Background: Nasally inoculated influenza cases reported milder symptoms and shed lower viral RNA load in exhaled breath aerosols (EBA) than people with classic influenza-like illness in a previous study. Whether nasally inoculated influenza is representative of mild natural influenza infection is unknown. We extend previous analyses to include a broader range of community-acquired cases.

Methods: We previously studied (A) volunteers intranasally inoculated with a dose of 5.5 log10TCID50 of influenza A/Wisconsin/67/2005 (H3N2) and (B) cases with classic influenza-like illness including fever recruited in 2013. We now add (C) cases from a 2017-2019 surveillance cohort of college dormitory residents and their contacts and (D) cases from a university health center in 2019. All cases had an influenza A(H3) infection. We collected 30-min EBA samples using a Gesundheit-II sampler.

Results: Community-acquired cases from the surveillance cohort (C) shed more EBA viral RNA and were more symptomatic than the inoculated cases (A) but shed less viral RNA than the symptom-selected natural cases (B) from 2013, but not (D) from 2019. Despite similar symptoms to the 2013 selected cases (B), the 2019 community-acquired cases (D) recruited post-infection had lower fine aerosol viral RNA.

Conclusions: Nasal inoculation of influenza virus did not reproduce EBA viral RNA shedding or symptoms observed in mild natural infection. Circulating strains of influenza A(H3) may differ year-to-year in the extent to which symptomatic cases shed virus into fine aerosols. New models, including possibly aerosol inoculation, are needed to study viral aerosol shedding from the human respiratory tract.