Evacuation behavior of households facing compound hurricane-pandemic threats

This study examines households' prospective evacuation behavior during a hurricane-pandemic compound threat. Data from a 2020 survey of coastal Virginia households help answer two questions: (1) What factors associated with the threat and impacts of the COVID-19 pandemic and hurricanes influence the prospective evacuation behavior of households during a compound hurricane-pandemic event? (2) What are the equity implications for emergency management policies and practices to support evacuation and sheltering during a compound hurricane-pandemic event? Households in the sample were split between those who stated they would evacuate away from the at-risk region and those who would stay. Greater household vulnerability to hurricanes and COVID-19 and having sufficient financial resources increase the likelihood of evacuation. Higher-income households were more likely to have resources to evacuate and were less likely to suffer financial consequences from a hurricane or pandemic. Racial minorities are more vulnerable to the pandemic and face greater resource challenges when evacuating.

Effect of the COVID-19 Pandemic on Bronchoscopy Indication and Bronchial Microbiology

Background: Lockdowns and mask wearing have impacted infectious disease patterns during the COVID-19 pandemic. We investigated changes in the use of bronchoscopy and the results of routine microbiology in bronchial lavage. Method(s): We included bronchoscopies from 2017-2021 at the LMU University Department of Pulmonology. In this we present an initial cohort comparing bronchoscopies in 2017-2018 to the initial phase of the COVID-19 pandemic in 2020. Comparisons used chi-squared and Fischer's exact tests in SPSS. Result(s): We analysed 480 bronchoscopies from before and 85 during the COVID-19 pandemic. Mean age: 62.6 y (+/-14.1) before vs. 55.2 y (+/-16.3) during the pandemic (p<0.001). Indication for bronchoscopy: secretions/atelectasis (n=122), suspected tumor (n=89) and intervention/therapy (n=80) before;suspected tumor (n=30), respiratory deterioration after lung transplant (n=19) and infection (n=7) during the pandemic. Staphylococcus aureus and Pseudomonas aeruginosa were common in both groups. Frequencies of EBV (p<0.001), CMV (p=0.003) and HHV6 (p<0.001) differed significantly. Conclusion(s): There were clinically relevant differences in the use of bronchoscopy before vs. during the COVID-19 pandemic: pandemic patients were younger and interventions such as bronchial stenting and recanalisation less common. Bacterial results were similar but the frequency of common viruses differed. The effect of lockdowns, mask wearing and social distancing on bronchial microbiology in patients with lung cancer or chronic lung disease will be investigated in further detail in this cohort. Clinical relevant differences may support continued mask wearing in some high-risk situations post-pandemic.

Myeloid-Dependent Immunosuppressive Features Drive and Predict IPF Progression

Rationale: Despite the availability of pharmacologic therapies, idiopathic pulmonary fibrosis (IPF) is still a clinical challenge with several unmet needs. Robust evidence supports monocytes as cellular biomarkers of progression in IPF. Yet, their precise role and whether specific subtypes might predict progression and drive disease is unknown. We reported, for the first time, that myeloidderived suppressor cells (MDSC), immature precursors of monocytes, are increased in numbers, functionally active in IPF. Monocytic MDSC is the predominant subtype in IPF, and yet, functional characterization and immune modulation properties have not been explored. Methods and Results: characterization of circulating myeloid populations in IPF by multicolor FACS confirmed the abundance of MDSC (Lin-, HLA-DRlo, CD33+, CD14+, S100A+, CD28L1+ and ICOSL+) in IPF (n=78) and fILD (n=83), also abundant in whole blood scRNA seq of severe Covid-19 patients that progressed into fibrosis, and not in mild Covid-19. Then, we prospectively followed 83 fILD patients (45% IPF, 55% non-IPF -EAA, CTD-ILD, NSIP-) over 1 year and immunophenotyped them every 3 months. Cross-sectional analysis showed that patients with a higher number circulating MDSC, had a higher GAP index (7-8) (p<0,001). Longitudinal follow-up showed that patients with constant higher circulating MDSC had lower transplant-free survival (p=0.0058). Primary isolated MDSC when co-cultured with autologous T cells induced CD8+ T cell exhaustion (PD1hi, Lag3hi, Tim3hi, TNFalpha lo, INFglo), and downregulation of co-stimulatory T cell signaling (CD28, ICOS, ITK, and LCK), preliminary data support the induction of de-novo FoxP3 Treg formation, creating a suppressive and immunosenescent microenvironment in IPF. FACS analysis of explanted lungs demonstrated the increase of tissue-resident MDSC in fibrosis (HP, NSIP, IPF) compared with donor lungs, as well as in bleomycin-induced fibrosis compared to PBS. Conclusion: Taking together, a high number of circulating MDSC reflects worse lung function and higher GAP index in cross-sectional analysis, and associates with lower transplant-free survival longitudinally. The role that immature and mature monocytes play during promotion of a suppressive microenvironment in IPF is an unexplored area that may lead to a paradigm shift in our understanding of the sequelae of exhaustion and immunosenescence, contributing to the identification of novel targets useful for therapeutic myeloid selection in IPF.

Changing Logistics of Evacuation Transportation in Hazardous Settings during COVID-19

The logistics of public-sponsored evacuation include transportation assets, personnel, and infrastructure. Effective orchestration leading up to a severe weather event is a complex undertaking requiring capacity that is matched to needs. However, under the compound hurricane-pandemic scenario, the demands for evacuation assistance and the capacity to meet demands change. Pre-event planning must be adjusted and transit modified to reduce risks posed to evacuees and essential workers. This study explores how visualizations of redistributed vulnerability and transportation resources influence planning. The research identifies how transportation, emergency management, and public health officials are adapting hurricane evacuation resources during the COVID-19 pandemic using original data from compound hazard workshops and participatory stakeholder focus groups. Findings show that by the peak of hurricane season, local evacuation recommendations were favored by officials, contracts were in place for noncongregate options, and public resources were adjusted to account for those requiring congregate sheltering. A need remained for coordinating interjurisdictional information about real-time weather, resources, staffing, and traffic as well as local knowledge of roadway flooding with ongoing hazard planning. (C) 2021 American Society of Civil Engineers.

Recombinant human pentraxin-2 (RHPTX-2;PRM-151) for idiopathic pulmonary fibrosis: Study design of starscape, a phase iii randomized double blind placebo controlled trial

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrosing, interstitial pneumonia which ultimately leads to an irreversible loss of lung function and respiratory compromise. The anti-fibrotic agents, pirfenidone and nintedanib have been shown to slow the rate of decline in forced vital capacity (FVC) but, neither treatment halts disease progression. Pentraxin-2 plays important biologically relevant roles in wound repair and prevention of fibrosis. Pentraxin-2, inhibits monocyte differentiation into pro-fibrotic fibrocytes and pro-inflammatory macrophages. Plasma pentraxin-2 concentrations are reduced in patients with IPF and correlate with disease severity. Recombinant human pentraxin-2 (rhPTX-2;also known as PRM-151) was evaluated for its therapeutic potential within a phase II trial (NCT02550873). This trial demonstrated statistically significant and clinically meaningful outcomes of rhPTX-2 treatment in patients with IPF. Here we report the phase III study design to further evaluate these findings. METHODS: STARSCAPE (NCT04552899) is a phase III, multi-center, randomized, double-blind, placebo controlled trial. 658 patients with IPF will be randomized (1:1) to receive either intravenous rhPTX-2 or matching placebo administered on Days 1, 3, 5 and every 4 weeks thereafter through 48 weeks. The primary endpoint is absolute change from baseline to Week 52 in FVC [mL]. The key secondary endpoint is absolute change from baseline to Week 52 in 6-minute walk distance. Eligible patients are 40-85 years, with a documented diagnosis of IPF confirmed centrally by high resolution computed tomography scan (and lung biopsy if available). Patients must demonstrate FVC ≥ 45%, FEV1/FVC ratio > 0.70 and DLCO ≥ 30% and ≤ 90% during screening. Patients are permitted to take background therapy with nintedanib or pirfenidone. Initiating a global phase III trial during the COVID-19 pandemic brings unique and unprecedented challenges. A large number of countries and sites will be included in order to mitigate potential regional recruitment challenges that may arise during the pandemic. In addition, SARS-CoV-2 serology testing will be conducted to allow exploratory analyses on the impact of COVID-19 on lung function parameters in patients with IPF. CONCLUSIONS: rhPTX-2 has demonstrated preliminary evidence of clinical efficacy on top of approved standard of care. The phase III STARSCAPE trial aims to confirm the therapeutic potential of rhPTX-2 through evaluation of a broad range of efficacy, safety, quality of life, pharmacokinetic and biomarker assessments over 52 weeks. Patients that complete this 52-week trial may be eligible to enroll into an open label extension trial.