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Micah Thomas McClain

Associate Professor of Medicine
Medicine, Infectious Diseases
Duke Box 102359, Durham, NC 27710
Room 161 Hanes House, Trent Drive, Durham, NC 27710

Selected Publications


Plasma Microbial Cell-Free DNA Sequencing in Immunocompromised Patients With Pneumonia: A Prospective Observational Study.

Journal Article Clin Infect Dis · March 20, 2024 BACKGROUND: Pneumonia is a common cause of morbidity and mortality, yet a causative pathogen is identified in a minority of cases. Plasma microbial cell-free DNA sequencing may improve diagnostic yield in immunocompromised patients with pneumonia. METHODS: ... Full text Link to item Cite

Implementation of a Prospective Index-Cluster Sampling Strategy for the Detection of Presymptomatic Viral Respiratory Infection in Undergraduate Students.

Journal Article Open Forum Infect Dis · March 2024 BACKGROUND: Index-cluster studies may help characterize the spread of communicable infections in the presymptomatic state. We describe a prospective index-cluster sampling strategy (ICSS) to detect presymptomatic respiratory viral illness and its implement ... Full text Link to item Cite

Epigenetic and transcriptional responses in circulating leukocytes are associated with future decompensation during SARS-CoV-2 infection.

Journal Article iScience · January 19, 2024 To elucidate host response elements that define impending decompensation during SARS-CoV-2 infection, we enrolled subjects hospitalized with COVID-19 who were matched for disease severity and comorbidities at the time of admission. We performed combined si ... Full text Link to item Cite

Host-response transcriptional biomarkers accurately discriminate bacterial and viral infections of global relevance.

Journal Article Sci 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 text Link to item Cite

A Multicenter, Controlled Human Infection Study of Influenza A(H1N1)pdm09 in Healthy Adults.

Journal Article J Infect Dis · August 11, 2023 BACKGROUND: We evaluated the associations between baseline influenza virus-specific hemagglutination inhibition (HAI) and microneutralization (MN) titers and subsequent symptomatic influenza virus infection in a controlled human infection study. METHODS: W ... Full text Link to item Cite

Early Outcomes of SARS-CoV-2 Infection in a Multisite Prospective Cohort of Inpatient Veterans.

Journal Article Open Forum Infect Dis · July 2023 BACKGROUND: Over 870 000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have occurred among Veterans Health Administration users, and 24 000 have resulted in death. We examined early outcomes of SARS-CoV-2 infection in hospitalized ... Full text Link to item Cite

C5a-licensed phagocytes drive sterilizing immunity during systemic fungal infection.

Journal Article Cell · June 22, 2023 Systemic candidiasis is a common, high-mortality, nosocomial fungal infection. Unexpectedly, it has emerged as a complication of anti-complement C5-targeted monoclonal antibody treatment, indicating a critical niche for C5 in antifungal immunity. We identi ... Full text Link to item Cite

Wearable Sensor-Based Detection of Influenza in Presymptomatic and Asymptomatic Individuals.

Journal Article J Infect Dis · April 12, 2023 BACKGROUND: The COVID-19 pandemic highlighted the need for early detection of viral infections in symptomatic and asymptomatic individuals to allow for timely clinical management and public health interventions. METHODS: Twenty healthy adults were challeng ... Full text Link to item Cite

Efficacy and safety of azithromycin versus placebo to treat lower respiratory tract infections associated with low procalcitonin: a randomised, placebo-controlled, double-blind, non-inferiority trial.

Journal Article Lancet 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 text Open Access Link to item Cite

Blood RNA alternative splicing events as diagnostic biomarkers for infectious disease.

Journal Article Cell Rep Methods · February 27, 2023 Assays detecting blood transcriptome changes are studied for infectious disease diagnosis. Blood-based RNA alternative splicing (AS) events, which have not been well characterized in pathogen infection, have potential normalization and assay platform stabi ... Full text Open Access Link to item Cite

Transcriptional responses define dysregulated immune activation in Hepatitis C (HCV)-naïve recipients of HCV-infected donor kidneys.

Journal Article PLoS One · 2023 Renal transplantation from hepatitis C (HCV) nucleic acid amplification test-positive (NAAT-positive) donors to uninfected recipients has greatly increased the organ donation pool. However, there is concern for adverse outcomes in these recipients due to d ... Full text Link to item Cite

Multi-objective optimization identifies a specific and interpretable COVID-19 host response signature.

Journal Article Cell Syst · December 21, 2022 The identification of a COVID-19 host response signature in blood can increase the understanding of SARS-CoV-2 pathogenesis and improve diagnostic tools. Applying a multi-objective optimization framework to both massive public and new multi-omics data, we ... Full text Link to item Cite

Host Gene Expression to Predict Sepsis Progression.

Journal Article Crit 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 text Link to item Cite

Single-cell genome-wide association reveals that a nonsynonymous variant in ERAP1 confers increased susceptibility to influenza virus.

Journal Article Cell 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 text Link to item Cite

Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion.

Journal Article Sci 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 text Open Access Link to item Cite

SARS-CoV-2 reinfection across a spectrum of immunological states.

Journal Article Health Sci Rep · July 2022 PURPOSE: Several cases of symptomatic reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after full recovery from a prior episode have been reported. As reinfection has become an increasingly common phenomenon, an improved unders ... Full text Open Access Link to item Cite

Transcriptional Profiles Elucidate Differential Host Responses to Infection with Cryptococcus neoformans and Cryptococcus gattii.

Journal Article J Fungi (Basel) · April 22, 2022 Many aspects of the host response to invasive cryptococcal infections remain poorly understood. In order to explore the pathobiology of infection with common clinical strains, we infected BALB/cJ mice with Cryptococcus neoformans, Cryptococcus gattii, or s ... Full text Link to item Cite

Prospective Validation of a Rapid Host Gene Expression Test to Discriminate Bacterial From Viral Respiratory Infection.

Journal Article JAMA 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 text Open Access Link to item Cite

Systematic comparison of published host gene expression signatures for bacterial/viral discrimination.

Journal Article Genome 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 text Open Access Link to item Cite

Plasma Microbial Cell-Free DNA Sequencing in Immunocompromised Patients With Pneumonia: A Prospective Observational Study.

Journal Article Clin Infect Dis · March 20, 2024 BACKGROUND: Pneumonia is a common cause of morbidity and mortality, yet a causative pathogen is identified in a minority of cases. Plasma microbial cell-free DNA sequencing may improve diagnostic yield in immunocompromised patients with pneumonia. METHODS: ... Full text Link to item Cite

Implementation of a Prospective Index-Cluster Sampling Strategy for the Detection of Presymptomatic Viral Respiratory Infection in Undergraduate Students.

Journal Article Open Forum Infect Dis · March 2024 BACKGROUND: Index-cluster studies may help characterize the spread of communicable infections in the presymptomatic state. We describe a prospective index-cluster sampling strategy (ICSS) to detect presymptomatic respiratory viral illness and its implement ... Full text Link to item Cite

Epigenetic and transcriptional responses in circulating leukocytes are associated with future decompensation during SARS-CoV-2 infection.

Journal Article iScience · January 19, 2024 To elucidate host response elements that define impending decompensation during SARS-CoV-2 infection, we enrolled subjects hospitalized with COVID-19 who were matched for disease severity and comorbidities at the time of admission. We performed combined si ... Full text Link to item Cite

Host-response transcriptional biomarkers accurately discriminate bacterial and viral infections of global relevance.

Journal Article Sci 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 text Link to item Cite

A Multicenter, Controlled Human Infection Study of Influenza A(H1N1)pdm09 in Healthy Adults.

Journal Article J Infect Dis · August 11, 2023 BACKGROUND: We evaluated the associations between baseline influenza virus-specific hemagglutination inhibition (HAI) and microneutralization (MN) titers and subsequent symptomatic influenza virus infection in a controlled human infection study. METHODS: W ... Full text Link to item Cite

Early Outcomes of SARS-CoV-2 Infection in a Multisite Prospective Cohort of Inpatient Veterans.

Journal Article Open Forum Infect Dis · July 2023 BACKGROUND: Over 870 000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have occurred among Veterans Health Administration users, and 24 000 have resulted in death. We examined early outcomes of SARS-CoV-2 infection in hospitalized ... Full text Link to item Cite

C5a-licensed phagocytes drive sterilizing immunity during systemic fungal infection.

Journal Article Cell · June 22, 2023 Systemic candidiasis is a common, high-mortality, nosocomial fungal infection. Unexpectedly, it has emerged as a complication of anti-complement C5-targeted monoclonal antibody treatment, indicating a critical niche for C5 in antifungal immunity. We identi ... Full text Link to item Cite

Wearable Sensor-Based Detection of Influenza in Presymptomatic and Asymptomatic Individuals.

Journal Article J Infect Dis · April 12, 2023 BACKGROUND: The COVID-19 pandemic highlighted the need for early detection of viral infections in symptomatic and asymptomatic individuals to allow for timely clinical management and public health interventions. METHODS: Twenty healthy adults were challeng ... Full text Link to item Cite

Efficacy and safety of azithromycin versus placebo to treat lower respiratory tract infections associated with low procalcitonin: a randomised, placebo-controlled, double-blind, non-inferiority trial.

Journal Article Lancet 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 text Open Access Link to item Cite

Blood RNA alternative splicing events as diagnostic biomarkers for infectious disease.

Journal Article Cell Rep Methods · February 27, 2023 Assays detecting blood transcriptome changes are studied for infectious disease diagnosis. Blood-based RNA alternative splicing (AS) events, which have not been well characterized in pathogen infection, have potential normalization and assay platform stabi ... Full text Open Access Link to item Cite

Transcriptional responses define dysregulated immune activation in Hepatitis C (HCV)-naïve recipients of HCV-infected donor kidneys.

Journal Article PLoS One · 2023 Renal transplantation from hepatitis C (HCV) nucleic acid amplification test-positive (NAAT-positive) donors to uninfected recipients has greatly increased the organ donation pool. However, there is concern for adverse outcomes in these recipients due to d ... Full text Link to item Cite

Multi-objective optimization identifies a specific and interpretable COVID-19 host response signature.

Journal Article Cell Syst · December 21, 2022 The identification of a COVID-19 host response signature in blood can increase the understanding of SARS-CoV-2 pathogenesis and improve diagnostic tools. Applying a multi-objective optimization framework to both massive public and new multi-omics data, we ... Full text Link to item Cite

Host Gene Expression to Predict Sepsis Progression.

Journal Article Crit 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 text Link to item Cite

Single-cell genome-wide association reveals that a nonsynonymous variant in ERAP1 confers increased susceptibility to influenza virus.

Journal Article Cell 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 text Link to item Cite

Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion.

Journal Article Sci 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 text Open Access Link to item Cite

SARS-CoV-2 reinfection across a spectrum of immunological states.

Journal Article Health Sci Rep · July 2022 PURPOSE: Several cases of symptomatic reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after full recovery from a prior episode have been reported. As reinfection has become an increasingly common phenomenon, an improved unders ... Full text Open Access Link to item Cite

Transcriptional Profiles Elucidate Differential Host Responses to Infection with Cryptococcus neoformans and Cryptococcus gattii.

Journal Article J Fungi (Basel) · April 22, 2022 Many aspects of the host response to invasive cryptococcal infections remain poorly understood. In order to explore the pathobiology of infection with common clinical strains, we infected BALB/cJ mice with Cryptococcus neoformans, Cryptococcus gattii, or s ... Full text Link to item Cite

Prospective Validation of a Rapid Host Gene Expression Test to Discriminate Bacterial From Viral Respiratory Infection.

Journal Article JAMA 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 text Open Access Link to item Cite

Systematic comparison of published host gene expression signatures for bacterial/viral discrimination.

Journal Article Genome 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 text Open Access Link to item Cite

Comparing the Diagnostic Accuracy of Clinician Judgment to a Novel Host Response Diagnostic for Acute Respiratory Illness.

Journal Article Open 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 text Open Access Link to item Cite

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

Journal Article Crit 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 text Open Access Link to item Cite

Asymptomatic or mild symptomatic SARS-CoV-2 infection elicits durable neutralizing antibody responses in children and adolescents.

Journal Article JCI Insight · September 8, 2021 As SARS-CoV-2 continues to spread globally, questions have emerged regarding the strength and durability of immune responses in specific populations. In this study, we evaluated humoral immune responses in 69 children and adolescents with asymptomatic or m ... Full text Link to item Cite

Assessment of the Feasibility of Using Noninvasive Wearable Biometric Monitoring Sensors to Detect Influenza and the Common Cold Before Symptom Onset.

Journal Article JAMA Netw Open · September 1, 2021 IMPORTANCE: Currently, there are no presymptomatic screening methods to identify individuals infected with a respiratory virus to prevent disease spread and to predict their trajectory for resource allocation. OBJECTIVE: To evaluate the feasibility of usin ... Full text Open Access Link to item Cite

Validation of a Host Gene Expression Test for Bacterial/Viral Discrimination in Immunocompromised Hosts.

Journal Article Clin Infect Dis · August 16, 2021 BACKGROUND: Host gene expression has emerged as a complementary strategy to pathogen detection tests for the discrimination of bacterial and viral infection. The impact of immunocompromise on host-response tests remains unknown. We evaluated a host-respons ... Full text Open Access Link to item Cite

The host transcriptional response to Candidemia is dominated by neutrophil activation and heme biosynthesis and supports novel diagnostic approaches.

Journal Article Genome Med · July 5, 2021 BACKGROUND: Candidemia is one of the most common nosocomial bloodstream infections in the United States, causing significant morbidity and mortality in hospitalized patients, but the breadth of the host response to Candida infections in human patients rema ... Full text Open Access Link to item Cite

Mucosal-associated invariant T cell responses differ by sex in COVID-19.

Journal Article Med · 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 text Open Access Link to item Cite

An atlas connecting shared genetic architecture of human diseases and molecular phenotypes provides insight into COVID-19 susceptibility.

Journal Article Genome 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 text Open Access Link to item Cite

A blood-based host gene expression assay for early detection of respiratory viral infection: an index-cluster prospective cohort study.

Journal Article Lancet Infect Dis · March 2021 BACKGROUND: Early and accurate identification of individuals with viral infections is crucial for clinical management and public health interventions. We aimed to assess the ability of transcriptomic biomarkers to identify naturally acquired respiratory vi ... Full text Open Access Link to item Cite

Dysregulated transcriptional responses to SARS-CoV-2 in the periphery.

Journal Article Nat 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 text Open Access Link to item Cite

The Host Response to Viral Infections Reveals Common and Virus-Specific Signatures in the Peripheral Blood.

Journal Article Front 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 text Open Access Link to item Cite

A comparison of host response strategies to distinguish bacterial and viral infection.

Journal Article PLoS One · 2021 OBJECTIVES: Compare three host response strategies to distinguish bacterial and viral etiologies of acute respiratory illness (ARI). METHODS: In this observational cohort study, procalcitonin, a 3-protein panel (CRP, IP-10, TRAIL), and a host gene expressi ... Full text Open Access Link to item Cite

Previously Derived Host Gene Expression Classifiers Identify Bacterial and Viral Etiologies of Acute Febrile Respiratory Illness in a South Asian Population.

Journal Article Open 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 text Open Access Link to item Cite

A transcriptional signature accurately identifies Aspergillus Infection across healthy and immunosuppressed states.

Journal Article Transl Res · May 2020 Invasive aspergillosis (IA) is a major cause of critical illness in immunocompromised (IC) patients. However, current fungal tests are limited. Disease-specific gene expression patterns in circulating host cells show promise as novel diagnostics, however i ... Full text Link to item Cite

Two Approaches to Classifying and Quantifying Physical Resilience in Longitudinal Data.

Journal Article J Gerontol A Biol Sci Med Sci · March 9, 2020 BACKGROUND: Approaches for quantifying physical resilience in older adults have not been described. METHODS: We apply two conceptual approaches to defining physical resilience to existing longitudinal data sets in which outcomes are measured after an acute ... Full text Link to item Cite

Epstein Barr virus nuclear antigen 1 (EBNA-1) peptides recognized by adult multiple sclerosis patient sera induce neurologic symptoms in a murine model.

Journal Article J Autoimmun · January 2020 Multiple sclerosis (MS) is an autoimmune demyelinating disease with progressive neurodegeneration and complex etiology likely involving genetic and environmental factors. MS has been associated with Epstein Barr virus (EBV) infection, with patients often s ... Full text Link to item Cite

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

Journal Article EBioMedicine · 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 text Open Access Link to item Cite

Utility of predictive tools for risk stratification of elderly individuals with all-cause acute respiratory infection.

Journal Article Infection · August 2019 PURPOSE: A number of scoring tools have been developed to predict illness severity and patient outcome for proven pneumonia, however, less is known about the utility of clinical prediction scores for all-cause acute respiratory infection (ARI), especially ... Full text Link to item Cite

An observer blinded, randomized, placebo-controlled, phase I dose escalation trial to evaluate the safety and immunogenicity of an inactivated West Nile virus Vaccine, HydroVax-001, in healthy adults.

Journal Article Vaccine · July 9, 2019 BACKGROUND: West Nile virus (WNV) is the most common mosquito-borne infection in the United States. HydroVax-001 WNV is a hydrogen peroxide inactivated, whole virion (WNV-Kunjin strain) vaccine adjuvanted with aluminum hydroxide. METHODS: We performed a ph ... Full text Link to item Cite

Efficacy and Safety of Danirixin (GSK1325756) Co-administered With Standard-of-Care Antiviral (Oseltamivir): A Phase 2b, Global, Randomized Study of Adults Hospitalized With Influenza.

Journal Article Open Forum Infect Dis · April 2019 BACKGROUND: Excessive neutrophil migration has been correlated with influenza symptom severity. Danirixin (GSK1325756), a selective and reversible antagonist of C-X-C chemokine receptor 2, decreases neutrophil activation and transmigration to areas of infl ... Full text Link to item Cite

A host gene expression approach for identifying triggers of asthma exacerbations.

Journal Article PLoS 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 text Open Access Link to item Cite

A crowdsourced analysis to identify ab initio molecular signatures predictive of susceptibility to viral infection.

Journal Article Nat Commun · October 24, 2018 The response to respiratory viruses varies substantially between individuals, and there are currently no known molecular predictors from the early stages of infection. Here we conduct a community-based analysis to determine whether pre- or early post-expos ... Full text Open Access Link to item Cite

A miRNA Host Response Signature Accurately Discriminates Acute Respiratory Infection Etiologies.

Journal Article Front 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 text Open Access Link to item Cite

Development of an objective gene expression panel as an alternative to self-reported symptom scores in human influenza challenge trials.

Journal Article J Transl Med · June 8, 2017 BACKGROUND: Influenza challenge trials are important for vaccine efficacy testing. Currently, disease severity is determined by self-reported scores to a list of symptoms which can be highly subjective. A more objective measure would allow for improved dat ... Full text Link to item Cite

Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection.

Journal Article EBioMedicine · March 2017 Infection of respiratory mucosa with viral pathogens triggers complex immunologic events in the affected host. We sought to characterize this response through proteomic analysis of nasopharyngeal lavage in human subjects experimentally challenged with infl ... Full text Open Access Link to item Cite

Host-Based Peripheral Blood Gene Expression Analysis for Diagnosis of Infectious Diseases.

Journal Article J Clin Microbiol · February 2017 Emerging pandemic infectious threats, inappropriate antibacterial use contributing to multidrug resistance, and increased morbidity and mortality from diagnostic delays all contribute to a need for improved diagnostics in the field of infectious diseases. ... Full text Link to item Cite

The effective rate of influenza reassortment is limited during human infection.

Journal Article PLoS Pathog · February 2017 We characterise the evolutionary dynamics of influenza infection described by viral sequence data collected from two challenge studies conducted in human hosts. Viral sequence data were collected at regular intervals from infected hosts. Changes in the seq ... Full text Link to item Cite

Deep Sequencing of Influenza A Virus from a Human Challenge Study Reveals a Selective Bottleneck and Only Limited Intrahost Genetic Diversification.

Journal Article J Virol · December 15, 2016 UNLABELLED: Knowledge of influenza virus evolution at the point of transmission and at the intrahost level remains limited, particularly for human hosts. Here, we analyze a unique viral data set of next-generation sequencing (NGS) samples generated from a ... Full text Link to item Cite

Response.

Journal Article Clin Trials · October 2016 Full text Open Access Link to item Cite

Transcriptomic Analysis of the Host Response and Innate Resilience to Enterotoxigenic Escherichia coli Infection in Humans.

Journal Article J Infect Dis · May 1, 2016 BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is a globally prevalent cause of diarrhea. Though usually self-limited, it can be severe and debilitating. Little is known about the host transcriptional response to infection. We report the first gene ex ... Full text Open Access Link to item Cite

Differential evolution of peripheral cytokine levels in symptomatic and asymptomatic responses to experimental influenza virus challenge.

Journal Article Clin Exp Immunol · March 2016 Exposure to influenza virus triggers a complex cascade of events in the human host. In order to understand more clearly the evolution of this intricate response over time, human volunteers were inoculated with influenza A/Wisconsin/67/2005 (H3N2), and then ... Full text Link to item Cite

Potential Cost-effectiveness of Early Identification of Hospital-acquired Infection in Critically Ill Patients.

Journal Article Ann Am Thorac Soc · March 2016 RATIONALE: Limitations in methods for the rapid diagnosis of hospital-acquired infections often delay initiation of effective antimicrobial therapy. New diagnostic approaches offer potential clinical and cost-related improvements in the management of these ... Full text Open Access Link to item Cite

A response adaptive randomization platform trial for efficient evaluation of Ebola virus treatments: A model for pandemic response.

Journal Article Clin Trials · February 2016 The outbreak of Ebola virus disease in West Africa is the largest ever recorded. Numerous treatment alternatives for Ebola have been considered, including widely available repurposed drugs, but initiation of enrollment into clinical trials has been limited ... Full text Link to item Cite

Host gene expression classifiers diagnose acute respiratory illness etiology.

Journal Article Sci 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 text Open Access Link to item Cite

A Genomic Signature of Influenza Infection Shows Potential for Presymptomatic Detection, Guiding Early Therapy, and Monitoring Clinical Responses.

Journal Article Open Forum Infect Dis · January 2016 Early, presymptomatic intervention with oseltamivir (corresponding to the onset of a published host-based genomic signature of influenza infection) resulted in decreased overall influenza symptoms (aggregate symptom scores of 23.5 vs 46.3), more rapid reso ... Full text Open Access Link to item Cite

What was old is new again: using the host response to diagnose infectious disease.

Journal Article Expert 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 text Link to item Cite

An integrated transcriptome and expressed variant analysis of sepsis survival and death.

Journal Article Genome Med · 2014 BACKGROUND: Sepsis, a leading cause of morbidity and mortality, is not a homogeneous disease but rather a syndrome encompassing many heterogeneous pathophysiologies. Patient factors including genetics predispose to poor outcomes, though current clinical ch ... Full text Open Access Link to item Cite

Longitudinal analysis of leukocyte differentials in peripheral blood of patients with acute respiratory viral infections.

Journal Article J Clin Virol · December 2013 BACKGROUND: Leukocyte counts and differentials are commonly acquired in patients with suspected respiratory viral infections and may contribute diagnostic information. However, most published work is limited to a single timepoint at initial presentation to ... Full text Link to item Cite

A host-based RT-PCR gene expression signature to identify acute respiratory viral infection.

Journal Article Sci Transl Med · September 18, 2013 Improved ways to diagnose acute respiratory viral infections could decrease inappropriate antibacterial use and serve as a vital triage mechanism in the event of a potential viral pandemic. Measurement of the host response to infection is an alternative to ... Full text Link to item Cite

Comparing influenza and RSV viral and disease dynamics in experimentally infected adults predicts clinical effectiveness of RSV antivirals.

Journal Article Antivir Ther · 2013 BACKGROUND: Antivirals reduce influenza viral replication and illness measures, particularly if initiated early, within 48 h of symptom onset. Whether experimental antivirals that reduce respiratory syncytial virus (RSV) load would also reduce disease is u ... Full text Link to item Cite

A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.

Journal Article PLoS One · 2013 There is great potential for host-based gene expression analysis to impact the early diagnosis of infectious diseases. In particular, the influenza pandemic of 2009 highlighted the challenges and limitations of traditional pathogen-based testing for suspec ... Full text Open Access Link to item Cite

Temporal dynamics of host molecular responses differentiate symptomatic and asymptomatic influenza a infection.

Journal Article PLoS Genet · August 2011 Exposure to influenza viruses is necessary, but not sufficient, for healthy human hosts to develop symptomatic illness. The host response is an important determinant of disease progression. In order to delineate host molecular responses that differentiate ... Full text Open Access Link to item Cite

H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination.

Journal Article PLoS One · 2011 BACKGROUND: During the recent H1N1 influenza pandemic, excess morbidity and mortality was seen in young but not older adults suggesting that prior infection with influenza strains may have protected older subjects. In contrast, a history of recent seasonal ... Full text Open Access Link to item Cite

Ribosomal P autoantibodies are present before SLE onset and are directed against non-C-terminal peptides.

Journal Article J Mol Med (Berl) · July 2010 Autoantibodies to ribosomal P (ribo P) are found in 15-30% of systemic lupus erythematosus (SLE) patients and are highly specific for SLE. The goal of this study is to assess the temporal association of anti-ribosomal P (anti-P) responses with SLE disease ... Full text Link to item Cite

60 kD Ro and nRNP A frequently initiate human lupus autoimmunity.

Journal Article PLoS One · March 10, 2010 Systemic lupus erythematosus (SLE) is a clinically heterogeneous, humoral autoimmune disorder. The unifying feature among SLE patients is the production of large quantities of autoantibodies. Serum samples from 129 patients collected before the onset of SL ... Full text Link to item Cite

Clinical criteria for systemic lupus erythematosus precede diagnosis, and associated autoantibodies are present before clinical symptoms.

Journal Article Arthritis Rheum · July 2007 OBJECTIVE: Specific events that occur during the development of systemic lupus erythematosus (SLE) can be quite variable among individual patients. The aim of this study was to identify patterns that distinguish early clinical events in SLE and to assess w ... Full text Link to item Cite

Hydroxychloroquine sulfate treatment is associated with later onset of systemic lupus erythematosus.

Journal Article Lupus · 2007 Systemic lupus erythematosus (SLE) is a clinically diverse, complex autoimmune disease which may present with coincident onset of many criteria or slow, gradual symptom accrual. Early intervention has been postulated to delay or prevent the development of ... Full text Link to item Cite

An altered immune response to Epstein-Barr nuclear antigen 1 in pediatric systemic lupus erythematosus.

Journal Article Arthritis Rheum · January 2006 OBJECTIVE: New examples support the concept that host immune responses to pathogenic organisms can act as the nidus for autoimmunity. Two such examples implicate the Epstein-Barr virus (EBV) in systemic lupus erythematosus (SLE), i.e., data consistent with ... Full text Link to item Cite

Modification of lupus-associated 60-kDa Ro protein with the lipid oxidation product 4-hydroxy-2-nonenal increases antigenicity and facilitates epitope spreading.

Journal Article Free Radic Biol Med · March 15, 2005 Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with autoantibodies as a near universal feature of the disease. The Ro ribonucleoprotein particle, composed of a 60-kDa protein noncovalently associated with human cytoplasmic RNA, is the t ... Full text Link to item Cite

Early events in lupus humoral autoimmunity suggest initiation through molecular mimicry.

Journal Article Nat Med · January 2005 The origins of autoimmunity in systemic lupus erythematosus (SLE) are thought to involve both genetic and environmental factors. To identify environmental agents that could potentially incite autoimmunity, we have traced the autoantibody response in human ... Full text Link to item Cite

The prevalence, onset, and clinical significance of antiphospholipid antibodies prior to diagnosis of systemic lupus erythematosus.

Journal Article Arthritis Rheum · April 2004 OBJECTIVE: To determine whether antiphospholipid antibodies (aPL) occur before the diagnosis of systemic lupus erythematosus (SLE) and before initial clotting events, and whether their presence early in the disease course influences clinical outcome. METHO ... Full text Link to item Cite

Structural availability influences the capacity of autoantigenic epitopes to induce a widespread lupus-like autoimmune response.

Journal Article Proc Natl Acad Sci U S A · March 9, 2004 A subset of lupus patients with severe nephritis and anti-nRNP reactivity produces autoantibodies primarily against two major epitopes of the nRNP A (also known as U1A) protein. These sequences span amino acids 44-56 (A3) and amino acids 103-115 (A6). Thes ... Full text Link to item Cite

Development of autoantibodies before the clinical onset of systemic lupus erythematosus.

Journal Article N Engl J Med · October 16, 2003 BACKGROUND: Although much is known about the natural history of systemic lupus erythematosus (SLE), the development of SLE autoantibodies before the diagnosis of the disease has not been extensively explored. We investigated the onset and progression of au ... Full text Link to item Cite

Infectious mononucleosis patients temporarily recognize a unique, cross-reactive epitope of Epstein-Barr virus nuclear antigen-1.

Journal Article J Med Virol · June 2003 The spectrum of antibodies against Epstein-Barr virus nuclear antigen-1 (EBNA-1) in patients with a recent history of infectious mononucleosis and nonaffected EBV-positive individuals has been characterized by epitope mapping. Sera were evaluated for antib ... Full text Link to item Cite

Rapid clinical progression to diagnosis among African-American men with systemic lupus erythematosus.

Journal Article Lupus · 2003 The initial clinical course of systemic lupus erythematosus (SLE) is variable, ranging from relatively minor manifestations progressing over years to rapid onset of fulminate disease. We sought to identify factors associated with the rapid manifestation of ... Full text Link to item Cite

Selective small antigenic structures are capable of inducing widespread autoimmunity which closely mimics the humoral fine specificity of human SLE.

Journal Article Scand J Immunol · October 2002 Recent data have suggested that autoantibodies in lupus can progress from simple immunity against a few antigenic structures to a complex response against multiple autoantigens. Our aim was to determine whether these diverse epitope patterns can indeed be ... Full text Link to item Cite

Anti-sm autoantibodies in systemic lupus target highly basic surface structures of complexed spliceosomal autoantigens.

Journal Article J Immunol · February 15, 2002 Autoantibodies directed against spliceosomal proteins are a common and specific feature of systemic lupus erythematosus. These autoantibodies target a collection of proteins, including Sm B, B', D1, D2, and D3. We define the common antigenic targets of Sm ... Full text Link to item Cite

Anti-U1A monoclonal antibodies recognize unique epitope targets of U1A which are involved in the binding of U1 RNA.

Journal Article J Mol Recognit · 2002 The U1A (or nRNP A) protein is known to play a critical role in eukaryotic pre-mRNA splicing and polyadenylation. Previous studies revealed that several mouse monoclonal antibodies (MAbs) recognized U1A as part of the U1snRNP, while MAb 12E12 was unique in ... Full text Link to item Cite

The role of Epstein-Barr virus in systemic lupus erythematosus.

Journal Article Front Biosci · October 1, 2001 Systemic lupus erythematosus (SLE) is a devastating autoimmune disease with no known cure. Lupus patients suffer from a myriad of clinical symptoms which variably include arthritis, pleuritis, pericarditis, vasculitis, and nephritis. The underlying mechani ... Full text Link to item Cite

Lupus autoantibodies recognize the product of an alternative open reading frame of SmB/B'.

Journal Article Biochem Biophys Res Commun · August 3, 2001 An unusual feature of the gene for the spliceosomal protein SmB/B' is the presence of an unusually long alternative open reading frame (aORF) which could encode 220 amino acids. We cloned and expressed this aORF protein and used immunological assays to det ... Full text Link to item Cite

Side-chain specificities and molecular modelling of peptide determinants for two anti-Sm B/B' autoantibodies.

Journal Article J Autoimmun · February 1999 Autoantibodies binding the Sm B and B' peptides (B/B') are commonly associated with systemic lupus erythematosus in man and in MRL lpr/lpr mice. The linear antigenic regions of two anti-Sm B/B' murine monoclonal auto-antibodies have been mapped using overl ... Full text Link to item Cite

Identification and analysis of peptide determinants of murine monoclonal anti-Sm B/B' autoantibodies

Journal Article FASEB Journal · March 20, 1998 The peptides Sm B and B' are components of the spliceosome which are commonly bound by autoantibodies in systemic lupus erythematosus in man and in MRL lpr/lpr mice. We have characterized anti-Sm B/B' murine monoclonal autoantibodies. Sequence analysis of ... Cite

Immunization with 60kD Ro leads to a diversified immune response to several lupus autoantigens

Journal Article FASEB Journal · 1998 Systemic lupus erythematosus is an autoimmune disorder characterized by the production of antibodies to ribonucleoproteins, including 60kD Ro (SS-A), La (SS-B), and 52kD Ro. Spliceosomal proteins, such as Sm and nRNP are also common targets of lupus autoim ... Cite

Immunization with a common epitope of nRNP a induces lupus autoimmunity

Journal Article FASEB Journal · 1998 Systemic lupus erythematosus is an autoimmune disorder characterized by the production of large amounts of autoantibodies. Over 40% of lupus patient sera contain anti-RNP antibodies. Two binding patterns to nRNP in patients have been found, one complex wit ... Cite