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Global catastrophe?

With the coronavirus making daily headlines around the world and the death toll continuing to rise, we ask if a virus will ever cause global catastrophe.

The test results come out positive today. Everything is settled. It is confirmed.” These are the bleak, final words Doctor Li Wenliang posted on social media before his death in the early hours of 7 February.

In December last year, Dr Li had sent a message to fellow medics warning of a virus he thought looked like severe acute respiratory syndrome (SARS) – the epidemic that caused a severe socio-political crisis in China and led to a “worldwide health threat” in 2002.

The SARS outbreak claimed 774 lives – a number that by early February the coronavirus had surpassed. Among the dead was Dr Li, who had been warned by police to “stop making false comments” and was being investigated for “spreading rumours”.

Ignoring his early warnings not only led to the virus claiming his life, but hundreds of others, with no indication of when, or how, the outbreak will be contained.

Epidemics

The exact number of deaths in China due to the current epidemic is probably not known (and is likely underestimated), as the testing facilities are under such strain. But with Chinese cities on lockdown, planes grounded, quarantined cruise ships stranded at sea and shops selling out of face masks, plastic gloves and antibacterial hand gels, the crisis shows no sign of abating.

At the time of writing, coronavirus remains an epidemic, as there have been only two confirmed deaths outside mainland China: one in Hong Kong and one in the Philippines. For the virus to reach pandemic status, it should occur “worldwide, or over a very wide area, crossing international boundaries and usually affecting a large number of people”.

Previous pandemics

While the current outbreak has not reached this point, we do not have to look back far in our history to see a number of pandemics that shook the world.

Hitting its devastating peak from 2005 to 2012, the HIV/AIDS pandemic is believed to have claimed more than 36 million lives since 1981.

Going back just over 100 years from the present day, Spanish influenza was responsible for at least 40 million deaths – more than double those recorded for military personnel and civilians due to World War I.

Between these pandemics was Asian flu. This was an outbreak of Influenza A (H2N2 subtype) that originated in China in 1956 and lasted until 1958. In these two-years, Asian flu travelled from the Chinese province of Guizhou to Singapore, Hong Kong, and the United States. Estimates for the death toll vary widely, depending on the source, but the World Health Organization places the final tally at approximately two million deaths, 69,800 of those in the United States.

Future predictions

We asked four virology experts to draw on the past, consider the present and decide whether in the future they believe a virus can cause global catastrophe. Here are their answers.


IT IS THEORETICALLY POSSIBLE

Mohamed Ahmed
Associate Lecturer and Clinical Researcher in Biosciences
London Metropolitan University

History has proven that viruses can arise and cause global pandemics, resulting in an increase in morbidity and mortality greater than any other global catastrophe. Although our scientific and medical understanding of infectious outbreaks continues to advance, there is a real risk that humanity could experience an outbreak that would cause a major global catastrophe. Importantly, to cause a global catastrophe the virus doesn’t need to kill its host. This could occur via the mutation of a known pathogen or a new virus not previously encountered. Furthermore, it could also arise via an existent or new cross-species transmission route infecting humans. However, for such a global catastrophe scenario to occur, several factors are likely to be necessary.  

The primary factor could be a previously encountered virus that is significantly antigenically different, or a completely new virus to which human populations have no pre-existing immunity. The world is much more connected than ever before. Every day millions of people travel across continents and countries within short timeframes and with relative ease. Should a viral outbreak occur, it could spread across the planet’s human population in a matter of days. The outbreak of the COVID-19 coronavirus is a prime example – 25 countries have confirmed cases of the virus (at the time of writing). Such a virus is of greater threat to populations considered to be immunocompromised, such as the elderly, infants and people with underlying health conditions, such as diabetes, asthma and other chronic conditions. Globally, the elderly and infant population is increasing, as people are living longer and population numbers are growing. In addition, chronic diseases, such as type 2 diabetes, are increasing.

“Should a viral outbreak occur, it could spread across the planet’s human population in days”

The replicative rate and ability of the virus to transmit easily between people would also be another factor that would influence the potential global catastrophic effect. This would clearly have a dramatic impact in urban areas. Therefore, the impact of climate change on vector species (e.g. mosquitoes) and in relation to predicted coastal and rural populations moving to urban areas are important factors to consider. Importantly, for a viral pandemic to have a catastrophic effect, it would need to cause significant pathology in an estimated one-third of the population, and be able to disable their daily activities of living, causing a significant impact on the functioning of society. It would also need to breach our medical services. If hospitals and physicians failed to manage the number of infected people, or there was a lack of medical supplies, it would compromise our ability to control the spread of infection. Given such a scenario, another important factor would be 
the effect on the supply chain for food and water. Lack of adequate food would further impact on a new viral pandemic, as the effects of poor nutrition on immunity and infectious disease are well documented. All the above could significantly impact the global economy – the current outbreak of COVID-19 is already beginning to affect economies.  

A viral pandemic could, therefore, have a wider, large-scale impact on society, affecting industry, the labour force and the economy. This type of scenario could affect every aspect of day-to-day life and could impact how society itself operates, leading to a potential breakdown within communities and social structures in some parts of the world.

It is theoretically possible that a virus could cause a global catastrophe. The virus would need to be new or a variation of an existing human or animal virus that could transmit easily between species and people, as well as having a high replicative rate. Another factor would be a lack of pre-existing immunity in the human population, such as a new pathogen or one significantly different antigenically. Furthermore, the virus would need to cause significant pathology that would affect a relatively high proportion of the human population and therefore impact societies globally.

The author would like to thank Dr Laurence S Harbige, Senior Lecturer in Biosciences, and Professor Gary McLean, Reader in molecular immunology, both at London Metropolitan University, for their input into this article.


THE HUMAN-ANIMAL INTERFACE

Alistair Gammie
ValuMetrix Global Senior Director
Ortho Clinical Diagnostics

Before one considers whether there are any circumstances, one should look back at those viruses that have created global pandemics, or epidemics that create global fear. The influenza A virus has created pandemics through antigenic shift, which arises from the viral reassortment of two different influenza viruses that co-infect the same host, creating a new virus.

If the novel virus can infect humans and achieve human-to-human transmission, and possesses virulence for humans, a pandemic may arise, as humans are unlikely to have appreciable immunity to the novel strain. Within the past hundred years, four pandemics have resulted from the emergence of a novel influenza strain for which humans possessed little or no immunity: the H1N1 Spanish flu (1918), the H2N2 Asian flu (1957), the H3N2 Hong Kong flu (1968), and the H1N1 swine flu (2009). The outbreak of SARS was created through a similar facilitation in China. SARS coronavirus (SARS-CoV) was identified in 2003. It is thought to be an animal virus from an as-yet-uncertain animal reservoir, perhaps bats, that spread to other animals (civet cats) and first infected humans in the Guangdong province of southern China in 2002.

The risks intensify when human beings have facilitated the bringing together of different species and have created a human-animal interface.

The Ebola virus has been shown to be associated with humans eating bush meat with the primary vector thought to be fruit bats. The multimammate mouse (Mastomys natalensis) is the reservoir for Lassa virus (LASV). Zoonotic transmission occurs when humans are directly or indirectly exposed to fluids of the multimammate mouse, such as urine, saliva, and blood. Housing characteristics and domestic organisation affect rodent density in and around households and villages and are likely to be a risk factor for Lassa fever in humans where the reservoir exists.

There are many more examples of viruses that have either mutated to cross from animals into humans, or have directly infected humans with a virus that is more harmful to humans.  

The simple fact is that they almost always occur where humans live in unsanitary conditions, share their homes with multiple animals, prepare and eat animals in non-hygienic conditions and have poor personal habits, such as spitting and hawking. Not every one of these conditions needs to be met to create a global catastrophe. The recent coronavirus outbreak (COVID-19) started in Wuhan due to some of these conditions being met. The unfortunate confounder in this outbreak was the timing just prior to the Chinese New Year, a time that sees the greatest migration of people to or from one country. In 2018, it was estimated that Chinese travellers made around three billion trips during the 40-day Spring festival period.

This means that people who would not normally encounter each other were crowded into bus terminals, train stations and airport terminals. In Wuhan province, although the outbreak had already started, the local officials allowed the Lunar festival to take place.

So, are there any circumstances in which another virus can cause a global pandemic? The answer is clearly “yes”. 

Is the circumstance preventable? Yes, but it is not about vaccines or surveillance, it is about education and changing the behaviour of people. Is this possible to do? Consider two practices, one legal and one illegal, that have changed dramatically in the UK over the last 25 years. Smoking (legal) was banned from public places in July 2007 and now this has become the accepted norm. Drink driving (illegal) has now become socially unacceptable. In fact, a recent government survey stated that people who take drugs before getting behind the wheel of a car believe it is a “much more acceptable” thing to do than driving while drunk.

Does one believe that the Chinese authorities will consider that this epidemic is grounds for major social change that could prevent further virus outbreaks? In this case, the financial cost to manufacturing and export, as well as the effect on the middle-income Chinese who are mainly working from home, may possibly become the driver for change, not the virus itself.


ADVANCES MINIMISE RISK

Zara Josephs
Independent researcher
Clinical biochemistry and molecular pathology

Yes, but only under very extreme circumstances, such as a major solar flare or meteorite strike. Pandemics are a significant cause for concern, their potential for causing widespread fatalities and socioeconomic chaos are incalculable: the 1918 influenza outbreak, which killed an estimated 50 million people globally (3% of the world’s population), caused more deaths than any pandemic disease before or since, including the sixth-century Plague of Justinian; the mediaeval Black Death; or swine flu in 2009. However, 100 years on, developments in epidemiology and technology have considerably minimised the risk of such catastrophes.

Risk factors for viral pandemics include contact with wildlife or livestock (from which all human viruses originate); the activities of super-spreaders (i.e. those able to spread disease to an unusually large number of people); crowded conditions, which bring super-spreaders into close proximity with one another; malnutrition on a large scale (as during wars and natural disasters), which increases susceptibility 
to infection; and increasing global travel, which increases the range of viral spread.

The plethora of organisations monitoring potential sites of disease outbreaks includes the Global Public Health Intelligence Network (GPHIN), which scans informal news sources for unusual disease events and rumours of outbreaks; Global Viral Forecasting, which monitors global medical intelligence in order to catch pandemic signs early; and Global Outbreak Alert and Response Network, a World Health Organization-sponsored collaboration of institutions working on the rapid confirmation of, and response to, disease outbreaks of international importance.

“Our understanding of the drivers and dynamics of emerging infectious diseases can only improve”

Information from these monitoring organisations is complemented by advanced molecular biology tools that enable rapid identification of pathogens; and epidemiological tools to monitor “digital signals” of potential infections, with the goal of predicting pandemics, as well as rapidly identifying hotspots and super-spreaders.

A primary focus of these investigations is the group that constitutes “sentinels”: people (including blood transfusion recipients, health care workers and flight attendants) most at risk of infection from newly emerging pathogen strains. The success of these combined efforts is highlighted by a notably increased efficiency of disease containment: it was GPHIN that issued the first alert of unusual respiratory illness in China to WHO, which helped to limit deaths from that outbreak of SARS coronavirus to 774.

While deaths from the more recent outbreak of the related coronavirus COVID-19 have surpassed those from SARS-CoV, the tools are in place to combat its pandemic potential and they seem robust enough to avert a
global catastrophe.

Our understanding of the drivers and dynamics of emerging infectious diseases can only improve. Evolving technology, improving search engine algorithms and increasing computational speed will lead to increasingly sophisticated surveillance methods and more accurate predictive models to help rein in an incipient pandemic. However, the international collaboration of governments, NGOs, public health networks and scientists is vital for the timely detection of, and response to, novel threats of pandemic disaster.

Given the number of safeguards in place, therefore, a catastrophic pandemic is by no means inevitable. The combined action of medical, veterinary, health, science and environmental personnel is needed to direct educational and research toward developing integrated global disease surveillance systems, diagnostic tools and preventive interventions.


GLOBALISATION HAS INCREASED RISK

Bamidele Farinre
Senior Executive Officer
National Infection Service, Public Health England

Viruses can cause global catastrophes, if the appropriate measures are not put in place to contain them. A global catastrophe is a future event in which biological agents, such as viruses, could lead to an abrupt widespread disaster beyond the immediate control of combined capability of national and international governments and the private sector.

There is a unanimous value in developing a full understanding of the scope of the viral world and to be able to develop better situational awareness – an accurate, up-to-date view of potential or ongoing infectious disease threats. This includes through traditional surveillance in humans and animals and the resources available to manage those pressures in preparedness of any imminent global catastrophe.

Disease-causing viruses exhibit certain characteristics that elevate their prominence above those microbes that are capable of causing only sporadic or limited human infections.

Most worrying is the ability 
of the virus to transmit during incubation periods, coupled with the occurrence of mild illnesses furthering the augmentation of disease spread. Broad-spectrum antivirals are not effective in the treatment of viral infections, compared with bacteria, fungi, and parasites, which are susceptible to antimicrobials; making viruses a more likely cause of a global catastrophe.

The respiratory route is the most feared mechanism that is likely to lead to epidemic spread. This is primarily due to the fact that interventions to interrupt this method of spread are more challenging to implement, when the natural act of breathing can spread a pathogen. The prolific spread of viruses such as influenza, measles, and coronaviruses authenticates this fact.

Viruses have a high affinity for genetic mutability, due to the structure of their genomes and the generation time for viral replication. Conversely, the RNA viral class poses the greatest health concern, compared to the DNA viral class, due to their high mutability. This fact is supported by the evidence that the stability of RNA as a genomic material is less than that of DNA, giving more genomic flexibility 
to the RNA viruses.

Additionally, RNA viruses that are spread via the respiratory route have been shown to have the characteristics that are most concerning, in terms of their ability to cause global catastrophic uncertainties. Based on these concerns, surveillance, science, and countermeasure development programmes, efforts must be strategic in logically allocating significant resources. Presently, there is no consensus methodology for estimating the economic impacts of global catastrophe.

The likelihood of a viral cause of a global catastrophe has increased greatly due to increased global travel and integration, urbanisation, changes in land use, and greater exploitation of the natural environment. The recent outbreak of coronavirus is an excellent example of how viruses can cause catastrophe. Without strategic contingency preparedness in place, a virus outbreak could lead to abrupt, unexpected, widespread disaster beyond the cooperative capability of national and international governments and the private sector to control. If unconstrained, the aftermath would lead to great suffering, loss of life, and sustained damage to national governments, international relationships, economies, societal stability and global security. Furthermore, all sectors of the economy face disruption, potentially leading to shortages, rapid price increases for staple goods, and economic stresses for households, private firms, and governments. Accordingly, situational preparedness will necessitate the health care workforce to recognise the illness and to have the technical and laboratory capacity to identify the pathogen or rule out known pathogens and respond to the influx of clinical specimens in a timely manner. Rapid identification reduces risk by enabling infected persons to be isolated and given appropriate clinical care.

There is only one Food and Drug Administration-approved antiviral for the treatment of respiratory-spread RNA viruses (ribavirin) aside from anti-influenza antivirals. There are currently no approved antivirals for 
any other respiratory-spread RNA viruses in the world.

There’s no one-size-fits-all response to a public health emergency; stratagems must be tailored to the local context and to the severity and type of event. In safeguarding against the threat of a virus causing a global catastrophe, more work needs to be done to improve surveillance of respiratory-borne RNA viruses. Despite improved preparedness to mitigate the impact of global catastrophe through refined standards and funding for building health capacity, substantial gaps exist in pandemic preparedness.   

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