical outcomes in hospitalized men with COVID-19? Findings In this randomized clinical trial including 96 men, androgen suppression with the addition of degarelix vs placebo plus standard care did not show reduction of the composite end point of mortality, ongoing hospitalization, or requirement for mechanical ventilation at day 15 after randomization. Meaning This randomized clinical trial found that androgen suppression did not improve outcomes in men hospitalized for COVID-19.
Background Therapeutic targeting of host-cell factors required for SARS-CoV-2 entry is an alternative strategy to ameliorate COVID-19 severity. SARS-CoV-2 entry into lung epithelium requires the TMPRSS2 cell surface protease. Pre-clinical and correlative data in humans suggest that anti-androgenic therapies can reduce the expression of TMPRSS2 on lung epithelium. Accordingly, we hypothesize that therapeutic targeting of androgen receptor signaling via degarelix, a luteinizing hormone-releasing hormone (LHRH) antagonist, will suppress COVID-19 infection and ameliorate symptom severity. Methods This is a randomized phase 2, placebo-controlled, double-blind clinical trial in 198 patients to compare efficacy of degarelix plus best supportive care versus placebo plus best supportive care on improving the clinical outcomes of male Veterans who have been hospitalized due to COVID-19. Enrolled patients must have documented infection with SARS-CoV-2 based on a positive reverse transcriptase polymerase chain reaction result performed on a nasopharyngeal swab and have a severity of illness of level 3–5 (hospitalized but not requiring invasive mechanical ventilation). Patients stratified by age, history of hypertension, and severity are centrally randomized 2:1 (degarelix: placebo). The composite primary endpoint is mortality, ongoing need for hospitalization, or requirement for mechanical ventilation at 15 after randomization. Important secondary endpoints include time to clinical improvement, inpatient mortality, length of hospitalization, duration of mechanical ventilation, time to achieve a normal temperature, and the maximum severity of COVID-19 illness. Exploratory analyses aim to assess the association of cytokines, viral load, and various comorbidities with outcome. In addition, TMPRSS2 expression in target tissue and development of anti-viral antibodies will also be investigated. Discussion In this trial, we repurpose the FDA approved LHRH antagonist degarelix, commonly used for prostate cancer, to suppress TMPRSS2, a host cell surface protease required for SARS-CoV-2 cell entry. The objective is to determine if temporary androgen suppression with a single dose of degarelix improves the clinical outcomes of patients hospitalized due to COVID-19. Trial registration ClinicalTrials.gov NCT04397718. Registered on May 21, 2020
Background: During the COVID-19 pandemic, the need for judicious use of diagnostic tests and to limit personnel exposure has led to increased use and dependence on point-ofcare ultrasound (POCUS) examinations. We reviewed POCUS findings in patients admitted to the intensive care unit (ICU) for acute respiratory failure with COVID-19 and correlated the findings to severity of illness and 30-day outcomes. Methods: Patients admitted to the ICU in March and April 2020 were reviewed for inclusion (acute hypoxemic respiratory failure secondary to COVID-19 pneumonia; documentation of POCUS findings). Results: Forty-three patients met inclusion criteria. B lines and pleural thickening were associated with a lower PaO 2 / FiO 2 by 71 (P = .005; adjusted R 2 = 0.24). Right ventricle (RV) dilation was more common in patients with 30-day mortality (P = .02) and was a predictor of mortality when adjusted for hypertension, diabetes mellitus, and age (odds ratio,12.0; P = .048). All patients with RV dilation had bilateral B lines with pleural irregularities. Conclusions: Although lung ultrasound abnormalities are prevalent in patients with severe disease, RV involvement seems to be predictive of outcomes. Further studies are needed to discern the etiology and pathophysiology of RV dilation in COVID-19.
Various cardiovascular complications have been reported in patients with coronavirus disease 2019. Common complications include acute myocardial injury, myocarditis, arrhythmia, pericarditis, heart failure, and shock. We present a case of cor pulmonale diagnosed with serial point of care ultrasound. Given the current shortage of personal protective equipment (PPE) and high infectivity of this virus, we acknowledge the utility of this tool in obtaining important clinical information while minimizing exposure and PPE consumption.
Thrombosis is one of the major underlying pathogenetic mechanisms leading to increased morbidity and mortality among COVID-19 patients. Thromboembolic events as well as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are the major causes of death in this continued pandemic. While elevated D-dimer level suggests worse thrombotic outcomes, levels at which benefits of anticoagulation outweigh the bleeding risk is yet to be determined. In this report, we present a case of a 72-year-old man with COVID-19 presented with confusion and subsequently developed acute hypoxic respiratory failure. On hospital day 7, patient developed extensive peripheral arterial thrombosis with acute rise of D-dimer from 800 to 14,899 ng/ml. He was treated with heparin drip and underwent urgent brachial, radial and ulnar embolectomy under general anesthesia. In this report, we also discuss the pathogenetic mechanisms and management of thromboembolism in COVID-19 patients, highlighting the role of early detection and aggressive therapeutic interventions that could be life and / or limb saving strategy.
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