bioRxiv2017
Little is known about the amount and infectiousness of influenza virus shed into exhaled breath. This contributes to uncertainty about the importance of airborne influenza transmission. We screened 355 symptomatic volunteers with acute respiratory illness and report 142 cases with confirmed influenza infection who provided 218 paired nasopharyngeal (NP) and 30-minute breath samples (coarse >5 m and fine <5 m fractions) on days 1 to 3 post symptom onset. We assessed viral RNA copy number for all samples and cultured NP swabs and fine aerosols. We recovered infectious virus from 52 (39%) of the fine aerosols and 150 (89%) of the NP swabs with valid cultures. The geometric mean RNA copy numbers were 3.8x104/30-min fine, 1.2x104/30-min coarse aerosol sample, and 8.2x108 per NP swab. Fine and coarse aerosol viral RNA was positively associated with body mass index (fine p<0.05, coarse p<0.10) and number of coughs (fine p<0.001, coarse p<0.01) and negatively associated with increasing days since symptom onset (fine p<0.05 to p<0.01, coarse p<0.10) in adjusted models. Fine aerosol viral RNA was also positively associated with having influenza vaccination for both the current and prior season (p<0.01). NP swab viral RNA was positively associated with upper respiratory symptoms (p<0.01) and negatively associated with age (p<0.01) but was not significantly associated with fine or coarse aerosol viral RNA or their predictors. Sneezing was rare, and sneezing and coughing were not necessary for infectious aerosol generation. Our observations suggest that influenza infection in the upper and lower airways are compartmentalized and independent.\n\nSignificanceLack of human data on influenza virus aerosol shedding fuels debate over the importance of airborne transmission. We provide overwhelming evidence that humans generate infectious aerosols and quantitative data to improve mathematical models of transmission and public health interventions. We show that sneezing is rare and not important for, and that coughing is not required for influenza virus aerosolization. Our findings, that upper and lower airway infection are independent and that fine particle exhaled aerosols reflect infection in the lung, open a new pathway for understanding the human biology of influenza infection and transmission. Our observation of an association between repeated vaccination and increased viral aerosol generation demonstrated the power of our method, but needs confirmation.