Abstract

Acute respiratory tract infections are a major cause of respiratory morbidity and mortality in pediatric patients worldwide. However, accurate viral and immunologic markers to predict clinical outcomes of this patient population are still lacking. Droplet digital PCR assays for influenza and respiratory syncytial virus (RSV) were designed and performed in 64 respiratory samples from 23 patients with influenza virus infection and 73 samples from 19 patients with RSV infection. Samples of patients with hematologic malignancies, solid tumors, or sickle cell disease were included. Clinical information from institutional medical records was reviewed to assess disease severity. Samples from patients with fever or respiratory symptoms had a significantly higher viral loads than those from asymptomatic patients. Samples from patients with influenza virus and RSV infection collected at presentation had significantly higher viral loads than those collected from patients after completing a course of oseltamivir or ribavirin, respectively. RSV loads correlated positively with clinical symptoms in patients ≤5 years of age, whereas influenza viral loads were associated with clinical symptoms, irrespective of age. Patients receiving antivirals for influenza and RSV had a significant reduction in viral loads after completing therapy. Digital PCR offers an effective method to monitor the efficacy of antiviral treatment for respiratory tract infections in immunocompromised hosts.

Highlights

  • Acute respiratory tract infections are the leading cause of morbidity and mortality in infants and children worldwide [1]

  • We developed and validated two Digital PCR (dPCR) assays for quantitative detection of influenza virus (64 samples from 23 patients) and respiratory syncytial virus (RSV) (73 samples from 19 patients) in respiratory tract samples from patients with hematologic malignancies, solid tumors, and Sickle-cell disease (SCD)

  • We found that RSV viral load correlates with the presence of clinical symptoms in patients 5 years of age, whereas influenza viral load is associated with presence of clinical symptoms, irrespective of age

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Summary

Introduction

Acute respiratory tract infections are the leading cause of morbidity and mortality in infants and children worldwide [1]. Molecular quantitative assays have been suggested to detect and monitor clinical viral respiratory disease, in immunosuppressed pediatric patients [10] Their results are conflicting and there continues to be a lack of clinical tests to accurately measure viral load [5, 6, 8, 9]. Quantitative determination of viral load may provide an important tool to directly evaluate the efficiency of antiviral therapy, to determine if changes in therapy are necessary and to assess need for further isolation to protect transmission to other highly susceptible hosts These problems highlight the importance and potential value of developing assays for absolute, precise and reliable quantitative viral detection to improve the accuracy of clinical decision making in immunocompromised children with viral respiratory infections

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