Part 2:Quarantine And Testing Strategies To Ameliorate Transmission Due To Travel During The COVID-19 Pandemic: A Modelling Study
Mar 24, 2022
Contact: joanna.jia@wecistanche.com / WhatsApp: 008618081934791
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Results
Country-specific quarantines
Evaluation using our full model with all parameters determined by the epidemic situation observed on November 21, 2021, yielded sufficient quarantine durations—when a reverse-transcription polymerase chain reaction (RT-PCR) test is conducted on exit from quarantine—to enable travel without increasing within-country transmission (Fig. 2). From the estimated country-specific travel quarantine strategies that are individualized for the origin and destination pairs, we found that travel can be allowed among most pairings without increasing the within-country imminent infections in the destination country (Fig 2, Fig S1). Coun- tries with lower prevalences of disease tended to require more stringent regimens of quarantine and testing (Fig. S2). For example, as of November 21, Spain was classified in Red EU travel status and exhibited the lowest case burden per capita among the 26 European countries studied. We found that quarantine durations ranging between 0−4 days would result in fewer imminent infections in Spain than closed borders for most of the origin countries, with a travel ban for travelers from the UK (Fig. 2A, Fig. S1). Malta was also in Red status with a minimum sufficient quarantine duration between 2−10 days, with a travel ban for travelers from Germany and Poland (Fig. 2B, Fig. S1). Cyprus, Portugal, the UK, Greece, and Austria—each with Dark Red EU travel status—exhibited minimum sufficient quarantine durations ranging from 0−2 days to 0−12 days with the implementation of travel bans (Fig. 2C−G, Fig. S1). A Dark Red EU travel status destination country such as Hungary—with high prevalence—can require no quarantine (Fig. 2H, Fig. S1). In general, we found that the recommended duration of travel quarantine increases with the ratio of the prevalence in the origin country to the destination country (Fig. 2I, Fig. S1).
In particular, our analysis for November 21 illustrates that the minimum sufficient quarantine duration for destination countries with lower prevalence (Red status) had a median of four days, whereas in destination countries with high prevalence (Dark Red status) the median estimated quarantine duration was zero days. Compared to November 21, there was more diversity in the EU status among countries on August 8 (Fig. S32). Specifically, the estimated case burden of COVID-19 on August 8 indicates that there was one country in Green status, three in Amber, 13 in Red, and nine in Dark Red compared to the situation on November 21 when none
of the 26 countries was Green or Amber status. For August 8, the minimum sufficient quarantine duration for destination countries with low prevalence(ie. Green status)had a median of four days, moderate prevalence (ie. Amber status)two days, whereas in destination countries with high prevalence (Dark Red status)the median estimated quarantine duration was zero days. Similarly, the estimated duration of travel quarantine required for travelers from origin countries with high prevalence (Dark Red status; median one days)was longer than that for travelers departing from origin countries with low prevalence(Green status; median zero days).
In addition to the prevalence of disease, travel volume has a notable impact on quarantine and testing strategies that are sufficient to enable travel without increasing within-country transmission (Fig. S2). For instance, a comparison of Dark Red status Norway and Greece reveal that sufficient quarantines to visit Greece would need to be longer due to differences in typical travel asymmetries in and out of the country (Fig. 2D; Fig. Sr). For a few destination countries(such as Spain, Malta, Cyprus, Portugal, and Greece), we found that even a travel quarantine duration of I4 days would be insufficient to keep within-country imminent infections equivalent to or lower than that achieved by a complete travel ban (Fig. 2l; Fig. Sr). This result can arise when there is a substantial asymmetry in the number of travelers abroad. For example, travel asymmetry between the UK and Greece is high; consequently, a ban on travel for visitors from the UK would be required to ensure transmission within Greece is not increased. A large number of travelers in the country and fewer residents abroad leads to serious challenges in minimizing quarantine and testing strategies to maintain travel at normal levels. These results indicate that a multitude of factors can simultaneously influence the importation of infection, impacting the minimum sufficient quarantine durations. Sensitivity analysis of the minimum sufficient quarantine durations for each parameter revealed that the natural immunity and number of daily travelers in both the destination and origin countries daily incidence per capita and disease prevalence in the destination country; as well as vaccine-elicited immunity in the origin country exhibited substantial impact on the quarantine duration (Fig. S2). The number of travelers abroad in the destination and origin country, vaccine-elicited immunity in the destination country, and disease prevalence in the origin country had a moderate impact, while age demographics and population sizes had negligible effects on the duration of travel quarantine (Fig. S2). As the pandemic situation evolves in each country, the changes in population immunity and disease prevalence will impact the minimum sufficient quarantine (Fig. SI vs Fig S32). The estimates are fairly stable on a monthly time scale; the minimum sufficient quarantine durations calculated as of October 3
Figure 2. The estimated minimum duration of travel quarantine for specified origin-destination country pairs that reduces within-country imminent infections to be equivalent to border closure for the pandemic as of November 21. Specifying age-dependent vaccine effectiveness and proportion of asymptomatic infections, as well as country-specific demographics, incidence, the prevalence of non-isolated infections, vaccine coverage, natural immunity, and travel flow, we determine the minimum sufficient duration of travel quarantine with an RT-PCR test on exit from quarantine (color gradient) that should be stated by the destination country for individuals arriving from the origin country based on data for November 21, 2021. The countries are ranked based on their estimated incidence per 100,000 over the last two weeks (November 8 to November 21) and stratified based on the European Union country classification system: Green, < 25 cases per 100,000; Amber, 25− 150 cases per 100,000; Red, 150−500 cases per 100,000; and Dark Red, > 500 cases per 100,000. We consider travel quarantine durations of zero-days (white) to no travel (dark purple with an “X”, i.e., sufficient travel quarantine would exceed 14 days) for destination countries (A) Spain, (B) Malta, (C) Cyprus, (D) Portugal, (E) the United Kingdom, (F) Greece, (G) Austria, (H) Hungary, and (I) 18 of 26 countries analyzed (cf. Fig. S1). Within-country travel quarantine is not evaluated in the analysis (black). Travel flow data was not available for all origin-destination country pairs (grey). For quarantine duration of 1 day or longer, there was a 24-h delay in obtaining the RT-PCR test result. For a zero-day travel quarantine, the RT-PCR test was conducted 24 h before travel.
Figure 3. The estimated minimum duration of travel quarantine for specified origin-destination country pairs that reduces imminent infections to be equivalent to banning travel when considering variants of concern for the pandemic as of November 21, 2021. Specifying age-dependent vaccine effectiveness and proportion of asymptomatic infections, as well as a country-specific demographics, incidence, prevalence of non-isolated infections, percentage of variants of concern, vaccine coverage, natural immunity, and travel flow, we determine the minimum sufficient duration of travel quarantine with an RT-PCR test on exit from quarantine (col- our gradient) that should be stated by the destination country for individuals arriving from the origin country when considering (A) transmission of the variant of concern Delta G/478K.V1, (B) transmission of the variant of concern Omicron B.1.1.529+BA, (C) transmission of the variants except Delta G/478K.V1 and Omicron B.1.1.529+BA, and (D) general transmission and transmission of the variants of concern Delta G/478K.V1 and Omicron B.1.1.529+BA based on data for November 21, 2021. We consider travel quarantine durations of zero-days (white) to no travel (dark purple, i.e., specified quarantine can exceed 14 days). Within-country travel quarantine is not evaluated in the analysis (black). Travel flow data was not available for all country pairs (grey). The countries are ranked based on their estimated incidence per 100,000 over the last two weeks (November 8 to November 21) and stratified based on the European Union country classification system: Green, < 25 cases per 100,000; Amber, 25 to 150 cases per 100,000; Red, 150−500 cases per 100,000; and Dark Red, > 500 cases per 100,000. For travel quarantine duration of 1 day or longer, there was a 24-h delay in obtaining the RT-PCR test result. For a zero-day travel quarantine, the RT-PCR test was conducted 24 h before travel.
would not lead to imminent infection greater than border closure for 68 ¢9% of country pairings through to November 21 (Fig. S26). To maintain a relevant mini- mum sufficient quarantine for a country, access to an open-source interactive spreadsheet has been made available (Supplementary File).
Variants of concern
Considering variants of concern, we quantified the sufficient durations of travel quarantine when an RT-PCR test is conducted on exit from quarantine with the goal of no net increase in the incidence of Delta G/478K. V142 and Omicron B.1.1.529+BA43 for estimates of their circulation within the destination and origin countries.40
As of November 21, the highly contagious Delta G/478K.V1 variant was widespread across much of
Europe. Therefore, among countries with surveillance enabling estimation of the number of cases attributed to the variant, sufficient quarantine, and testing is similar for these variants to that determined for general transmission without stratification by variants(Fig. 2I vs. Fig.3A). In contrast, the emerging Omicron B.I.I.529+BA variant and all other variants excluding Delta G/478K.VI and Omicron B.I.I.529+BA were at relatively lower frequency in most European countries, with much greater variance in prevalence. Consequently, sufficient quarantine durations would be longer for these variants than that determined in a general analysis of COVID-I9 transmission (Fig. 3B-C vs. Fig. 2I and Fig.3A). Combining multiple variants of concern leads to sufficient quarantines for each origin-destination pair determined by the maximum of those deemed sufficient for each variant. Consequently, incorporating additional variants of concern into the goal of
Figure 4. The estimated minimum duration of travel quarantine for origin-destination country pairs sufficient to prevent additional within-country imminent infections due to travel, using prevalence associated with European Union traffic-light categorization of COVID-19 risk. The minimum sufficient durations of travel quarantine (color gradient) are calculated including (A) no testing, (B) an RT-PCR test on exit from quarantine, (C) a rapid antigen test on exit from quarantine, and (D) a rapid antigen test on both entry to and exit from quarantine, specifying age-dependent vaccine effectiveness and proportion of asymptomatic infections, average European age structure, 42% vaccine-acquired immunity, and 32% natural immunity, for origin countries whose EU traffic-light status is Green (25 cases per 100,000), Amber (150 cases per 100,000), Red (500 cases per 100,000), or Dark Red (1,000 cases per 100,000). For travel quarantine duration of one day or longer, there was a 24-h delay in obtaining the RT-PCR test result and no delay in obtaining the rapid antigen test. For a zero-day travel quarantine, the RT-PCR test was conducted 24-h before travel.
assuring no additional infections due to travel leads to potentially longer quarantines and significant travel restrictions (Fig.3D vs Fig.2I and Fig.3A-C and Fig. S; vs Fig.Sr). Sufficient duration of travel quarantine increased substantially when making policy based on the multiple variants of concern compared to evaluation that does not distinguish between variants (among all country-pairings common to both data sets: median of; days vs the median of zero-days; 32-2% travel ban vsI·5% travel ban; Fig. S3 vs Fig. Sr).
Travel quarantine based on European Union traffic-light system
We calculated sufficient quarantines based on the input used by the EU COVID risk classification system,47 specifying population sizes, pre-existing immunity, travel duration, and travel flow as the average of obtained data on the countries analyzed and age-specific vaccine coverage observed within Europe. We found that for origin countries at equal or lower COVID-19 status than the destination country, a zero-day travel quarantine with RT-PCR test is equivalent to or better than a travel ban(Fig. 4).As the ratio of the two-week case count per capita in the origin country to the destination country increases, the specified duration of travel quarantine increases (Fig. 4).
Because testing approaches and quarantine durations vary across different countries, we compared sufficient travel quarantine durations under alternative strategies of no testing, and RT-PCR test on exit, a rapid antigen test on exit, and a rapid antigen test on both entry and exit. Regardless of the testing approach, discrete tier categorization, as opposed to quantitative calculation, led to the sufficiency of zero-day travel quarantine in any origin-destination pair for which the destination EU traffic-light status was equivalent or worse than the original EU traffic-light status(Fig.4; cf.Fig. 2G). Among origin countries with greater disease prevalence than the destination country, the median minimum sufficient quarantine duration with no test was four days, with a range of two to eight days (Fig. 4A).With an RT.
PCR test on exit from quarantine, the median duration of travel quarantine was two days, and durations ranged from one to four days (Fig.4B). Except for a Green destination and Dark-Red origin country, switching to a less sensitive but inexpensive and logistically flexible rapid antigen test yields results identical to those derived using an RT-PCR test on exit (Fig. 4C vs. Fig.4B). Performing a rapid antigen test on entry to quarantine in addition to exit from quarantine allowed for a day shorter quarantine duration when the destination country is Green and the status of the origin country is Dark Red (Fig.4D vs. Fig.4B), Furthermore, quarantine for a destination country in Red and origin country in Dark Red can be eliminated (Fig. 4D vs. Fig.4B).
We also quantified the effects of these alternative testing strategies in the context of our richly parameterized country-pair analysis (Fig. S4-S6) and found that these trends were largely consistent with the results obtained from a tier-based analysis (Fig. Sz and Fig. S33). Specifically, when the origin country was assigned lower-risk status than the destination country, the duration of quarantine for travelers from the origin country were equal to the median for equivalent country pairs in the tier-based analysis(Fig. S7 and Fig. S33). When the origin country was assigned a higher-risk status, the tier-based analysis exhibited the same increasing trend of quarantine duration with increasing EU risk status as the country-pair analysis. The greatest discrepancy was associated with the strategy of no test for a Red status destination and a Dark Red status origin for the epidemic status as of November 2I (Fig. S-B), where the median of quarantine duration from the country-pair analysis was six days longer than that deter-mined from the tier-based analysis.
Scenario analysis
We quantified the impact of longer incubation periods of 8-2g days and Ir-66 days on the sufficient quarantine durations compared to the baseline incubation period of 5-72 days. In the country-pair analysis, the sufficient quarantine durations for an RT-PCR test on exit from quarantine did not change for 62.9% of the origin-destination pairs using an 8-29-day incubation period (Fig. SI vs. Fig.Sro), and 54·4% remained unaltered for an Ir.66-day incubation period (Fig. SI vs. Fig. SIs). Among the pairs where the quarantine duration changed, the median quarantine duration for the incubation period of 8.2g days was one day longer than the median quarantine for the incubation period of 5-72 days, while the median quarantine duration for the r.66-day incubation period was three days longer. For the latter incubation period, 55-4% of country pairs could implement a sufficient o-day quarantine with an RT-PCR test on exit, compared to 65-o% for the baseline incubation period of s-72 days. With the EU traffic
light analysis, the minimum sufficient quarantine increased at most two days when considering an incubation period of 8.29 days for all testing strategies (Fig.4 vs. Fig. SI4). For the longer incubation period of Ir.66 days, the minimum sufficient quarantine increased at most seven days (Fig. 4 vs. Fig. SI9).
In our baseline analysis, we performed a policy evaluation based on Ioo% adherence to self-isolation upon symptom onset and within the quarantine. If adherence to self-isolation were to decrease from Ioo% to as low as 25%, we found that I4·5% of the estimated quarantine durations would change in the country-pair analysis with an RT.PCR test on exit from quarantine (Fig. S2o -S22). As adherence to the quarantine policy diminishes, there is a greater chance that a country would have to enforce border closure. With an RT-PCR test on exit from quarantine, the proportion of origin-destination pairs that require no travel increases from I.6% to Is-o% when adherence to quarantine declines from Ioo% to 75% (Fig. S23). At 25% adherence to the quarantine policy,37-I%of the country pairs would require a travel ban—a majority of which are imposed on origin countries with higher case burden over the last two weeks than the destination country (Fig. S2s).
The average daily travel flow was informed by annual arrivals for all forms of paid accommodation. In an alternative scenario, we used annual air passenger transport between countries to measure average daily travel flow between countries. Among all country-pair-ings common to both data sets, travel flow informed by air passengers resulted in no quarantine for 49·5% and border closure for no country pairings compared to 64-9% and I-7% respectively in the baseline analysis (Fig. S27 vs Fig. Sr). Comparing the quarantine durations of the two analyses,4g.8% of quarantine durations differed (Fig. S27 vs Fig. Sr). Among those that differed, we found that more stringent quarantines were suggested under travel flow informed by the number of air passengers (median of two days longer quarantine compared to baseline). Under the EU-tier based analysis, there was no change in the sufficient quarantine durations when using the air passenger transport between countries (Fig. 4 vs Fig. S3r).
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Discussion
Here we have identified strategies of travel quarantine and testing that prevent within-country imminent trans-mission beyond what would occur under a travel-ban scenario. We conducted our analysis for a snapshot in time based on the epidemic situation observed on November 2I,2o2I in 26 European countries. We demonstrated that quarantines for European destinations can be informed by country-specific prevalence, daily incidence, vaccine coverage, immunity, age-demo-graphics, and travel flow from the country of origin Our analysis for this specified time of the epidemic
indicated that for nearly half of these European origin-destination country pairs, no quarantine or test is necessary to prevent increased within-country imminent transmission from travelers, and for the majority, a test with no quarantine would be sufficient. For many other country pairs, a travel quarantine of a few days combined with testing on exit would suffice. The duration of travel quarantine is influenced mainly by the relative prevalence of disease between the origin and destination countries, immunity in both countries, and the asymmetry of travel. With a goal of preventing the introduction of variants of concern, quarantine and testing strategies that are sufficient for the general case will usually help to prevent the rise of imminent VOC trans-mission within-country as well. The strategies diverge when variants of concern are infrequent and prevalence is heterogeneous on the international scale.
The incubation period of a disease often determines the standard quarantine durations. However, quarantine durations quantified from our analysis are generally shorter than those implemented in most countries. These short but non-trivial quarantine durations arise from a multitude of factors. Firstly, unlike standard quarantines that aim for no post-quarantine transmission, our framework only requires quarantines where travel does not elevate infection rates in the destination country relative to the border closure. Also, infected travelers are more likely to enter quarantine later in infection compared to traced contacts who enter during the early stages postinfection. Other external factors, such as prevalence, travel flow, and immunity, also influence these quarantine durations. Therefore, accounting for the duration of the incubation period as well as external factors is essential for determining the appropriate travel quarantine strategy.
The sufficient travel quarantines for European coun-tries presented here are informed by the epidemic scenario on November 2I. The framework presented here can be used to guide short-term policy recommendations over the course of the epidemic by reevaluating quarantine durations based on changes in the epidemic scenario. Heterogeneity in the sufficient quarantine durations determined for country pairs across Europe demonstrates the importance of accounting for country-specific characteristics, such as asymmetry in travel These estimates could. in principle, be updated regularly using our cun-try-pair model based on the evolving epidemic situations in each country(Supplementary File). However, implementing travel quarantine and testing policies that are specific to many input parameters, dependent on the country of origin as well as destination-and that change dynamically as waves of the pandemic strike and recede—is logistically challenging. Indeed, some countries have a spec. ified a single quarantine duration for any traveler entering their country.89A single policy may be unduly restrictive—or in some cases may not be restrictive enough. An intermediate approach is to simplify input
parameters and discretize country classification in accordance with existing frameworks, such as the incidence-based EU traffic-light system. By considering European averages for other parameters, we demonstrated the feasibility of mapping our more highly parameterized approach to the EU traffic-light system.
The agreement between the results of our highly parameterized country-pair analysis and those we obtained from mapping to the prevalence-only EU traffic-light categories is imperfect. For example, Greece (Dark Red EU-status) requires a travel ban for travel from the UK (Dark Red EU-status) in the country-pair model, whereas no quarantine is indicated for the EU traffic-light model. The EU traffic-light model relies only on differences in incidence. Expanding beyond the EU traf-fic-light model to include country-specific vaccination coverage is possible, with the consequence of higher complexity of policy decision-making. However, any individual country can still improve the accuracy of the tier-based model by categorizing the rest of Europe in the EU tier-system and parameterizing the model (e.g. travel flow, immunity, and demographics) specific to their country as well European averages for origin countries. Therefore, our results from the EU traffic light model provide guidance regarding a simplified approach that aligns with current practices and illus. rates easy communication of appropriate travel quarantine duration. Together, the two models provide insight as to an effective quarantine duration for travel within Europe and provide analytical justification for decision-making that can otherwise be politicized rather than evil. evidence-based.
The sufficient quarantine durations are influenced by prevalence and immunity in the two countries, as well as the asymmetry in travel flow, consistent with previous studies highlighting importation risks are determined by multiple simultaneous factors. There are uncertainties associated with travel as well as the epidemiological state of a country that may alter the length of sufficient quarantine duration, Where disease prevalences and immunity levels are unknown or poorly monitored, countries may adopt a precautionary principle and take a restrictive approach to border control. Because travel volumes during the pandemic are uncertain, we used the annual number of arrivals to paid accommodations in 2org to inform a fixed daily travel flow, which underestimates the overall travel flow across country borders during 2oIg. However, we expect that it would still be greater than the reduced travel flow during the pandemic. Thus, our estimates for the sufficient travel quarantine can be considered conservative relative to the extent of travel during the pandemic. While we present our results based on average daily travel flow, seasonal fluctuations in travel could distort these aver-age relationships, affecting imminent transmissions as seen during 2O2o summer travel in Europe.°Our sensitivity analysis indicates that a disproportionate
increase of travelers into a destination country requires longer quarantines, while quarantine restrictions can be lessened when residents are more willing to travel. Therefore, re-evaluation of the sufficient quarantine to account for changes in travel flow between countries may be necessary to ensure continued safe travel.
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Our analyses focused on within-country imminent infection in comparison to travel ban, justifying the imposition of quarantine and testing strategies only insofar as they reduce within-country transmission more than a travel ban policy. However, whether the sufficient quarantine and testing strategies identified here are worthwhile from a public health or cost-effectiveness perspective requires additional consideration. For instance, high rates of hospitalization can over-whelm the healthcare infrastructure in a country. Stringent disease control measures were found to slow the local disease progression, delaying the peak in incidence and potentially preventing a crash of the local health system. Thus, policymakers may consider applying travel quarantines to ensure that the hospitalization rate remains manageable. Hospitalization rates in the destination country are likely not influenced by traveler origin or even by quarantine duration because of the rel. actively small numbers of travelers when compared with widespread infection among the resident population during a fully emerged pandemic.5' In this circum-stance, travel quarantines will have an almost trivial impact on within-country imminent infections and a proportionately small contribution toward hospitalization rate. For countries looking to shift toward a zero-COVID policy, the minimum sufficient quarantines determined from this framework are inadequate because they allow for a level of transmission similar to that estimated under a travel ban and do not halt the importation of cases. A balanced consideration of quarantine duration should come both from an understanding of the relative impact of travel on infection and on the public health consequences of infections.
With the implementation and relaxation of different disease-control efforts—along with differences in con-tact patterns and age demographics—the reproduction number will differ across countries, and constantly change over the course of the pandemic.2 The mini-mum sufficient quarantine duration is estimated under the specification that the implicit contact patterns were similar between residents and non-residents. This homogeneity impacts the number of infections occurring in and produced from travelers. Accounting for heterogeneity in the implicit contact patterns between travelers and residents can increase or decrease the minimum sufficient quarantine duration. Indeed, the number of infections that will occur among the residents of the destination country is influenced by the reproduction number. However, our estimates of mini. mum sufficient travel quarantine is independent of any changes in the reproduction number, as this
number factors out of the calculation (Supplementary material: Sufficient travel quarantine). Therefore, we chose to use a homogeneous reproduction number without incorporating the effects of self-isolation and vaccination for all countries. Our choice to use the basic reproduction number (and not the effective reproduction number) is conservative as it does not account for interventions.
Our analysis focuses on the European region, where SARS-CoV-2 infection is already widespread. Globally, there are only a few instances where the virus has been forestalled at a national》 or geographic border. Over the course of the pandemic, for instance, New Zealand has effectively maintained a low number of COVID-19 cases. Travel to New Zealand was restricted to citizens of that country, who were only allowed entry upon a negative test prior to departure, followed by a highly effective I4-day quarantine with two negative tests. o.%New Zealand aims to maintain closed borders with most of the globe until there is sufficient vaccine protection.5.55 This strategy is supported by our analysis for a country with very low or zero daily incidences and prevalence.
Similarly, our approach would recommend border closure by many countries early in the pandemic before the global spread of infection—a closure that did not happen for a variety of geopolitical reasons, but also because of technological and supply limitations that prevented rapid global testing. Even after several months into the pandemic, infections may still be under-reported due to limited health resources and a high proportion of asymptomatic infections.56-59 In part, for this reason, the EU traffic-light system elevates their assessment of risk for countries that have high rates of test positivity. Disproportionate under-reporting of infections in the origin country relative to the destination would limit the informativeness of our analyses using only reported infections. To overcome this limitation, an analytical layer could be added that adjusts reported prevalence by test positivity.9.6o
As the pandemic progresses, quarantine decisions may shift completely toward the prevention of one or multiple variants of concern that are more transmissible or can escape natural and vaccine-mediated immunity, which may justify the imposition of highly restrictive quarantine and testing strategies or even border closure. Just as in the early COVID-19 pandemic, strong implementation of travel restrictions could forestall specific variants of concern at the border. However, detection of such variants can be substantially delayed relative to their introduction or establishment in a country, Gs,6 which can lessen the effectiveness of border closure. Moreover, early detection of low-frequency emerging variants is unlikely—even by an aggressive surveillance effort. Consequently, our estimates of minimum sufficient quarantine durations for variants of concern should be understood as applying only to those already
identified. Analysis on quarantines aimed to prevent the invasion of an emerging variant would be useful, but there is no methodology evident to us for doing so. Rapid and accurate identification of variant properties is crucial for policy decisions because attempting to fore-stall even a low-frequency variant would often entail near-complete border closure, which may be unnecessary if the public health threat of the variant is minor compared to other circulating variants. National efforts to address disease spread would be tremendously aided by genomic approaches to rapidly and accurately assess variant properties. Building international capacity for such surveillance should be a priority for all nations so that decisions can be informed and judicious.
Our study focused on specifying quarantine durations for travel between only 26 European countries. However, some guidance for other countries may be obtained by finding the European country pairs most similar in circumstance to any origin-destination pair of interest. Furthermore, our modeling framework can be used directly by policymakers to inform travel quarantine duration between any two countries using country-specific input data. The applicability of our approach is not limited to travel between countries—where border controls are typically strongest and easiest to impose—but can be applied to any distinct populations for which disease prevalence, travel flow, and other input data can be quantified. Ultimately, international quarantine and testing should not be considered a substitute for national policy preventing the spread of disease at a more localized scale within the country itself. Even if an o-day quarantine is sufficient between countries, widespread local travel may lead to infections where there were previously none.64,65
The expected success of quarantine and testing can be undermined by non-compliance. We found that the level of adherence to self-isolation upon symptom onset had less impact on the estimated minimum sufficient quarantine duration than decreasing adherence to the quarantine policy. As adherence to quarantine decreases, the duration of sufficient quarantines increases. It is worth noting that non-compliance is increased by the stringency of the requirement so that it is possible to achieve less by requiring more. For example, some entrants to Canada opt not to comply 66-68 As the first with its I4-day quarantine requirement.
days of quarantine are often the most important to the prevention of SARS-CoV-2 transmission, it can be disadvantageous to public health goals to require a longer quarantine that elicits poor adherence instead of a shorter quarantine with improved compliance. Furthermore, shorter country-specifc quarantine durations could free up resources for measures that improve compliance such as providing low-cost, safe accommodations and convenient, rapid. and accurate testing.
There is some controversy as to whether antigen testing can substitute for RT-PCR testing.697i Rapid
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antigen tests have the advantage of faster turnaround time, but it comes at the cost of lower sensitivity and specificity than the RT-PCR tests. Inferior specificity of rapid antigen tests would lead to a higher false-positive rate, but this effect on imminent infections will be negligible if nonzero. Nevertheless, false positives may incur additional expenses for travelers such as validation tests, opportunity costs, and psychological damage. With regard to their lower sensitivity, our results indicate that rapid antigen tests can play a significant role in effective quarantine and testing. The faster turn-around for the processing of antigen tests permits its use a day later during quarantine than the RT-PCR test. This feature enables its timing just before travel departure, while RT-PCR would need to be scheduled days in advance and infection in its early stages may not be detected We also showed that multiple rapid antigen tests could potentially be equivalent to or better than RT-PCR tests for prevention of post-quarantine trans-mission. Furthermore, the use of an antigen test does not preclude one from sampling variants of concern, as positives can be referred for RT-PCR validation and genetic sequencing. However, the high volumes of testing required for travel quarantine pose challenges for the utility of both RT-PCR and rapid antigen tests. The processing time of numerous RT-PCR samples could be made more feasible using high-throughput assays, while additional training for travelers may be required to reduce the number of missed cases from rapid antigen tests.
Our analytical approach was designed to determine sufficient quarantines during the global COVID-19 pan-demic. However, the model can be reparameterized with the properties of other emerging diseases that may carry a global risk, to obtain policies of quarantine and testing that are sufficient to prevent increased within-country transmission. Border closure would be recommended during very early stages of pandemic spread to limit the global dissemination of an emerging disease from the epicenter, but such a measure provides limited benefits once community transmission is established in the country. As the trajectory of a pandemic continues to unfold and country-specific prevalence, circulation of variants, and potentially vaccination coverage changes, travel quarantine strategies can be adjusted to enable effective and judicious responses to new epidemiological conditions. The use of our model can provide an evidence-based approach to ameliorate policy decisions that often otherwise result in polarised, entirely permissive, or overly restrictive states. Our quantitative approach facilitates equitable and safe international travel conditions between countries.
