A new paradigm for pandemic preparedness

PURPOSE OF REVIEW: Preparing for pandemics requires a degree of interdisciplinary work that is challenging under the current paradigm. This review summarizes the challenges faced by the field of pandemic science and proposes how to address them. RECENT FINDINGS: The structure of current siloed systems of research organizations hinders effective interdisciplinary pandemic research. Moreover, effective pandemic preparedness requires stakeholders in public policy and health to interact and integrate new findings rapidly, relying on a robust, responsive, and productive research domain. Neither of these requirements are well supported under the current system. SUMMARY: We propose a new paradigm for pandemic preparedness wherein interdisciplinary research and close collaboration with public policy and health practitioners can improve our ability to prevent, detect, and treat pandemics through tighter integration among domains, rapid and accurate integration, and translation of science to public policy, outreach and education, and improved venues and incentives for sustainable and robust interdisciplinary work.CCF-2200052 - National Science FoundationPublished versio

Geographic Variations in Urban‐Rural Particulate Matter (PM2.5) Concentrations in the United States, 2010–2019

Abstract Fine particulate matter 2.5 (PM2.5) is a widely studied pollutant with substantial health impacts, yet little is known about the urban‐rural differences across the United States. Trends of PM2.5 in urban and rural census tracts between 2010 and 2019 were assessed alongside sociodemographic characteristics including race/ethnicity, poverty, and age. For 2010, we identified 13,474 rural tracts and 59,065 urban tracts. In 2019, 13,462 were rural and 59,055 urban. Urban tracts had significantly higher PM2.5 concentrations than rural tracts during this period. Levels of PM2.5 were lower in rural tracts compared to urban and fell more rapidly in rural than urban. Rural tract annual means for 2010 and 2019 were 8.51 [2.24] μg/m3 and 6.41 [1.29] μg/m3, respectively. Urban tract annual means for 2010 and 2019 were 9.56 [2.04] μg/m3 and 7.51 [1.40] μg/m3, respectively. Rural and urban majority Black communities had significantly higher PM2.5 pollution levels (10.19 [1.64] μg/m3 and 9.79 [1.10] μg/m3 respectively), in 2010. In 2019, they were: 7.75 [1.1] μg/m3 and 7.09 [0.78] μg/m3, respectively. Majority Hispanic communities had higher PM2.5 levels and were the highest urban concentration among all races/ethnicities (8.01 [1.73] μg/m3), however they were not the highest rural concentration among all races/ethnicities (6.22 [1.60] μg/m3) in 2019. Associations with higher levels of PM2.5 were found with communities in the poorest quartile and with higher proportions of residents age<15 years old. These findings suggest greater protections for those disproportionately exposed to PM2.5 are needed, such as, increasing the availability of low‐cost air quality monitors

Caregiver subjective and physiological markers of stress and patient heart failure severity in family care dyads

Greater family caregiver exposure to uncontrolled patient symptoms is predictive of greater caregiver psychological and physiological stress in dementia and other chronic illnesses, but these phenomena have not been well-studied in heart failure (HF) - a disease with high symptom burden. The purpose of this study was to test the hypothesis that worse patient functional status (as reflected by increasing HF symptoms) would be associated with elevated psychological and physiological stress for the caregiver. This was a secondary analysis of data from 125 HF caregivers in the Caregiver Opportunities for Optimizing Lifestyle (COOL) study. Psychological stress was measured on four dimensions: care-related strain/burden (Oberst Caregiving Burden Scale), depression (Center for Epidemiological Studies Depression Scale), anxiety (State-Trait Anxiety Index), and general stress (Perceived Stress Scale). Physiological stress was measured by markers of HPA axis function (elevated cortisol awakening response [CAR]), endothelial dysfunction (increased PAI-1), and inflammation (increased IL-6, hsCRP). HF patient functional status was quantified by caregiver assessment of New York Heart Association (NYHA) Class. Generalized linear models were used to test associations between patient NYHA Class and stress (one model per indicator). NYHA Class (ordinal) was backwards difference coded in each model to examine caregiver stress in relation to increasing levels of HF severity. Caregivers were mostly female and in their mid-fifties, with a slight majority of the sample being African American and the patient's spouse. Overall, patient functional status was associated with greater caregiver psychological and physiological stress. In terms of psychological stress, higher NYHA Class was significantly associated with greater caregiver anxiety and general stress, but not with caregiver burden or depression. In terms of physiological stress, higher NYHA Class was associated with elevated markers in all models (elevated CAR and higher IL-6, hsCRP, and PAI-1). Across models, most associations between NYHA Class and stress were present at relatively early stages of functional limitation (i.e. Class II), while others emerged when functional limitations became more severe. To inform timing and mechanisms for much-needed caregiver interventions, research is needed to determine which aspects of HF symptomatology are most stressful for caregivers across the HF trajectory

Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial

We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978. Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50–72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74–1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67–1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74–1·58]; BRII-196 plus BRII-198 1·00 [0·68–1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91–1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88–1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90. Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19. US National Institutes of Health and Operation Warp Spee