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Background: Despite vaccination, patients receiving anti-CD20 monoclonal antibodies (mAbs) for multiple sclerosis (MS) or neuromyelitis optica spectrum disorders (NMOSD) have an increased risk of developing severe or protracted COVID-19. The aim of this study was to describe the effect of COVID-19 convalescent plasma (CCP) in patients with MS or NMOSD exposed to anti-CD20 and infected by SARS-CoV-2., Methods: This French national, retrospective cohort study was conducted between November 2020 and June 2023. Patients with MS or NMOSD, under anti-CD20 mAbs, with symptomatic COVID-19 and treated by CCP were screened. Protracted COVID-19 was defined by a duration of symptoms >21 days. The primary endpoint was the overall survival 30 days after CCP administration., Results: Ninety-two patients from 34 hospitals were included, 84 (91%) with MS and 8 (9%) with NMOSD. Overall, 30-day survival was 97% (IC95%: 91-99). SARS-CoV-2 viremia was positive in 47/75 (61%) patients before CCP versus 9/59 (15%) seven days post-CCP. In the 52 patients (57%) with protracted COVID-19, the duration of symptoms before CCP was 51 [28-69] days, including fever in 75% of cases, which disappeared in 100% of patients 7 days post-CCP., Conclusions: CCP could be a therapeutic option in patients exposed to anti-CD20 mAbs for inflammatory demyelinating disease, particularly in those with protracted COVID-19., Competing Interests: Declarations of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: KL has received funds from Gilead, MSD, Janssen, ViiV Healthcare and Abbvie for expert boards and travel grants. None of those funds target COVID-19. CL has received compensation for travel fees, consulting services or speaker honoraria from Biogen, Merck Serono, Novartis, Sanofi and Roche and IIT Research grant from Biogen. AF reports honorariat by Fisher & Paykel for a lecture during SFMU Congress 2022, outside the submitted work. AM is president of an association that has received funding from GSK and Blueprint, hospitality from GSK, Novartis, Sanofi, Janssen, Teva, Shire, Ipsen, training funding from Novartis, LFB, Leo Pharma, and has a contract to speak at scientific events from Leo Pharma. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Group A Streptococcus is responsible for severe and potentially lethal invasive conditions requiring intensive care unit (ICU) admission, such as streptococcal toxic shock-like syndrome (STSS). A rebound of invasive group A streptococcal (iGAS) infection after COVID-19-associated barrier measures has been observed in children. Several intensivists of French adult ICUs have reported similar bedside impressions without objective data. We aimed to compare the incidence of iGAS infection before and after the COVID-19 pandemic, describe iGAS patients' characteristics, and determine ICU mortality associated factors., Methods: We performed a retrospective multicenter cohort study in 37 French ICUs, including all patients admitted for iGAS infections for two periods: two years before period (October 2018 to March 2019 and October 2019 to March 2020) and a one-year after period (October 2022 to March 2023) COVID-19 pandemic. iGAS infection was defined by Group A Streptococcus isolation from a normally sterile site. iGAS infections were identified using the International Classification of Diseases and confirmed with each center's microbiology laboratory databases. The incidence of iGAS infections was expressed in case rate., Results: Two hundred and twenty-two patients were admitted to ICU for iGAS infections: 73 before and 149 after COVID-19 pandemic. Their case rate during the period before and after COVID-19 pandemic was 205 and 949/100,000 ICU admissions, respectively (p < 0.001), with more frequent STSS after the COVID-19 pandemic (61% vs. 45%, p = 0.015). iGAS patients (n = 222) had a median SOFA score of 8 (5-13), invasive mechanical ventilation and norepinephrine in 61% and 74% of patients. ICU mortality in iGAS patients was 19% (14% before and 22% after COVID-19 pandemic; p = 0.135). In multivariate analysis, invasive mechanical ventilation (OR = 6.08 (1.71-21.60), p = 0.005), STSS (OR = 5.75 (1.71-19.22), p = 0.005), acute kidney injury (OR = 4.85 (1.05-22.42), p = 0.043), immunosuppression (OR = 4.02 (1.03-15.59), p = 0.044), and diabetes (OR = 3.92 (1.42-10.79), p = 0.008) were significantly associated with ICU mortality., Conclusion: The incidence of iGAS infections requiring ICU admission increased by 4 to 5 after the COVID-19 pandemic. After the COVID-19 pandemic, the rate of STSS was higher, with no significant increase in ICU mortality rate., (© 2023. The Author(s).)

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.

Background: During the COVID-19 pandemic, many more patients were turned prone than before, resulting in a considerable increase in workload. Whether extending duration of prone position may be beneficial has received little attention. We report here benefits and detriments of a strategy of extended prone positioning duration for COVID-19-related acute respiratory distress syndrome (ARDS)., Methods: A eetrospective, monocentric, study was performed on intensive care unit patients with COVID-19-related ARDS who required tracheal intubation and who have been treated with at least one session of prone position of duration greater or equal to 24 h. When prone positioning sessions were initiated, patients were kept prone for a period that covered two nights. Data regarding the incidence of pressure injury and ventilation parameters were collected retrospectively on medical and nurse files of charts. The primary outcome was the occurrence of pressure injury of stage ≥ II during the ICU stay., Results: For the 81 patients included, the median duration of prone positioning sessions was 39 h [interquartile range (IQR) 34-42]. The cumulated incidence of stage ≥ II pressure injuries was 26% [95% CI 17-37] and 2.5% [95% CI 0.3-8.8] for stages III/IV pressure injuries. Patients were submitted to a median of 2 sessions [IQR 1-4] and for 213 (94%) prone positioning sessions, patients were turned over to supine position during daytime, i.e., between 9 AM and 6 PM. This increased duration was associated with additional increase in oxygenation after 16 h with the PaO 2 /FiO 2 ratio increasing from 150 mmHg [IQR 121-196] at H+ 16 to 162 mmHg [IQR 124-221] before being turned back to supine (p = 0.017)., Conclusion: In patients with extended duration of prone position up to 39 h, cumulative incidence for stage ≥ II pressure injuries was 26%, with 25%, 2.5%, and 0% for stage II, III, and IV, respectively. Oxygenation continued to increase significantly beyond the standard 16-h duration. Our results may have significant impact on intensive care unit staffing and patients' respiratory conditions., Trial Registration: Institutional review board 00006477 of HUPNVS, Université Paris Cité, APHP, with the reference: CER-2021-102, obtained on October 11th 2021. Registered at Clinicaltrials (NCT05124197)., (© 2022. The Author(s).)

Impaired immune response with uncontrolled inflammation and various immunological disorders have been reported during SARS-CoV-2 infection. Here, we report a case of cold agglutinin disease occurring during a severe coronavirus disease 2019 (COVID-19) in a French intensive care unit. A patient was presented with acute respiratory distress syndrome, acute renal failure and haemolytic anaemia. Direct antiglobulin test was positive with a cold agglutinin titre of 1/512. No other cause than COVID-19 explained the occurrence of cold agglutinin disease; however, causality could not be formally established. Persistent anaemia despite transfusion therapy and the short-term life-threatening, prompted the infusion of a monoclonal anti-C5 antibody (eculizumab). Eculizumab therapy quasi-fully resolved haemolysis within a few days, but ultimately the patient died from his severe COVID-19 infection. Data regarding the specific treatment of cold agglutinin disease during COVID-19 are rare. Although additional studies are warranted, eculizumab may be considered in critical situations., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

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.)