Influenza A (H3) viral aerosol shedding in nasally inoculated and naturally infected cases

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 including fever, in a previous study. Whether nasally inoculated influenza is representative of mild natural influenza infection, the majority of natural infections, is unknown. Here, we extend our previous analyses to include a broader range of community-acquired influenza cases. Previously, we reported on two groups: (A) volunteers intranasally inoculated with a dose of 5.5 log10TCID50 of influenza A/Wisconsin/67/2005 (H3N2) and (B) cases with cough and sore throat plus fever or a positive rapid antigen test recruited on a college campus in the same year (2013). Here we added two additional groups from a later study: (C) cases from a 2017-2019 surveillance cohort of college dormitory residents and their contacts, and (D) cases recruited from a university health center in 2019. All cases had an influenza A(H3) infection. Using a Gesundheit-II sampler, we collected 30-minute EBA samples. Community-acquired cases from the surveillance cohort (C) shed more EBA viral RNA and were more symptomatic than the nasally inoculated cases (A) but shed less viral RNA than the natural cases that were selected for symptoms (B) in 2013, but not (D) recruited in 2019. Despite sharing a similar symptomatic profile with the 2013 selected natural cases (B), the 2019 community-acquired cases (D) recruited post-infection showed a lower fine aerosol viral RNA load. 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.