# Comparison of Viral Aerosol Shedding by Mild and Moderately Symptomatic Community‐Acquired and Nasally Inoculated Influenza A(H3) Infection

## TL;DR

This study compares how much influenza virus is spread through breath aerosols in people with mild and moderate symptoms from natural and lab-induced infections.

## Contribution

The study shows that nasal inoculation does not replicate natural mild influenza in terms of aerosol shedding and symptoms.

## Key findings

- Nasally inoculated cases shed less viral RNA and show milder symptoms than natural infections.
- Community-acquired cases from 2017–2019 shed more viral RNA than inoculated cases but less than 2013 cases.
- 2019 community cases had lower aerosol viral RNA despite similar symptoms to 2013 cases.

## Abstract

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.

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.

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.

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.