Demographic and clinical features at enrolment.

<p>Demographic and clinical features at enrolment.</p

Treatment and clinical progression during admission.

<p>Treatment and clinical progression during admission.</p

CONSORT Flow Diagram.

<p>Consort diagram of patients eligible, recruited, numbers followed up and included in analysis.</p

BAL Fluid Metabolomics - Metaboanalyst Data Frame

Raw metabolomics data frame used for Metaboanalyst data analyses on BAL fluid collected from obese and non-obese patients.</p

Obesity dysregulates the pulmonary antiviral immune response

Obesity is a well-recognized risk factor for severe influenza infections but the mechanisms underlying susceptibility are poorly understood. Here, we identify that obese individuals have deficient pulmonary antiviral immune responses in bronchoalveolar lavage cells but not in bronchial epithelial cells or peripheral blood dendritic cells. We show that the obese human airway metabolome is perturbed with associated increases in the airway concentrations of the adipokine leptin which correlated negatively with the magnitude of ex vivo antiviral responses. Exogenous pulmonary leptin administration in mice directly impaired antiviral type I interferon responses in vivo and ex vivo in cultured airway macrophages. Obese individuals hospitalised with influenza showed dysregulated upper airway immune responses. These studies provide insight into mechanisms driving propensity to severe influenza infections in obesity and raise the potential for development of leptin manipulation or interferon administration as novel strategies for conferring protection from severe infections in obese higher risk individuals.</p

Patient screening and enrolment.

<p>*One patient did not give consent. One patient was not competent to give consent, and a suitable proxy to provide consent could not be identified within inclusion time limits. **Two patients who died within 48 h of admission were excluded from the primary outcome analysis, as specified in the protocol.</p

Survival plot with futility boundary for TKM-130803 recipients.

<p>The red line denotes the futility boundary. The points and dashed line denote the number of survivors at day 14 plotted against the number of day 14 reports.</p

COVID-19 risk-mitigation in reopening mass cultural events: population-based observational study for the UK Events Research Programme in Liverpool City Region

Objectives: To understand SARS-CoV-2 transmission risks, perceived risks, and the feasibility of risk-mitigations from experimental mass cultural events before COVID-19 restrictions were lifted. Design: Prospective, population-wide observational study. Setting: Four events (two nightclubs; outdoor music festival; business conference) open to Liverpool City Region UK residents, requiring a negative lateral flow test (LFT) within the 36 hours before the event, but not requiring social distancing or face-coverings. Participants: 12,256 individuals attending one or more event between 28th April and 2nd May 2021. Main outcome measures: SARS-CoV-2 infections detected using audience self-swabbed (5-7 days post-event) PCR tests, with viral genomic analysis of cases, plus linked NHS COVID-19 testing data. Audience experiences were gathered via questionnaires, focus groups and social media. Indoor CO2 concentrations were monitored. Results: 12 PCR-positive cases (likely 4 index; 8 primary or secondary), 10 from the nightclubs. Two further cases had positive LFTs but no PCR. 11,896 (97.1%) participants with scanned tickets were matched to a negative pre-event LFT: 4972 (40.6%) returned a PCR within a week. CO2 concentrations showed areas for improving ventilation at the nightclubs. Population infection rates were low, yet with a concurrent outbreak of >50 linked cases around a local swimming pool without equivalent risk-mitigations. Audience anxiety was low and enjoyment high. Conclusions: We observed minor SARS-CoV-2 transmission and low perceived risks around events when prevalence was low and risk-mitigations prominent. Partnership between audiences, event organisers and public health services, supported by information systems with real-time linked data can improve health security for mass cultural events.</p

Box and whisker plot of vital signs in TKM-130803 recipients, before, during, and after TKM-130803 infusions.

<p>Heart rate, respiratory rate, mean arterial blood pressure, and tympanic temperature in patients administered TKM-130803 at the following time points: immediately prior to TKM-130803 infusion (PRE), during the infusion, immediately at the end of the infusion (END), and at 1, 2, 4, and 8 h after the end of the infusion. The middle line shows the median value, the box shows the interquartile range, and the whiskers spread from the lower to the upper adjacent values. Outside values, that is, observations that are larger/smaller than the upper/lower adjacent values, are shown as circles.</p

Baseline demographic and clinical characteristics of trial population.

<p>Baseline demographic and clinical characteristics of trial population.</p