Early plasma angiopoietin-2 is prognostic for ARDS and mortality among critically ill patients with sepsis.

Angiopoietin-2 (Ang-2) is associated with vascular endothelial injury and permeability in the acute respiratory distress syndrome (ARDS) and sepsis. Elevated circulating Ang-2 levels may identify critically ill patients with distinct pathobiology amenable to targeted therapy. We hypothesized that plasma Ang-2 measured shortly after hospitalization among patients with sepsis would be associated with the development of ARDS and poor clinical outcomes. To test this hypothesis, we measured plasma Ang-2 in a cohort of 757 patients with sepsis, including 267 with ARDS, enrolled in the emergency department or early in their ICU course before the COVID-19 pandemic. Multivariable models were used to test the association of Ang-2 with the development of ARDS and 30-day morality. We found that early plasma Ang-2 in sepsis was associated with higher baseline severity of illness, the development of ARDS, and mortality risk. The association between Ang-2 and mortality was strongest among patients with ARDS and sepsis as compared to those with sepsis alone (OR 1.81 vs. 1.52 per log Ang-2 increase). These findings might inform models testing patient risk prediction and strengthen the evidence for Ang-2 as an appealing biomarker for patient selection for novel therapeutic agents to target vascular injury in sepsis and ARDS.

Movement behaviors during COVID-19 among Latin American/Latino toddlers and pre-schoolers in Chile, Mexico and the US.

Movement behaviors (physical activity, sedentary behavior, and sleep) have been impacted by the COVID-19 pandemic. We report changes in and factors that influenced movement behaviors during COVID-19 among Latin American/Latino children aged 1 to 5 years in Chile, Mexico, and the USA. We conducted a cross-sectional study between April and August 2020. Caregivers of 4,136 children (mean age [SD], 3.1 [1.4] years; 51% boys) reported family and household characteristics and changes in their child's movement behaviors. The proportion of children who met the WHO Guidelines decreased significantly in all countries, with the largest declines in meeting the physical activity and screen time guidelines. Factors associated with negative changes in movement behaviors were being an older child, unable to attend an early childhood education and care service, higher parental education levels, not having the opportunity to play with someone, and not having access to spaces to play. The findings highlight the need to minimize disparities faced by families by providing access to early childhood education and care and safe places for children to play.

Plasma SARS-CoV-2 nucleocapsid antigen levels are associated with progression to severe disease in hospitalized COVID-19.

BACKGROUND: Studies quantifying SARS-CoV-2 have focused on upper respiratory tract or plasma viral RNA with inconsistent association with clinical outcomes. The association between plasma viral antigen levels and clinical outcomes has not been previously studied. Our aim was to investigate the relationship between plasma SARS-CoV-2 nucleocapsid antigen (N-antigen) concentration and both markers of host response and clinical outcomes. METHODS: SARS-CoV-2 N-antigen concentrations were measured in the first study plasma sample (D0), collected within 72 h of hospital admission, from 256 subjects admitted between March 2020 and August 2021 in a prospective observational cohort of hospitalized patients with COVID-19. The rank correlations between plasma N-antigen and plasma biomarkers of tissue damage, coagulation, and inflammation were assessed. Multiple ordinal regression was used to test the association between enrollment N-antigen plasma concentration and the primary outcome of clinical deterioration at one week as measured by a modified World Health Organization (WHO) ordinal scale. Multiple logistic regression was used to test the association between enrollment plasma N-antigen concentration and the secondary outcomes of ICU admission, mechanical ventilation at 28 days, and death at 28 days. The prognostic discrimination of an externally derived "high antigen" cutoff of N-antigen ≥ 1000 pg/mL was also tested. RESULTS: N-antigen on D0 was detectable in 84% of study participants. Plasma N-antigen levels significantly correlated with RAGE (r = 0.61), IL-10 (r = 0.59), and IP-10 (r = 0.59, adjusted p = 0.01 for all correlations). For the primary outcome of clinical status at one week, each 500 pg/mL increase in plasma N-antigen level was associated with an adjusted OR of 1.05 (95% CI 1.03-1.08) for worse WHO ordinal status. D0 plasma N-antigen ≥ 1000 pg/mL was 77% sensitive and 59% specific (AUROC 0.68) with a positive predictive value of 23% and a negative predictive value of 93% for a worse WHO ordinal scale at day 7 compared to baseline. D0 N-antigen concentration was independently associated with ICU admission and 28-day mechanical ventilation, but not with death at 28 days. CONCLUSIONS: Plasma N-antigen levels are readily measured and provide important insight into the pathogenesis and prognosis of COVID-19. The measurement of N-antigen levels early in-hospital course may improve risk stratification, especially for identifying patients who are unlikely to progress to severe disease.

Revisión rápida: evidencia de transmisión por Covid-19 e infecciones respiratorias agudas similares en espacios públicos abiertos.

 Objetivo. Describir la evidencia disponible sobre la trans-misión por Covid-19 e infecciones respiratorias agudas simi-lares al Covid-19 en espacios públicos abiertos. Material y métodos. La búsqueda incluyó 4 926 artículos en inglés de los años 2000 a 2020. Seis investigadores revisaron el título y el resumen de los artículos de Embase y PubMed; dos inves-tigadores revisaron los de medRxiv. Todos los investigadores revisaron textos completos y otros resolvieron las discre-pancias. Resultados. De los 21 artículos seleccionados, se observó que la presencia de virus en superficies públicas, aguas residuales y áreas exteriores no fue indicativa de trans-misión. No obstante, se observó que el uso de cubrebocas, el lavado de manos, el distanciamiento social, no asistir a eventos masivos y la movilidad individual a espacios públicos podría ayudar a reducir el riesgo de transmisión. Conclusión. Esta información podría coadyuvar a generar recomendaciones en salud pública, sin embargo, es recomendable actualizar esta revisión conforme avance la evidencia científica.

Self-Reported Impacts of the COVID-19 Pandemic on Diet-Related Behaviors and Food Security in 5 Countries: Results from the International Food Policy Study 2020.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of daily life, including dietary intake; however, few studies have reported its impacts on dietary behaviors and food security across multiple countries. OBJECTIVES: We examined self-reported impacts of COVID-19 on food behaviors, food security, and overall diet healthfulness in 5 countries. METHODS: Adults aged 18-100 years (n = 20,554) in Australia, Canada, Mexico, the United Kingdom, and the United States completed an online survey in November and December 2020 as part of the International Food Policy Study, an annual, repeat cross-sectional survey. Survey measures assessed perceived impacts of the COVID-19 pandemic on eating food prepared away from home, having food delivered from a restaurant, and buying groceries online, as well as perceived food security and overall diet healthfulness. Regression models examined associations between each outcome and sociodemographic correlates. RESULTS: Across all countries, 62% of respondents reported eating less food prepared away from home due to the pandemic, while 11% reported eating more. Some participants reported having less food delivered from a restaurant (35%) and buying fewer groceries online (17%), while other respondents reported more of each (19% and 25%, respectively). An average of 39% reported impacts on their food security, and 27% reported healthful changes to their overall diet. The largest changes for all outcomes were observed in Mexico. Participants who were younger, ethnic minorities, or had lower income adequacy tended to be more likely to report food-related changes in either direction; however, these relationships were often less pronounced among respondents in Mexico. CONCLUSIONS: Respondents reported important changes in how they sourced their food during the pandemic, with trends suggesting shifts towards less food prepared away from home and more healthful diets overall. However, changes in diet and food behaviors occurred in both healthful and less healthful directions, suggesting that dietary responses to the pandemic were highly variable.

I-SPY COVID adaptive platform trial for COVID-19 acute respiratory failure: rationale, design and operations.

INTRODUCTION: The COVID-19 pandemic brought an urgent need to discover novel effective therapeutics for patients hospitalised with severe COVID-19. The Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis (ISPY COVID-19 trial) was designed and implemented in early 2020 to evaluate investigational agents rapidly and simultaneously on a phase 2 adaptive platform. This manuscript outlines the design, rationale, implementation and challenges of the ISPY COVID-19 trial during the first phase of trial activity from April 2020 until December 2021. METHODS AND ANALYSIS: The ISPY COVID-19 Trial is a multicentre open-label phase 2 platform trial in the USA designed to evaluate therapeutics that may have a large effect on improving outcomes from severe COVID-19. The ISPY COVID-19 Trial network includes academic and community hospitals with significant geographical diversity across the country. Enrolled patients are randomised to receive one of up to four investigational agents or a control and are evaluated for a family of two primary outcomes-time to recovery and mortality. The statistical design uses a Bayesian model with 'stopping' and 'graduation' criteria designed to efficiently discard ineffective therapies and graduate promising agents for definitive efficacy trials. Each investigational agent arm enrols to a maximum of 125 patients per arm and is compared with concurrent controls. As of December 2021, 11 investigational agent arms had been activated, and 8 arms were complete. Enrolment and adaptation of the trial design are ongoing. ETHICS AND DISSEMINATION: ISPY COVID-19 operates under a central institutional review board via Wake Forest School of Medicine IRB00066805. Data generated from this trial will be reported in peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: NCT04488081.

Changes Among Mexican Adults in Physical Activity and Screen Time During the COVID-19 Lockdown Period and Association With Symptoms of Depression, Anxiety, and Stress, May 29-July 31, 2020.

INTRODUCTION: We examined the association between changes in physical activity and leisure screen time and mental health outcomes during the early stages of the recommended COVID-19 stay-at-home period in a national sample of Mexican adults aged 18 years or older. METHODS: A cross-sectional online survey conducted from May 29 through July 31, 2020, among 1,148 participants, reported time spent in physical activity and leisure screen time during a typical week before (retrospectively) and a week during the COVID-19 stay-at-home period. Mental health outcomes during this period were measured with the Depression, Anxiety and Stress Scale (DASS-21). Linear regression models were used to estimate the associations between changes in physical activity and leisure screen time and mental health outcomes by socioeconomic status (SES), adjusting for potential confounders. RESULTS: Compared with maintaining high levels of physical activity or increasing them, decreasing physical activity was associated with higher stress scores overall, and among people of high SES, with higher scores for DASS-21, depression, and anxiety. Among participants of low and medium SES only, increasing screen time was associated with higher DASS-21, depression, anxiety, and stress scores compared with maintaining low or decreasing leisure screen time. CONCLUSION: Results highlight the potential protective effect of physical activity and limited leisure screen time on mental health in the context of COVID-19 stay-at-home restrictions.

Cross-sectional examination of 24-hour movement behaviours among 3- and 4-year-old children in urban and rural settings in low-income, middle-income and high-income countries: the SUNRISE study protocol.

INTRODUCTION: 24-hour movement behaviours (physical activity, sedentary behaviour and sleep) during the early years are associated with health and developmental outcomes, prompting the WHO to develop Global guidelines for physical activity, sedentary behaviour and sleep for children under 5 years of age. Prevalence data on 24-hour movement behaviours is lacking, particularly in low-income and middle-income countries (LMICs). This paper describes the development of the SUNRISE International Study of Movement Behaviours in the Early Years protocol, designed to address this gap. METHODS AND ANALYSIS: SUNRISE is the first international cross-sectional study that aims to determine the proportion of 3- and 4-year-old children who meet the WHO Global guidelines. The study will assess if proportions differ by gender, urban/rural location and/or socioeconomic status. Executive function, motor skills and adiposity will be assessed and potential correlates of 24-hour movement behaviours examined. Pilot research from 24 countries (14 LMICs) informed the study design and protocol. Data are collected locally by research staff from partnering institutions who are trained throughout the research process. Piloting of all measures to determine protocol acceptability and feasibility was interrupted by COVID-19 but is nearing completion. At the time of publication 41 countries are participating in the SUNRISE study. ETHICS AND DISSEMINATION: The SUNRISE protocol has received ethics approved from the University of Wollongong, Australia, and in each country by the applicable ethics committees. Approval is also sought from any relevant government departments or organisations. The results will inform global efforts to prevent childhood obesity and ensure young children reach their health and developmental potential. Findings on the correlates of movement behaviours can guide future interventions to improve the movement behaviours in culturally specific ways. Study findings will be disseminated via publications, conference presentations and may contribute to the development of local guidelines and public health interventions.

Factors associated with changes in movement behaviors in toddlers and preschoolers during the COVID-19 pandemic: A national cross-sectional study in Mexico.

Little is known about physical activity, screen time and sleep among Mexican toddlers and preschoolers. The COVID-19 pandemic led to the closure of childcare education centers and restrictions to spend time outdoors. This study aimed to investigate the correlates of changes in movement behaviors from before to during the early stages of the COVID-19 lockdown in a national sample of toddlers and preschoolers in Mexico. A cross-sectional study was conducted using an open online survey completed by caretakers of children aged 1-5 years from April to July 2020. The questionnaire enquired about the time spent in each movement behavior during a regular week before and during lockdown, and family and household characteristics. Factors associated with changes in movement behaviors were explored using adjusted linear regression models. A total of 631 children (3.3y, 95% CI: 3.1, 3.4) were included in the study. During lockdown, physical activity decreased by 25%, screen time doubled, and sleep quality declined in 17% (p < 0.001). Toddlers and preschoolers of older age, attending a childcare education center before the lockdown, with a screen in their bedroom, higher access to electronic devices, and lower socioeconomic level experienced greater changes during this period. Those with limits on the use of electronic devices, who had someone available to play with them, and availability of toys experienced less pronounced changes. Pandemic restrictions have impacted movement behaviors of toddlers and preschoolers, with disproportionate effects among lower socioeconomic levels. Interventions with a multi-level equity-oriented approach are urgently needed to mitigate these effects.

Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS.

The immunological features that distinguish COVID-19-associated acute respiratory distress syndrome (ARDS) from other causes of ARDS are incompletely understood. Here, we report the results of comparative lower respiratory tract transcriptional profiling of tracheal aspirate from 52 critically ill patients with ARDS from COVID-19 or from other etiologies, as well as controls without ARDS. In contrast to a "cytokine storm," we observe reduced proinflammatory gene expression in COVID-19 ARDS when compared to ARDS due to other causes. COVID-19 ARDS is characterized by a dysregulated host response with increased PTEN signaling and elevated expression of genes with non-canonical roles in inflammation and immunity. In silico analysis of gene expression identifies several candidate drugs that may modulate gene expression in COVID-19 ARDS, including dexamethasone and granulocyte colony stimulating factor. Compared to ARDS due to other types of viral pneumonia, COVID-19 is characterized by impaired interferon-stimulated gene (ISG) expression. The relationship between SARS-CoV-2 viral load and expression of ISGs is decoupled in patients with COVID-19 ARDS when compared to patients with mild COVID-19. In summary, assessment of host gene expression in the lower airways of patients reveals distinct immunological features of COVID-19 ARDS.

Impaired immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19.

Secondary bacterial infections, including ventilator-associated pneumonia (VAP), lead to worse clinical outcomes and increased mortality following viral respiratory infections including in patients with coronavirus disease 2019 (COVID-19). Using a combination of tracheal aspirate bulk and single-cell RNA sequencing (scRNA-seq) we assessed lower respiratory tract immune responses and microbiome dynamics in 28 COVID-19 patients, 15 of whom developed VAP, and eight critically ill uninfected controls. Two days before VAP onset we observed a transcriptional signature of bacterial infection. Two weeks prior to VAP onset, following intubation, we observed a striking impairment in immune signaling in COVID-19 patients who developed VAP. Longitudinal metatranscriptomic analysis revealed disruption of lung microbiome community composition in patients with VAP, providing a connection between dysregulated immune signaling and outgrowth of opportunistic pathogens. These findings suggest that COVID-19 patients who develop VAP have impaired antibacterial immune defense detectable weeks before secondary infection onset.