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Importance: Given the high risk of thrombosis and anticoagulation-related bleeding in patients with hypoxemic COVID-19 pneumonia, identifying the lowest effective dose of anticoagulation therapy for these patients is imperative., Objectives: To determine whether therapeutic anticoagulation (TA) or high-dose prophylactic anticoagulation (HD-PA) decreases mortality and/or disease duration compared with standard-dose prophylactic anticoagulation (SD-PA), and whether TA outperforms HD-PA; and to compare the net clinical outcomes among the 3 strategies., Design, Settings, and Participants: The ANTICOVID randomized clinical open-label trial included patients with hypoxemic COVID-19 pneumonia requiring supplemental oxygen and having no initial thrombosis on chest computer tomography with pulmonary angiogram at 23 health centers in France from April 14 to December 13, 2021. Of 339 patients randomized, 334 were included in the primary analysis-114 patients in the SD-PA group, 110 in the HD-PA, and 110 in the TA. At randomization, 90% of the patients were in the intensive care unit. Data analyses were performed from April 13, 2022, to January 3, 2023., Interventions: Patients were randomly assigned (1:1:1) to receive either SD-PA, HD-PA, or TA with low-molecular-weight or unfractionated heparin for 14 days., Main Outcomes and Measures: A hierarchical criterion of all-cause mortality followed by time to clinical improvement at day 28. Main secondary outcome was net clinical outcome at day 28 (composite of thrombosis, major bleeding, and all-cause death)., Results: Among the study population of 334 individuals (mean [SD] age, 58.3 [13.0] years; 226 [67.7%] men and 108 [32.3%] women), use of HD-PA and SD-PA had similar probabilities of favorable outcome (47.3% [95% CI, 39.9% to 54.8%] vs 52.7% [95% CI, 45.2% to 60.1%]; P = .48), as did TA compared with SD-PA (50.9% [95% CI, 43.4% to 58.3%] vs 49.1% [95% CI, 41.7% to 56.6%]; P = .82) and TA compared with HD-PA (53.5% [95% CI 45.8% to 60.9%] vs 46.5% [95% CI, 39.1% to 54.2%]; P = .37). Net clinical outcome was met in 29.8% of patients receiving SD-PA (20.2% thrombosis, 2.6% bleeding, 14.0% death), 16.4% receiving HD-PA (5.5% thrombosis, 3.6% bleeding, 11.8% death), and 20.0% receiving TA (5.5% thrombosis, 3.6% bleeding, 12.7% death). Moreover, HD-PA and TA use significantly reduced thrombosis compared with SD-PA (absolute difference, -14.7 [95% CI -6.2 to -23.2] and -14.7 [95% CI -6.2 to -23.2], respectively). Use of HD-PA significantly reduced net clinical outcome compared with SD-PA (absolute difference, -13.5; 95% CI -2.6 to -24.3)., Conclusions and Relevance: This randomized clinical trial found that compared with SD-PA, neither HD-PA nor TA use improved the primary hierarchical outcome of all-cause mortality or time to clinical improvement in patients with hypoxemic COVID-19 pneumonia; however, HD-PA resulted in significantly better net clinical outcome by decreasing the risk of de novo thrombosis., Trial Registration: ClinicalTrials.gov Identifier: NCT04808882.

Rationale: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with pulmonary endothelial dysfunction. There are limited data available on the outcomes of coronavirus disease (COVID-19) in patients with pulmonary hypertension (PH), a disease characterized by pulmonary endothelial dysfunction. Objectives: To describe characteristics and outcomes of patients with precapillary PH and COVID-19. Methods: We prospectively collected characteristics, management, and outcomes of adult patients with precapillary PH in the French PH network who had COVID-19 between February 1, 2020, and April 30, 2021. Clinical, functional, and hemodynamic characteristics of PH before COVID-19 were collected from the French PH registry. Measurements and Main Results: A total of 211 patients with PH (including 123 with pulmonary arterial hypertension, 47 with chronic thromboembolic PH, and 41 with other types of PH) experienced COVID-19, and 40.3% of them were outpatients, 32.2% were hospitalized in a conventional ward, and 27.5% were in an ICU. Among hospitalized patients ( n  = 126), 54.0% received corticosteroids, 37.3% high-flow oxygen, and 11.1% invasive ventilation. Right ventricular and acute renal failure occurred in 30.2% and 19.8% of patients, respectively. Fifty-two patients (all hospitalized) died from COVID-19. Overall mortality was 24.6% (95% CI [confidence interval], 18.8-30.5) and in-hospital mortality 41.3% (95% CI, 32.7-49.9). Nonsurvivors were significantly older, more frequently male and suffering comorbidities (diabetes, chronic respiratory diseases, systemic hypertension, chronic cardiac diseases, and/or chronic renal failure), and had more severe PH at their most recent evaluation preceding COVID-19 diagnosis (in terms of functional class and 6-minute-walk distance; all P  < 0.05). Use of pulmonary arterial hypertension therapy was similar between survivors and nonsurvivors. Conclusions: COVID-19 in patients with precapillary PH was associated with a high in-hospital mortality. The typical risk factors for severe COVID-19 and severity of PH were associated with mortality in this population.

Background: Approval of biologics has recently revolutionized T2 severe asthma management. However, predictive biomarkers remain highly needed to improve patient's selection., Objective: This study aims to determine whether serum immunoglobulins (Igs) levels might be predictive biomarkers of response to anti-interleukin-5 (IL5)/IL5Rα therapies., Methods: Severe asthma patients eligible for mepolizumab or benralizumab were included herein. Serum immunoglobulin quantification was performed at baseline before mepolizumab or benralizumab initiation. After a 6-month treatment of mepolizumab or benralizumab, patients presented a second serum immunoglobulin quantification. The treatment response was evaluated by the GETE (Global Evaluation of Treatment Effectiveness) score at 6 months., Results: A total of 50 patients were included. Median age was 56 [IQR 48.8-65.3] and 50% were females. Compared to baseline, a significant increase in IgG was observed at 6 months (9.2 [7.8-10.2] g/l vs 10.1 [8.8-11.1] g/l, p = 0.04). The area under the ROC curve was 0.58 [95%IC 0.40-0.77] for blood eosinophil count (p = 0.37), 0.75 [95%IC: 0.58-0.92] for serum IgG concentration (p = 0.009) for predicting the treatment response. According to the Youden index, serum IgG concentration ≥ 9.2 g/l predicts the response to anti-IL5 therapies with a sensitivity of 76.9% and a specificity of 75.7%., Conclusion: Baseline serum IgG concentrations may be a useful tool to predict the response to anti-IL5/IL5Rα therapies but should be confirmed in larger clinical trials. Interestingly, anti-IL5/IL5Rα therapies are associated with a significant increase in serum IgG concentrations at 6 months., Competing Interests: Disclosure of interest LG has been an investigator in clinical trials for AstraZeneca, MSD and Novartis, reports grants or fees for consulting from AstraZeneca, GlaxoSmithKline, Novartis and Sanofi-Regeneron, and fees for consulting from Bayer, Chiesi, MSD, not related to the submitted work DB has been an investigator in clinical trials for AstraZeneca, GSK, MSD and Novartis SL, ENS, GP, NG, LR declare no disclosure of interest AD has been an investigator in clinical trials for AstraZeneca, GSK and Novartis, reports grants or fees for consulting from AstraZeneca, GlaxoSmithKline, Novartis and Sanofi-Regeneron, and fees for consulting from Bayer, Chiesi, MSD, outside the submitted work, (Copyright © 2021. Published by Elsevier Masson SAS.)

Introduction: COVID-19 induces venous, arterial and microvascular thrombosis, involving several pathophysiological processes. In patients with severe COVID-19 without macrovascular thrombosis, escalating into high-dose prophylactic anticoagulation (HD-PA) or therapeutic anticoagulation (TA) could be beneficial in limiting the extension of microvascular thrombosis and forestalling the evolution of lung and multiorgan microcirculatory dysfunction. In the absence of data from randomised trials, clinical practice varies widely., Methods and Analysis: This is a French multicentre, parallel-group, open-label, randomised controlled superiority trial to compare the efficacy and safety of three anticoagulation strategies in patients with COVID-19. Patients with oxygen-treated COVID-19 showing no pulmonary artery thrombosis on computed tomography with pulmonary angiogram will be randomised to receive either low-dose PA, HD-PA or TA for 14 days. Patients attaining the extremes of weight and those with severe renal failure will not be included. We will recruit 353 patients. Patients will be randomised on a 1:1:1 basis, and stratified by centre, use of invasive mechanical ventilation, D-dimer levels and body mass index. The primary endpoint is a hierarchical criterion at day 28 including all-cause mortality, followed by the time to clinical improvement defined as the time from randomisation to an improvement of at least two points on the ordinal clinical scale. Secondary outcomes include thrombotic and major bleeding events at day 28, individual components of the primary endpoint, number of oxygen-free, ventilator-free and vasopressor-free days at day 28, D-dimer and sepsis-induced coagulopathy score at day 7, intensive care unit and hospital stay at day 28 and day 90, and all-cause death and quality of life at day 90., Ethics and Dissemination: The study has been approved by an ethical committee (Ethics Committee, Ile de France VII, Paris, France; reference 2020-A03531-38). Patients will be included after obtaining their signed informed consent. The results will be submitted for publication in peer-reviewed journals., Trial Registration Number: NCT04808882., Competing Interests: Competing interests: AMD reports lectures for Leo Pharma. EA reports personal fees from GBT, personal fees from Hemanext, both unrelated to the present study. GV received research grant from Bio-Mérieux, SOS Oxygène, Janssen, all unrelated to the present study; and advisory board fees from BioMérieux that are unrelated to the present study. VL receives advisory board fees from Amomed, unrelated to the present study., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)