1. Epidemiology and Global Health
Download icon

Quarantine: Should I stay or should I go?

  1. Mirjam Kretzschmar  Is a corresponding author
  2. Johannes Müller
  1. University Medical Center Utrecht, Utrecht University, Netherlands
  2. Department of Mathematics, Technical University of Munich, Germany
  3. Institute for Computational Biology, Helmholtz Center Munich, Germany
Insight
  • Cited 0
  • Views 815
  • Annotations
Cite this article as: eLife 2021;10:e67417 doi: 10.7554/eLife.67417

Abstract

Analysing the characteristics of the SARS-CoV-2 virus makes it possible to estimate the length of quarantine that reduces the impact on society and the economy, while minimising infections.

Main text

The COVID-19 pandemic started just over a year ago, so there is a good chance that you have been in quarantine because you or one of your family, friends or colleagues tested positive for SARS-CoV-2. But how long should a person stay in quarantine before they can safely mix with others without posing a threat? Many countries implemented a 14 day quarantine period during the first wave of the pandemic, but it turned out that adherence to quarantine declined towards the end of this period (CDC, 2021; ECDC, 2020; Quilty et al., 2021; Steens et al., 2020). In many cases, this was because people could not afford to miss work for such a long time (Wright et al., 2020). If large numbers of people need to quarantine, this will impact productivity and be costly for the economy. At the same time, it is not clear that longer quarantines actually prevent many new infections. Because of this, many countries shortened their quarantines to ten days, and some allow release even earlier if individuals test negative before that time.

But, what is the optimal duration of quarantine that still ensures an effective control of SARS-CoV-2 transmission, while minimizing the individual and societal impact? Now, in eLife, Peter Ashcroft (ETH Zurich), Sebastian Bonhoeffer (ETH) and colleagues – Sonja Lehtinen (ETH), Daniel Angst (ETH) and Nicola Low (University of Bern) – report how they have used mathematical modelling to address this question (Ashcroft et al., 2021).

Based on estimated distributions of the time between a person getting infected and them infecting another person with COVID-19, the incubation period, and the infectivity of the virus, Ashcroft et al. quantified the impact of isolation and quarantine on onward transmission for index cases (the first identified case within a cluster) and their contacts. Index cases are identified through testing either when the individual develops symptoms, or when they return from travel from a country with high risk and get tested regardless of symptoms on entering their home country.

In the first case, knowing the distribution of incubation periods provides information about the possible time of infection and, therefore, the length of time an index case has had to infect others. For travellers, this information is less precise because it is harder to determine when they were infected, which will depend on the duration of travel and on how likely they are to have been exposed to infectious people in the country they travelled to. The analysis by Ashcroft et al. relies on estimating what proportion of onward transmissions could be prevented by various quarantine strategies.

At this point, Ashcroft et al. are faced with some arbitrariness in how to deal with optimizing a quarantine strategy that has several objectives (Denysiuk et al., 2015). On the one hand, reducing the spread of infection (the longer the quarantine is, the fewer onward infections), on the other, minimizing the societal and psychological consequences of quarantine. Ashcroft et al. manage this problem by using a utility function that measures the proportion of transmissions prevented per extra day of quarantine, merging the two aspects that need to be optimized. However, this is just one of several possible ways to handle the task, and it is not clear that it is the best approach.

Furthermore, Ashcroft et al. may be underestimating the effect of quarantine, since they are only counting the number of prevented direct infections, but not the people these prevented infectees would otherwise be infecting. In regions where the virus is highly prevalent, these infection chains might overlap, and affect the net number of prevented cases. Even if the utility ratio were the best approach to optimize a quarantine strategy, this ratio will depend on the state of the epidemic.

Ashcroft et al.’s results have implications for how to best balance public health needs with societal interests of reducing the costs of quarantine. First, the delay between exposure of an index case and isolation and quarantine of their contacts should be minimized in order to prevent as much onward transmission as possible. Second, quarantine periods of less than five days after exposure are not effective, but effectiveness hardly increases after ten days of quarantine. Between these bounds, the optimal quarantine duration lies between six and eight days, with contacts being released if they test negative after that time (Figure 1). This strategy would decrease the load on society by reducing the number of people in quarantine at the same time, and likely lead to higher adherence to quarantine measures. To further reduce the probability of transmission after release from quarantine, the timing of testing should also be optimized (Wells et al., 2021).

Costs versus benefits of quarantine depending on time.

The costs of quarantine (yellow bars and arrow) increase steadily with time, while the benefits (green arrow) – measured as number of onward transmissions (red bars) prevented – increase steeply at first, and then flatten. Ashcroft et al. estimate that balance between costs and benefits – known as the utility (blue arrow) – increases at first, reaching a peak after 6–8 days, and then decreases.

The analysis reported by Ashcroft et al. assumes that quarantine is complete in the sense that as long as a person is in quarantine, onward transmission is prevented completely. In practice, this will often not be the case, as people live in households with others, where they may not be able to avoid contact and transmission. Therefore, quarantine needs to be extended to the people who live with the contacts of an infected person, meaning that the costs incurred by quarantine depend on household size and other factors that determine how well quarantine can be implemented in practice. There is no question, however, that a test-and-release strategy, preferably using rapid tests with high sensitivity, can help to combine control of the pandemic with societal acceptance of the measure.

These results emphasize the impact of implementing widespread, low-threshold testing strategies. Additionally, they underline the importance of clearly communicating that people do not need to stay in quarantine longer than necessary, but that there is an evidence-based strategy behind their having to stay home (Smith et al., 2020; Webster et al., 2020). It will be possible to go out again, but not too early. The virus can tell us when the time has come.

References

Article and author information

Author details

  1. Mirjam Kretzschmar

    Mirjam Kretzschmar is in the University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands

    For correspondence
    M.E.E.Kretzschmar@umcutrecht.nl
    Competing interests
    No competing interests declared
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4394-7697
  2. Johannes Müller

    Johannes Müller is in the Department of Mathematics, Technical University of Munich, Garching, Germany, and the Institute for Computational Biology, Helmholtz Center Munich, Neuhenberg, Germany

    Competing interests
    No competing interests declared
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5892-8598

Publication history

  1. Version of Record published: March 16, 2021 (version 1)

Copyright

© 2021, Kretzschmar and Müller

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 815
    Page views
  • 47
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease
    Kelsey M Sumner et al.
    Research Article

    Background:Asymptomatic Plasmodium falciparum infections are common in sub-Saharan Africa, but their effect on subsequent symptomaticity is incompletely understood.

    Methods:In a 29-month cohort of 268 people in Western Kenya, we investigated the association between asymptomatic P. falciparum and subsequent symptomatic malaria with frailty Cox models.

    Results:Compared to being uninfected, asymptomatic infections were associated with an increased 1-month likelihood of symptomatic malaria [adjusted Hazard Ratio (aHR):2.61, 95%CI:2.05-3.33], and this association was modified by sex, with females [aHR:3.71, 95%CI:2.62-5.24] at higher risk for symptomaticity than males [aHR:1.76, 95%CI:1.24-2.50]. This increased symptomatic malaria risk was observed for asymptomatic infections of all densities and in people of all ages. Long-term risk was attenuated but still present in children under 5 [29-month aHR:1.38, 95%CI:1.05-1.81].

    Conclusions:In this high-transmission setting, asymptomatic P. falciparum can be quickly followed by symptoms and may be targeted to reduce the incidence of symptomatic illness.

    Funding:This work was supported by the National Institute of Allergy and Infectious Diseases (R21AI126024 to WPO, R01AI146849 to WPO and SMT).

    1. Epidemiology and Global Health
    Manoj Kumar et al.
    Tools and Resources Updated

    The COVID-19 pandemic originating in the Wuhan province of China in late 2019 has impacted global health, causing increased mortality among elderly patients and individuals with comorbid conditions. During the passage of the virus through affected populations, it has undergone mutations, some of which have recently been linked with increased viral load and prognostic complexities. Several of these variants are point mutations that are difficult to diagnose using the gold standard quantitative real-time PCR (qRT-PCR) method and necessitates widespread sequencing which is expensive, has long turn-around times, and requires high viral load for calling mutations accurately. Here, we repurpose the high specificity of Francisella novicida Cas9 (FnCas9) to identify mismatches in the target for developing a lateral flow assay that can be successfully adapted for the simultaneous detection of SARS-CoV-2 infection as well as for detecting point mutations in the sequence of the virus obtained from patient samples. We report the detection of the S gene mutation N501Y (present across multiple variant lineages of SARS-CoV-2) within an hour using lateral flow paper strip chemistry. The results were corroborated using deep sequencing on multiple wild-type (n = 37) and mutant (n = 22) virus infected patient samples with a sensitivity of 87% and specificity of 97%. The design principle can be rapidly adapted for other mutations (as shown also for E484K and T716I) highlighting the advantages of quick optimization and roll-out of CRISPR diagnostics (CRISPRDx) for disease surveillance even beyond COVID-19. This study was funded by Council for Scientific and Industrial Research, India.