ABSTRACT
Abstract BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) and dysregulated myeloid cell responses are implicated in the pathophysiology and severity of coronavirus disease 2019 (COVID-19). METHODS: In this randomised, sequential, multicentre, placebo-controlled, double-blind study, adults aged 18-79â years (Part 1) or ≥70â years (Part 2) with severe COVID-19, respiratory failure, and systemic inflammation (elevated C-reactive protein/ferritin) received a single intravenous infusion of otilimab 90â mg (human anti-GM-CSF monoclonal antibody) plus standard care (NCT04376684). The primary outcome was the proportion of patients alive and free of respiratory failure at Day 28. RESULTS: In Part 1 (N=806 randomised 1:1 otilimab:placebo), 71% of otilimab-treated patients were alive and free of respiratory failure at Day 28 versus 67% who received placebo; the model-adjusted difference of 5.3% was not statistically significant (95% CI -0.8, 11.4; p=0.09). A nominally significant model-adjusted difference of 19.1% (95% CI 5.2, 33.1; p=0.009) was observed in the predefined 70-79â years subgroup, but this was not confirmed in Part 2 (N=350 randomised) where the model-adjusted difference was 0.9% (95% CI -9.3, 11.2; p=0.86). Compared with placebo, otilimab resulted in lower serum concentrations of key inflammatory markers, including the putative pharmacodynamic biomarker CCL17, indicative of GM-CSF pathway blockade. Adverse events were comparable between groups and consistent with severe COVID-19. CONCLUSIONS: There was no significant difference in the proportion of patients alive and free of respiratory failure at Day 28. However, despite the lack of clinical benefit, a reduction in inflammatory markers was observed with otilimab, in addition to an acceptable safety profile.
ABSTRACT
Since the detection of the first cases of COVID-19, reported by the People's Republic of China on the 31st December 2019, up to the confirmation of the first cases in Portugal, on the 2nd March, countries like Italy and Spain faced the collapse of their healthcare systems. Anticipating this possibility, the Portuguese National Health Service carried out measures to prepare for this reality. This paper describes the changes implemented in the Anesthesiology department of a tertiary hospital center in Portugal, aiming to ensure the safety of both patients and healthcare professionals. The measures implemented had to do mostly with scientific preparation and team reorganization; management of personal protective equipment; redesigning the department's clinical common areas, separation of patient circuits with creation of a designated COVID Operating Room, Post-Anesthetic Care Unit; rescheduling of elective surgery and testing all patients before anesthesia procedures and consulting other hospital departments. The reported data covers the period between the 2nd March and the 30th April of 2020. In this period, 64 cases with COVID-19 or with high clinical suspicion were approached. To date, there have been no cases of in-hospital spread to other patients or to professionals in this department. With this paper we intend to start a reflection that will end up with the optimization of strategies that allows health systems to deal better with COVID-19, keeping patients and health providers safe.
Desde os primeiros casos de COVID-19 reportados pela República Popular da China, a 31 de dezembro de 2019, até à confirmação dos primeiros casos em Portugal, a 2 de março, países como Itália e Espanha depararam-se com o colapso dos seus sistemas de saúde. Antevendo essa possibilidade, o Serviço Nacional de Saúde preparou-se para enfrentar esta nova realidade. Neste documento descreve-se especificamente a preparação do serviço de Anestesiologia de um centro hospitalar terciário português, por forma a garantir a segurança dos seus doentes e profissionais de saúde. As medidas implementadas incidiram na preparação científica e reorganização das equipas; gestão do equipamento de proteção individual; reorganização dos espaços comuns do serviço; separação dos fluxos de doentes com a criação do Bloco Operatório e Unidade de Cuidados Pós-Anestésicos COVID; reprogramação da cirurgia eletiva; rastreio de todos os doentes propostos a procedimentos anestésicos e consultoria a outros serviços. Os dados apresentados compreendem a atividade desenvolvida entre 2 de março e 30 de abril de 2020. Nesse período foram abordados 64 casos com COVID-19 ou com elevada suspeita clínica, sendo que até à data não foram registados casos de contágio intra-hospitalar de outros doentes ou de profissionais neste serviço. Com este trabalho pretende-se iniciar uma reflexão que culmine numa futura otimização de estratégias que permitam aos serviços de saúde lidar com a COVID-19, mantendo a segurança dos outros doentes e dos profissionais de saúde.