Journal ArticleSci Rep · December 18, 2023
Diagnostic limitations challenge management of clinically indistinguishable acute infectious illness globally. Gene expression classification models show great promise distinguishing causes of fever. We generated transcriptional data for a 294-participant ...
Full textLink to itemCite
Journal ArticleLancet Respir Med · September 2023
BACKGROUND: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine a ...
Full textLink to itemCite
Journal ArticleJAMA · July 25, 2023
IMPORTANCE: Immune dysregulation contributes to poorer outcomes in COVID-19. OBJECTIVE: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Ra ...
Full textOpen AccessLink to itemCite
Journal ArticleLancet Infect Dis · April 2023
BACKGROUND: Lower respiratory tract infections are frequently treated with antibiotics, despite a viral cause in many cases. It remains unknown whether low procalcitonin concentrations can identify patients with lower respiratory tract infection who are un ...
Full textOpen AccessLink to itemCite
Journal ArticleAnn Intern Med · April 2023
BACKGROUND: Patients hospitalized with COVID-19 have an increased incidence of thromboembolism. The role of extended thromboprophylaxis after hospital discharge is unclear. OBJECTIVE: To determine whether anticoagulation is superior to placebo in reducing ...
Full textLink to itemCite
Journal ArticleBMJ Open · February 20, 2023
OBJECTIVES: We evaluated the performance of commonly used sepsis screening tools across prospective sepsis cohorts in the USA, Cambodia and Ghana. DESIGN: Prospective cohort studies. SETTING AND PARTICIPANTS: From 2014 to 2021, participants with two or mor ...
Full textOpen AccessLink to itemCite
Journal ArticleCrit Care Med · December 1, 2022
OBJECTIVES: Sepsis causes significant mortality. However, most patients who die of sepsis do not present with severe infection, hampering efforts to deliver early, aggressive therapy. It is also known that the host gene expression response to infection pre ...
Full textLink to itemCite
Journal ArticleCell Genom · November 9, 2022
During pandemics, individuals exhibit differences in risk and clinical outcomes. Here, we developed single-cell high-throughput human in vitro susceptibility testing (scHi-HOST), a method for rapidly identifying genetic variants that confer resistance and ...
Full textLink to itemCite
Journal ArticlemedRxiv · September 26, 2022
BACKGROUND: We investigated whether abatacept, a selective costimulation modulator, provides additional benefit when added to standard-of-care for patients hospitalized with Covid-19. METHODS: We conducted a master protocol to investigate immunomodulators ...
Full textLink to itemCite
Journal ArticlemedRxiv · September 26, 2022
BACKGROUND: Immune dysregulation contributes to poorer outcomes in severe Covid-19. Immunomodulators targeting various pathways have improved outcomes. We investigated whether infliximab provides benefit over standard of care. METHODS: We conducted a maste ...
Full textLink to itemCite
Journal ArticleThe Lancet. Respiratory medicine · September 2022
BackgroundBaricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progress ...
Full textOpen AccessCite
Journal ArticleSci Rep · July 9, 2022
SARS-CoV-2 infection triggers profound and variable immune responses in human hosts. Chromatin remodeling has been observed in individuals severely ill or convalescing with COVID-19, but chromatin remodeling early in disease prior to anti-spike protein IgG ...
Full textOpen AccessLink to itemCite
Journal ArticleLancet Infect Dis · May 2022
BACKGROUND: 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 (hereaf ...
Full textLink to itemCite
Journal ArticleRes Sq · April 7, 2022
SARS-CoV-2 infection triggers profound and variable immune responses in human hosts. Chromatin remodeling has been observed in individuals severely ill or convalescing with COVID-19, but chromatin remodeling early in disease prior to anti-spike protein IgG ...
Full textOpen AccessLink to itemCite
Journal ArticleJAMA Netw Open · April 1, 2022
IMPORTANCE: Bacterial and viral causes of acute respiratory illness (ARI) are difficult to clinically distinguish, resulting in the inappropriate use of antibacterial therapy. The use of a host gene expression-based test that is able to discriminate bacter ...
Full textOpen AccessLink to itemCite
Journal ArticleGenome Med · February 21, 2022
BACKGROUND: Measuring host gene expression is a promising diagnostic strategy to discriminate bacterial and viral infections. Multiple signatures of varying size, complexity, and target populations have been described. However, there is little information ...
Full textOpen AccessLink to itemCite
Journal ArticleLancet Respir Med · December 2021
BACKGROUND: Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compare ...
Full textOpen AccessLink to itemCite
Journal ArticleOpen Forum Infect Dis · December 2021
BACKGROUND: Difficulty discriminating bacterial from viral infections drives antibacterial misuse. Host gene expression tests discriminate bacterial and viral etiologies, but their clinical utility has not been evaluated. METHODS: Host gene expression and ...
Full textOpen AccessLink to itemCite
Journal ArticleCrit Care Med · October 1, 2021
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 b ...
Full textOpen AccessLink to itemCite
Journal ArticleContemp Clin Trials · October 2021
While benefits of prone position in mechanically-ventilated patients have been well-described, a randomized-control trial to determine the effects of prone positioning in awake, spontaneously-breathing patients with an acute pneumonia has not been previous ...
Full textLink to itemCite
Journal ArticleMed · June 11, 2021
BACKGROUND: Sexual dimorphisms in immune responses contribute to coronavirus disease 2019 (COVID-19) outcomes, but the mechanisms governing this disparity remain incompletely understood. METHODS: We carried out sex-balanced sampling of peripheral blood mon ...
Full textOpen AccessLink to itemCite
Journal ArticleGenome Med · May 17, 2021
BACKGROUND: While genome-wide associations studies (GWAS) have successfully elucidated the genetic architecture of complex human traits and diseases, understanding mechanisms that lead from genetic variation to pathophysiology remains an important challeng ...
Full textOpen AccessLink to itemCite
Journal ArticleN Engl J Med · March 11, 2021
BACKGROUND: LY-CoV555, a neutralizing monoclonal antibody, has been associated with a decrease in viral load and the frequency of hospitalizations or emergency department visits among outpatients with coronavirus disease 2019 (Covid-19). Data are needed on ...
Full textLink to itemCite
Journal ArticleN Engl J Med · March 4, 2021
BACKGROUND: Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known. METHODS: We conducted a double-blind, rando ...
Full textLink to itemCite
Journal ArticleNat Commun · February 17, 2021
SARS-CoV-2 infection has been shown to trigger a wide spectrum of immune responses and clinical manifestations in human hosts. Here, we sought to elucidate novel aspects of the host response to SARS-CoV-2 infection through RNA sequencing of peripheral bloo ...
Full textOpen AccessLink to itemCite
Journal ArticleFront Immunol · 2021
Viruses cause a wide spectrum of clinical disease, the majority being acute respiratory infections (ARI). In most cases, ARI symptoms are similar for different viruses although severity can be variable. The objective of this study was to understand the sha ...
Full textOpen AccessLink to itemCite
Journal ArticlePloS one · January 2021
ObjectivesCompare three host response strategies to distinguish bacterial and viral etiologies of acute respiratory illness (ARI).MethodsIn this observational cohort study, procalcitonin, a 3-protein panel (CRP, IP-10, TRAIL), and a host ...
Full textOpen AccessCite
Journal ArticlemedRxiv · December 22, 2020
While genome-wide associations studies (GWAS) have successfully elucidated the genetic architecture of complex human traits and diseases, understanding mechanisms that lead from genetic variation to pathophysiology remains an important challenge. Methods a ...
Full textLink to itemCite
Journal ArticlebioRxiv · December 9, 2020
SARS-CoV-2 infection triggers highly variable host responses and causes varying degrees of illness in humans. We sought to harness the peripheral blood mononuclear cell (PBMC) response over the course of illness to provide insight into COVID-19 physiology. ...
Full textOpen AccessLink to itemCite
Journal ArticleClin Infect Dis · June 10, 2020
Patient management relies on diagnostic information to identify appropriate treatment. Standard evaluations of diagnostic tests consist of estimating sensitivity, specificity, positive/negative predictive values, likelihood ratios, and accuracy. Although u ...
Full textOpen AccessLink to itemCite
Journal ArticleOpen Forum Infect Dis · June 2020
BACKGROUND: Pathogen-based diagnostics for acute respiratory infection (ARI) have limited ability to detect etiology of illness. We previously showed that peripheral blood-based host gene expression classifiers accurately identify bacterial and viral ARI i ...
Full textOpen AccessLink to itemCite
Journal ArticleBMC Infect Dis · October 28, 2019
BACKGROUND: Antibiotic resistance is rising at disturbing rates and contributes to the deaths of millions of people yearly. Antibiotic resistant infections disproportionately affect those with immunocompromising conditions, chronic colonization, and freque ...
Full textOpen AccessLink to itemCite
Journal ArticleEBioMedicine · October 2019
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 v ...
Full textOpen AccessLink to itemCite
Journal ArticlePLoS One · 2019
RATIONALE: Asthma exacerbations often occur due to infectious triggers, but determining whether infection is present and whether it is bacterial or viral remains clinically challenging. A diagnostic strategy that clarifies these uncertainties could enable ...
Full textOpen AccessLink to itemCite
Journal ArticleExpert Rev Mol Diagn · August 2018
A century of advances in infectious disease diagnosis and treatment changed the face of medicine. However, challenges continue to develop including multi-drug resistance, globalization that increases pandemic risks, and high mortality from severe infection ...
Full textOpen AccessLink to itemCite
Journal ArticleFront Microbiol · 2018
Background: Acute respiratory infections (ARIs) are the leading indication for antibacterial prescriptions despite a viral etiology in the majority of cases. The lack of available diagnostics to discriminate viral and bacterial etiologies contributes to th ...
Full textOpen AccessLink to itemCite
Journal ArticleSci Adv · March 2017
Sepsis is a deleterious inflammatory response to infection with high mortality. Reliable sepsis biomarkers could improve diagnosis, prognosis, and treatment. Integration of human genetics, patient metabolite and cytokine measurements, and testing in a mous ...
Full textOpen AccessLink to itemCite
Journal ArticleSci Transl Med · January 20, 2016
Acute respiratory infections caused by bacterial or viral pathogens are among the most common reasons for seeking medical care. Despite improvements in pathogen-based diagnostics, most patients receive inappropriate antibiotics. Host response biomarkers of ...
Full textOpen AccessLink to itemCite
Journal ArticleExpert Rev Mol Diagn · 2015
A century of advances in infectious disease diagnosis and treatment changed the face of medicine. However, challenges continue to develop including multi-drug resistance, globalization that increases pandemic risks and high mortality from severe infections ...
Full textLink to itemCite