Unraveling SARS-CoV-2 Host-Response Heterogeneity through Longitudinal Molecular Subtyping.

Hospitalized COVID-19 patients exhibit diverse immune responses during acute infection, which are associated with a wide range of clinical outcomes. However, understanding these immune heterogeneities and their links to various clinical complications, especially long COVID, remains a challenge. In this study, we performed unsupervised subtyping of longitudinal multi-omics immunophenotyping in over 1,000 hospitalized patients, identifying two critical subtypes linked to mortality or mechanical ventilation with prolonged hospital stay and three severe subtypes associated with timely acute recovery.

T32 programs in emergency medicine: A report from the ACEP-SAEM Federal Research Funding Workgroup.

Advancing care in Emergency Medicine (EM) requires the development of well-trained researchers, but our specialty has lower amounts of research funding compared to similar medical fields. Increasing the number of pathways available for research training supports the growth of new investigators. To address the need for more EM researchers, the Society of Academic Emergency Medicine and the American College of Emergency Physicians convened a Federal Research Funding Workgroup.

Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality.

BACKGROUNDPatients hospitalized for COVID-19 exhibit diverse clinical outcomes, with outcomes for some individuals diverging over time even though their initial disease severity appears similar to that of other patients. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity.METHODSWe performed deep immunophenotyping and conducted longitudinal multiomics modeling, integrating 10 assays for 1,152 Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study participants and identifying several immune cascades that were significant drivers of differential clinical outcomes.

Host-microbe multiomic profiling reveals age-dependent immune dysregulation associated with COVID-19 immunopathology.

Age is a major risk factor for severe coronavirus disease 2019 (COVID-19), yet the mechanisms behind this relationship have remained incompletely understood. To address this, we evaluated the impact of aging on host immune response in the blood and the upper airway, as well as the nasal microbiome in a prospective, multicenter cohort of 1031 vaccine-naïve patients hospitalized for COVID-19 between 18 and 96 years old. We performed mass cytometry, serum protein profiling, anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays, and blood and nasal transcriptomics.

Host-Microbe Multiomic Profiling Reveals Age-Dependent COVID-19 Immunopathology.

Age is a major risk factor for severe coronavirus disease-2019 (COVID-19), yet the mechanisms responsible for this relationship have remained incompletely understood. To address this, we evaluated the impact of aging on host and viral dynamics in a prospective, multicenter cohort of 1,031 patients hospitalized for COVID-19, ranging from 18 to 96 years of age. We performed blood transcriptomics and nasal metatranscriptomics, and measured peripheral blood immune cell populations, inflammatory protein expression, anti-SARS-CoV-2 antibodies, and anti-interferon (IFN) autoantibodies.

IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition.

The glycosylation of IgG plays a critical role during human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, activating immune cells and inducing cytokine production. However, the role of IgM N-glycosylation has not been studied during human acute viral infection. The analysis of IgM N-glycosylation from healthy controls and hospitalized coronavirus disease 2019 (COVID-19) patients reveals increased high-mannose and sialylation that correlates with COVID-19 severity.

Features of acute COVID-19 associated with post-acute sequelae of SARS-CoV-2 phenotypes: results from the IMPACC study.

Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based on reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated with female sex and distinctive comorbidities.

Integrated longitudinal multi-omics study identifies immune programs associated with COVID-19 severity and mortality in 1152 hospitalized participants.

Hospitalized COVID-19 patients exhibit diverse clinical outcomes, with some individuals diverging over time even though their initial disease severity appears similar. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity. In this study, we carried out deep immunophenotyping and conducted longitudinal multi-omics modeling integrating ten distinct assays on a total of 1,152 IMPACC participants and identified several immune cascades that were significant drivers of differential clinical outcomes.

AWAreness during REsuscitation - II: A multi-center study of consciousness and awareness in cardiac arrest.

Introduction: Cognitive activity and awareness during cardiac arrest (CA) are reported but ill understood. This first of a kind study examined consciousness and its underlying electrocortical biomarkers during cardiopulmonary resuscitation (CPR).

Methods: In a prospective 25-site in-hospital study, we incorporated a) independent audiovisual testing of awareness, including explicit and implicit learning using a computer and headphones, with b) continuous real-time electroencephalography(EEG) and cerebral oxygenation(rSO) monitoring into CPR during in-hospital CA (IHCA).

IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition.

The glycosylation of IgG plays a critical role during human SARS-CoV-2, activating immune cells and inducing cytokine production. However, the role of IgM N-glycosylation has not been studied during acute viral infection in humans. evidence suggests that the glycosylation of IgM inhibits T cell proliferation and alters complement activation rates.

Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients.

The IMPACC cohort, composed of >1,000 hospitalized COVID-19 participants, contains five illness trajectory groups (TGs) during acute infection (first 28 days), ranging from milder (TG1-3) to more severe disease course (TG4) and death (TG5). Here, we report deep immunophenotyping, profiling of >15,000 longitudinal blood and nasal samples from 540 participants of the IMPACC cohort, using 14 distinct assays. These unbiased analyses identify cellular and molecular signatures present within 72 h of hospital admission that distinguish moderate from severe and fatal COVID-19 disease.

Status Asthmaticus Gravidus: Emergency and Critical Care Management of Acute Severe Asthma During Pregnancy.

One-third of women with asthma have deterioration of their asthma during pregnancy, and one-fourth of pregnant women with asthma will experience severe exacerbations necessitating emergency department (ED) visits or hospitalizations. Early recognition of acute severe asthma, including life-threatening status asthmaticus, and aggressive medical interventions with β2-agonists, anticholinergic agents, and systemic corticosteroids are necessary to treat maternal airway bronchoconstriction, support maternal and fetal oxygenation, and avoid adverse fetal outcomes. This review describes management of acute severe asthma in pregnancy, including status asthmaticus, in the ED and intensive care unit.

Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study.

Background: Better understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management.

Methods: Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness.

A Target for Increased Mortality Risk in Critically Ill Patients: The Concept of Perpetuity.

Background: Emergency medicine is acuity-based and focuses on time-sensitive treatments for life-threatening diseases. Prolonged time in the emergency department, however, is associated with higher mortality in critically ill patients. Thus, we explored management after an acuity-based intervention, which we call perpetuity, as a potential mechanism for increased risk.

Emergency medicine research: 2030 strategic goals.

All academic medical specialties have the obligation to continuously create new knowledge that will improve patient care and outcomes. Emergency medicine (EM) is no exception. Since its origins over 50 years ago, EM has struggled to fulfill its research mission.

Masking for COVID-19 Is Associated with Decreased Emergency Department Utilization for Non-COVID Viral Illnesses and Respiratory Conditions in Maryland.

Background: Masking, which is known to decrease the transmission of respiratory viruses, was not widely practiced in the United States until the coronavirus disease 2019 (COVID-19) pandemic. This provides a natural experiment to determine whether the percentage of community masking was associated with decreases in emergency department (ED) visits due to non-COVID viral illnesses (NCVIs) and related respiratory conditions.

Methods: In this observational study of ED encounters in a 11-hospital system in Maryland during 2019-2020, year-on-year ratios for all complaints were calculated to account for "lockdowns" and the global drop in ED visits due to the pandemic.

Discriminating Bacterial and Viral Infection Using a Rapid Host Gene Expression Test.

Objectives: Host gene expression signatures discriminate bacterial and viral infection but have not been translated to a clinical test platform. This study enrolled an independent cohort of patients to describe and validate a first-in-class host response bacterial/viral test.

Design: Subjects were recruited from 2006 to 2016.

Evaluation of Vasopressor Exposure and Mortality in Patients With Septic Shock.

Objectives: The objectives of this study were to: 1) determine the association between vasopressor dosing intensity during the first 6 hours and first 24 hours after the onset of septic shock and 30-day in-hospital mortality; 2) determine whether the effect of vasopressor dosing intensity varies by fluid resuscitation volume; and 3) determine whether the effect of vasopressor dosing intensity varies by dosing titration pattern.

Design: Multicenter prospective cohort study between September 2017 and February 2018. Vasopressor dosing intensity was defined as the total vasopressor dose infused across all vasopressors in norepinephrine equivalents.

Variation in Fluid and Vasopressor Use in Shock With and Without Physiologic Assessment: A Multicenter Observational Study.

Objectives: To characterize the association between the use of physiologic assessment (central venous pressure, pulmonary artery occlusion pressure, stroke volume variation, pulse pressure variation, passive leg raise test, and critical care ultrasound) with fluid and vasopressor administration 24 hours after shock onset and with in-hospital mortality.

Design: Multicenter prospective cohort study between September 2017 and February 2018.

Settings: Thirty-four hospitals in the United States and Jordan.

Impact of Point-of-Care Ultrasound in the Emergency Department on Care Processes and Outcomes in Critically Ill Nontraumatic Patients.

Unlabelled: Outcomes data on point-of-care ultrasound (POCUS) in critically ill patients are lacking. This study examines the association between POCUS in the emergency department and outcomes in critically ill patients.

Design: Retrospective cohort study of critically ill emergency department patients in two academic emergency departments.

Validation of a host response test to distinguish bacterial and viral respiratory infection.

Background: Distinguishing bacterial and viral respiratory infections is challenging. Novel diagnostics based on differential host gene expression patterns are promising but have not been translated to a clinical platform nor extensively tested. Here, we validate a microarray-derived host response signature and explore performance in microbiology-negative and coinfection cases.

Recruitment of Dual-Career Academic Medicine Couples.

Today it is not uncommon to discover that a candidate for a faculty position has a partner or spouse who is also an academician, adding complexity to the recruitment process. Here, the authors address two practical obstacles to the recruitment of faculty who have an academic partner: dual recruitment and conflict of interest. The authors have found that tandem recruitment works best when suitable positions for both spouses are first identified so that recruitment can proceed synchronously.

Immune plasma for the treatment of severe influenza: an open-label, multicentre, phase 2 randomised study.

Background: Influenza causes substantial morbidity and mortality despite available treatments. Anecdotal reports suggest that plasma with high antibody titres to influenza might be of benefit in the treatment of severe influenza.

Methods: In this randomised, open-label, multicentre, phase 2 trial, 29 academic medical centres in the USA assessed the safety and efficacy of anti-influenza plasma with haemagglutination inhibition antibody titres of 1:80 or more to the infecting strain.