Introduction
The current outbreak (COVID-19) of the new coronavirus (SARS-CoV-2) in China and the
beginning of its subsequent global spread is already impacting global health systems
and the global economy [1]. How countries and international organizations respond
to the challenges it presents may have profound lasting impacts for global health.
The decisions taken, both at national and international levels, will help to inform
how we react to future pandemics and health security challenges.
Global disease outbreaks and pandemics have been increasing exponentially over the
last 40 years, and experts have long been warning of the potentially devastating effects
of a severe pandemic, although it is important to note that the improvement in diagnostic
capabilities undoubtedly plays a role (Figure 1, Figure 2
) [2,3]. By analysing the causes of this and similar pandemics, as well as the physiopathological,
human and political influences on its spread, we hope to shed some light on the current
health risks, decision-making dynamics and future implications of the current coronavirus
pandemic.
Figure 1
Emerging infectious disease (EID) events (defined as the temporal origin of an EID,
represented by the original case or cluster of cases that represents a disease emerging
in the human population – see Methods) are plotted with respect to: (a) pathogen type,
(b) transmission type, (c) drug resistance and (d) transmission mode.
Figure 1
Figure 2
Global number of human infectious disease outbreaks and richness of causal diseases
1980–2010. Outbreak records are plotted with respect to: (a) total global outbreaks
(left axis, bars) and total number of diseases causing outbreaks in each year (right
axis, dots), (b) host type, (c) pathogen taxonomy and (d) transmission mode.
Figure 2
Coronaviruses are single-stranded, positive-sense enveloped RNA viruses of the subfamily
Orthocoronavirinae, family Coronaviridae, order Nidovirales. Among those, four are
widely distributed human coronaviruses (HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1)
and cause the common cold. Severe acute respiratory syndrome coronavirus (SARS-CoV)
and Middle East respiratory syndrome coronavirus (MERS-CoV) are zoonotic. In 2002–2003,
SARS-CoV caused an outbreak of pneumonia in 8000 affected cases, distributed over
30 countries and five continents, and is now considered to be eradicated. MERS-CoV
was discovered in 2012 [4]. It originates from bats, with dromedary camels as the
intermediate host, causes pneumonia in humans and has a mortality rate of over 30%.
Nosocomial spread has also been described. No specific antiviral treatment is available
and treatment is mainly supportive and symptomatic [5].
SARS-CoV-2 belongs to the Betacoronavirus genus of the Coronaviridae family. It shares
more than 79% homology with SARS-CoV [6], and causes mild to severe disease with fatal
bilateral viral pneumonia described in humans [7,8]. It is referred to as a novel
coronavirus because it has not been observed previously in humans. Its likely reservoir
is bats, with pangolins identified as the likely intermediate host [9]. It is worth
mentioning that pangolins are endangered and the most trafficked animal in the world
[10]. As the pangolin trade is illegal, this would explain why they were not listed
in the official registers of the Wuhan market, making it difficult for researchers
to identify the source of the virus. Some researchers are suggesting that the virus
may have been circulating previously, and the market may have been an amplification
setting rather than the source of the spillover [11].
Why the rate of pandemics is increasing
There are numerous reasons for the exponential growth of global pandemics, but the
most frequently cited include expansion of the human population, destabilization of
ecosystems and globalization. Humans are coming into contact with environments that
were previously untouched, meaning that they will also come into contact with the
viruses and bacteria that are inherent to those environments. Many of these will have
no impact on human health but some do [2,12].
Human actions that impact animals, such as changes in land use and climate change,
have a profound effect on how these diseases spread. As our climate changes, certain
populations of animals (especially mosquitos or other animals that function as disease
vectors) increase and spread into geographic zones that were previously uninhabitable
to them, and they are more likely to spread the diseases that they carry to new regions.
Changes in land use and changes in human/animal contact also affect the emergence/re-emergence
and spread of disease, as does the unmanageable explosion of the global wildlife trade.
Legal and illegal wildlife trade is estimated to affect one in four mammal and bird
species globally, and to generate between US$7.8 and US$10 billion annually [13,14].
In response to COVID-19, China placed a temporary ban on wildlife trade on 26th January
2020 [15]. Although this will likely only affect the legal wildlife trade (temporarily),
it is a step in the right direction.
How we raise our food is just as important, and zoonotic diseases such as avian influenza
(including the 2006 H5N1 epidemic) and swine influenza (including the 2009 H1N1 pandemic)
are often associated with industrial farming. The ‘monoculture effect’ is well known
in agriculture, but there is mounting evidence that it is also important in animal
farming [16,17]. Although the aforementioned studies look at wild animal populations,
there is a high indication that it holds true for animals raised for food. Often large
populations of specific species of animals raised for food are kept in suboptimal
conditions. Without even mentioning the inherent issues of waste management and animal
welfare, industrial farming also creates health risks for humans in multiple ways
if these populations are not isolated from wild animals of similar species. In the
case of avian influenza, the virus, which circulates naturally in wild bird populations,
came into contact with large homogeneous populations of birds in poultry farms [18].
Due to the disease potential associated with intensive animal farming, animals are
often treated with vaccines and antibiotics. Both avian and swine influenza continue
to be managed through regular vaccination of livestock [19]. Although the main reason
for antibiotic use in farming is to preserve human and animal health and prevent zoonoses,
widespread use of antibiotics in terrestrial animal production (including first-line
antibiotics such as colistin) promotes antibiotic resistance [20,21]. In farming,
antibiotics are used as prophylactics to make up for crowded unhealthy conditions,
and growth promoters as well as therapeutic treatments for specific disease outbreaks.
Therefore, although they are relevant tools for decreasing zoonoses, antibiotic use
in animals can also become the catalyst for the development of zoonoses that are resistant
to antibiotics [22].
These issues are compounded by globalization in two main ways: interconnectedness
and mobility. Our interconnectedness means that there are huge global markets for
specific products from specific environments, which can speed up environmental degradation.
Deforestation has already been linked to the emergence (and re-emergence) of Nipah
virus, Lassa fever, Lyme disease and, possibly, Zika virus [3,23].
A current example of this is how the international drive for palm oil (a cheap and
stable oil) in Malaysia has led to the upsurge of malaria in the region. Currently,
the world's highest rate of deforestation is of Malaysian forests for the creation
of palm oil plantations [[24], [25], [26]]. The zoonotic malaria species Plasmodium
knowlesi has recently become the principal cause of human malaria in Borneo, and this
has been linked directly to deforestation on the island [27,28]. Considering the dynamics
at the human–animal–ecosystem interface, it is not surprising that the worst epidemics
and pandemics (including human immunodeficiency virus, SARS-CoV, avian influenza,
swine influenza, Ebola virus and Zika virus) of the past 40 years were all of zoonotic
or vector origin.
Human populations are also more mobile than they have ever been, and air travel enables
a pathogen to be transported across the globe in a matter of hours. Currently, over
4 billion trips are taken by air every year, and this frequency of travel in an infected
and moving global population gives a disease unprecedented opportunity to spread and
spread quickly [29]. In that sense, the timing of COVID-19 was very bad luck. Chinese
New Year is the biggest mass migration in the world, with 385 million people making
approximately 3 billion trips during the holiday period [30,31]. The fact that the
outbreak happened during this time makes it that much more difficult to trace and
control, and certainly influences the speed at which it is spreading. In a globalized
world, the security of countries is interdependent, and in the case of a severe global
pandemic, the world is (arguably) only as prepared as its weakest country [32].
Potential impact
The issue that needs to be assessed is the level of risk that more frequent outbreaks
of emerging and re-emerging diseases pose for the human population. Impact can be
assessed in different ways, including global morbidity, mortality, economic burden
and geopolitical implications.
The stakes are high: the World Health Organization (WHO) estimates that a moderate
to severe pandemic would cost approximately US$500 billion or 0.6% of global income
[33]. As has been shown repeatedly, an epidemic does not need to reach severe levels
or have many (or, technically speaking, any) casualties in order to destabilize national
health systems or put a strain on the networks responsible for international and global
response and the economy.
In order to quantify risk and forecast possible scenarios of transmission, it is necessary
to look at the traits of a specific pathogen. There are numerous characteristics that
can predict how well a pathogen could spread through and damage a population. These
traits include virulence, clinical severity, ease of human-to-human transmission,
and if the pathogen is transmissible during the disease incubation period (if it is,
the length of the incubation period is of importance).
Health system and human factors will also impact the spread of a virus. Health system
capacity factors include the availability of treatment or vaccine, and the level of
resources (human, material and financial) available for allocation. Human factors
include whether the population is immunologically naïve or not, how well the human
immune system can respond to the virus, age structure of a population, population
density, mobility and cultural behaviours.
Individuals' behaviour is informed by cultural beliefs and mores, and these can impact
movement within a community, contact with others and likelihood to comply with official
recommendations. Level of education and previous knowledge of general infection prevention
measures also play a role [34].
Systemic factors that will determine the severity of an outbreak or pandemic include
the resilience of health systems; co-existing external factors that would hinder an
appropriate response; and the ability of a governing body to respond to the outbreak,
implement infection control measures in the population, and continue to function despite
a health emergency. Health systems are varied. A small outbreak of influenza in a
high-resource country with a robust health system will likely only have a small impact
on the continual habitual or average delivery of health services that have nothing
to do with the outbreak. A health system that is fragile, or already overloaded by
either routine care or another emergency, needs only a little disruption to damage
it or even cause it to collapse. Traditionally, supranational organizations, international
institutions and non-governmental organizations will fill that response vacuum as
well as is possible. An example of this and how difficult it is to implement effectively
would be the international response to the 2014 Ebola epidemic [35,36].
An outbreak in one country can deeply affect not only that country's economy, but
also the world economy and the country's political relationships with other countries
(e.g. trade agreements, opening or closing national borders, etc.). Economists are
expecting China's economic growth to slow to 4.5% because of the outbreak [37].
Close-up of SARS-CoV-2
SARS-CoV-2 fulfils many of the qualities that a pathogen needs to cause a worldwide
pandemic. It seems to be quite virulent. As SARS-CoV-2 has not been seen before in
humans, the population is completely naïve. The virus has also been shown to have
high interhuman transmission. Sufficient data are not yet available for exact figures
concerning the spread, but there have been initial estimates that each infected person
would infect, on average, 2.6 other people (uncertainty range 1.5–3.5) [38]. WHO estimates
are a little less daunting, reporting a preliminary reproductive number (R
0) estimate of 1.4–2.5 [39]. Importantly, calculations from Imperial College London
estimate that infection control measures need to block well over 60% of transmissions
to be effective in controlling the outbreak [38]. That number is most likely inaccurate,
but this will be easier to assess as time goes on. In the case that the virus can
be transmitted by an asymptomatic individual [40], it will be even more difficult
to implement a 60% effective infection and control (IPC) strategy, especially because
most of the people infected will be in the community and not in healthcare settings.
However, the initial report of asymptomatic transmission in Germany was inaccurate,
which is encouraging [41]. A further challenge is posed by the decision of foreign
governments to evacuate and repatriate their citizens from China. The inevitable quarantines
and infection control measures that need to be taken as people arrive back in their
home countries will be crucial for preventing the spread of the virus [42]. The Diamond
Princess cruise ship outbreak of SARS-CoV-2 in Japan, with more than 691 infected
people and four deaths (as of 25th February 2020), is an example of inadequate IPC
in the community that led to a disaster [[43], [44], [45]].
The SARS-CoV-2 genome has already been sequenced, and countries are working hard to
develop a vaccine [[46], [47], [48]]. It is difficult to tell what the actual mortality
of the virus is, as the current death toll includes all-cause mortality of infected
people and is likely overestimated by the testing of mostly sicker patients, although
this information will emerge over time. SARS-CoV-2 seems to be spread mainly by droplets
and not through air. Nosocomial transmission has been described [49], and superspreading
events in hospital settings may occur. SARS-CoV-2 is possibly spreading indirectly
through contaminated surfaces and hand contamination as well, but the lack of aerosol
transmission will make the spread less efficient. According to WHO, 25% of current
cases are considered severe [39], but this proportion would presumably decrease while
more patients and contacts would have been searched for and screened. The reason for
this is that most of the cases screened are for relatively severe infections, especially
in areas where tests are limited. Once more people are screened (including milder
cases), the percentage of severe cases (and the death rate) will inevitable drop and
get closer to its true value.
Contact tracing of SARS-CoV-2 suggests that there is a low R
0 and limited person-to-person transmission [50]. The exponential spread of the number
of cases, however, may suggest that superspreaders of the virus may be playing a major
role, either from individuals or a zoonotic source [50]. Superspreading individuals
were found to have a major impact in the previous MERS, SARS and Ebola pandemics [34].
The current death toll is rising much more slowly than the current number of cases
[80,234 confirmed cases and 2701 deaths (as of 25th February 2020), overall fatality
rate of 3.36%] [51]. Due to under-reporting, a shortage of test kits, reporting of
all-cause mortality and a prevalence of patients with mild symptoms, it is highly
likely that the death rate will be much lower than initially expected [52,53]. There
are some estimates that currently only approximately 5% of current cases of the virus
have been identified [53]. If this is true, then COVID-19 is far less lethal than
it seems.
What this means for infection prevention and control
It might be easy for IPC experts to get caught up in the frenzy of getting prepared
for a new pandemic. Granted, we do not know what, if any, long-term effects this virus
might have on the human body. But what is most important is to keep a healthy perspective
and avoid getting distracted by all of the hype and forecasting. Although sufficient
information is not yet available, SARS-CoV-2 may be less deadly than the influenza
virus that hospitals deal with on an annual basis, and transmission seems to occur
mainly through droplets. Even a high estimate of the R
0 rate is many times lower than for airborne diseases such as measles, for instance
[54]. It is important to remember that the R
0 rate refers to the average transmissibility of the disease, and does not give information
on how fast it will spread. Seasonal influenza has an R
0 of approximately 1.3, but circulates through the whole human population every year
[55]. Human immunodeficiency virus, on the other hand, spreads far more slowly through
the population, yet has a highly variable reproductive rate [56]. Still, SARS-CoV-2
causes pneumonia in healthy people [57], even if most of the deaths are described
in elderly, comorbid patients. More epidemiological data are needed in order to determine
the full spectrum of the disease.
In order to better understand this dynamic, it might make sense to look at SARS-CoV.
This has a similar reproductive rate to estimates of the R
0 of SARS-CoV-2, but only infected approximately 8000 people. In the early phase of
the 2003 SARS-CoV outbreak, the lack or inappropriateness of IPC measures used proved
to be associated with increased risk for cross-transmission and within-hospital spread
of the disease among both visitors and healthcare staff [[58], [59], [60]]. In contrast,
when applied appropriately, IPC measures were extremely effective during the SARS
epidemic [61]. Similarly, IPC measures will certainly prove to be extremely effective
in respect to SARS-CoV-2, but more detailed transmission models are needed [62]. In
a 2003 analysis of SARS in Hong Kong that excluded superspreading events, the reproductive
rate dropped from 2.9 during the initial phase of the epidemic to 0.4 after the implementation
of IPC measures [63]. Usually, once the reproductive rate falls below 1, the outbreak
will die out on its own. Therefore, having a strong and adapted IPC response to this
outbreak will be crucial to stopping it. An additional factor is that people infected
by SARS-CoV felt unwell and were likely to seek care in hospitals. SARS-CoV-2 seems
to cause a wider range of symptoms, and if people only show mild infections, the infection
may go unnoticed (with people thinking that they have a common cold). This can cause
the disease to be underdiagnosed, which means that people will be more likely to continue
to spread the virus.
It is essential that we prepare ourselves for what seems like the inevitability of
having the virus at our doorstep, but we must think ahead to enact commonsense policies
that will not cripple the normal functioning of our healthcare institutions. That
may mean sending people home while waiting for a test result to come back, providing
home care to mild cases [64], or figuring ahead of time how to handle an extra influx
of patients.
Healthcare institutions can organize beds and isolation rooms, and IPC teams can set
up hotlines in anticipation of the virus. Although more easily said than done, having
a clear definition of what constitutes a suspect case is crucial. The case definition
will evolve rapidly in a context where the epidemiological risk changes with geographic
spread of the disease, and possible new information about its epidemiology. In order
to contain the outbreak, the case definition should be broad at an early stage. It
is also important for IPC teams to work with hospitals in expanding their triage capacity,
and deciding how to organize the activities during a period with a potentially unusually
high influx of patients suspected to have the virus. Liaising with the virology laboratory
to define additional hours and workforce if needed can be an additional step to prepare
an institution. Healthcare staff must be reminded of the importance of hand hygiene,
standard precautions, contact precautions and any complementary measures in preventing
the spread of the disease.
Developing countries face more critical challenges during outbreaks compared with
higher-income countries, preventing effective management worldwide (Major Issues and
Challenges of Influenza Pandemic Preparedness in Developing Countries: oshitani) [96].
The lack of IPC in developing countries with limited resources is a major dilemma
that leads to high rates of healthcare-associated infections [65]. Hand hygiene is,
arguably, the most important infection control procedure, and is often neglected by
healthcare workers in these countries [66]. While developing countries still lack
the equipment, expertise and health infrastructure to detect and manage patients [65],
SARS-CoV-2 is spreading rapidly in these unprepared countries [67]. Prompt prioritization
of resources, precise surveillance and capacity development have been recommended
in countries with low preparedness for diagnosing the virus and limiting transmission
[68].
What is most essential is that regular care activities do not suffer because of a
pandemic condition, and that control of the far more common (and far more deadly)
pathogens that hospitals deal with on a daily basis remains of utmost importance.
Response and politics of pandemics
The scale of China's response to the pandemic is unprecedented. Extreme cordon sanitaire-type
quarantine measures have questionable efficacy, and can jeopardize trust between healthcare
providers and the population. This was seen in the 2014 Ebola epidemic, when the Government
of Sierra Leone imposed a 3-day quarantine, and sent police and military house to
house to educate the population and to find people harbouring patients with Ebola
patients in their homes [69,70]. That said, the COVID-19 outbreak is a delicate situation
and a difficult decision for the Chinese Government to make – any decision will have
major risks. Still, quarantining a major region will most certainly result in practices
that could be considered human rights violations [71].
It is worth noting that it would be much more difficult for a government to implement
such a large-scale dedicated disaster response in a democratic country. China worked
day and night to construct two hospitals within a matter of days. They are made of
prefabricated buildings, and serve to help handle the overwhelming number of patients
[72]. On 28th January 2020, after just 48 h of construction, China opened another
1000-bed hospital that had been retrofitted into an empty building [73]. China has
an impressive track record for being able to implement huge engineering projects at
record pace; during the 2003 SARS epidemic, they were able to construct a 1000-bed
hospital in under 1 week using prefabricated buildings. At the height of the epidemic,
the Xiaotangshan Hospital treated one-seventh of patients with SARS in China [74].
Countries are often motivated to be cautious in declaring an emergency rather than
alarmist, as this has severe economic repercussions. The speculations that China knew
about the outbreak before they declared it seem to be well founded: on 27th January
2020, the Mayor of Wuhan, Zhou Xianwang, admitted that ‘we haven't disclosed information
in a timely manner and also did not use effective information to improve our work’
[75]. Locally, officials might have little motivation to declare an emergency to their
superiors [53]. Quarantines were announced hours before they were put in place, which
could have encouraged people to flee; approximately 5 million residents reportedly
left Wuhan before the quarantine was in place [75]. Deciding when to declare a national
or international emergency is always a difficult risk–benefit analysis. The risks
of doing so can disrupt trade and severely hurt a region's economy, but policy makers
often do not have many options, especially when faced with public scrutiny.
Europe is now faced with the same dilemma after the recent spike of cases in Italy
(but on a far smaller scale). The Italian Government has put a number of towns on
lock down and cancelled carnival celebrations to attempt to stem the spread of COVID-19.
The first example of major spread of the virus in Europe also highlights issues concerning
the open borders between European countries [76].
Epidemics impact people's health and livelihoods far beyond the direct effects of
the outbreak in the sectors of the countries where the disease occurs [77]. During
the 2003 SARS epidemic, the global economy lost an estimated US$40 billion [78]. The
direct economic burden of the 2014 Ebola outbreak is estimated to be between US$2.8
billion [79] and US$32.6 billion of lost gross domestic product. With the comprehensive
economic and social costs factored in, the cost to the global economy was estimated
at over US$51 billion, with US$18 billion in deaths from non-Ebola causes [80]. The
impact of the outbreak of SARS-CoV-2 has spread from Asia to other parts of the world,
including Europe. With the emergence of many SARS-CoV-2 cases in Italy and South Korea
as two of the world's major economies, concerns have been raised regarding global
economic damage [81].
After some debate, WHO declared SARS-CoV-2 a public health emergency of international
concern (PHEIC) on 30th January 2020. The process leading up to this decision is complex
and impacts many people; on the one hand, such a declaration is an international call
for alarm, but on the other hand, it does not guarantee that the outbreak will be
ended or the exact nature of the international response [82]. WHO initially declined
to label the coronavirus outbreak as a PHEIC, as doing so would be extremely disruptive.
The member views concerning this decision were quite divided during the first meeting,
but WHO agreed to re-assess this decision in a few days' time [39], and changed its
global risk assessment for SARS-CoV-2 from ‘moderate’ to ‘high’ [83]. It maintains
that there is no evidence that donors withhold disaster relief funds if a PHEIC is
not declared [84]. It is worth noting that WHO repeatedly declined to label the 2018
Ebola outbreak as a PHEIC, showing that there is a tendency to err on the side of
caution [85]. When it did so in 2019, there was prevailing opinion that the PHEIC
designation would be game changing in terms of resources allocated and international
response [86]. We predict that the PHEIC designation for SARS-CoV-2 will help to mobilize
the response on a global scale.
What now?
Although China has been praised for its rapid sequencing of the virus genome, and
the impressive construction of health facilities and mobilization of the response,
it has been struggling with managing the human element [53]. Effects of outbreak situations
such as SARS-CoV-2 are always difficult to predict because there are so many variables
to consider. Firstly, we do not know much about this virus, and secondly, so much
of its spread will be dictated by human behaviour, decisions and, ultimately, luck.
There is much that can be done in terms of reducing the likelihood that novel viruses
will jump from animals to humans, but these measures often include the type of environmental
regulation that is difficult to implement in an international system inherently focused
on growth and short-term profit. There are also cultural and practical issues associated
with changing how we farm and stopping the wildlife trade, which are equally difficult
to implement.
The magnitude of effort needed to address this issue is daunting. Warning systems,
response networks and real-time tracking are important tools for containing outbreaks,
but they do not actually prevent them from occurring in the first place. Projects
that catalogue and study novel viruses do not equal preparedness. The same scientific
work that is used to study a disease can in and of itself create biological risk [87,88].
Both national governments and supranational organizations state that this issue is
of utmost importance, and have pledged their commitment [[89], [90], [91]]. Nonetheless,
expert consensus is that there is a high chance of the world dealing with a devastating
pandemic in the near future, and that we are quite unprepared [87,[92], [93], [94]].
Still, the number of cases in countries other than China continues to grow. Outside
of China, there is a growing number of cases and casualties, with 12 deaths in Iran,
10 in South Korea, seven in Italy, four on the Diamond Princess cruise ship, two in
Hong Kong, and one each in France, Japan, Taiwan and the Phillippines [45]. Coupled
with the exponential growth of the pandemic, the very short pre- or pauci-symptomatic
and infectious incubation period of the virus, as well as the possible prolonged high-level
carriage, makes it quite difficult to contain [40]. One probable scenario is that
SARS-CoV-2 will just become another human virus that the world deals with on a regular
basis. WHO Director-General Dr Tedros warned of a potential global pandemic: ‘The
window of opportunity is still there, but our window of opportunity is narrowing’,
he said on 21st February 2020. ‘We need to act quickly before it closes completely’
[95]. It seems to be less dangerous than initially thought, so perhaps, once again,
humanity will be lucky. Hopefully, we can learn from our mistakes before our luck
runs out.
Conflict of interest statement
None declared.
Funding sources
This work is supported by the Infection Control Programme (SPCI), University of Geneva
Hospitals and Faculty of Medicine, Geneva, Switzerland; hand hygiene research activities
at SPCI are also supported by the Swiss National Science Foundation (Grant No. 32003B_163262).