Relative role of border restrictions, case finding and contact tracing in controlling SARS-CoV-2 in the presence of undetected transmission

ABSTRACT

BackgroundSeveral countries have controlled the spread of COVID-19 through varying combinations of border restrictions, case finding, contact tracing and careful calibration on the resumption of domestic activities. However, evaluating the effectiveness of these measures based on observed cases alone is challenging as it does not reflect the transmission dynamics of missed infections. MethodsCombining data on notified local COVID-19 cases with known and unknown sources of infections (i.e. linked and unlinked cases) in Singapore in 2020 with a transmission model, we reconstructed the incidence of missed infections and estimated the relative effectiveness of different types of outbreak control. We also examined implications for estimation of key real-time metrics -- the reproduction number and ratio of unlinked to linked cases, using observed data only as compared to accounting for missed infections. FindingsPrior to the partial lockdown in Singapore, initiated in April 2020, we estimated 89% (95%CI 75-99%) of the infections caused by notified cases were contact traced, but only 12.5% (95%CI 2-69%) of the infections caused by missed infectors were identified. We estimated that the reproduction number was 1.23 (95%CI 0.98-1.54) after accounting for missed infections but was 0.90 (95%CI 0.79-1.1) based on notified cases alone. At the height of the outbreak, the ratio of missed to notified infections was 34.1 (95%CI 26.0-46.6) but the ratio of unlinked to linked infections was 0.81 (95%CI 0.59-1.36). Our results suggest that when case finding and contact tracing identifies at least 50% and 20% of the infections caused by missed and notified cases respectively, the reproduction number could be reduced by more than 14%, rising to 20% when contact tracing is 80% effective. InterpretationDepending on the relative effectiveness of border restrictions, case finding and contact tracing, unobserved outbreak dynamics can vary greatly. Commonly used metrics to evaluate outbreak control -- typically based on notified data -- could therefore misrepresent the true underlying outbreak. FundingMinistry of Health, Singapore. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed, BioRxiv and MedRxiv for articles published in English up to Mar 20, 2021 using the terms (2019-nCoV OR "novel coronavirus" OR COVID-19 OR SARS-CoV-2) AND (border OR travel OR restrict* OR import*) AND ("case finding" OR surveillance OR test*) AND (contact trac*) AND (model*). The majority of modelling studies evaluated the effectiveness of various combinations of interventions in the absence of outbreak data. For studies that reconstructed the initial spread of COVID-19 with outbreak data, they further simulated counterfactual scenarios in the presence or absence of these interventions to quantify the impact to the outbreak trajectory. None of the studies disentangled the effects of case finding, contact tracing, introduction of imported cases and the reproduction number, in order to reproduce an observed SARS-CoV-2 outbreak trajectory. Added value of this studyNotified COVID-19 cases with unknown and known sources of infection are identified through case finding and contact tracing respectively. Their respective daily incidence and the growth rate over time may differ. By capitalising on these differences in the outbreak data and the use of a mathematical model, we could identify the key drivers behind the growth and decline of both notified and missed COVID-19 infections in different time periods -- e.g. domestic transmission vs external introductions, relative role of case finding and contact tracing in domestic transmission. Estimating the incidence of missed cases also allows us to evaluate the usefulness of common surveillance metrics that rely on observed cases. Implications of all the available evidenceComprehensive outbreak investigation data integrated with mathematical modelling helps to quantify the strengths and weaknesses of each outbreak control intervention during different stages of the pandemic. This would allow countries to better allocate limited resources to strengthen outbreak control. Furthermore, the data and modelling approach allows us to estimate the extent of missed infections in the absence of population wide seroprevalence surveys. This allows us to compare the growth dynamics of notified and missed infections as reliance on the observed data alone may create the illusion of a controlled outbreak.