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Influenza A illness and viral aerosol shedding from symptomatic naturally infected and experimentally infected cases
  • +9
  • Paul Jacob Bueno de Mesquita,
  • Jonathan Nguyen-Van-Tam,
  • Ben Killingley,
  • Joanne Enstone,
  • Robert Lambkin-Williams,
  • Anthony S. Gilbert,
  • Alexander Mann,
  • John Forni,
  • Jing Yan,
  • Jovan Pantelic,
  • Michael L. Grantham,
  • Donald K. Milton
Paul Jacob Bueno de Mesquita
University of Maryland at College Park
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Jonathan Nguyen-Van-Tam
University of Nottingham School of Medicine
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Ben Killingley
University of Nottingham School of Medicine
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Joanne Enstone
University of Nottingham School of Medicine
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Robert Lambkin-Williams
hVIVO
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Anthony S. Gilbert
hVIVO
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Alexander Mann
hVIVO
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John Forni
hVIVO
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Jing Yan
University of Maryland at College Park
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Jovan Pantelic
University of Maryland at College Park
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Michael L. Grantham
University of Maryland at College Park
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Donald K. Milton
University of Maryland at College Park, University of Maryland
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Abstract

Background: It has long been known that nasal inoculation with influenza A virus produces asymptomatic to febrile infections. Uncertainty persists about whether these infections are sufficiently similar to natural infections for studying human-to-human transmission. Methods: We compared influenza A viral aerosol shedding from volunteers nasally inoculated with A/Wisconsin/2005 (H3N2) and college community adults naturally infected with influenza A/H3N2 (2012-2013), selected for influenza-like illness with objectively measured fever or a positive Quidel QuickVue A&B test. Propensity scores were used to control for differences in symptom presentation observed between experimentally and naturally infected groups. Results: Eleven (28%) experimental and 71 (86%) natural cases shed into fine particle aerosols (p<0.001). The geometric mean (geometric standard deviation) for viral positive fine aerosol samples from experimental and natural cases was 5.1E+3 (4.72) and 3.9E+4 (15.12) RNA copies/half hour, respectively. The 95th percentile shedding rate was 2.4 log10 greater for naturally infected cases (1.4E+07 versus 7.4E+04). Certain influenza-like illness related symptoms were associated with viral aerosol shedding. The almost complete lack of symptom severity distributional overlap between groups did not support propensity score adjusted shedding comparisons. Conclusions: Due to selection bias, the natural and experimental infections had limited symptom severity distributional overlap precluding valid, propensity score adjusted comparison. Relative to the symptomatic naturally infected cases, where high aerosol shedders were found, experimental cases did not produce high aerosol shedders. Studying the frequency of aerosol shedding at the highest observed levels in natural infections without selection on symptoms or fever would support helpful comparisons.

Peer review status:Published

15 May 2020Submitted to Influenza and other respiratory viruses
18 May 2020Submission Checks Completed
18 May 2020Assigned to Editor
24 May 2020Reviewer(s) Assigned
08 Jun 2020Review(s) Completed, Editorial Evaluation Pending
08 Jun 2020Editorial Decision: Revise Minor
09 Jul 20201st Revision Received
09 Jul 2020Submission Checks Completed
09 Jul 2020Assigned to Editor
09 Jul 2020Editorial Decision: Accept
23 Jul 2020Published in Influenza and Other Respiratory Viruses. 10.1111/irv.12790