Infectious bronchitis virus infection in chicken: viral load and immune responses in Harderian gland, choanal cleft and turbinate tissues compared to trachea.

1. The role of the Harderian gland (HG), choanal cleft (CC) and turbinate in terms of IBV M41 viral load compared to the trachea, and immune (innate, cellular and mucosal) responses were studied in 21-day-old commercial broiler chickens.2. After virulent IBV M41 challenge, the antigen concentration detected either by quantitative RT-PCR or immunohistochemistry peaked at 2-3 days post challenge (dpc) in all tissues. Significant increases of lachrymal IBV-specific IgA and IgY levels were found at 4-5 dpc.3. Gene transcription showed a significant up-regulation of TLR3, MDA5, IL-6, IFN-α and IFN-ß, where patterns and magnitude fold-change of mRNA transcription were dependent on the gene and tissue type.4. The results demonstrated active IBV M41 replication in the HG, CC and turbinate, comparable to levels of replication found in the trachea. Data on immune-related genes in head-associated tissues provide further understanding on the immunobiology of IBV and offer opportunities to identify their use as quantitative biomarkers in pathogenicity and vaccination-challenge studies.

Implementation of corticosteroids in treatment of COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK: prospective, cohort study

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.