Compassionate use of JAK1/2 inhibitor ruxolitinib for severe COVID-19: a prospective observational study.

Overwhelming inflammatory reactions contribute to respiratory distress in patients with COVID-19. Ruxolitinib is a JAK1/JAK2 inhibitor with potent anti-inflammatory properties. We report on a prospective, observational study in 34 patients with COVID-19 who received ruxolitinib on a compassionate-use protocol. Patients had severe pulmonary disease defined by pulmonary infiltrates on imaging and an oxygen saturation ≤ 93% in air and/or PaO2/FiO2 ratio ≤ 300 mmHg. Median age was 80.5 years, and 85.3% had ≥ 2 comorbidities. Median exposure time to ruxolitinib was 13 days, median dose intensity was 20 mg/day. Overall survival by day 28 was 94.1%. Cumulative incidence of clinical improvement of ≥2 points in the ordinal scale was 82.4% (95% confidence interval, 71-93). Clinical improvement was not affected by low-flow versus high-flow oxygen support but was less frequent in patients with PaO2/FiO2 < 200 mmHg. The most frequent adverse events were anemia, urinary tract infections, and thrombocytopenia. Improvement of inflammatory cytokine profile and activated lymphocyte subsets was observed at day 14. In this prospective cohort of aged and high-risk comorbidity patients with severe COVID-19, compassionate-use ruxolitinib was safe and was associated with improvement of pulmonary function and discharge home in 85.3%. Controlled clinical trials are necessary to establish efficacy of ruxolitinib in COVID-19.

Results of comprehensive cardiovascular diagnostic work-up in HIV positive patients.

Cardiovascular disease (CVD) in the HIV population accounts for a large proportion of morbidity and mortality and, with the increased life expectancy, the burden of CVD is expected to rise. Inflammation, immune dysfunction, side effects of HIV medications, high prevalence of other risk factors are the likely pathogenic mechanisms for accelerated atherosclerosis. We aimed to evaluate the diagnostic yield of a cardiovascular multimodality diagnostic work-up in a contemporary cohort of HIV-infected patients. From November 2017 to October 2019, HIV infected patients were screened in a cardiovascular diagnostic work-up program including clinical history, physical examination, arterial blood pressure measurement, 12-lead ECG, and Transthoracic Echocardiogram (TTE). Advanced non-invasive cardiovascular imaging tests, like Coronary Computed Tomography Angiography (CCTA), stress-echocardiography, Cardiac Magnetic Resonance (CMR), were performed in patients with suspicion of chronic coronary syndrome (CCS) or non-ischemic heart disease (NIHD). 117 HIV-infected consecutive patients underwent this cardiovascular diagnostic work-up and were included in our study. Fifty-two patients (45%) had evidence of CVD. Of them, 22 presented Coronary Artery Disease (CAD), whereas 47 cases showed NIHD. In 17 cases both conditions were present. Among patients with CAD, 8 showed critical coronary stenosis; among them, 5 were treated with percutaneous coronary intervention, 2 with Aorto-Coronary By-Pass Grafting (CABG), and one with medical therapy. Hypertension and diabetes were significantly associated with the development of CVD (respectively p<0.001 and p< 0.05), while current smoking (p<0.02) and hypertension (p<0.007) were positively associated to CAD. A comprehensive cardiovascular diagnostic work-up including advanced multimodality diagnostic imaging modalities led to early detection of CVD in nearly half of an HIV population with immediate interventions required in 6.8% of them, and aggressive prevention treatment started in the remaining HIV patients.