Influenza A (H3) illness and viral aerosol shedding from symptomatic naturally infected and experimentally infected cases

BackgroundIt 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.MethodsWe 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.ResultsEleven (28%) experimental and 71 (86%) natural cases shed into fine particle aerosols (P [less than] .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 vs 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. ConclusionsDue 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

Code to reproduce analysis of manuscript: Minimal transmission in an influenza A (H3N2) human challenge-transmission model with exposure events in a controlled environment

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Estimating Risk of Airborne Influenza Transmission in a Controlled Environment

Pandemic preparedness is weakened by uncertainty about the relative importance of influenza transmission modes, particularly airborne droplet nuclei (aerosols). A human-challenge transmission trial in a controlled environment was conducted to address this uncertainty. Healthy, seronegative volunteer ‘Donors’ (N=52) were randomly selected for intranasal challenge with influenza A/Wisconsin/67/2005 (H3N2) and exposed to seronegative ‘Recipients’ randomized to intervention (N=40) or control (N=35) groups. Intervention recipients wore face shields and hand sanitized frequently to limit large droplet and contact transmission. A transmitted infection, confirmed by serology in a control recipient, yielded a 1.3% SAR overall. This was significantly less than the expected 16% SAR (p <0.001) based on a proof-of-concept study that used half as many Donors and exposure days. The main difference between these studies was mechanical building ventilation in the follow-on study, suggesting a possible role for aerosols. The extent to which Donor viral shedding was similar to that of mild, natural infections and may be useful for studying transmission was investigated. The only available aerosol shedding comparison data comes from a population of adults with influenza A H3 infection enrolled on the basis of febrile illness plus cough or sore throat, or positive Quidel QuickVue rapid test (N=83). Systematic differences in case selection compared with Donors yielded more severe cases and introduced bias. To account for differences in illness severity, propensity score matching, stratification, and inverse weighting ultimately demonstrated that the experimental and naturally infected groups were too different to compare without bias. While acknowledging the uncertainty in the generalizability of the current challenge model, observed aerosol shedding and CO2 were used in the rebreathed-air version of the Wells-Riley equation to compute average quantum generation rates (95% CI) 0.029 (0.027, 0.03) and 0.11 (0.088, 0.12) per hour for infected Donors and fine aerosol shedding Donors, respectively. Donors shed 1.4E+5 (1.0E+5, 1.8E+5) airborne viral RNA copies per quantum (ID63). This dissertation provides evidence for airborne transmission, presents a methodology for estimating an airborne dose, and suggests a role for building ventilation in reducing risk and the need for future observational studies to evaluate transmission modes in non-experimental settings with greater generalizability

The effect of COVID-19 stay-at-home order and campus closure on the prevalence of acute respiratory infection symptoms in college campus cohorts.

Evaluation of population-based COVID-19 control measures informs strategies to quell the current pandemic and reduce the impact of those yet to come. Effective COVID-19 control measures may simultaneously reduce the incidence of other acute respiratory infections (ARIs) due to shared transmission modalities. To assess the impact of stay-at-home orders and other physical distancing measures on the prevalence of ARI-related symptoms, we compared symptoms reported by prospective college cohorts enrolled during two consecutive academic years. ARI-related symptoms declined following campus closure and implementation of stay-at-home orders, demonstrating the impact of population-based physical distancing measures on control of a broad range of respiratory infections