Review 3: "Quantifying the impact of quarantine duration on COVID-19 transmission"

RR:C19 Evidence Scale rating by reviewer:

• Strong. The main study claims are very well-justified by the data and analytic methods used. There is little room for doubt that the study produced has very similar results and conclusions as compared with the hypothetical ideal study. The study’s main claims should be considered conclusive and actionable without reservation.

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Review:

Quarantine has been widely used to curtail the spread of SARS-CoV-2. Typically, individuals known to have been exposed to COVID-19 and returning travelers are required to isolate for an extended period of time to eliminate the possibility that they spread the virus to others. While quarantine is effective at limiting transmission, it comes with high economic and societal costs. In this paper, the authors use mathematical models to quantify how different quarantine scenarios correspond to reductions in transmission. Furthermore, they calculate the overall utility of the various scenarios, which they define as the ratio of reductions in transmission to the average number of days spent in quarantine.

The authors find that reductions in quarantine duration are always associated with decreases in the fraction of transmission prevented, but quarantine durations of six to eight days maximize utility compared to the current standard duration of 10 days (for Switzerland). They also advocate for the use of ‘test and release’ strategies to reduce the duration and increase the utility of quarantine, advise that hygiene measures be reinforced to individuals leaving quarantine, and suggest that significantly shortening quarantine duration to increase adherence is of limited effectiveness.

The models presented in this paper are well thought-out, comprehensive, and appropriate for the questions the authors are investigating. Importantly, the models include distributions of relevant epidemiological parameters rather than simply using mean values, and the authors parameterize these models using high-quality data. Furthermore, the models include relevant details, such as the rate at which tests return false negatives and delays between test administration and results. The authors are also careful to point out when their results are sensitive to underlying assumptions such as the prevalence of infection amongst quarantined individuals. One important factor not included in the analysis is the potential for tests to return false positive results. Overall, the results of this paper should be viewed as reliable and robust.

One challenge for readers might be properly contextualizing the predictions of the model. Because the models used in this paper do not describe the dynamics of the SARS-CoV-2 pandemic but rather focus on reductions in transmission and utility, there is no simple mapping between the predicted outcomes of the quarantine strategies discussed and societal impacts. However, this model formulation makes the results of this paper much more generalizable, and in many ways also more transparent, as the complexity and uncertainty associated with epidemiological forecasting is avoided entirely. The authors are very up-front about the limitations of their results and discuss how they should be taken into account alongside societal and epidemiological factors when making policy decisions.

The results and conclusions of this paper are likely to have large policy implications. Currently, long quarantine times designed to eliminate all transmission are the norm. The authors focus on Switzerland’s policy, which mandates that quarantine should last ten days, but elsewhere, including many U.S. states, mandated quarantine times are as long as two weeks. This paper suggests that current standards should be reconsidered due to their high associated costs. By identifying strategies like “test and release” to reduce the duration of quarantine while still preventing a large fraction of transmission, the authors lay the theoretical foundation for a reform of quarantine policies.

In conclusion, this paper presents a clear and reliable assessment of current quarantine practices and reasonable alternatives. While translating the results into policy will not be straightforward due to differences in the desirability of reduced quarantine time versus reduced transmission between countries and regions, this paper is nonetheless likely to spur changes in thinking and practices surrounding quarantine.