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Publicly Available Published by De Gruyter January 28, 2020

The novel coronavirus (2019-nCoV) outbreak: think the unthinkable and be prepared to face the challenge

  • Giuseppe Lippi EMAIL logo and Mario Plebani
From the journal Diagnosis

A new and threatening viral outbreak, originating from the Chinese city of Wuhan, has been declared. According to the most recent updates of the World Health Organization (WHO), this outbreak – sustained by a newly identified strand of coronavirus – has already been confirmed in 581 patients in six different countries, causing 95 critically ill cases and 17 deaths, as of January 23, 2020, and with number of contagion events (and deaths) rapidly escalating [1]. A first case has been announced by the Centers for Disease Control and Prevention (CDC) in the United States, on January 21, 2020 [2]. The responsible pathogen has been isolated on January 7, 2020, and has been temporarily named 2019 novel coronavirus (2019-nCoV). The identification of this specific microorganism follows that of two similar viruses, causing quite similar epidemics, i.e. the severe acute respiratory syndrome (SARS-CoV) in 2002 and the Middle East respiratory syndrome (MERS-CoV) in 2012. Overall, the former condition has involved 8437 people, causing as many as 813 SARS-CoV-associated deaths in 32 different countries, whilst 2494 laboratory-confirmed cases of infection with MERS-CoV have been identified so far, leading to 858 deaths in 27 different countries [3], [4] (Table 1). There are some major and most obvious similarities among these three outbreaks, encompassing the virus (i.e. all three belong to the Coronavirus family), the narrow geographical origin (i.e. Middle East and China), as well as the biological and clinical characteristics of human involvement (Table 1). Regarding the former aspect, all these conditions can be classified as zoonoses (i.e. diseases caused by microorganisms spreading from animals to humans). As concerns the clinical manifestations, although more accurate information would be needed to precisely portend the 2019-nCoV epidemic (the outbreak has apparently originated from a fish and wild animal market in Wuhan, China, traceable to snake origin), clinical symptoms and complications seem nearly overlapping among the three syndromes, as one would expect from diseases caused by viruses belonging to the same family [5]. Another important analogy is the capability of these viruses to spread from person to person, thus producing secondary cases among nearby contacts, including relatives and healthcare operators [6].

Table 1:

Main characteristics of severe acute respiratory syndrome (SARS-CoV), Middle East respiratory syndrome (MERS-CoV) and new 2019 coronavirus (2019-nCoV) outbreaks.

Likely originChinaMiddle EastChina
VectorBats, civet catsDromedary camelsSnakes
Human-to-human transmissionYesYesLikely
Laboratory-confirmed casesa84372494278
Incubation2–10 days2–14 days2–14 days
SymptomsFever, malaise, myalgia, headache, diarrhea, shivering, cough, shortness of breathFever, myalgia, diarrhea, cough, shortness of breathFever, myalgia, cough, shortness of breath
Major complicationsPneumonia, severe acute respiratory distress syndrome, deathPneumonia, severe acute respiratory distress syndrome, deathPneumonia, severe acute respiratory distress syndrome, death
  1. aLast WHO update: 21 January, 2020.

Coronaviruses encompass a large family of single-strand, positive-sense RNA viruses, with a ~26–32 kilobase genome, which usually causes mild disease, mostly mimicking influenza, though some specific strains (such as SARS-CoV, MERS-CoV and 2019-nCoV) may be associated with a more severe pathology, which can then evolve toward severe acute respiratory distress syndrome and death [7], [8]. Looking at the recent epidemiology of these outbreaks, what emerges clearly is that nearly 10 years have passed between SARS and MERS, whilst the period between MERS and 2019-nCoV epidemics is limited to approximately 7 years. Although it would be inappropriate to draw definitive conclusions from this limited evidence, the 3-year shorter period characterizing the origin of MERS-CoV and 2019-nCoV outbreaks would lead to speculate that the frequency of appearance of novel and divergent coronavirus outbreaks in humans is narrowing, thus leading the way to some important reflections.

The first important consideration concerns the causes of the relatively frequent recombination events occurring in coronaviruses. Some theories have been elaborated on this matter. Coronaviruses are characterized by a moderate-to-high mutation rate compared to other single-stranded RNA viruses (i.e. average substitution rate: ~10−4 substitutions per year per site) [8]. Despite the precise genetic recombination mechanisms remaining almost unclear, template switching leading to homologous recombination in similar genes from different lineages of coronaviruses or other viruses has been proposed, a process that is probably amplified in these microorganisms by their large circulation in multiple animal reservoirs [8]. Notably, climate has a considerable impact on most living organisms, including viruses [9]. The recently developing climate changes may hence press the viruses to adapt dynamic responses to a changing environment, inducing natural adaptation, and ultimately promoting the generation of new and potentially virulent strands. Another, less credible – but worthwhile mentioning – theory involves genetic engineering, for either clinical or unfair purposes [10]. A deliberate release of SARS-CoV [11] and MERS-CoV [12] has been hypothesized as a possible cause of these two recent viral outbreaks, whereby some inconsistencies have been found in the epidemiology of SARS and MERS, more strictly fitting sporadic than epidemic patterns. This evidence would persuade us to report here Julia Rosen’s thought, that “thinking the unthinkable” may be occasionally reasonable when facing some unpredictable and unexpected natural hazards [13].

Irrespective of the underlying nature of these three recent coronavirus outbreaks, the most reasonable steps for preventing and/or mitigating the unfavorable consequences of viral epidemics (or pandemics) on mankind entail the development of active surveillance programs, coupled with laboratory preparedness to face new environmental and biological challenges (Figure 1) [14], [15]. In case of serious biohazards, such as viral outbreaks, laboratory medicine plays a pivotal role in rapid and accurate identification of new microorganisms by means of molecular diagnostic assays [16], which represent a cornerstone in diagnostic virology [17]. This would hence entail widespread diffusion of molecular epidemiology, specifically aimed at detecting new viral strands in animal reservoirs, such as bats for most of the virulent mammalian coronaviruses [18], as well as the introduction of molecular diagnostic techniques in reference medical laboratories, which would thus enable rapid identification, isolation and treatment of affected cases (Figure 1). This demonstrates, once more, that laboratory medicine is integral to most care pathways [19], and will perhaps remain so for many years to come.

Figure 1: Natural history and management of recent coronavirus outbreaks in humans.CoV, coronavirus; SARS, severe acute respiratory syndrome; MERS, Middle East respiratory syndrome; 2019-nCoV, new 2019 coronavirus.
Figure 1:

Natural history and management of recent coronavirus outbreaks in humans.

CoV, coronavirus; SARS, severe acute respiratory syndrome; MERS, Middle East respiratory syndrome; 2019-nCoV, new 2019 coronavirus.

Corresponding author: Prof. Giuseppe Lippi, Associate Editor of Diagnosis, Section of Clinical Biochemistry, Department of Neuroscience, Biomedicine and Movement, University Hospital of Verona, Piazzale L.A. Scuro, 10, 37134 Verona, Italy, Phone: 0039-045-8122970, Fax: 0039-045-8124308

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.


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Published Online: 2020-01-28
Published in Print: 2020-05-26

©2020 Walter de Gruyter GmbH, Berlin/Boston

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