title: Respiratory syncytial virus load, viral dynamics, and disease severity in previously healthy naturally infected children.
abstract: BACKGROUND
  Respiratory syncytial virus (RSV) disease severity was thought to be a result of host immunopathology but alternatively may be driven by high-level viral replication. The relationships between RSV load, viral clearance dynamics, and disease severity have not been carefully evaluated.
  
  
  METHODS
  Previously healthy RSV-infected children <2 years old were recruited. RSV load was measured in respiratory secretions by fresh quantitative culture over 3 hospital days. Measures of disease severity were hospital admission, duration of hospitalization, requirement for intensive care, and respiratory failure.
  
  
  RESULTS
  Multivariate logistic regression models revealed independent predictors of increased duration of hospitalization: male sex, lower weight, and higher viral load on any day. Viral loads at day 3 were more significantly associated with requirement for intensive care and respiratory failure than were viral loads at earlier time points. Faster RSV clearance was independently associated with shorter hospitalization.
  
  
  CONCLUSIONS
  These observations challenge the immunopathology-based pathogenesis paradigm. They also have major therapeutic implications, suggesting that application of antiviral agents early in the disease course, even at a time when viral replication is at its highest, might improve subsequent morbidity by significantly lowering viral load and direct viral cytopathic effects, and aborting the potential downstream immunopathology.
authors: Division of Pediatric Infectious Diseases, Department of Pediatrics, Harvard Medical School, Massachusetts General Hospital for Children, Boston, USA.
authors: Chadi M
authors: CM
authors: El Saleeby
authors: Andy J
authors: AJ
authors: Bush
authors: Lisa M
authors: LM
authors: Harrison
authors: Jody A
authors: JA
authors: Aitken
authors: John P
authors: JP
authors: Devincenzo
mesh_terms: D003422:Critical Care; D005260:Female; D006760:Hospitalization; D006801:Humans; D007223:Infant; D007902:Length of Stay; D016015:Logistic Models; D008297:Male; D017817:Nasal Lavage Fluid / Q000821:virology; D011446:Prospective Studies; D012131:Respiratory Insufficiency / Q000209:etiology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000503:physiopathology* / Q000821:virology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology; D012720:Severity of Illness Index; D013997:Time Factors; D019562:Viral Load