This is a preprint version of an article submitted for publication in the Medical Journal of Australia. Changes may be made before final publication. Click here for the PDF version.
China appears to have constrained transmission of COVID-19 outside of Hubei Provence through rapid and intensive containment and mitigation interventions. Most countries only attempt social distancing and hygiene interventions when widespread transmission is apparent. This gives the virus many weeks to spread with a higher basic reproduction number (R0) than if they were in place before transmission was detected or widespread. Pre-emptive, low cost, hygiene enhancement and social distancing in the context of imminent community transmission of novel coronavirus COVID-19 should be considered. Early interventions to reduce the average frequency and intensity of exposure to the virus might reduce infection risk, reduce the average viral infectious dose of those exposed, and result in less severe cases who are less infectious. A pre-emptive phase would also assist government, workplaces, schools, and businesses to prepare for a more stringent phase. Countries, and subregions of countries, without recognised COVID-19 transmission should assume it is present and consider implementation of low cost enhanced hygiene and social distancing measures.
Rationale for pre-emptive interventions
It is estimated that approximately two thirds of COVID-19 cases exported from China from 1 to 13 January 2020 have gone undetected globally (1). Most of these exported cases will be mild and may only be detected after several hundred cases have accumulated and severe or fatal cases are recognised 5 to 8 weeks later, as has likely occurred in the recent COVID-19 outbreaks in Iran, South Korea, Italy, and Seattle in the USA (2).
The spread of novel coronavirus COVID-19 transmission globally has been very rapid. The basic reproduction number is estimated at between 2 to 3 (3)(4). The mode of transmission is thought to be droplet and contact infection, although opportunistic or close range airborne infection may be involved (4).
The transmission dynamics of the early cases of COVID-19 were significantly different to those during the SARS epidemic. In particular the proportion of cases from healthcare settings was low and the proportion with no known risk exposures was high (4). Another significant factor is that viral loads in nasopharyngeal and respiratory secretions are highest soon after symptom onset in COVID-19 cases (5) compared with a peak of around 10 days in SARS cases (6), making transmission before entering health care facilities more likely.
Even though the understanding of transmission dynamics is at an early stage, they do suggest that the step-wise introduction of stringent measures will be necessary to control this epidemic and highlights the importance of early community control.
Quarantine, city “lockdowns”, complete childcare, school, university and work closures, and cancellation of mass gatherings/events have significant social and economic impact and are unlikely to be implemented until significant transmission is confirmed – when it may be less effective. However, there are a range of lower level, potentially cost neutral, pre-emptive interventions that could be considered when transmission is only suspected or anticipated. Here we explore whether low cost pre-emptive enhanced hygiene and social distancing should be implemented prior to confirmation of community transmission in countries without, or with minimal, confirmed person-to-person transmission of COVID-19.
The purpose of pre-emptive interventions is to slow the transmission of disease and limit the impact on health services, particularly hospitals and intensive care units, to ensure access to high level care when needed.
The concept of pre-emptive deployment is based upon the following assumptions which require further exploration and are elaborated upon below:
- Community wide COVID-19 transmission may be occurring undetected or may only be recognised after containment is no longer feasible.
- Interventions implemented after community wide transmission is detected will be less effective.
- Reducing the force of infection, particularly early, will delay the epidemic peak, blunt the epidemic peak, spread cases over a longer time, and help to limit the potential for critical care services to be overwhelmed, which may be lifesaving (7)(8).
- Enhanced hygiene and social distancing interventions should:
a. Decrease the total number of cases per week but extend duration of the epidemic
b. Decrease the severity of cases through reducing viral inocula.
Figure 1 below (available in the PDF version) illustrates the concept of limiting the peak in cases so that health services are less likely to be overwhelmed (red dashed line) and there is less unmet health service need. Unmet need may include inability to admit patients to a hospital or to provide hospitalised patients in critical condition access to intensive care. Interventions to reduce infection lead to longer, but less peaked, epidemics. A slower evolution in the epidemic also allows time for health care staff to provide better care, for recovery of infected health care workers, for learning and adapting to the evolving situation by administrators, and for vaccines and treatments to be developed. Although we have not validated this principle for COVID-19 epidemics it is sufficiently validated in simulations for influenza that it would appear a reasonable assumption in response to this emergent disease (9).
Enhanced hygiene and social distancing measures may reduce both numbers of cases and severity of cases through several mechanisms
We suggest that a pre-emptive implementation of low cost interventions prior to detection, but in imminent expectation of community transmission should be considered because it may decrease both the total numbers of cases and severity of cases. This principle applies equally well to subregions of countries that have not as yet detected community transmission events.
The basic reproductive number (R0) is the average number of secondary cases of an infectious disease that arise from cases in a totally susceptible population, and reflects the epidemic potential of a pathogen (10). R0 is a function of the number of contacts an infectious person has, the risk of transmission per contact, and the duration of infectiousness.
Social distancing mostly acts on the first factor, by reducing the number of contacts each person makes. Hygiene measures mostly act on the second factor, as they reduce the risk of transmission if a contact occurs. There are epidemiological observations from the outbreak in China that might indicate the effectiveness of pre-emptive implementation of the measures in the community. The WHO-China Joint Mission on COVID-19 determined that widespread community transmission and outbreaks occurred in Wuhan prior to the implementation of comprehensive control measures (4). However in other parts of China, community transmission has been limited and most transmission has occurred in families. For example, among 344 clusters involving 1308 cases (out of a total 1836 cases reported) in Guangdong Province and Sichuan Province, 78%-85% have occurred in families (4). This is likely due to the intense quarantine and social distancing measures implemented in areas outside Hubei prior to the establishment of widespread community transmission.
Community wide interventions may decrease the average viral exposure dose encountered in the community. People exposed to a higher viral dose (inoculum) are more likely to become infected and suffer more severe disease. Animal models for other coronavirus infections demonstrate that increased viral inocula lead to more severe disease and higher viral loads in the lungs and other organs/fluids (11). The Amoy Gardens SARS outbreak in 2003 provided evidence that cases with presumed higher exposure to the index case had higher nasopharyngeal viral loads and more severe illness (12). Modelling of the 2009 influenza pandemic also supported a hypothesis that severe illness was due to a higher infectious dose of the virus mediated by the number of simultaneous infectious contacts (13). Viral loads in severe MERS cases were higher than those in a mild group and the patients in the severe group had more prolonged viral shedding in respiratory secretions, beyond 21 days after the onset of symptoms, whereas viral RNA was no longer detected by 21 days in the mild group (14).
Therefore, it is proposed that early measures that lower the number of contacts, the likelihood of transmission, and average viral infective dose in an area of new transmission could have a multiplier effect leading to less cases, and less severe cases who are less infectious. This early reduction of the R0 would result in fewer cases overall and have a significant negative multiplier effect on the overall impact of the epidemic, including the number of deaths (Figure 2 – available in the PDF version). The higher case fatality rate in Wuhan, compared with other provinces in China may partially relate to health-care resource availability and shortages in the face of overwhelming community transmission, as well as greater severity of disease due to higher infection doses (7)(12). These interventions will be particularly important for people over 60 years of age and those with underlying medical conditions.
Low cost hygiene and social distancing interventions
Organisational capacity benefits
A pre-emptive phase would assist organisations to build capacity for future implementation of more stringent social distancing interventions including allocating responsibilities, consulting with staff and adapting protocols and practicing implementation. WHO is supportive of pre-emptive interventions to prevent COVID-19 in work places (17).
The costs of pre-emptive intervention
The suite of low cost pre-emptive interventions, other than a working from home policy, is unlikely to affect work productivity and may provide the community with some reassurance that all is being done to prevent the epidemic. Some may see it as an over-reach but thus far communities seem to accept or voluntarily adopt low cost interventions and acceptance may be enhanced through consultation and trust building (18)(19).
For regions approaching their influenza season, optimal prevention and control of seasonal influenza, such as vaccination, in the face of potential COVID-19 co-circulation is also crucial, to minimise the double burden on health services. The measures discussed here (enhanced hygiene and social distancing) are also effective against influenza, resulting in potential co-benefits for both pathogens.
Most of the research on mitigation is based on influenza control and it is clear that SARSCoV-2 transmission dynamics will be different, however, droplet, contact and airborne precautions and the interventions deployed in China align with recommended influenza transmission controls. The assumptions should be modelled to better understand the costs and benefits. The use of masks outside of health settings is controversial and it is important that masks not be diverted from health care supplies. However, surgical masks are protective of large droplet spread and have approximately half the effectiveness of N95 mask for small droplet transmission, and are suggested to be cost saving in some modelled pandemic influenza scenarios (20) They may have a limited role in the community setting prior to widespread transmission if there are adequate supplies and should be considered for use in households caring for COVID-19 cases at home (16).
Given the ongoing global dissemination of COVID-19, as of early March 2020, it would be sensible for most countries and regions to assume they have had an importation of at least one case of COVID-19 and that the disease is spreading locally whether recognised or not. We believe these practices should be implemented in all countries as soon as possible.
- Sangeeta Bhatia, Natsuko Imai, Gina Cuomo-Dannenburg, Marc Baguelin, Adhiratha Boonyasiri, Anne Cori, Zulma Cucunubá et al. Relative sensitivity of international surveillance. Imperial College London. Accessed at: https://www.imperial.ac.uk/media/imperial-college/medicine/sph/ide/gidafellowships/Imperial-College---COVID-19---Relative-Sensitivity-International-Cases.pdf
- MacIntyre, C.R., 2020. Global spread of COVID-19 and pandemic potential. Global Biosecurity, 1(3), p.None. DOI: http://doi.org/10.31646/gbio.55
- Liu, Y., Gayle, A. A., Wilder-Smith, A. & Rocklöv, J. The reproductive number of COVID-19 is higher compared to SARS coronavirus. Journal of Travel Medicine. 2020. doi:10.1093/jtm/taaa021
- WHO. Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19) 24th February, 2020 https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-oncovid-19-final-report.pdf
- Zou L, Ruan F, Huang M, Liang L, Huang H, Hong Z, et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N Engl J Med. 2020 Feb 19 [Epub ahead of print]. https://www.nejm.org/doi/pdf/10.1056/NEJMc2001737
- JS Peiris, CM Chu, VC Cheng, et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet, 361 2003, pp. 1767-1772
- Yunpeng Ji,Zhongren Ma, Maikel P Peppelenbosch, Qiuwei Pan. Potential association between COVID-19 mortality and health-care resource availability. 2020 DOI: https://doi.org/10.1016/S2214-109X(20)30068-1
- Fong MW, Gao H, Wong JY, Xiao J, Shiu EYC, Ryu S, et al. Nonpharmaceutical measures for pandemic influenza in nonhealthcare settings—social distancing measures. Emerg Infect Dis. 2020 May. https://doi.org/10.3201/eid2605.190995
- Kelso, J.K., Milne, G.J. & Kelly, H. Simulation suggests that rapid activation of social distancing can arrest epidemic development due to a novel strain of influenza. BMC Public Health 2009 9, 117. https://doi.org/10.1186/1471-2458-9-117
- Fine, P. Introduction: the basics - infections, transmission and models. In: Vynnycky E & White R. An Introduction to Infectious Disease Modelling. 2010. UK: Oxford University Press.
- Douglas, M. G., Kocher, J. F., Scobey, T., Baric, R. S. & Cockrell, A. S. Adaptive evolution influences the infectious dose of MERS-CoV necessary to achieve severe respiratory disease. Virology 2018 517, 98–107.
- Chu C-M, Cheng VCC, Hung IFN, Chan K-S, Tang BSF, Tsang THF, et al. Viral load distribution in SARS outbreak. Emerg Infect Dis 2005 Dec http://dx.doi.org/10.3201/eid1112.040949.
- Paulo AC, Correia‐Neves M, Dominguos T et al. Influenza infectious dose may explain the high mortality of the second and third wave of 1918–19 influenza pandemic. PLoS ONE 2010; 5: e11655. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0011655#s2
- Oh MD, Park WB, Choe PG, Choi SJ, Kim JI, Chae J, Park SS, Kim EC, Oh HS, Kim EJ, Nam EY, Na SH, Kim DK, Lee SM, Song KH, Bang JH, Kim ES, Kim HB, Park SW, Kim NJ. Viral load kinetics of MERS coronavirus infection. N Engl J Med 2016 375:1303–1305. DOI: 10.1056/NEJMc1511695
- Chan KH, Peiris JS, Lam SY, Poon LL, Yuen KY, Seto WH. The Effects of Temperature and Relative Humidity on the Viability of the SARS Coronavirus. Adv Virol. 2011;2011:734690. doi: 10.1155/2011/734690
- Wein LM, Atkinson MP. Assessing infection control measures for pandemic influenza. Risk Anal. 2009;29:949–962.
- World Health Organisation. Getting your workplace ready for COVID-19. 28th February. https://www.who.int/docs/default-source/coronaviruse/getting-workplace-ready-for-covid-19.pdf
- Braunack-Mayer, A.J., Street, J.M., Rogers, W.A. et al. Including the public in pandemic planning: a deliberative approach. BMC Public Health 10, 501 (2010). https://doi.org/10.1186/1471-2458-10-501
- Gabriele Prati, Luca Pietrantoni, Bruna Zani, Compliance with recommendations for pandemic influenza H1N1 2009: the role of trust and personal beliefs, Health Education Research, Volume 26, Issue 5, October 2011, Pages 761–769, https://doi.org/10.1093/her/cyr035
- Mukerji S, MacIntyre CR, Newall AT. Review of economic evaluations of mask and respirator use for protection against respiratory infection transmission. BMC Infect Dis. 2015;15:413. Published 2015 Oct 13. doi:10.1186/s12879-015-1167-6.
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