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. 2011 Oct 1;204(7):996-1002.
doi: 10.1093/infdis/jir494.

Respiratory syncytial virus load, viral dynamics, and disease severity in previously healthy naturally infected children

Chadi M El Saleeby  1 , Andy J Bush, Lisa M Harrison, Jody A Aitken, John P Devincenzo
Affiliations

Respiratory syncytial virus load, viral dynamics, and disease severity in previously healthy naturally infected children

Chadi M El Saleeby et al. J Infect Dis. .

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.

Discussion: 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.

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Figures

Figure 1.
Figure 1.
Viral load and viral dynamics. A, Viral loads on study day 1 measured simultaneously from both deep tracheal aspirates and nasal aspirates (n = 35 pairs). Each data point represents a single study subject. B, Viral loads on study days 1, 2, and 3 measured simultaneously from deep tracheal aspirates and nasal aspirates (n = 62 pairs). C, Representative viral load curves from individual subjects; D, Mean viral load at enrollment as a function of duration of symptoms prior to specimen collection. Individual observations are mean RSV viral loads. Error bars represent the standard error of the mean. E, Mean viral loads on study days 1, 2, and 3 dichotomized by duration of hospitalization (<4 days; ≥4 days). Error bars represent the standard error of the mean.
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