Evidence before this study
On Sept 20, 2020, we searched PubMed for articles reporting on factors influencing transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the risk of developing symptomatic COVID-19. Search terms included “COVID-19”, “SARS-CoV-2”, “transmission”, “incubation time”, and “risk”, with no language restrictions. Various authors had reported on retrospective analyses of clusters of index cases and their corresponding contacts, as well as series of patients who developed symptomatic COVID-19 after a positive PCR result. Besides describing the secondary attack rate, these studies identified risk factors for transmission associated with the place and duration of exposure and not using personal protective equipment. A single study suggested that individuals who were symptomatic might be more likely to transmit than those without symptoms, but we found no clear evidence regarding the influence of viral load of the index case on transmission risk. Similarly, although various retrospective series of patients with positive PCR results had reported incubation times elsewhere, the characteristics of index case and contacts that might influence the risk of developing symptomatic COVID-19 and the time to this event had been barely addressed.
Added value of this study
We analysed data from a large cluster-randomised clinical trial on post-exposure therapy for COVID-19 that provided new information on SARS-CoV-2 transmission dynamics. Several design components add value to this dataset. Notably, quantitative PCR was available for the index cases to estimate risk of transmission. Additionally, quantitative PCR was also done on asymptomatic contacts at the time of enrolment allowing us to investigate the dynamics of symptomatic disease onset among them. We found that the viral load of the index case was the leading determinant of the risk of SARS-CoV-2 PCR positivity among contacts. Among contacts who were SARS-CoV-2 PCR positive at baseline, viral load significantly influenced the risk of developing the symptomatic disease in a dose-dependent manner. This influence also became apparent in the incubation time, which shortened with increasing baseline viral loads.
Implications of all the available evidence
Our results provide important insights into the knowledge regarding the risk of SARS-CoV-2 transmission and COVID-19 development. The fact that the transmission risk was primarily driven by the viral load of index cases, more than other factors such as their symptoms or age, suggests that all cases should be considered potential transmitters irrespective of their presentation and encourages the assessment of viral load in patients with a larger number of close contacts. Similarly, our results regarding the risk and expected time to developing symptomatic COVID-19 encourage risk stratification of newly diagnosed SARS-CoV-2 infections on the basis of the initial viral load.
