key: cord-290965-7qs4w9xh authors: Kwok, W. C.; Wong, C. K.; Ma, T. F.; Ho, K. W.; Fan, W. T. L.; Chan, K. P. F.; Chan, S. K. S.; Tam, C. C. T.; Ho, P. L. title: Border Restriction as a Public Health Measureto Limit Outbreak of Coronavirus Disease 2019 (COVID-19) date: 2020-11-03 journal: nan DOI: 10.1101/2020.10.29.20222190 sha: doc_id: 290965 cord_uid: 7qs4w9xh Background: Coronavirus Disease 2019 (COVID-19) led to pandemic that affected almost all countries in the world. Many countries have implemented border restriction as a public health measure to limit local outbreak. However, there is inadequate scientific data to support such a practice, especially in the presence of an established local transmission of the disease. Method: A novel metapopulation Susceptible-Exposed-Infectious-Recovered (SEIR) model with inspected migration was applied to investigate the effect of border restriction between Hong Kong and mainland China on the epidemiological characteristics of COVID-19 in Hong Kong. Isolation facilities occupancy was also studied. Results: At R0 of 2.2, the cumulative COVID-19 cases in Hong Kong can be reduced by 13.99% (from 29,163 to 25,084) with complete border closure. At an in-patient mortality of 1.4%, the number of deaths can be reduced from 408 to 351 (57 lives saved). However, border closure alone was insufficient to prevent full occupancy of isolation facilities in Hong Kong; effective public health measures to reduce local R0 to below 1.6 was necessary. Conclusion: As a public health measure to tackle COVID-19, border restriction is effective in reducing cumulative cases and mortality. Conclusion: As a public health measure to tackle COVID-19, border restriction is effective in reducing cumulative cases and mortality. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted November 3, 2020. ; https://doi.org/10.1101/2020.10.29.20222190 doi: medRxiv preprint Article summary A novel metapopulation SEIR model with inspected migration was developed to investigate the epidemiological characteristics of COVID-19 in Hong Kong, Guangdong and the rest of China (excluding Hubei) in the presence or absence of border restriction. The presented model is also suitable for further analysis of other emerging infectious diseases. Border restriction is an effective public health measure in reducing cumulative cases and mortality for COVID-19. Interaction was assumed to be well-mixed within patch. The spatial effect in disease transmission within each patch is ignored, which can have a non-trivial effect on the dynamic of infectious disease. The proposed model is deterministic in nature which ignores the randomness in migration and in the interactions among people; a stochastic model would be more realistic especially early in the disease. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. whereas later cases were predominantly mediated by human-to-human transmission (3) . Transmission through asymptomatic contact also seemed highly probable (4), a feature that was not previously seen with SARS-CoV or MERS-CoV. Clinical spectrum of SARS-CoV-2 infection ranges from flu-like illness to pneumonia with rapid progression to acute respiratory distress syndrome (ARDS) and death (1, (5) (6) (7) . Among hospitalized patients, 32% to 51% had underlying disease and 26% to 32% of them required intensive care unit admission. The fatality rates for hospitalized COVID-19 patients varies between 0·6% to 15% (1, 6, 7) but the true disease-specific mortality rate is unclear because the proportion of asymptomatic and mild infections remains uncertain. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted November 3, 2020. ; https://doi.org/10.1101/2020.10.29.20222190 doi: medRxiv preprint COVID-19 rapidly evolved and became a pandemic. As of 20 th July 2020, there were more than 14 million COVID-19 over the world (8) . To limit the scale of local disease outbreak, many countries implemented travel restriction towards travellers from regions with severe COVID-19 outbreak and even all other countries, despite the World Health Organization (WHO) advising against implementing travel restriction as a public health measure to tackle COVID-19. Hong Kong is a Special Administrative Region of the People's Republic of China and border control exists between the two regions. Owing to the tight geographical and socio-economic ties, more than forty-million individuals travelled from mainland China to Hong Kong in a year (9) . China was the earliest country with COVID-19 outbreak. On 23 rd January 2020, Hong Kong confirmed its first imported case of COVID-19 from Hubei (10). In the subsequent weeks, the number of imported cases rapidly rose despite initiation of various public health measures. Medical professionals and the general public repeatedly urged the Hong Kong government to close the Hong Kong-Chinese border to stop further influx. However, some questioned the effectiveness of such measure as there was already sign of local transmission in Hong Kong. Some believed that border restriction is not useful in the presence of established local transmissions as the final disease burden might be primarily driven by local transmission instead of importing of foreign cases. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted November 3, 2020. ; https://doi.org/10.1101/2020.10.29.20222190 doi: medRxiv preprint To date, there is inadequate scientific data to support border restriction as a public health measure to limit local outbreak of an emerging infectious disease in the presence of an established local transmission. The objective of this study is to assess the impact of border restriction on cumulative caseload and hospital occupancy with a novel metapopulation Susceptible-Exposed-Infectious-Recovered (SEIR) model with inspected migration. Projection of COVID-19 epidemiology in Hong Kong and mainland China will be performed as an illustration. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted November 3, 2020. ; https://doi.org/10.1101/2020.10.29.20222190 doi: medRxiv preprint In this study, a novel metapopulation SEIR model with inspected migration was applied to investigate the epidemiological characteristics of COVID-19 in Hong Kong, Guangdong and the rest of China (excluding Hubei) in the presence or absence of border restriction. Guangdong was separately analyzed from the rest of China because Guangdong province had significantly higher confirmed cases per population (11·7 per million) than the rest of China (excluding Hubei) (9·5 per million) as of 20 th February 2020. Hubei province, with the highest case density in China (1048·4 per million), was excluded from analysis as all Hubei-Hong Kong travel was banned after the Wuhan lockdown on 23 rd January 2020. Real world data up to 8 th February 2020 was used. SEIR type models are commonly adopted to simulate epidemiology of infectious disease of a single region over time. It is based on a system of ordinary differential equations (ODE) that governs the number of 4 types of individuals: susceptible (S), exposed but latent (E), infectious (I), and recovered (or death) (R). Conventional single-patch SEIR models are not suitable for studying the impact of border restriction of an emerging infectious disease. A novel modified metapopulation SEIR model with inspected migration was used in this study. In addition to simulating population migration, parameters such as efficiency of custom inspection in blocking infected travellers were also being incorporated. Details of the model were described in Appendix 1. Assumption All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted November 3, 2020. ; https://doi.org/10.1101/2020.10.29.20222190 doi: medRxiv preprint It was assumed that there were no vital dynamics and well-mixed within patch for simplicity. Disease transmission between patches was assumed to be contributed by migra- The mean incubation and infectious period was taken as 5·2 and 5·0 days respectively (3) . Coronavirus transmissibility has been hypothesized to reduce as temperature rises (13), hence ܴ 0 is set to be inversely correlated with temperature. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The Hong Kong public health system had a maximum of 952 isolation beds in 490 isolation single rooms according to the data from Hospital Authority press conference on 1 st March 2020. It was assumed that all isolation facilities were used exclusively for COVID-19 purposes. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted November 3, 2020. of 1·6 -2·1, complete border closure was projected to cause a 11·54 -13·71% reduction in cumulative cases and mortality ( Figure 1 and Table 2 ). The results suggested that even in the presence of established local transmission, travel restriction remains an effective measure to reduce the cumulative cases in the recipient region. COVID-19 associated mortality can also be decreased with this measure. Maintaining complete border closure and having effective public health measures to keep ܴ 0 below 1.6 is required to allow Hong Kong to meet its isolation room require-All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted November 3, 2020. ; https://doi.org/10.1101/2020.10.29.20222190 doi: medRxiv preprint ment. Other permutations are shown in Table 3 , and graphically represented in Figure 2 . Countries or cities with a high population density and aged population including Hong Kong is at risk of severe outbreak of emerging infectious diseases such as COVID-19. As the disease is spreading rapidly in multiple continents, many countries implemented border restrictions towards regions with severe outbreak in order to reduce local case number and mortality. This is particularly important for developing countries with inadequate medical resources to tackle massive local outbreak. However, the WHO advised against utilizing travel restriction as an infection control measure. Furthermore, it is particularly challenging to implement border restriction in certain regions due to political, social and economical reasons. To date there is inadequate scientific data to support border restriction as a public health measure to limit the scale of local outbreak in the presence of an established local transmission. Using Hong Kong and mainland China as an example, we quantitatively illustrated border restriction is effective in reducing cumulative caseload, mortality and healthcare facility occupancy with a novel metapopulation SEIR model with inspected migration. It was projected that complete border closure will result in meaningful reduction of cumulative cases (4079 cases at ܴ 0 of 2·2), mortality (57 deaths at 1·4% in-patient mortality) and a delay in isolation facility overload in Hong Kong. It is important to emphasize that in our projection, border closure alone is insufficient to prevent healthcare overload, as measured by isolation facilities occupancy. Effective All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted November 3, 2020. In the past few months, multiple regions had exponential rise in COVID-19 cases which caused extreme stress to their local health care system. In Wuhan, which was the epicenter of the COVID-19 outbreak in China, severe shortage in isolation facilities urged urgent construction of multiple temporary hospitals. COVID-19 related mortality in regions with severe outbreak tend to be higher due to relative shortage of medical resources outweigh demand. Advanced life support facilities such as intensive care unit, ventilators, extracorporeal membrane oxygenation (ECMO) machines and anti-viral All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted November 3, 2020. ; https://doi.org/10.1101/2020.10.29.20222190 doi: medRxiv preprint medications were essential in severe COVID-19 cases but their availability is limited. In addition, COVID-19 also severely hinder other non-COVID-19 related medical services. In Hong Kong, although the total confirmed COVID-19 cases is less than the available isolation facilities at the moment, a significant proportion of other less urgent medical services include elective investigations and surgeries have been suspended to reserve resources for COVID-19. In less resourceful regions, the effect may even be more pro- The spread of infectious disease is closely related to the migration of population between regions (19, 20) . Conventional single-patch SEIR models are not suitable for such analysis. A novel metapopulation SEIR model with inspected migration was specifically developed for this purpose. In addition to COVID-19, the developed model can be used to perform projection for other emerging infectious diseases in the future. Furthermore, parameters such as effectiveness of custom inspection were included to improve All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted November 3, 2020. ; https://doi.org/10.1101/2020.10.29.20222190 doi: medRxiv preprint accuracy of projection. The presented model is also suitable for further analysis of other emerging infectious diseases. Firstly, interaction was assumed to be well-mixed within patch. The spatial effect in disease transmission within each patch is not directly addressed in the model, which can have a non-trivial effect on the dynamic of infectious disease (21) . Secondly, the proposed model is deterministic in nature which ignores the randomness in migration and in the interactions among people; a stochastic model would be more realistic especially early in the disease. Thirdly, key parameters such as rate of spread is still unclear so we assumed a parametric form of the rate of spread with reference to 2003-SARS. In general, parameter calibration can be performed by some criteria, for example, minimizing residuals sum of square between the historical and fitted infected cases. Meanwhile, missing information, such as travel history across regions, leads to crucial statistical uncertainty. A stochastic metapopulation migration model to explore the corresponding statistical properties with data would be a fruitful direction in the future. While the above shortcomings may be the expected tradeoff between computation time and model simplicity, it will not negate the signal that core message that border restriction reduces cumulative case, mortality and delay healthcare system exhaustion. Lastly, economic impact is beyond the scope of this study. While full border closure can have a negative impact on the economy, one cannot ignore the negative economic impact from an otherwise preventable major outbreak. At time of writing, COVID-19 was perceived to have developed into a pandemic situation and global stock market plummeted with The Dow Jones Index and Hang Seng Index both fell more than 9% percent since 2/1/2020. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted November 3, 2020. ; https://doi.org/10.1101/2020.10.29.20222190 doi: medRxiv preprint As a public health measure to tackle COVID-19, border restriction is effective in reducing cumulative cases and mortality. Hospital occupancy can be reduced but effective public health measures to achieve significant reduction in ܴ 0 would be necessary to prevent full occupancy of available isolation facilities. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted November 3, 2020. ; https://doi.org/10.1101/2020.10.29.20222190 doi: medRxiv preprint This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. No potential conflict of interest was reported by the authors. The lead author (the manuscript's guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained. Ethical approval is not required as this study does not involve patients. Our study is reported according to the GATHER statement. · Data sharing: No additional data available. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted November 3, 2020. ; (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 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