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Transmission of COVID-19 in 282 clusters in Catalonia, Spain: a cohort study

Our take —

This prospective cohort study was nested in a randomized controlled trial, and found that among 314 index patients with COVID-19, there were 753 contacts across 282 potential transmission clusters of which 32% had a transmission case. Increased viral load amongst the index case, household contacts, and age of contacts were associated with transmission; notably, respiratory symptoms of the index case were not associated with transmission. Additionally, among infected contacts testing positive but asymptomatic at first assessment, higher viral load within the contact was associated with their eventual onset of symptoms and time-to-symptom onset (higher viral load resulted in symptom onset in fewer days). A key limitation is that no asymptomatic index cases were included, however the study yielded important insights into the impact of viral load on transmission. Findings suggest that viral load, and not respiratory symptoms among index cases, predicts transmission, and that viral load amongst secondary infections impacts symptom onset.

Study design

Randomized Controlled Trial, Prospective Cohort

Study population and setting

The study objective was to identify transmission factors and clusters of COVID-19 in the Catalonia region of Spain using data from a randomized controlled trial conducted between March 17 and April 28, 2020 for hydroxychloroquine to reduce transmission of SARS-CoV-2. Eligibility criteria for cases included aged 18 years or older, not hospitalized, positive PCR results at baseline, an onset of mild symptoms within 5 days preceding enrollment, and no reported symptoms of COVID-19 at the home or workplace. Participants were identified using the Epidemiological Surveillance Emergency Service registry and their contacts were traced. Adult contacts were household members, nursing home residents, or healthcare worker contacts who had direct exposure to the index case for 15 or more minutes and no reported symptoms in the 7 days prior to index case enrollment. Contacts were followed for 14 days with visits on Day 1 and 14. The study used symptom questionnaires and collected age and sex information on cases and contacts. Authors assessed the relationship of viral load from PCR results and SARS-CoV-2 transmission.

Summary of Main Findings

From 314 patients with COVID-19, investigators identified 753 contacts from 282 (90%) of patients. Of these 282 potential connections across individuals, 90 (32%) had at least one transmission event documented by the study. Among the 125 index cases with viral load data available, viral load among the index case was associated with fever in the index case and was negatively associated with days since onset of symptoms (reinforcing that viral load is highest around timing of symptom onset). In terms of transmission, the viral load of the index case, being a household contact, and age of the contact were all positively associated with transmission. Age and sex of the index case, respiratory symptoms of the index case, and mask use of contacts were not associated with transmission. Further, among 421 contacts testing positive at their first visit and asymptomatic, viral load amongst contacts at first infection detection was associated with eventual development of symptoms and time to symptom onset.

Study Strengths

The study had viral load data available to understand differences in transmission related to viral load. It also had longitudinal follow-up for all contacts to track symptoms and positive tests. The study used epidemiologic surveillance systems that were coupled with mandated contact tracing to ensure a large sample size, though it was nested in a randomized controlled trial (RCT).


By nesting this analysis in an RCT, investigators had stringent eligibility requirements for index cases that may not be representative of all or most cases in Catalonia at large. In particular, asymptomatic individuals were not enrolled as index cases. Finally, total time of exposure was not included in the analysis, which may have underestimated the protective nature of masks if household contacts used masks but also had a longer time period of exposure; further, mask use of the index cases was not factored into the analysis.

Value added

This is one of the largest studies investigating viral load, as opposed to just COVID-19 infection status. It has important insights into the impact viral load has on transmission.

This review was posted on: 26 February 2021