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Dampening of the respiratory cytokine storm is promoted by inhaled budesonide in patients with early COVID-19
Jonathan R Baker; Mahdi Mahdi; Dan V Nicolau Jr.; Sanjay Ramakrishnan; Peter J Barnes; Jodie L Simpson; Steven Cass; Richard E K Russell; Louise E Donnelly; Mona Bafadhel.
Affiliation
  • Jonathan R Baker; National Heart and Lung Institute, Imperial College London, London, United Kingdom
  • Mahdi Mahdi; National Institute of Health Research (NIHR) Oxford Biomedical Research Centre (BRC), University of Oxford, United Kingdom
  • Dan V Nicolau Jr.; Nuffield Department of Medicine, University of Oxford, United Kingdom
  • Sanjay Ramakrishnan; National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), University of Oxford, United Kingdom
  • Peter J Barnes; National Heart and Lung Institute, Imperial College London, London, United Kingdom
  • Jodie L Simpson; School of Medicine and Public Health, Priority Centre for Healthy Lungs, University of Newcastle, Australia
  • Steven Cass; National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), University of Oxford, United Kingdom
  • Richard E K Russell; National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), University of Oxford, United Kingdom
  • Louise E Donnelly; National Heart and Lung Institute, Imperial College London, London, United Kingdom
  • Mona Bafadhel; National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), University of Oxford, United Kingdom
Preprint in En | PREPRINT-MEDRXIV | ID: ppmedrxiv-21265512
ABSTRACT
Vaccinations against SARS-CoV-2 are effective in COVID-19. However, with limited vaccine access, vaccine hesitancy and variant breakthroughs, there is still a need for effective and safe early treatments. Two community-based clinical trials of the inhaled corticosteroid, budesonide, have recently been published showing and improvement in patients with COVID-19 treated early with budesonide1,2. To understand mechanistically how budesonide was beneficial, inflammatory mediators were assessed in the nasal mucosa of patients recruited to the Steroids in COVID (STOIC1) trial and a cohort of SARS-CoV-2 negative individuals. Here we show that in early COVID-19, elevation in viral response proteins and Th1 and Th2 inflammation occurs. Longitudinal sampling in the natural course of COVID-19 showed persistently high interferon levels and elevated concentrations of the eosinophil chemokine, CCL11. In patients who deteriorate, the initial nasal mucosal signal is characterised by a marked suppression of the early inflammatory response, with reduced concentrations of interferon and inflammatory cytokines, but elevated eosinophil chemokines. Systemic inflammation remained altered in COVID-19 patients, implying that even after symptom resolution, changes in immunological mediators do not resolve. Budesonide treatment decreased IL-33 and IFN-{gamma}, implying a reduction in epithelial damage and dampening of the interferon response. Budesonide treatment also increased CCL17 concentrations, suggesting an improved T-cell response; and significantly alters inflammatory pathways giving further insight into how this treatment can accelerate patient recovery. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=92 SRC="FIGDIR/small/21265512v1_ufig1.gif" ALT="Figure 1"> View larger version (27K) org.highwire.dtl.DTLVardef@849719org.highwire.dtl.DTLVardef@dc1087org.highwire.dtl.DTLVardef@1c13369org.highwire.dtl.DTLVardef@1163fb4_HPS_FORMAT_FIGEXP M_FIG C_FIG
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Full text: 1 Collection: 09-preprints Database: PREPRINT-MEDRXIV Type of study: Cohort_studies / Observational_studies / Prognostic_studies / Rct Language: En Year: 2021 Document type: Preprint
Full text: 1 Collection: 09-preprints Database: PREPRINT-MEDRXIV Type of study: Cohort_studies / Observational_studies / Prognostic_studies / Rct Language: En Year: 2021 Document type: Preprint