Social distancing and self-isolation 100 years after the 1918 influenza pandemic: what have we learnt from pandemics of the past?

What is ‘the curve’, how can we ‘flatten it’ and do the measures work? Over a century after the largest influenza virus pandemic on record, we reflect on some of the pandemics of the past to determine what roles non-pharmaceutical interventions play in tackling disease outbreaks.

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On March 11 2020, the World Health Oragnization officially declared the current outbreak of the novel coronavirus, COVID-19 – a disease caused by SARS-CoV-2, which originated in Wuhan (Hubei, China) – a pandemic. The outbreak is of a magnitude previously unseen for decades and governments the world over are exercising protocols and policies that exert significant social and economic impacts on our day-to-day lives.

But how evidence-based and effective are some of these strategies? What practices have been tried and tested throughout civilian history?

Over 1–2 April 2020, The Evidence Base® was due to co-host the first, inaugural Real-World Evidence 2020: Rare Diseases and Innovative Therapies. Unfortunately, we have taken the difficult, though necessary decision to postpone the event amid the current climate.

Instead, in this feature, we explore the historical and novel evidence concerning some of the severe non-pharmaceutical interventions being implemented today, to determine what we have learnt about social distancing and self-isolation from pandemics of the past and what they look like in the 21st century.


From 1918 to 2020: how far have we truly come?

As a population this is not the first time that we have been faced with a viral pandemic. From 1918—1919, three consecutive waves of a mysterious virus spread around the world, infecting more than one-third of the world’s population and killing approximately 50 million individuals [1—2].

Then, the etiological agent that caused this disease was unknown; now, however, we reflect on this time as the renowned 1918 H1N1 influenza pandemic – the largest influenza virus pandemic on record.

Since then, the world has witnessed various additional, less severe, viral pandemics, including the relatively recent SARS outbreak of 2003—2004, to which the virus responsible for the current COVID-19 disease is related.

In 1918, sheer limitations in medical knowledge meant that we did not have available, nor could manufacture, a targeted vaccine for use against the virus strain.

Today, despite strides that have been made in our research and manufacturing capabilities, and our understanding of virus transmission, we are once again experiencing an outbreak of a disease against which we have no targeted vaccine currently available.

It is estimated that the de novo development of such a targeted vaccination could from 6–18 months, potentially longer if initial trials demonstrate poor vaccine efficacy [3—4].

In these unprecedented times, many fast-track and unparalleled designations for potential treatments and management strategies have been granted, and various international research collaborations have been spearheaded to hopefully expedite the production of an effective, targeted treatment against SARS-CoV-2.


Discover how the medical 3D-printing community is responding to the outbreak and shortage of medical equipment in this column on our sister site 3DMedNet, which is updated daily>>


However, though research is rapidly progressing, viral transmission is progressing faster. As a result, international governments have resorted to instituting so called ‘non-pharmaceutical interventions’, which have historically played – and are once again playing – essential roles in the management of viral pandemics, buying time until a vaccination against the virus strain is successfully and ethically developed [1—3, 9—11].


You can read about the latest progress in treatment and vaccination development in our COVID-19 Digital Hub on our sister site, IDHub>>


Mitigating viral transmission with non-pharmaceutical interventions

These ‘old-school’ interventions include both personal measures – such as frequent hand washing and self-isolation if unwell – and more impactful, community-wide measures, including the cancelation of mass gatherings and the closures of schools, workplaces and non-essential commodities. These actions are implemented with the intention of promoting so called ‘social distancing’. As the majority of SARS- and influenza-like viral transmission occurs via vapor droplets released when an infected individual coughs or sneezes, restricting face-to-face contact between individuals represents an effective, albeit severe, means of mitigating disease spread [4—7].

...restricting face-to-face contact between individuals represents an effective, albeit severe, means of mitigating disease spread."

Though the quality of the epidemiological data assessed in retrospective studies evaluating the effectiveness of social distancing protocols in historical virus outbreaks are often poor, due to disease underreporting and various additional factors, many studies demonstrate associations between the introduction of both personal and community-wide non-pharmaceutical interventions and reduced overall mortality, fewer fatal viral cases at the peak of historical pandemics and delayed peak-case timing. These effects have been referred to as those that ‘flatten the curve’.

Emerging real-world evidence is already supporting the use of these interventions in the current outbreak.

In new research analyzing the effects of non-pharmaceutical measures on the spread of COVID-19 in the first 50 days of the outbreak in China [12–13], contributing study author Christopher Dye (University of Oxford, UK), commented: “The number of confirmed cases in China by day 50 (19 February 2020) of the epidemic was around 30,000. Our analysis suggests that without the Wuhan travel ban and the national emergency response there would have been more than 700,000 confirmed COVID-19 cases outside of Wuhan by that date."

"China’s control measures appear to have worked by successfully breaking the chain of transmission – preventing contact between infectious and susceptible people,” Dye concluded.

Regarding personal non-pharmaceutical interventions, frequent, thorough hand washing was associated with the greatest benefit for mitigating SARS viral transmission [5].

Further, both historical and novel modeling research suggests that the implementation of multiple non-pharmaceutical interventions – such as frequent hand washing, social distancing and home quarantine of confirmed cases – results in even greater ‘flattening the curve’ effects compared with any one strategy alone [3, 7].

Recent modeling research has also suggested that prolonged institution of social-distancing protocols may be beneficial for protecting against secondary peaks of virus outbreak [10].


What is ‘the curve’?

Graphically, when epidemiologists and researchers model the trajectory of an infectious disease such as SARS or COVID-19, the shape of the graph takes on that of a normal distribution, or sombrero (for those non-statisticians out there), with a skinnier, more exaggerated peak.

This ‘curve’ depicts the number of confirmed cases of a specific disease over time. Social-distancing measures are instated with two main aims: to reduce the total number of peak disease cases and to delay reaching the time when peak cases will be reported. The effects of the these on the curve will be to ‘shift’ and ‘flatten’ it.

These behaviors are essential for mitigating the devastating effects of an infectious disease and buying critical time for the development of targeted therapies, so that already overwhelmed healthcare systems can cope as best they can and fatalities due to restricted numbers of resources are prevented.


COVID-19: a novel virus

It is important to bear in mind that COVID-19 is a novel coronavirus disease; it is not an influenza, nor is it identical to SARS. Whilst emerging research and real-world evidence demonstrate that social distancing is associated with reduced mortality rates and disease spread, it is imperative to remember that models of the outbreak spread based on historical data on influenza or SARS will likely not truly capture the precise outbreak trajectory.

It is important to bear in mind that COVID-19 is a novel coronavirus disease; it is not an influenza, nor is it identical to SARS."

This is because we are still learning about COVID-19: are asymptomatic individuals with COVID-19 as contagious as asymptomatic individuals with influenza? Are individuals with cancer at greater risk of contracting the virus? How affected are children by the virus? In the 2009 'swine flu' pandemic, for example, younger individuals were disproportionately affected by the disease [1].

The effectiveness of social-distancing measures has also been shown to be affected by high 'R0' values [7] – the basic 'reproduction number' of a virus. How high is R0 truly for COVID-19?

Further, the demographic of the global population has dramatically changed over recent decades; today we have increasingly elderly populations in many high-income countries and a significant proportion of the population live with at least one additional chronic condition or are receiving immunosuppressive treatment.

It is imperative to regularly check reliable, government sites for the most up-to-date information about COVID-19 and how this reforms public policy. Relaible government sites include:


Harnessing 21st century technology

According to recent employment statistics, an estimated 20—25% of all weekly contacts made by individuals over the age of 16 years in the USA occur in the workplace. Further, influenza transmission in the workplace represents, on average, 16% of all transmissions [7].

Though these statistics, coupled with research discussed here, support the implementation of social-distancing strategies for mitigating virus spread, many factors outside of their simple implementation are key to their success.

Studies have suggested that the timing of protocol implementation is one the most critical determinants of strategy success [2].

In research, mentioned earlier, evaluating the success of social-distancing measures in Chinese cities during the first 50 days of the COVID-19 outbreak [12], the authors concluded: “…this analysis shows that suspending intra-city public transport, closing entertainment venues and banning public gatherings, which were introduced at different times in different places, were associated with the overall containment of the epidemic.”

However, the authors noted: “Cities that implemented control measures pre-emptively reported fewer cases, on average, in the first week of their outbreaks compared with cities that started control later.”

In addition, public adherence to such extreme social-distancing policies may decrease the longer these measures remain in place. Though recent modeling research suggests that, with strict and rapid adherence, intermittent implementation of social-distancing protocols, with periods of relaxed measures in between, may constitute a possible mitigation strategy for COVID-19, abrupt relief of these measures could have devastating consequences and result in mortality spiking due to rapid, unmitigated disease spread [3].

Harnessing modern technology will be critical in our response against this pandemic."

Christophe Fraser, a Professor at Oxford University’ Big Data Institute (Oxford, UK) recently stated: “To effectively tackle this pandemic we need to harness 21st century technology.”

Fraser was commenting on his team’s analysis of the feasibility of developing an instant contact-tracing app for use by European governments to establish accurate histories of individuals who develop COVID-19. And progress in the field is not slowing down; in the last few days, an app for real-time symptom tracking has been made publicly available in both the UK and USA, to help monitor, and hopefully slow, COVID-19 spread.

These projects will be essential for accurate surveillance during the outbreak, furthering our understanding of how the disease spreads, who is most at risk of developing a fatal form of the disease and how we can rapidly identify individuals who should self-isolate, all hopefully enhancing our ability to combat disease spread and mortality [4].


You can read about the latest progress in treatment and vaccination development in our COVID-19 Digital Hub on our sister site, IDHub>>


Social distancing and self-isolation are terms that many would rather live without hearing. However, the data available suggest these practices are effective at mitigating viral transmission and protocol adherence is a crucial factor to the success of these community-wide strategies to combat infectious diseases outbreaks, which we can contribute toward.


Concerned about the impacts of the pandemic on mental health? Sharon Salt, Senior Editor of our sister site NeuroCentral, recently explored this in an encouraging editorial on the site, which can be viewed here>>


References:

[1] Short KR, Kedzierska K, van de Sandt CE. Back to the future: lessons learned from the 1918 influenza pandemic. Front. Cell. Infect. Microbiol. 8:343 (2018).

[2] Markel H, Lipman HB, Navarro JA et al. Nonpharmaceutical interventions implemented by US cities during the 1918-1919 influenza pandemic. JAMA. 298(6):644—654 (2007).

[3] Imperial College COVID-19 Response Team. Impact of non-pharmaceutical interventions (NPIs) to reduce COVID19 mortality and healthcare demand.
www.imperial.ac.uk/media/imperial-college/medicine/sph/ide/gida-fellowships/Imperial-College-COVID19-NPI-modelling-16-03-2020.pdf
[Accessed 03/29/2020]

[4] Ferretti L, Wymant C, Kendall M et al. Quantifying SARS-CoV-2 transmission suggests epidemic control with digital contact tracing. Science. doi:10.1126/science.abb6936 (2020) (Epub ahead of print).

[5] Jefferson T, Foxlee R, Del Mar C et al. Physical interventions to interrupt or reduce the spread of respiratory viruses: systematic review. BMJ. 336(7635):77—80 (2008).

[6] Jefferson T, Del Mar CB, Dooley L et al. Physical interventions to interrupt or reduce the spread of respiratory viruses. Cochrane Database Syst Rev. 7:CD006207 (2010).

[7] Ahmed F, Zviedrite N, Uzicanin A. Effectiveness of workplace social distancing measures in reducing influenza transmission: a systematic review. BMC Public Health. 18(1):518 (2018).

[8] Wilder-Smith A, Freedman DO. Isolation, quarantine, social distancing and community containment: pivotal role for old-style public health measures in the novel coronavirus (2019-nCoV) outbreak. J Travel Med. doi:10.1093/jtm/taaa020 (2020) (Epub ahead of print).

[9] Koo JR, Cook AR, Park M et al. Interventions to mitigate early spread of SARS-CoV-2 in Singapore: a modelling study. Lancet Infect Dis. doi:10.1016/S1473-3099(20)30162-6 (2020) (Epub ahead of print).

[10] Prem K, Liu Y, Russell TW et al. The effect of control strategies to reduce social mixing on outcomes of the COVID-19 epidemic in Wuhan, China: a modelling study. Lancet Public Health. doi:10.1016/S2468-2667(20)30073-6 (2020) (Epub ahead of print).

[11] Pambuccian SE. The COVID-19 pandemic: Implications for the cytology laboratory. JASC. doi:10.1016/j.jasc.2020.03.001 (2020) (Epub ahead of print).

[12] Tian H, Liu Y, Li Y et al. An investigation of transmission control measures during the first 50 days of the COVID-19 epidemic in China. Science. doi:10.1126/science.abb6105 (2020) (Epub ahead of print).

[13] www.oxfordmartin.ox.ac.uk/news/china-prevented-700-000-covid-19-cases/


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