Influenza virus shedding and symptoms: Dynamics and implications from a multi-season household transmission study

Abstract

AbstractIsolation of symptomatic infectious persons can reduce influenza transmission. However, virus shedding that occurs without symptoms will be unaffected by such measures. Identifying effective isolation strategies for influenza requires understanding the interplay between individual virus shedding and symptom presentation. From 2017–2020, we conducted a case-ascertained household transmission study using influenza real-time reverse transcription quantitative PCR (RT-qPCR) testing of nasal swabs and daily symptom diary reporting for up to 7 days after enrollment (≤14 days after index onset). We assumed real-time RT-qPCR cycle threshold (Ct) values were indicators of quantitative virus shedding and used symptom diaries to create a score that tracked influenza-like-illness (ILI) symptoms (fever, cough, or sore throat). We fit phenomenological nonlinear mixed-effects models stratified by age and vaccination status and estimated two quantities influencing isolation effectiveness: shedding before symptom onset and shedding that might occur once isolation ends. We considered different isolation end points (including 24 hours after fever resolution or 4 days after symptom onset) and assumptions about the infectiousness of Ct shedding trajectories. Of the 116 household contacts with ≥2 positive tests for longitudinal analyses, 105 (91%) experienced ≥1 ILI symptom. On average, children <5 years experienced greater peak shedding, longer durations of shedding, and elevated ILI symptom scores compared with other age groups. Most individuals (63/105) shed <10% of their total shed virus before symptom onset, and shedding after isolation varied substantially across individuals, isolation end points, and infectiousness assumptions. Our results can inform strategies to reduce transmission from symptomatic individuals infected with influenza.Significance StatementIndividuals infected with influenza are encouraged to avoid contact with others for a period following symptom onset. This action should reduce the likelihood of onward transmission if infectious virus shedding is associated with symptom presentation. We modeled influenza virus shedding and symptom dynamics in participants of a multi-season household transmission study. On average, children <5 years shed more virus for longer durations and experienced elevated influenza-like-illness symptoms compared with older age groups. Most shedding took place after symptom onset, and estimated shedding that might remain after a period of avoiding contact with others depended on how the end of this period was defined. Our results can help inform strategies to reduce transmission from symptomatic individuals infected with influenza.