April 17, 2020

PUBLIC HEALTH INTERVENTIONS

A few terms:

R0 = basic reproduction number (the average number of people that one person will infect). An outbreak is expected to end if R0 < 1

Rt = R0 over time

What is the evidence on transmission risk of SARS-CoV-2 in fitness centers and how can this risk be decreased?

Answered in May 10, 2020 Newsletter

  • There is limited evidence available on the transmission of SARS-CoV-2, MERS-CoV, or SARS-CoV in fitness centers.

  • One study analyzed the risk of infection of influenza and tuberculosis in a few different gyms by using the Wells-Riley model.(1) They demonstrated an increased risk of infection at all of the fitness centers. The study established that increased ventilation intensity, high occupancy concentration and poor ventilation in the infrastructure were key factors in increasing transmission risk, all of which are factors commonly present in fitness centers.

  • The Wells-Riley model predicts infection risks in indoor environments depending on ventilation rate.(2) The equation assumes that individuals have the same ventilation rate, there is uniform distribution of air and infectious agent in the room, and that all individuals are susceptible to the infectious agent. Furthermore, it is important to note that the Wells-Riley equation was created for airborne pathogens and extrapolation of results to a non-airborne pathogen would be problematic. As discussed in this week’s infection prevention and control section, SARS-CoV-2 is predominantly transmitted by droplets and close contact.

  • As there is no specific evidence regarding transmission of SARS-CoV-2 in fitness centers, general considerations to decrease risk include proper cleaning of shared equipment and high touch surfaces, appropriate spacing of equipment to allow for physical distancing, setting a time limitation to visit, and ventilation consideration. In Manitoba, fitness centers reopening are currently part of post phase two of reopening public services.(3)

  1. Andrade A, Dominski FH, Pereira ML, de Liz CM, Buonanno G. Infection risk in gyms during physical exercise. Environ Sci Pollut Res. 2018;25(20):19675-19686. doi:10.1007/s11356-018-1822-8

  2. Sze To GN, Chao CYH. Review and comparison between the Wells-Riley and dose-response approaches to risk assessment of infectious respiratory diseases. Indoor Air. 2010;20(1):2-16. doi:10.1111/j.1600-0668.2009.00621.x 

  3. Manitoba G of. Restoring Safe Services - Manitoba’s Pandemic and Economic Roadmap for Recovery. 2020;(May).

Contact tracing apps are a possible adjunct to conventional methods of contact tracing. What are the available options and what is the evidence that they can help?

Answered in May 10, 2020 Newsletter

  • There are currently three types of mobile phone apps available:(1)

    • Bluetooth-based apps – These apps use Bluetooth Low Energy to detect and log other phones with the app that spend a pre-set amount of time in their close vicinity. If one of the users tests positive for SARS-CoV-2, the users that encountered them will be notified that they may have been exposed. 

    • Location-monitoring apps – These apps can record an individual’s location, which can then be cross-referenced with data from other devices in order to trace contacts. Due to privacy concerns, this has not been a popular option.

    • QR code scanning apps – These apps are used to scan QR codes located in public places as a “check in”. Similarly, the idea has been put forward of an app that can generate its own unique code that others can scan as a “check in”.(2) This could then be used for contact tracing of individuals meeting in groups at private residences as well as in public spaces.

  • A key factor in the effectiveness of the app is how widely it would need to be adopted. There is currently no real-world data on this, but there have been modelling studies. A report from Oxford University for the National Health Service (NHS) in the UK determined that the app would need to be adopted by 80% of mobile phone users or 56% of the total population in order for the epidemic to be suppressed.(3) This study used assumptions in their model that included an urban population of 1 million individuals, individuals over 70 years old continued to quarantine, assumed no app use in < 10 years old, and a higher R0 was used to account for faster doubling time in Europe.

  • Another modelling study found that an epidemic/outbreak may be better controlled with increasing adoption rate of a contact tracing app.(2) This information was presented in the following figure which compares infection curves from simulations of varying adoption rates of a peer-to-peer contact tracing app. The proportion of the population with active infection is plotted across time for the various app adoption rates and the results of 10 random simulations per adoption rate are shown.

  • There is currently no data regarding effectiveness of contact tracing apps compared to traditional methods for the current COVID-19 pandemic. However, apps have been previously used for contact tracing in sexually transmitted diseases. In one study, investigators found that the use of an app to notify people of their test results reduced the time from testing to treatment on average from 12 to 10 days.(4) Although the two settings are different enough to preclude direct comparison and extrapolation, there is a possibility that contact tracing apps could have a similar beneficial effect, among others.

  1. Meixner S. Australia has COVIDSafe. Here is how other countries are using contact tracing apps in the fight against coronavirus. ABC News [Internet]. 27 April 2020 [Cited 7 May 2020].

  2. Yasaka TM, Lehrich BM, Sahyouni R. Peer-to-Peer Contact Tracing: Development of a Privacy-Preserving Smartphone App. JMIR Mhealth Uhealth [Internet]. 7 April 2020 [Cited 7 May 2020] 8 (4).

  3. Hinch R, Probert W, Nurtay A, Kendall M, Wymant C, Hall M, et al. Effective Configurations of a Digital Contact Tracing App: A report to NHSX. University of Oxford [Internet]. 16 April 2020 [Cited 7 May 2020].

  4. Cohen AC, Zimmerman F, Prelip M, Glik D. A Smartphone Application to Reduce Time-to-Notification of Sexually Transmitted Infections. American Journal of Public Health [Internet]. 2017 [Cited 7 May 2020] 107 (11): 1795-1800.

What are some of the privacy concerns of contact tracing apps and how are they addressed?

Answered in May 10, 2020 Newsletter

  • The main privacy concern with using contact tracing apps is the possibility of being monitored and having personal information exploited for ulterior motives.(1)

 

  • There are two general types of contact tracing apps:(2,3)

    • Centralized apps: information collected (including personal and/or location depending on the type of app) are stored and processed in a central database held by a national authority (e.g. healthcare services). This type of approach appeals to the aforementioned privacy concerns. This type of app carries the above-mentioned concerns.

    • Decentralized apps: information collected is stored locally on the device and shared on if the user agrees following a confirmed COVID-19 diagnosis. This information is then disseminated anonymously in a peer-to-peer manner to inform close contacts about a possible risk of exposure. The concern with this model is that it relies on an honesty system where individuals can choose to conceal their COVID-19 diagnosis.

  • There are apps currently in development that possess both centralized and decentralized features.(4) For example, Privacy Kit, an app developed by MIT (Massachusetts Institute of Technology) and Harvard, can disseminate encrypted information about one’s location and COVID-19 diagnosis between app users. The app also enables users to directly share their information with national authorities who can then store the data into a central database.

  • There has been great interest in many countries, including Canada, with adopting a digital platform to assist with contact tracing. As healthcare in Canada is provincially regulated, each province is making their own considerations in terms of the type of contact tracing app they may adopt and with it, the type of information they want to collect.

  1. Cooke R. Can digital contact tracing be done without creeping surveillance? Privacy commissioner is hopeful | CBC News [Internet]. 2020 [cited 2020 May 7].

  2. Lomas N. Germany ditches centralized approach to app for COVID-19 contacts tracing | TechCrunch [Internet]. 2020 [cited 2020 May 6].

  3. McCarthy K. UK finds itself almost alone with centralized virus contact-tracing app that probably won’t work well, asks for your location, may be illegal • The Register [Internet]. 2020 [cited 2020 May 7].  

  4. Heaven WD. A new app would say if you’ve crossed paths with someone who is infected | MIT Technology Review [Internet]. 2020 [cited 2020 May 7].

What is the transmission risk of SARS-CoV-2 with reusable grocery bags?

Answered in May 1, 2020 Newsletter

  • Most reusable grocery bags are made from cloth or recycled plastic; brown paper bags are sometimes also used. SARS-CoV-2 can remain viable for up to 3(1) to 7(2) days on plastic, up to two days on cloth,2 and up to 3 hours on paper.(2) No data exist for SARS-CoV-2 stability on recycled plastic and extrapolation from smooth plastic surfaces may not be possible as SARS-CoV-2 seems to be more stable on smooth surfaces,2 whereas recycled plastic surfaces are rough. The authors note that these times should not be understood to indicate real world transmissibility of the virus from casual contact with a surface because they eluted the virus by soaking the material in viral transport medium for 30 minutes(2) or eluted with 1mL of viral culture medium.(1)

  • Based on the above data, if people follow current advice not to go shopping frequently, any viral particles picked up by their reusable bag should become non-viable before the next shopping trip.

  • The possibility of SARS-CoV-2 transmission on reusable bags cannot be ruled out. However, in the context of physical distancing, shoppers with contaminated bags most likely inoculated the bags themselves, and so the concern would be the theoretical transmission to others. In any case, good hand hygiene during grocery shopping should be observed and anyone who is ill should stay home.

  1. van Doremalen N, Morris DH, Holbrook MG, Gamble A, Williamson BN, Tamin A, Harcourt JL, Thornburg NJ, Gerber SI, Lloyd-Smith JO, de Wit E, Munster VJ. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. NEJM. 2020;382(16). 

  2. Chin AWH, Chu, JTS, Perera MRA, Hui KPY, Yen HL, Chan MCW, Peiris M, Poon LLM. Stability of SARS-CoV-2 in different environmental conditions. Lancet Microbe. 2020; (published online April 2).

What is the transmission risk of SARS-CoV-2 in outdoors settings?

Answered in May 1, 2020 Newsletter

  • There is currently very little evidence regarding outdoor transmission of SARS-CoV-2. A preprint study in China examining outbreak cases found that of the 7,324 cases of COVID-19, only one outbreak occurred outdoors.(1) This cluster involved two cases that was linked to a conversation held outdoors. Another preprint study from Japan postulated that indoor transmission of SARS-CoV-2 was 18.7 times more likely than outdoor transmission.(2)

  • Besides the outdoors being an open space, other variables include temperature, humidity, and UV index. As mentioned in April 17, 2020 newsletter, it is difficult to predict the impact of variations in temperature and humidity on SARS-CoV-2 transmission. UV radiation is effective at inactivating SARS-CoV(3) and is known to inactivate influenza, thus we can likely extrapolate this to SARS-CoV-2. However, these experiments were done in a lab and it is unclear what the real-world effect of sunlight is on the virus.

  • A preprint study postulated that viral particles may be able to travel in droplets further than 1.5 meters behind a person when released in a slipstream of air currents generated by runners or bikers.4 The authors, however, noted that this was done using a simulation that assumed there was no wind. Given that the simulation was only focused on the physics aspect of droplet transmission, it is difficult to predict if there would be enough viable viral particles to cause infection. The infectious dose, ID50, (amount of virions required to produce infection in 50% of exposed people) for SARS-CoV-2 is currently unknown. For SARS-CoV the ID50 was estimated to be 280 plaque forming units.(5) SARS-CoV-2’s ID50 has been postulated to be lower given its higher infectivity.

  • Overall, although it seems that outdoor spread of SARS-CoV-2 is relatively lower than in other scenarios, there is little evidence that provides a clear understanding of the factors involved and how they interact. Environmental conditions may play a role in reducing spread, but factors such as crowding and contact with contaminated surfaces may increase risk. Therefore, precautions such as physical distancing and diligent hand hygiene continue to be important.

  1. Qian H, Miao T, Liu L, Zheng X, Luo D, Li Y. Indoor transmission of SARS-CoV-2. medRxiv [Internet. Preprint]. 2020 [Cited 29 April 2020].  

  2. Nishiura H, Oshitani H, Kobayashi T, Saito T, Sunagawa T, Matsui T, et al.  Closed environments facilitate secondary transmission of coronavirus disease 2019 (COVID-19). medRxiv [Internet. Preprint]. 2020 [Cited 29 April 2020].  

  3. Duan SM, Zhao XS, Wen RF, Huang JJ, Pi GH, Zhang SX, et al. Stability of SARS coronavirus in human specimens and environment and its sensitivity to heating and UV irradiation. Biomedical and environmental sciences [Internet]. 2003 [Cited 29 April 2020] 16 (3): 246-55.  

  4. Blocken B, Malizia F, van Druen T, Marchal T. Towards aerodynamically equivalent COVID19 1.5 m social distancing for walking and running. Urban Physics [Internet, Preprint]. 2020 [Cited 29 April 2020].

  5. Watanabe T, Bartrand TA, Weir MH, Omura T, Haas CN. Development of a Dose‐Response Model for SARS Coronavirus. Risk Analysis [Internet]. 2010 [Cited 29 April 2020] 30 (7): 1129-1138.

What is the evidence regarding transmission of SARS-CoV-2 on university campuses? Are there special considerations for rearranging residences to allow students to stay?

Answered in May 1, 2020 Newsletter

  • Numerous university campuses have closed to decrease potential transmission. There is limited evidence about transmission of SARS-CoV-2 on university campuses. Studies of transmission dynamics from previous pandemics may offer insight.

  • There is data on intra-campus transmission during the 2009 H1N1 Influenza pandemic.(1,2) Transmission was likely due to high contact activities and congregate settings on campus such as student clubs, lectures, labs, and the use of common areas (e.g. libraries and canteens). Closure of campuses and cancellation of classes would limit these routes of transmission. Studies also observed a moderate degree of transmission from the general community into the campus.(1,3)

  • There are conflicting results in studies about the transmission of influenza in campus housing (e.g. residence halls and dormitories). Some data indicates clustering of cases was present at residence sites,(1) but other studies suggest that no clustering was found there.(3) Currently, measures regarding student residences vary from school to school. Some institutions are allowing some students to stay in their current residence, but enforcing proper hygiene and social distancing measures.(4)

  1. Virk RK, Gunalan V, Lee HK, et al. Molecular evidence of transmission of influenza A/H1N1 2009 on a University Campus. PLoS One. 2017;12(1):1-11.

  2. Uchida M, Tsukahara T, Kaneko M, Washizuka S, Kawa S. How the H1N1 influenza epidemic spread among university students in Japan: Experience from Shinshu University. Am J Infect Control. 2012;40(3):218-220. 

  3. Holmes EC, Ghedin E, et al. Extensive Geographical Mixing of 2009 Human H1N1 Influenza A Virus in a Single University Community. J Virol. 2011;85(14):6923-6929.  

  4. Loriggio P. Students at several colleges and universities asked to vacate dorms over COVID-19. The Canadian Press. Published 2020.

Assuming that SARS-CoV-2 will not spontaneously disappear, what indicators should be used to determine when to decrease or increase public health measures?

Answered in April 24, 2020 Newsletter

  • There is currently no concrete evidence in the literature regarding what metrics should be used to determine when public health measures can be lifted. The World Health Organization has recommended that restrictions be lifted in a stepwise incremental fashion, once a steady state of low-level or no transmission has been achieved.(1) The WHO has outlined six criteria for lifting measures:

    • COVID-19 transmission is controlled

    • Sufficient health system and public health capacity is in place

    • Outbreak risks in high-vulnerability settings are minimized

    • Workplace preventive measures are established

    • Risk of imported cases is managed

    • Communities are fully engaged

  • Some studies have suggested that public health measures could be “turned on and off” based on indicators in the population.(2,3) There are several indicators proposed:

    • Prevalence of cases.(4) To use this indicator, extensive testing must be in place. For example, a modelling study using R0 = 2.2 and USA data found that physical distancing measures should be turned on when COVID-19 prevalence reaches 35 per 10,000 and turned off at 5 cases per 10,000.(4)

    • ICU bed occupancy.(2,3) Of note, ICU bed use lags behind SARS-CoV-2 transmission more than the other indicators. To deal with this, an Ontario modelling study suggested that public health measures be turned on when 40% of available ICU beds are filled with COVID-19 cases.(3)

    • Instantaneous reproduction number (Rt),(5) which is the average number of secondary cases due to a single primary case at time t. A modelling study in mainland China recommended maintaining Rt < 1 to determine adjustments to public health interventions.

  • Concerns have been raised that a second outbreak may occur once public health measures are relaxed. One modelling study, using data from China, calculated that maintaining social distancing for one extra month would delay the peak of a possible resurgence by two months.(6) However, there are many challenges with maintaining ongoing strict public health measures. Close monitoring of the local epidemiology and good communication with the public will be important as measures are re-evaluated.

  1. COVID-19 strategy update – 14 April 2020. World Health Organization [Internet]. 14 April 2020 [Cited 22 April 2020].

  2. Ferguson NM, Laydon D, Nedjati-Gilani G, Imai N, Ainslie K, Baguelin M. Report 9: Impact of non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand. Imperial College London [Internet]. 16 March 2020 [Cited 22 April 2020].

  3. Tuite AR, Fisman DN, Greer AL. Mathematical modelling of COVID-19 transmission and mitigation strategies in the population of Ontario, Canada. CMAJ [Internet]. 9 April 2020 [Cited 22 April 2020] 192 (16). 

  4. Kissler SM, Tedijanto C, Goldstein E, Grad YH, Lipsitch M. Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period. Science [Internet]. 2020 [Cited 22 April 2020].

  5. Leung K, WU JT, Liu D, Leung GM. First-wave COVID-19 transmissibility and severity in China outside Hubei after control measures, and second-wave scenario planning: a modelling impact assessment. The Lancet [Internet]. 2020 [Cited 22 April 2020]. 

  6. Prem K, Liu Y, Russell TW, Kucharski AJ, Eggo RM, Davies N. The effect of control strategies to reduce social mixing on outcomes of the COVID-19 epidemic in Wuhan, China: a modelling study. The Lancet [Internet]. 25 March 2020 [Cited 22 April 2020].

What is the evidence for the order in which public health measures should be relaxed?

Answered in April 24, 2020 Newsletter

  • There is no clear evidence on the optimal order of public health measure cessation. As China eases restrictions, their course of action and the ensuing second wave or lack thereof may provide some guidance for the rest of the world.

  • China’s current approach includes:(1)

    • Removal of travel restrictions in the province of Hubei (including Wuhan).

    • Extensive testing and contact tracing to find new infections.

    • Maintenance of social distancing practices.

    • Keeping the country closed to non-citizens to prevent cases from being imported and imposing mandatory 14-day quarantine on returning residents.

    • Allowing residents of Hubei to return to work and reopening factories, while universities, schools, and child-care centres remain closed.

  • As governments look at easing restrictions, it is important for them to work with the community and businesses on ways this can be done safely and to maximize the chances of success. British Columbia, for example, is working with the restaurant sector to develop ways of reopening restaurants while maintaining social distancing.(2)

  1. Cyranoski D. ‘We need to be alert’: Scientists fear second coronavirus wave as China’s lockdowns ease. Nature [Internet]. 30 March 2020 [Cited 22 April 2020].  

  2. Shaw R. COVID-19: Restaurants in B.C. developing plans to re-open under social distancing rules. Vancouver Sun [Internet]. 21 April 2020 [Cited 22 April 2020].

What is the evidence on transmission of SARS-CoV-2 in grade schools?

Answered in April 24, 2020 Newsletter

  • Many countries have closed schools to decrease the transmission of SARS-CoV-2 from and within the school setting.(1) This measure is based on data from previous viral outbreaks as SARS-CoV-2 specific data is limited.

  • Evidence from previous outbreaks:

    • Coronavirus outbreaks (SARS, MERS): Limited evidence is available on the transmission of SARS and MERS within schools, though some studies suggest there was minimal to no transmission in schools.(1)

    • H1N1 Influenza Pandemic: Transmission rates were high within schools as children were the main vectors of transmission.(1,2,3) School closures decreased contact among children which decreased and delayed the peak of the outbreak.(1,3) This was effective due to a low R0 (<2), early implementation, and a higher attack rate in children than adults.(1,4)

  • There is limited evidence regarding the transmission and contact patterns of SARS-CoV-2 within schools. The current understanding is that children are more likely to be mildly symptomatic or asymptomatic, but the relationship between the severity of symptoms and the transmission of SARS-CoV-2 is still unclear.(5) Younger people appear to have a lower attack rate than adults, which is in contrast to previous Influenza outbreaks. Modelling studies have demonstrated conflicting data about the effectiveness of school closures in the context of SARS-CoV-2.(1,6)

  1. Viner RM, Russell SJ, Croker H, et al. Review School closure and management practices during coronavirus outbreaks including COVID-19 : a rapid systematic review. Lancet child Adolesc Heal. 2020;2019(20):1-8.

  2. Clamer V, Dorigatti I, Fumanelli L, Rizzo C, Pugliese A. Estimating transmission probability in schools for the 2009 H1N1 influenza pandemic in Italy. Theor Biol Med Model. 2016;13(1):1-13.

  3. Gemmetto V, Barrat A, Cattuto C. Mitigation of infectious disease at school: Targeted class closure vs school closure. BMC Infect Dis. 2014;14(1):1-10.

  4. Jackson C, Mangtani P, Hawker J, Olowokure B, Vynnycky E. The effects of school closures on influenza outbreaks and pandemics: Systematic review of simulation studies. PLoS One. 2014;9(5).

  5. Davies ANG, Klepac P, Liu Y, et al. Age-dependent effects in the transmission and control of COVID-19 epidemics. medRxiv [preprint]. 2020:1-31.

  6. Kim S, Kim Y-J, Peck KR, Jung E. School Opening Delay Effect on Transmission Dynamics of Coronavirus Disease 2019 in Korea : Based on Mathematical Modeling and Simulation Study. J Korean Med Sci. 2020;35(13):e143.

What needs to be in place to allow learning in an in-class setting to resume?

Answered in April 24, 2020 Newsletter

  • Currently, there is no data available on the efficacy of implementing social distancing interventions in schools during infectious disease outbreaks.(1)

  • In 2009, the World Health Organization suggested several school interventions to help reduce transmission of the H1N1 Pandemic Influenza virus.(2) These interventions could be considered to allow reopening of schools during the COVID-19 pandemic:

    • Promote consistent and correct hand hygiene and respiratory etiquette.

    • Students and staff should stay home if are sick. If they become sick while at school, they should be isolated immediately and sent home.

    • All surfaces shared by students or staff are to be cleaned regularly with soap & water, household cleaning products, or disinfectants.

    • Ensure all classrooms and hallways are well ventilated. Natural ventilation can be achieved by keeping windows open.

    • Limit gatherings in confined spaces (e.g. lunchrooms or assembly halls).

    • Collaboration between schools and national/local health authorities with the dissemination of public health messages to parents, students, and staff.

    • Planning at a school and regional level for the maintenance of essential services and supplies that are critical in reducing viral transmission.

  1. Viner RM, Russell SJ, Croker H, et al. Review School closure and management practices during coronavirus outbreaks including COVID-19 : a rapid systematic review. Lancet child Adolesc Heal. 2020;2019(20):1-8. doi:10.1016/S2352-4642(20)30095-X

  2. World Health Organization. Reducing Transmission of pandemic (H1N1) 2009 in school settings: A framework for national and local planning and response. WHO Int.

What is the evidence on how to prepare for and manage outbreaks in fly-in or remote communities?

Answered in April 17, 2020 Newsletter

  • There are currently no specific studies focused on ways of reducing the impact of COVID-19 on remote communities. Cases of COVID-19 have been reported in First Nation communities in Ontario and British Columbia.(1,2)

  • There has been research on Influenza epidemics in remote settings and is potentially applicable to the current pandemic. Experience with H1N1 Influenza has shown that remote communities and especially Indigenous communities are very vulnerable to pandemics.(3) Some of the most common barriers that promote high infection rates are overcrowded housing, insufficient human and financial resources, and inadequate community awareness.(4)

  • It has been noted that general strategies used for pandemic control (social distancing, isolation of cases and their contacts, and testing)(5,6) may be effective in remote communities, but may require modification. Close cooperation with the communities has been recommended to address their specific challenges.(4)

  • As the shortage of human resources becomes more apparent with the current pandemic, more technology based measures, such as telehealth,(7) may find their roles expanded.

  1. Wadhani A. Remote B.C. First Nation confirms positive COVID-19 case. Victoria News [Internet]. April 11, 2020 [cited April 15, 2020].

  2. Mcquigge M. Coronavirus: 1st COVID-19 case surfaces in northwestern Ontario Indigenous community. Global News [Internet]. April 6, 2020 [Cited April 15, 2020].

  3. Mostaco-Guidolin LC, Bowman CS, Greer AL, Fisman DN, Moghadas SM. Transmissibility of the 2009 H1N1 pandemic in remote and isolated Canadian communities: a modelling study. BMJ Open [Internet]. 2012 [Cited April 15, 2020] 2. 

  4. Charania N, Tsuji LJ. Assessing the effectiveness and feasibility of implementing mitigation measures for an influenza pandemic in remote and isolated First Nations communities: a qualitative community-based participatory research approach. Rural and Remote Health [Internet]. 2013 [Cited April 15, 2020] 13: 2566. 

  5. Anderson RM, Heesterbeek H, Klinkenberg D, Hollingsworth TD. How will country-based mitigation measures influence the course of the COVID-19 epidemic? The Lancet [Internet]. 2020 [Cited April 16, 2020] 395 (10228): 931-934. 

  6. Xu Y, Xiao M, Liu X, Xu S, Du T, Xu J, et al. Significance of Serology Testing to Assist Timely Diagnosis of SARS-CoV-2 infections: Implication from a Family Cluster. Emerging Microbes and Infection [Internet]. 2020 [Cited April 16, 2020]. 

  7. Gutierrez J, Kuperman E, Kaboli PJ. Using Telehealth as a Tool for Rural Hospitals in the COVID‐19 Pandemic Response. The Journal of Rural Health [Internet] Accepted Author Manuscript. 2020 [Cited April 15, 2020].

What are the strategies to assist individuals living in overcrowded housing to comply with self-isolation?

Answered in April 17, 2020 Newsletter

  • General strategies for reducing risk of secondary infection in household contacts was discussed on April 3, 2020.

  • Secondary transmission rates of COVID-19 among household contacts is up to 30%.1 The R0 (reproduction value) increases with more members and time spent in the household, which is significant in overcrowded housing.(2)

Interventions to assist individuals living in overcrowded housing include:

  • Evaluate the safety of current housing.(3) If possible, improve housing conditions to allow for appropriate, healthy behaviors. For patients with confirmed or suspected COVID-19, this involves arranging a separate room and bathroom for their use or cohort self-isolating individuals in a shared space.(4) Aim to maximize proper ventilation, sanitation, and physical distancing from others.

  • Relocate the individual requiring self-isolation outside of the home.(4) Mainland China and Hong Kong have created quarantine centers using vacant infrastructure (e.g. holiday villages, hotels, and gymnasiums) for individuals to self-isolate.(5,6) Policies and conditions of centers have varied. China has related this measure to its success in controlling the outbreak, but specific data regarding its effectiveness is limited.

  1. Wang Z, Ma W, Zheng X, Wu G, Zhang R. Household Transmission of SARS-CoV-2. J Infect [preproof]. 2020. 

  2. Baker M, McDonald A, Zhang J, Howden-Chapman P. Infectious diseases attributable to household crowding in New Zealand : a systematic review and burden of disease estimate, 2013 / Professor Michael G. Baker, Dr. Andrea McDonald, Jane Zhang, Professor Philippa Howden-Chapman. 2013:1-80.

  3. Ali SH, Foster T, Hall NL. The relationship between infectious diseases and housing maintenance in indigenous Australian households. Int J Environ Res Public Health. 2018;15(12). 

  4. Public Health Agency of Canada. Interim guidance: Public health management of cases and contacts associated with novel coronavirus disease 2019 (2019-nCoVCOVID-19) . Gov Canada. 2020:1-19.

  5. N. V. ‘Out-of-home quarantine’ measures in China helped limit spread of COVID-19, epidemiologists say. The Globe and Mail. Published 2020.

  6. Wu Z, McGoogan JM. Characteristics of and Important Lessons from the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72314 Cases from the Chinese Center for Disease Control and Prevention. JAMA - J Am Med Assoc. 2020;323(13).

What strategies can be used to help prevent transmission of SARS-CoV-2 amongst people without a fixed address?

Answered in April 17, 2020 Newsletter

  • Individuals with no fixed address (NFA) have high rates of respiratory infection.(1,2,3) For example 3.4% of deaths of adults with NFA in New York City from 2001-2003 were caused by Influenza or pneumonia.(1) The NFA population is at risk for SARS-CoV-2 infection due to lack of access to soap and water for hand washing, overcrowding at shelters, lack of access to a telephone for telehealth appointments, and high rates of chronic disease.(4,5) 

  • There are three distinct groups of people who need a place to isolate during the COVID-19 pandemic: (1) people awaiting test results or isolating after contact with a COVID-19 case, (2) people with mild cases of COVID-19 that do not require hospitalization, and (3) people >65 years old or with medical comorbidities.

  • The following strategies have been suggested to help prevent the spread of SARS-CoV-2 in this vulnerable population: 

  1. Communication with shelters to prevent losing people to follow-up after COVID-19 testing or for contact tracing.(6)

  2. Elimination of maximum stay durations at shelters to prevent guests from moving from one shelter to another and thereby decreasing the number of possible exposures.(6,7)

  3. Outreach clinics have been shown as effective ways to reach the NFA population.(4,5) 

  4. Training shelter staff on how to screen for COVID-19 and providing them with testing kits.(4) Also, provide shelters with PPE.(6) In Toronto, a recent SARS-CoV-2 outbreak at a shelter infected 11 guests and 12 staff.(8)

 

  • Some of the strategies currently in place in Manitoba include:

  1. Shelters have been trained on how to screen for COVID-19, and the province is working on helping them access appropriate PPE.

  2. In Winnipeg, a 39-unit apartment block opened to provide a place to self-isolate while waiting for test results.(9)

  3. In Brandon a shelter has partnered with a motel to house and feed individuals with chronic disease and those over 65 who need to protect themselves from the virus.(10)

  1. Badiaga S, Raoult D, Brouqui P. Preventing and controlling emerging and reemerging transmissible diseases in the homeless. Emerging Infectious Diseases. 2008 Sept; 14(9):1353-1359. 

  2. Bucher SJ, Brickener PW, Vincent RL. Influenzalike illness among homeless persons. Emerging Infectious Diseases. 2006 July;12(7):1162-1163.

  3. Raoult D, Foucault C, Brouqui P. Infectious in the homeless. Lancet Infectious Diseases. 2001 Sept;1:77-84.

  4. Tsai J, Wilson M. COVID-19: a potential public health problem for homeless populations. Lancet Public Health. 2020 March;5(4):186-187. 

  5. Wood LJ, Davies AP, Khan Z. COVID-19 precautions: easier said than done when patients are homeless. Medical Journal of Austalia. 2020 April. 

  6. Leung CS, Ho MM, Kiss A, Gundlapalli AV, Hwang SW. Homelessness and the response to emerging infectious disease outbreaks: Lessons from SARS. Journal of Urban Health. 2008;85(3):402-410. 

  7. Hwang SW, Kiss A, Ho MM, Leung CS, Gundlapalli AV. Infectious disease exposures and contact tracing in shelters. J Health care Poor Underserved. 2008 Nov; 19)4): 1163-1167. 

  8. Gray J. Toronto refugee shelter says 11 residents, a dozen staff have tested positive for coronavirus. The Globe and Mail. 2020 Apr 14.

  9. Grabish A. Winnipeg’s homeless struggle with physical distancing. CBC. 2020 Apr 10.

  10. Hatherly D. Brandon motel turns into safe place for homeless during pandemic. CBC. 2020 Apr 5.

To what degree do non-pharmaceutical public health interventions affect the epidemic curve? 

Answered in April 17, 2020 Newsletter

  • In the 1918 Influenza Pandemic, lower death rate was associated with earlier closure of schools and banning of public events in the US cities.(1) The median duration of these closures were 4 weeks (range 1-10 weeks). However, it is difficult to apply the required duration of intervention for COVID-19 as its incubation period is longer than Influenza (approximately 7-14 days versus 1-5 days).

  • Modeling data showed that in a society like Singapore, a combination of regulations including quarantine, school closure, and workplace distancing could reduce the number of infected patients with COVID-19 by 78.2% (assume R0 = 2.5), 93.0% (assume R0 = 2.0), and 99.3% (assume R0 =1.5) in 80 days.(2)

  • A modeling study using data from Ontario (based on a R0 = 2.3) found that ICU resources would be overwhelmed without either (1) substantial physical distancing (i.e.: contact reduced by 60%) or (2) a combination of moderate physical distancing (i.e.: contact reduced by 25%) with enhanced case finding.(3) The model propose a dynamic scenario where public health interventions are activated when approximately 40% of ICU beds are filled with patients with COVID-19. They suggest that using a dynamic scenario could maintain health system capacity while allowing periodic psychological and economic respite for the population.

  1. Markel H, Lipman HB, Navarro JA, Sloan A, Michalsen JR, Stern AM, et al. Nonpharmaceutical Interventions Implemented by US Cities During the 1918-1919 Influenza Pandemic. JAMA [Internet]. 2007 Aug 8;298(6):644–54. 

  2. Koo JR, Cook AR, Park M, Sun Y, Sun H, Lim JT, et al. Interventions to mitigate early spread of SARS-CoV-2 in Singapore: a modelling study. Lancet Infect Dis. 2020 Mar. 

  3. Tuite AR, Fisman DN, Greer AL. Mathematical modelling of COVID-19 transmission and mitigation strategies in the  population of Ontario, Canada. CMAJ. 2020 Apr. 18, 20

How effective is the use of temperature monitoring to screen for COVID-19 amongst healthcare workers or the general public? What method of temperature measurement is most effective – contact thermometry vs infrared?
 

Answered in April 10, 2020 Newsletter

  • Contact thermometry methods include rectal, oral, tympanic, and axillary – in decreasing order of accuracy.(1) Oral measurement is more accurate than infrared thermometry, but is more time consuming, has increased risk of contact with bodily fluids, and is more invasive.(2) Infrared thermometry accuracy is affected by many variables including individual factors (age, sex, facial hair, and cosmetic use) and external factors (model of device used and environmental settings).(1)

  • Thermal screening for healthcare workers has been described, but there is no data on its effectiveness for detecting COVID-19.

  • For screening the general population, most studies have focused on the airport setting. All studies on this topic found that temperature monitoring, in isolation, is an inadequate screening tool. One study estimated that as many as 46% of SARS-CoV-2 positive patients may be missed by this method.(3)

  • The challenges of relying on temperature screening alone for COVID-19 are multifactorial and include (i) asymptomatic or presymptomatic infection,(4) (ii) fever is not present in all symptomatic cases as discussed in our March 21st edition, (iii) purposeful deception by people taking antipyretics and thus masking their fever,(5) and (iv) thermometry equipment factors.

  • If employed, thermal monitoring should be used in conjunction with other screening methods for the detection of COVID-19.

  1. Nguyen A V, Cohen NJ, Lipman H, et al. Comparison of 3 Infrared Thermal Detection Systems and Self-Report for Mass Fever Screening. 2010;16(11).

  2. Tay MR, Low YL, Zhao X, Cook AR, Lee VJ. Comparison of Infrared Thermal Detection Systems for mass fever screening in a tropical healthcare setting. Public Health. 2015;129(11):1471-1478. 2015.07.023

  3. Quilty BJ, Clifford S, CMMID nCoV working group, Flasche S, Eggo RM. Effectiveness of airport screening at detecting travellers infected with novel coronavirus (2019-nCoV). Euro Surveill [Internet]. 2020 [Cited April 9, 2020] 25 (5): 2000080.

  4. Gou F.X., Zhang X.S., Yao J.X., Yu D.S., Wei K.F., Zhang H., Wu B., Liu X.F. LH. Epidemiological characteristics of COVID-19 in gansu province. Chinese J Epidemiol. 2020;41.

  5. Bwire GM, Paulo LS. Coronavirus disease-2019: is fever an adequate screening for the returning travelers? Trop Med Health [Internet]. 2020 [cited April 9, 2020] 48: 14.

What process is involved in vaccine development?

Answered in April 3, 2020 Newsletter

Without any proven effective treatment for SARS-CoV-2, there is an urgency for vaccine development. Vaccines can stagnate the progression of an outbreak, decrease transmission, and prevent future outbreaks. However, this is a long process on the scale of years.(1)

Steps in vaccine development:(2,3​)

 

1. Starts with analyzing and understanding the virus itself to determine potential targets for candidate vaccines.

2. Potential vaccines are developed and tested in non-clinical (preclinical) laboratory and/or animal settings, evaluating for effectiveness and safety.

3. Successful candidates move onwards to clinical human trials: Phase I, II, and III. The sequential phases include increasing number of trial participants. Phase I evaluates vaccine safety and whether it produces an immune response. Phase II includes the intended target population. Phase III is a large-scale trial to evaluate efficacy and safety.

4. Regulatory and review process and includes validation of manufacturing process.

5. Final steps are manufacturing and quality control.

  • Monitoring continues after vaccines are licensed and administered for any adverse effects that may not have been apparent during trial and initial administration.

  • On the road to vaccine development, several challenges can be expected due to the extensive development process which ensures safe, quality and effective vaccine development.(1)

  1. Zhang J, Zeng H, Gu J, Li H, Zheng L, Zou Q. Progress and Prospects on Vaccine Development against SARS-CoV-2. 2020;2(M):1-12.

  2. Noni E, MacDonald BJL. Canada’s eight-component vaccine safety system: A primer for health care workers. Canadian Pediatrics Society. Published 2017. Accessed April 1, 2020.

  3. Vaccine safety and pharmacovigilance: Canadian Immunization Guide. Government of Canada. Published 2019. Accessed April 1, 2020.

What are the different types of candidate SARS-CoV-2 vaccines?

Answered in April 3 2020 Newsletter

There are over 50 potential vaccine candidates in the pipeline globally that include a wide range of different technologies. The following is not an exhaustive list but includes a description of the most common types.

Whole virus vaccines(1,2)

  • Includes whole-cell killed, live attenuated, and vectored vaccines. The first two types make use of the original virus. Virus vector-based vaccines use a different live virus to express heterologous antigens from the virus of interest to promote immunity.

  • Whole virus vaccines present multiple antigenic components to the host, thus promoting a diverse immunogenic response. They can also stimulate toll-like receptors (TLRs).

  • Whole virus vaccines requires extensive additional testing to confirm their safety.

Subunit vaccines

  • Subunit vaccines utilize one or more antigens specific to the virus that have strong immunogenicity to promote an immunogenic response from the host. Many of the candidate SARS-CoV-2 vaccines use the viral S protein as the subunit of choice. This is the surface exposed protein that mediates the interaction with the host cell through the ACE2 receptor.(1,2)

  • This type of vaccine is safer and easier to produce, but often requires adjuvants. Adjuvants are substances that enhance the immunogenicity of highly purified antigens.(3) 

 

Nucleic acid vaccines

  • Includes DNA and mRNA vaccines. DNA vaccines are generally comprised of plasmid DNA molecules that encode one or more antigens. The DNA is taken up by cells and expressed in their nucleus, producing the characteristic antigen proteins, which then triggers an immunogenic response.(4)

  • DNA vaccines come with the risk of causing mutations in the host genome.1 mRNA vaccines work similarly, but do not integrate into the host genome, thus are safer.(5)

  1. Zhang J, Zeng H, Gu J, Li H, Zheng L, Zou Q. Progress and Prospects on Vaccine Development against SARS-CoV-2. Vaccines [Internet]. 2020 [Cited April 2, 2020] 8(2): 153.

  2. Chen WH, Strych U, Hotez PJ, Bottazi ME. The SARS-CoV-2 Vaccine Pipeline: an Overview. Curr Trop Med Rep [Internet]. 2020 [Cited April 2, 2020].

  3. Di Pasquale A, Preiss S, Da Silva FT, Garcon N. Vaccine Adjuvants: from 1920 to 2015 and Beyond. Vaccines [Internet]. 2015 [Cited April 2, 2020] 3(2): 320-343.

  4. Alarcon JB, Waine GW, McManus DP. DNA Vaccines: Technology and Application as Anti-parasite and Anti-microbial Agents. Advances in Parasitology [Internet]. 1999 [Cited April 2, 2020] 42: 343-410.

  5. Schlake T, Thess A, Fotin-Mleczek M, Kallen KJ. Developing mRNA-vaccine technologies. RNA Biol [Internet]. 2012 [Cited April 2, 2020] 9(11): 1319-1330.

Are there any candidate SARS-CoV-2 vaccines in human clinical trials?

Answered in April 3 2020 Newsletter

Currently there are two candidate vaccines in Phase I trials, one that is recruiting volunteers for Phase I trial, and one that is hoping to begin Phase I trial in April. Brief details of these are discussed below. There are many other vaccine candidates hoping to begin Phase I trials over the next few months.

mRNA-1273 (1,2)

  • Developer: Moderna Therapeutics and US National Institute of Allergy and Infectious Diseases (NIAID)

  • Type of vaccine: messenger RNA (mRNA) vaccine

  • Current development stage: Phase I human trial, funding by Coalition for Epidemic Preparedness Innovations (CEPI). Plan is to enroll 45 healthy adults to receive two doses separated by 1 month. First patient received their first dose on March 16, 2020. They hope to start Phase II trial in the Spring.

  • If successful, the vaccine will likely not be commercially available for at least 12-18 months, but the company believes that it might be available for emergency use by Fall 2020.

Ad5-nCoV (3)

  • Developer: CanSino and Institute of Biotechnology of the Academy of Military Medical Sciences

  • Type of vaccine: viral vector vaccine using the Adenovirus type 5 vector

  • Current development stage: Began Phase I human trial on March 16, 2020, and is studying low, medium, and high doses of the vaccine.

ChAdOx1 (3,4)

  • Developer: University of Oxford – Oxford Vaccine Group and the Jenner Institute

  • Type of vaccine: viral vector vaccine using a chimpanzee adenovirus vaccine vector to express the SARS-CoV-2 spike protein

  • Current development stage: Preclinical, but recruitment for Phase I human trial began at the end of March 2020. They are simultaneously working on scale-up of vaccine production.

INO-4800 (1,5)

  • Developer: Inovio Pharmaceuticals

  • Type of vaccine: DNA vaccine

  • Current development stage: preclinical, but they are collaborating with CEPI to begin Phase I trials in USA and with Beijing Advance for Phase I trials in China sometime in April. The company is targeting to scale up production with a goal of 1 million doses by the end of 2020, for either further trial use or emergency use.

  1. Pang J, Wang MX, Ang IYH, Tan SHX, Lewis RF, Chen JI-P, et al. Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review. J Clin Med. 2020 Feb;9(3).

  2. Moderna’s Work on a Potential Vaccine Against COVID-19 | Moderna, Inc. [Internet]. [cited 2020 Apr 2].

  3. Regulatory affairs professionals society [Internet]. Maryland: c2020. COVID-19 vaccine tracker; 2020 March 27 [cited 2020 Apr 2].

  4. Anadolu Agency [Internet]. London: c2019. Oxford university calls for COVID-19 vaccine volunteers; 2020 March 30 [cited 2020 Apr 2].

  5. Inovio Pharmaceuticals, Inc. [Internet]. Pennsylvania: c2020. Inovio accelerates timeline for COVID-19 DNA vaccine INO-4800; 2020 March 3 [cited 2020 Apr 2].

What are the transmission dynamics in congregated settings such as personal care homes and cruise ships?

Answered in March, 27, 2020 Newsletter

SARS-CoV-2 has the potential to spread extremely quickly in congregated settings such as cruise ships, personal care homes, places of worship and health care sites. 

Princess Diamond cruise ship:

  • 712 of 3,700 passengers and crews (19.2%) ended up testing positive for SARS-CoV-2.(1,2)

  • One study calculated 11.2 as the maximum value of Rt, which was much higher than the R0 for the virus in the community.(3)

  • Once the outbreak was recognized and quarantine measures put into place, the Rt was reduced to less than 1, meaning that the measures were effective.(3)

Personal care homes: 

  • Personal care homes represent a setting where infection with COVID-19 has been shown to be devastating due to close interactions of the elderly residents who are at higher risk of severe disease. Currently, there is limited data on the transmission dynamics in this setting. 

  • One outbreak occurred in a long-term care facility in King County, Washington, resulting in the infection of 81 residents, 34 staff members, and 14 visitors.  There were 23 deaths.(4)

  • As of March 24th, British Columbia has seen outbreaks in 8 long-term care facilities with 12 deaths associated with COVID-19.(5)

  • Many provinces have implemented reduced visitor access to personal care homes and set strict guidelines for staff. Manitoba, for example, has banned visitors and discontinued communal meal programs.(6)

  • It should be noted that social disconnectedness and isolation puts older adults at a higher risk of depression and anxiety, which may worsen other health conditions.(7) Technology may be one solution to this problem.

  1. Moriarty LF, Plucinski MM, Marston BJ, et al. Public Health Responses to COVID-19 Outbreaks on Cruise Ships — Worldwide, February–March 2020. MMWR Morb Mortal Wkly Rep. ePub: 23 March 2020. 

  2. Rocklöv J, Sjödin H, Wilder-Smith A. COVID-19 outbreak on the Diamond Princess cruise ship: estimating the epidemic potential and effectiveness of public health countermeasures. J Travel Med [Internet]. 2020 [cited 2020 Mar 25]. 

  3. Mizumoto K, Chowell G. Transmission potential of the novel coronavirus (COVID-19) onboard the diamond Princess Cruises Ship, 2020. Infect Disease Model [Internet]. 2020 [cited 2020 Mar 25] 5: 264-270. 

  4. McMichael TM, Clark S, Pogosjans S, et al. COVID-19 in a Long-Term Care Facility — King County, Washington, February 27–March 9, 2020. MMWR Morb Mortal Wkly Rep. ePub: 18 March 2020. 

  5. Updated: Seniors’ home in Vancouver’s West End hit hard by COVID-19 [Internet]. Vancouver Courier; March 24, 2020. [Cited March 25, 2020] 

  6. Media Bulletin – Manitoba Government [Internet]. COVID-19 BULLETIN #17; 2020 Mar 17 [cited 2020 Mar 25]. 

  7. Santini ZI, Jose PE, Cornwell EY, Koyanagi A, Nielsen L, Hinrichsen C, et al. Social disconnectedness, perceived isolation, and symptoms of depression and anxiety among older Americans (NSHAP): a longitudinal mediation analysis. The Lancet Public Health [Internet]. 2020 [cited 2020 Mar 25]; 5 (1): 62-70.

What public health interventions (PHIs) were taken in countries that have so far been successful in containing the COVID-19 outbreak? (PART 1)

Answered in March, 27, 2020 Newsletter

Singapore

  • As of March 25, Singapore had 564 documented cases of COVID-19 with a mortality rate of 0.35%.(1)

  • PHIs implemented after the first documented case of COVID-19 included: aggressive testing for COVID-19 (individuals that meet case definition, close contacts with positive cases, ill patients with pneumonia and based on physician’s clinical suspicion), isolating positive cases in hospitals, contact tracing, and active quarantine of close contacts.(2,3)

  • The quarantine process in Singapore is unique. To ensure compliance during quarantine, public health officials video-call close contacts thrice daily to verify their location. Quarantine violators are tagged with continuous tracking devices and are subject to prosecution.(2,4)

  • Additional measures taken since March 18-26 include: restricting social gatherings to less than 10 people, closing non-essential public venues and restricting travel abroad (all returning travelers must self-isolate for 14 days).(5,6)

South Korea 

  • As of March 25, South Korea had 9,137 documented cases of COVID-19 with a mortality rate of 1.38%.(1)

  • PHIs implemented after the surge in COVID-19 cases at the end of February included: wide scale aggressive testing for COVID-19 (35,7896 tests have been performed as of March 25th; up to 15,000 tests can be performed daily), isolating positive cases, contact tracing and quarantine of close contacts (violators are subject to prosecution) and transparent communication from the government.(2,4)

  • Contact tracing method is unique. The Korean government thoroughly identifies the location of confirmed cases and their close contacts by using credit card transaction logs and GPS to track cell phone location, as well as using closed circuit TVs to identify the route taken by the patient and to evaluate the exposure risk to contacts.(3)

  • One unique aspect of the Korean government’s communication strategy is to send messages to the public regarding the location where a person tests positive for COVID-19 and the places they recently visited in order to reduce movement in those locations.(4)

Singapore

  1. Ministry of Health Singapore. Updates on COVID-19 (coronavirus Disease 2019) local situation. Singapore: Ministry of Health Singapore [internet]; 2020[updated 2020 Mar 25; cited 2020 Mar 26]. 

  2. Lee V, Chiew C, Khong W. Interrupting transmission of COVID-19: lessons from containment efforts in Singapore. J Travel Med [Internet]. 2020 Mar pre-print [cited 2020 March 26].

  3. Ng Y, Li Z, Chua Yi et al. Evaluation of the Effectiveness of Surveillance and Containment Measures for the first 100 patients with COVID-19 in Singapore-January2–Feb29. CDC [Internet]. 2020 Mar [Cited 2020 Mar 26]; 69(11);307-311. 

  4. Pung R, Chiew C, Young B, Chin S, Chen M, Clapham H, et al. Investigation of three clusters of COVID-19 in Singapore: implications for surveillance and response measures. Lancet [Internet]. 2020 Mar pre-print [cited 2020 Mar 26]. 

  5. Ministry of Health Singapore. Tighter measures to minimise further spread of COVID-19. Singapore: Ministry of Health Singapore; 2020[updated 2020 Mar 25; cited 2020 Mar 26].

  6. Ministry of Health Singapore. Additional measures for travellers to reduce further importation of COVID-19 cases. Singapore: Ministry of Health Singapore; 2020[updated 2020 Mar 25; cited 2020 Mar 26]. 

Korea

  1. Ministry of Health and Welfare South Korea. Cases in Korea. South Korea: Ministry of Health and Welfare South Korea; 2020[updated 2020 Mar 25; cited 2020 Mar 26]. 

  2. Ministry of Health and Welfare South Korea. Quarantine System. South Korea: Ministry of Health and Welfare South Korea; 2020[updated 2020 Mar 19; cited 2020 Mar 26]. 

  3. Korea CDC. Contact Transmission of COVID-19 in South Korea: Novel Investigation Techniques for Tracing Contacts. Osong Public Health Res Perspect. 2020 Feb;11(1):60-63

  4. Zastrow M. South Korea is reporting intimate details of COVID-19 cases:hast it helped?. UK. Nature; 2020 [updated 2020 Mar 18; cited 2020 Mar 26].