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1.
LANCET DIGITAL HEALTH ; 4(4), 2022.
Article in English | Web of Science | ID: covidwho-1935260

ABSTRACT

Background Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. Methods We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. Findings Between June 17, 2020, and April 14, 2021, 47 795 (75.2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86.6%] of 12 909 vs 36 415 [72.4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0.79 [95% CI 0.70-0.89], p=0.0001, for 70-79 years;0.52 [0.46-0.58], p<0.0001, for >80 years), independent of patient demographics and illness severity. 84 (54.2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27.5% in the week before June 16, 2020, to 75-80% in January, 2021. Interpretation Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.

2.
QJM ; 115(8): 513-519, 2022 Aug 13.
Article in English | MEDLINE | ID: covidwho-1891021

ABSTRACT

Successful host defence against infectious disease involves resistance (reduce pathogen load) and tolerance (reduce tissue damage associated with pathogen presence). Integration of clinical, immunologic, genetic and therapeutic discoveries has identified defects in both of these responses in the progression from SARS-CoV-2 infection to life-threatening coronavirus disease 2019 (Covid-19) lung injury. Early after infection with SARS-CoV-2, resistance can be compromised by a failed type 1 interferon (IFN-I) response, due to direct viral antagonism of induction and signalling, deleterious host genetic variants (IFNAR2, IFNA10, TYK2 and PLSCR1), and neutralizing auto-antibodies directed against IFN-I (predominantly IFN-α). Later in the disease, after pathogen sensing has activated a pro-inflammatory response, a failure to appropriately regulate this response compromises tolerance resulting in virus-independent immunopathology involving the lung and reticuloendothelial system. Monocytes are activated in the periphery (involving M-CSF, GM-CSF, IL-6, NLRP1 inflammasomes, TYK2 and afucosylated anti-spike IgG) then recruited to the lung (involving CCR2::MCP-3/MCP-1 and C5a::C5aR1 axes) as pro-inflammatory monocyte-derived macrophages, resulting in inflammatory lung injury. Phenotypic and genotypic heterogeneity is apparent in all these responses, identifying 'treatable traits' (therapeutically relevant components of inter-individual variation) which could be exploited to achieve a stratified medicine approach to Covid-19. Overall, Covid-19 pathogenesis re-affirms the importance of resistance in surviving an infectious disease and highlights that tolerance is also a central pillar of host defence in humans and can be beneficially modified using host-directed therapies.


Subject(s)
COVID-19 , Communicable Diseases , Lung Injury , Humans , Macrophages , SARS-CoV-2
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