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Temporal dynamics in viral shedding and transmissibility of COVID-19

Our take —

This study leveraged clinical monitoring data of hospitalized COVID-19 patients alongside epidemiologic data on incubation periods and serial intervals between cases in transmission chains to understand temporal dynamics in viral shedding and transmissibility. Findings suggest that viral shedding is highest immediately at or before symptom onset and may begin 2 to 3 days before the appearance of the first symptoms, with nearly half of onward transmission occurring prior to symptom onset. While RNA viral load may not reflect infectiousness, utilization of linked pairs in this analysis bolsters the findings. The presence of significant pre-symptomatic transmission has important implications for the effectiveness of control measures, suggesting that contact tracing should inquire about contacts 2-3 days prior to symptom presentation and that social distancing measures should be followed.

Study design

Other

Study population and setting

This study reports temporal patterns of viral shedding in 94 patients with laboratory-confirmed COVID-19 admitted to Guangzhou Eighth People’s Hospital in Guangdong, China between January 21 to February 14, 2020. Participants had at least one positive result (cycle threshold (Ct) value <40) from throat samples, and testing was conducted from symptom onset up to 32 days after onset for clinical monitoring. Additionally, a separate sample of 77 transmission pairs obtained from publicly available sources within and outside mainland China, defined as two confirmed COVID-19 cases identified in the epidemiologic investigation by showing a clear epidemiologic link with each other, such that one case (infectee) was highly likely to have been infected by the other (infector).

Summary of Main Findings

Viral load from throat swabs was highest at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. This study suggests that infectiousness started from 2.3 days (95% CI, 0.8–3.0 days) before symptom onset and peaked at 0.7 days (95% CI, −0.2–2.0 days) before symptom onset. Infectiousness was estimated to decline quickly within 7 days of symptom onset, until detection limit was reached at 21 days. Viral load did not differ based on age, sex, or disease severity. The serial interval was estimated to have a mean of 5.8 days (95% CI: 4.8–6.8 days) and a median of 5.2 days (95% CI: 4.1–6.4 days). The study estimated that 44% (95% CI: 25–69%) of secondary cases were infected during the index cases’ pre-symptomatic stage, across a combination of settings with substantial household clustering, active case finding and quarantine outside the home.

Study Strengths

This study leverages multiple data sources to understand the temporality of transmission dynamics. Importantly, the study included serial testing among patients with COVID-19 to understand viral load and potential transmissibility throughout the infectious period.

Limitations

Several limitations should be considered for this study. Symptom onset relies on patient recall after confirmation of COVID-19, leading to potential recall bias. Viral shedding dynamics were based on data from individuals in a hospital setting, which may represent more severe cases. Additionally, individuals were receiving treatment per their respective national protocols, which may have modified viral shedding.

Value added

Importantly, this study includes clinical data of serial testing among patients with COVID-19 to understand viral load and potential transmissibility through the infectious period, and potential transmission of pre-symptomatic cases.