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Olfactomedin 4 serves as a marker for disease severity in pediatric Respiratory Syncytial Virus (RSV) infection

ABSTRACT: Respiratory viral infections follow an unpredictable clinical course in young children ranging from a common cold to respiratory failure. The transition from mild to severe disease occurs rapidly and is difficult to predict. The pathophysiology underlying disease severity has remained elusive. There is an urgent need to better understand the immune response in this disease to come up with biomarkers that may aid clinical decision making. In a prospective study, flow cytometric and genome-wide gene expression analyses were performed on blood samples of 26 children with a diagnosis of severe, moderate or mild Respiratory Syncytial Virus (RSV) infection. Differentially expressed genes were validated using Q-PCR in a second cohort of 80 children during three consecutive winter seasons. FACS analyses were also performed in the second cohort and on recovery samples of severe cases in the first cohort. Severe RSV infection was associated with a transient but marked decrease in CD4+ T, CD8+ T, and NK cells in peripheral blood. Gene expression analyses in both cohorts identified Olfactomedin4 (OLFM4) as a fully discriminative marker between children with mild and severe RSV infection, giving a PAM cross-validation error of 0%. Patients with an OLFM4 gene expression level above -7.5 were 6 times more likely to develop severe disease, after correction for age at hospitalization and gestational age. In conclusion, by combining genome-wide expression profiling of blood cell subsets with clinically well-annotated samples, OLFM4 was identified as a biomarker for severity of pediatric RSV infection.

ORGANISM(S): Homo sapiens

PROVIDER: GSE69606 | GEO | 2015/06/06

SECONDARY ACCESSION(S): PRJNA285966

REPOSITORIES: GEO

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Project description:While the majority of infants infected with respiratory syncytial virus (RSV) exhibit mild or no symptoms, approximately 3 million children under the age of five are hospitalized every year due to complications from RSV. This research sought to explore the biological processes and related biomarkers responsible for the varied manifestations of RSV disease in young infants. The goal is to pave the way for a more precise categorization of RSV-infected infants based on their medical requirements. Whole blood samples are collected from infant case-control cohort study, the RESCEU case-control cohort is a multinational, multicenter, observational study (clinical trial registration number: NCT03756766). Infants < 12 months old with RSV disease were recruited from the University Medical Center Utrecht (UMCU) in The Netherlands, Hospital Clínico Universitario de Santiago (SERGAS) in Spain, Imperial College (IMPERIAL) National Health Service Trust (NHS) and Oxford University Hospital NHS Trust (OXFORD) in the United Kingdom during the RSV seasons 2017-2018, 2018-2019, and 2019-2020. Healthy controls without underlying comorbidities were recruited outside of the RSV season. Eligibility criteria included hospitalization for less than 48 hours at enrolment or within 96 hours of disease onset, no previous receipt of medications to treat RSV infection, no prior exposure to an investigational RSV vaccine or medication, no previous receipt of immunoglobulins or monoclonal antibodies, and had not used montelukast or oral steroids within seven days before enrolment. Infants with co-morbidities were not evaluated in the manuscript. RSV was detected using RSV point-of-care test (POCT) by either a rapid antigen detection test (Alere I) (Alere Inc, Waltham, Massachusetts) or rapid RSV polymerase chain reaction (PCR) test at the hospital setting, or a RSV PCR test at the laboratory. Convalescence samples were collected 7 ±1 weeks after a positive RSV diagnostic test result. We used microarray to assist us to identify biomarkers for severe RSV disease.

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Olfactomedin 4 serves as a marker for disease severity in pediatric Respiratory Syncytial Virus (RSV) infection

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