key: cord-1040590-eyhkn9c2
authors: Godin, Arnaud; Xia, Yiqing; Buckeridge, David L.; Mishra, Sharmistha; Douwes-Schultz, Dirk; Shen, Yannan; Lavigne, Maxime; Drolet, Mélanie; Schmidt, Alexandra M.; Brisson, Marc; Maheu-Giroux, Mathieu
title: The role of case importation in explaining differences in early SARS-CoV-2 transmission dynamics in Canada - a mathematical modeling study of surveillance data
date: 2020-10-25
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2020.10.046
sha: e265f052199d4aac42a879ab85fc855a23e49047
doc_id: 1040590
cord_uid: eyhkn9c2

OBJECTIVE: North American COVID-19 epidemics exhibited distinct early trajectories. In Canada, Quebec had the highest COVID-19 burden and its earlier March school break, taking place two weeks before those of the rest of the country, could have shaped early transmission dynamics. METHODS: We combined a semi-mechanistic model of SARS-CoV-2 transmission with detailed surveillance data from Quebec and Ontario (accounting for 85% of Canadian cases). We then explored the impact of case importation and timing of control measures on cumulative hospitalization. RESULTS: A total of 1,544 and 1,150 cases among returning travelers were laboratory-confirmed in Quebec and Ontario, respectively (symptoms onset ≤2020-03-25). Hospitalizations could have been reduced by 55% (95%CrI: 51-59%) had no cases been imported after Quebec’s March break. However, had Quebec experienced Ontario’s number of introductions, hospitalizations would have only been reduced by 12% (95%CrI: 8-16%). Early public health measures mitigated epidemic spread as delaying them by one week could have resulted in twice as many hospitalizations (95%CrI: 1.7-2.1). CONCLUSION: Beyond introductions, factors such as public health preparedness, responses, and capacity could play a role in explaining interprovincial differences. In a context where regions are considering lifting travel restrictions, coordinated strategies and proactive measures are to be considered.

Both American and Canadian epidemics of coronavirus disease 2019 (COVID-19) are marked by stark geographic heterogeneities [1] . Despite reporting its first case on February 28, 2020 -close to a month after Ontario on January 25 th and British Columbia on January 28 th -Québec quickly became the epicenter of the Canadian COVID-19 epidemic. The disease's mortality burden in that province, at 653 per million population, was 3.5 times as high as neighboring Ontario (186 per million) and 19 times that of British Columbia (at 35 per million) at the end of the first spring 2020 wave [2] . Quebec also had one of the highest ratios of confirmed cases per million population in the world in the spring of 2020 ( Figure   S1 ) [3] albeit these comparisons are caveated by the underlying testing efforts.

Such interprovincial epidemic differences across Canada are puzzling, given general similarities in age structure, universal health care systems, and timing of local physical distancing measures. For example, British Columbia and Ontario's ratios of confirmed cases per population are 11 and 2.6 times lower, respectively, than that recorded in Québec (as of July 5 th 2020). One hypothesis for these differences, is that the timing of the "semaine de relâche", or March break, played a major role in seeding the Quebec epidemic. This March break took place during the week of March 2 nd in Quebec-up to 2-weeks earlier than other Canadian provinces. Increased travel over that week could have led to a sudden and high number of imported cases -at a time when physical distancing measures had yet to be enacted and implemented. In other provinces, public health authorities recommended against travel during their later March break [4, 5] .

J o u r n a l P r e -p r o o f A systematic examination of the impact of imported cases on observed heterogeneities in COVID-19 burden has yet to be conducted. In this study, we analyze and compare surveillance data from Quebec and Ontario, the two largest provinces in Canada, regarding the number and timing of imported cases. Using a dynamic mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, we then estimate the impact of reducing case importation on the size of the epidemic in Quebec as of [6, 7] . The model is semi-mechanistic in the sense that it does not explicitly model interventions. Rather, the impact of those interventions is captured by allowing the transmission rate to vary with time. The model can be described ( Figure S2 ) using ordinary differential equations (Text S1) and the main model parameters are described in Table S1 . Cases that have acquired SARS-CoV-2 outside the province are directly imported into the infectious compartments one day before their date of symptom onset. Since only symptomatic cases could have been detected upon arrival, we accounted for underreporting of asymptomatic cases by importing infectious individuals in the homonymous compartment proportionally to the fraction of cases that are asymptomatic transmission dynamic, calibrated to detailed surveillance data, we found that cases acquired outside the province played an important role in the initial spread of COVID-19 in Quebec and that early interventions had a strong impact on transmission. Had Quebec not experienced any imported cases after its March break, but otherwise implemented the same interventions, the cumulative number of hospitalizations could have been halved. However, case importation alone is not sufficient to fully explain why Quebec suffered a much more severe epidemic as compared to its close neighbor, Ontario. That province also had many travel-related cases and, had Quebec received Ontario's daily number of imported cases, the epidemic could have been 12-19% smaller in terms of hospitalizations.

In Quebec, a public health state of emergency was declared on March 13 th by the Ministry of Health and Social Services, followed by a range of physical distancing recommendations, restrictions, and closures [10] . Ontario followed Quebec's path and declared a state of public health emergency four days later. In Quebec, had this sequence of restrictions and public health measures been implemented one week later, the number of cumulative hospitalizations could have been twice as high during the first spring wave. Our results highlight the importance of early interventions to rapidly control transmission.

The large difference in epidemic sizes of COVID-19 between Quebec and Ontario remains puzzling. Health system preparedness and capacity to respond to emerging epidemics could have played a role. For instance, Ontario recorded its first SARS-CoV-2 case J o u r n a l P r e -p r o o f close to a month before Quebec. As such, the largest Canadian province could have better prepared for tracing contacts and isolating imported cases-important non-pharmaceutical interventions to prevent onward transmission [6, 7] . While public health capacity itself remains difficult to evaluate, Québec's regional public health agencies have been subjected to reforms in 2015, with budget decreases of 30% and changes in the organizational structure that could have made coordination more challenging [11, 12] . Other factors such as suboptimal surveillance systems for early outbreak detections, bottlenecks in testing capacity, initial unavailability of personal protective equipment, and shortages of healthcare personnel, among other things, could have negatively affected transmission in Quebec.

These results need to be interpreted considering certain limitations. First, our model mainly reflects transmission in the community and outbreaks occurring in LTCF are not modeled explicitly. As such, it is unclear if the modeled proportional reductions in cumulative hospitalizations for our different scenarios could have directly translated in reduced deaths as most of them occurred in LTCF. Second, the validity of our provincial comparison hinges on the assumption that a comparable fraction of all symptomatic travelrelated COVID-19 cases were detected by surveillance systems in both provinces. This assumption could be violated if, for example, more travelers in one province would be returning from countries which were at the time deemed at low risk of COVID-19 (hence less likely to be tested). Given the reasonably low positivity of 5% before March 25 th in Quebec, however, incomplete case detection could have been limited. This is also supported by a retrospective analysis conducted of more than 1,000 samples collected by the National Public Health Laboratory of Quebec from patients with flu-like symptoms between November 2019 and early March 2020 that did not detect SARS-CoV-2 [13] .

Alternatively, more non-resident tourists from high-risk areas could have visited one province, leading to local chains of transmission, and these tourists would have been missed by case surveillance systems. Assessing levels of SARS-CoV-2 introduction by non-resident tourists is challenging, but we note that Ontario received twice as many non-resident tourists from Europe and the United States during February and March of 2020 (521,081 and 245,521 in Ontario and Quebec, respectively), albeit Quebec had higher numbers of visitors from France [14, 15] . A recent genomic analysis provides credence to our assumptions.

Reporting on 734 high-quality SARS-CoV-2 consensus sequence from March 2020, the authors found that most case importations occurred through Europe and the Americas around March Break and that there were very few cryptic transmission chains before early

March [16] , as suggested by our epidemiological analyses.

Our analytical framework has several strengths. First, we used detailed surveillance data to inform model development, parameterization, and calibration. Second, the model was calibrated to hospitalization data which is believed to be more robust than case surveillance data, which are affected by time-varying COVID-19 testing efforts, testing protocols, and health-seeking behaviors. Third, we contrasted the experience of Quebec and Ontario in terms of imported cases. These two provinces experienced different epidemic trajectories but otherwise share many similarities.

In conclusion, the rapid importation of more than a thousand COVID-19 cases in Quebec to date resulted in major outbreaks with more than six thousand cumulative 

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