Symptom scores
Symptom scores were measured three times per day for experimental cases and once per day for natural cases during a research clinic visit where exhaled breath was collected. Scores taken closest in time to exhaled breath collection were selected for analysis. The upper respiratory score was sum of runny nose, stuffy nose, sneezing, sore throat, earache symptom scores (range 0-15). The lower respiratory score was the sum of shortness of breath, and cough scores (range 0-6). The systemic symptom score was the sum of malaise, headache, muscle/join ache scores (range 0-9). The tympanic temperature for experimental and oral for naturally infected cases was recorded. Observed cough counts were recorded during half-hour breath collections.
Adjustment for qRT-PCR detection limit
Tobit regression was used to impute fine aerosol RNA copy number for qRT-PCR replicates below detection limit where one or more replicates for a sample had detectable RNA. Imputation of RNA copies was not done for samples without any replicates above detection limit, differing from the approach used by Yan and colleagues, where there were a minority of fine aerosol samples below detection limit (14%).15It is less reasonable to do the same for the experimentally infected population where 72% of the observations would be imputed. Tobit regression imputed values for samples with qRT-PCR detectable RNA in ≥1 replicate. For both experimentally and naturally infected populations, Tobit models consisted of fixed effects of cough and study day with random effect of person. Fixed effects for these models were selected based on a priori evidence of an association with fine aerosol shedding.15