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Bird's Eye View

Parham Habibzadeh1, Emily K Stoneman2
Abstract
The novel coronavirus (2019-nCoV) outbreak, which initially began in China, has spread to 1
Persian BayanGene
many countries around the globe, with the number of confirmed cases increasing every day. Research and Train-
ing Center, Shiraz
With a death toll exceeding that of the SARS-CoV outbreak back in 2002 and 2003 in China, University of Medical
2019-nCoV has led to a public health emergency of international concern, putting all health Sciences, Shiraz, Iran
organizations on high alert. Herein, we present on an overview of the currently available 2
Division of Infectious
information on the pathogenesis, epidemiology, clinical presentation, diagnosis, and treat- Diseases and Depart-
ment of Infection
ment of this virus. Prevention and Epide-
miology, University of
Michigan, Ann Arbor,
Keywords: Coronavirus; Novel coronavirus; 2019-nCoV; Middle East respiratory syndrome USA
coronavirus; SARS coronavirus; Outbreak; China; Wuhan; Emerging viruses

Introduction are frequently infected with four human

coronaviruses (229E, NL63, OC43, and

C
oronaviruses typically result in HKU1 with the first two classified as anti-
respiratory and enteric infections genic group 1 and the latter two belonging
affecting both animals and humans, to group 2) typically leading to an upper
and were considered relatively benign respiratory tract infection manifested by
to humans before the severe acute respi- common cold symptoms. However, coro-
ratory syndrome (SARS-CoV) outbreak naviruses, which are zoonotic in origin,
in 2002 and 2003 in China.1-4 A decade can evolve into a strain that can infect
later, Middle East respiratory syndrome human beings leading to fatal illness.8
coronavirus (MERS-CoV), another patho- Examples are SARS-CoV, MERS-CoV, and
genic coronavirus with a clinical picture the recently identified 2019-nCoV.
reminiscent of SARS, was isolated in The expansion of genetic diversity
patients presenting with pneumonia in the among coronaviruses and their conse-
Middle Eastern countries.5 Just recently, quent ability to cause disease in human
in December 2019, a novel coronavirus beings is mainly achieved through infect-
(2019-nCoV) has emerged in Wuhan, Chi- ing peridomestic animals, which serve as
na and has turned into a global health con- intermediate hosts, nurturing recombina-
cern.6 tion and mutation events.9 The spike gly-
coprotein (S glycoprotein), which attach-
Virology and Pathogenesis es the virion to the host cell membrane, Correspondence to
is postulated to play a dominant role in Emily K. Stoneman, MD,
F4007 University Hos-
Coronaviruses are enveloped positive- host range restriction.10 While SARS-CoV pital South, 1500 East
Medical Center Drive,
stranded RNA viruses that belong to infects type 2 pneumocytes and ciliated Ann Arbor, MI 48109-
the family Coronaviridae and the order bronchial epithelial cells utilizing angio- 5226, USA
Tel: +1-734-936-5205
Nidovirales.7 People around the globe tensin converting enzyme 2 as a receptor, Fax: +1-734-936-2737
E-mail: emilyks@umich.
edu
Cite this article as: Habibzadeh P, Stoneman EK. The novel coronavirus: A bird's eye view. Int J Occup Environ Received: Feb 3, 2020
Med 2020;11:65-71. doi: 10.15171/ijoem.2020.1921 Accepted: Feb 4, 2020
Online first: Feb 5, 2020

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review

The Novel Coronavirus

Figure 1: Timeline of the key events in the early stages of the outbreak
MERS-CoV exploits dipeptidyl peptidase 4 seven critically ill patients; one death was
(DPP4), a transmembrane glycoprotein, to noted in the subsequent report on Janu-
infect type 2 pneumocytes and unciliated ary 11, 2020.20 The Chinese authorities
bronchial epithelial cells.11-14 reporting to WHO stated that some of the
In general, coronaviruses first repli- patients were operating dealers or ven-
cate in epithelial cells of the respiratory dors in the Huanan seafood market, which
and enteric cells, which leads to cyto- was subsequently reported to be selling
pathic changes.15 Thorough studies have live and freshly slaughtered hunted ani-
not yet been conducted to elucidate the mals.16,21 Several reports of clusters of cases
molecular basis of the pathogenicity of among families and infection of 16 health
2019-nCoV. However, preliminary data care workers pointed to human-to-human
obtained through whole-genome sequenc- transmission of the virus.16,22,23
ing of the viral RNA extracted from host Despite recognition of the outbreak
cell-depleted nasopharyngeal and sputum within a few weeks by the Chinese using
samples and subsequent bioinformatics their efficient surveillance network and
analyses have shown that the novel virus laboratory infrastructure, efforts to pre-
is phylogenetically related to SARS-relat- vent the spread of this virus were not suffi-
ed coronaviruses first isolated in Chinese cient; as of February 3, 2020, at least 17 496
horseshoe bats during the period of 2015 cases with a death toll of 362 in more than
to 2017.16,17 It has also been hypothesized 25 countries have been reported (Fig 2).24
that the novel virus might use angiotensin With a crowded population eclipsing that
converting enzyme 2 as a receptor simi- of New York City by more than 2.5 million
lar to SARS-CoV.18 Unlike SARS-CoV or and its role as one of China's major trans-
MERS-CoV, primary human airway epi- portation hubs, the city of Wuhan was the
thelial cells provide better growth condi- ideal breeding ground for an outbreak.25
tions for 2019-nCoV than standard tissue Peak travel season due to the Chinese New
culture cells.6 Year was probably an important factor that
led to the global spread of the infection.
Epidemiology In a study of 425 cases infected up to
January 4, the basic reproductive num-
A series of patients with pneumonia of ber, or R0, of the virus was estimated to
unknown etiology were initially reported be approximately 2.2.26 This means that
by the Health Commission of Hubei prov- each patient can, on average, spread the
ince, China, on December 31, 2019 (Fig infection to more than two healthy per-
1).19 Although 27 patients were initially sons. This number was around 3 for the
announced to be afflicted with this myste- SARS-CoV outbreak, which was eventu-
rious disease, the number rose to 41 with ally contained as a result of efficient infec-

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P. Habibzadeh, E. K. Stoneman

Figure 2: Global distribution of 2019-nCoV as of February 3, 2020

tion control measures.9,27 Presence of typical human coronavirus has an incuba-
cases with mild clinical presentation and tion period of 2–4 days; it is estimated to
lack of infrastructure to provide isolation be 3–6 days for the 2019-nCoV, and 4–6
for infected individuals and their close days for SARS-CoV.15,16,29,30 Infection with
contacts, particularly in resource-limited 2019-nCoV, similar to SARS-CoV, pres-
countries, are nonetheless all hurdles to ents with non-specific symptoms such
control this infection. Furthermore, based as malaise, fever, and dry cough at the
on experience, proper precautionary mea- prodromal phase.16,29,30 In a study of 425
sures to prevent nosocomial transmission patients with confirmed 2019-nCoV infec-
of the virus is mandatory; the majority of tion, the mean duration from illness onset
patients with SARS-CoV and MERS-CoV to the first medical visit was 5.8 (95% CI
had become infected in health care set- 4.3 to 7.5) days for cases with disease onset
tings.28 Considering the plethora of comor- before January 1, 2020, and 4.6 (95% CI
bid conditions present in hospital popula- 4.1 to 5.1) days for patients with illness
tions, dire complications could arise in the onset between January 1 and 11.26 A report
setting of an outbreak. by Huang, et al, on 41 confirmed cases of
2019-nCoV infection who were admitted
Clinical Manifestations and to Wuhan Hospital indicated that fever
Diagnosis (98%), cough (76%), dyspnea (55%), and
myalgia or fatigue (44%) were the most
Overall, infection caused by the 2019- common presenting signs and symptoms.30
nCoV shares many clinical similarities In another report from China, these find-
with infection caused by SARS-CoV. A ings were corroborated.29 In contrast to

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The Novel Coronavirus

patients with typical human coronavirus ed with 2019-nCoV is an onerous task for
infections, few of those affected with the health care professionals around the globe.
novel coronavirus had upper respiratory Eliciting the exposure history of suspicious
tract signs and symptoms (eg, sore throat, cases could have been an effective strate-
rhinorrhea). Unlike SARS-CoV, intestinal gy in the earlier stages of the outbreak in
presentations (eg, diarrhea) seem to be China. However, the global spread of the
infrequent in patients with 2019-nCoV.29-31 virus and human-to-human transmis-
Given the similarities between SARS-CoV sion seen in recent weeks have made the
and 2019-nCoV, it is tempting to speculate situation more complicated.34 In general,
about viremia and affected tissues beyond infected patients had a median age rang-
the respiratory tract. However, we are not ing from 49 to 61 years; male individuals
aware of any data on this yet. are more frequently infected.26,29,30 Lack of
Chest X-ray and computed tomogra- serious disease in children is also a feature
phy (CT) findings showed bilateral lung of SARS-CoV infection, and a feature of
involvement in 114 (81%) of 140 con- some (but not all) coronavirus infections
firmed patients studied in two reports,29,30 in other species.15 Immune-related genes
again similar to infection with SARS-CoV. on the X chromosome and sex hormones,
Among these 140 cases, 61 (44%) had lym- which influence both innate and adap-
phopenia; 58 (41%) had an elevation of tive immune responses, might explain the
either aspartate aminotransferase (AST) higher susceptibility to the infection in
or alanine aminotransferase (ALT) above males.35,36 Higher likelihood of exposure to
the upper limit of the reference range29,30 the virus due to occupational risk could be
(also seen in SARS-CoV). Among infec- another contributory factor.
tion-related biomarkers, procalcitonin lev- The full genomic sequence of the 2019-
els have been normal among most of the nCoV was released shortly after the start of
reported individuals; elevated levels were the outbreak to public databases.37 This, in
observed in those with secondary infec- turn, paved the way for the development of
tions.29,30 However, elevated serum ferritin PCR assays to detect the virus. Rapid col-
and C-reactive protein levels were, respec- lection and nucleic acid amplification test-
tively, reported in 63% and 86% of the ing of appropriate respiratory samples (ie,
patients reported by Chen, et al.29 Similar nasopharyngeal and oropharyngeal swab
to the findings in SARS-CoV infection, an in outpatient cases and sputum and/or
increase in plasma pro-inflammatory cyto- endotracheal aspirate or bronchoalveolar
kines levels has also been reported, cor- lavage in patients with more critical con-
relating with the severity of the illness.30,32 ditions) for suspicious cases are currently
However, increased levels of interleukin recommended by WHO.38
10, which is an anti-inflammatory cyto-
kine, suggest a pattern different from that Treatment
of SARS-CoV infection.30,33 Further inves-
tigations to characterize the cytokine pro- There are no vaccines or specific antivi-
file of patients could shed light on 2019- rals for 2019-nCoV.39 Nonetheless, there
nCoV pathogenesis. are ongoing efforts for vaccine develop-
In the wake of the peak of influenza and ment.40 Remdesivir, an antiviral drug
other respiratory viral infections in the developed for the treatment of Ebola virus
northern hemisphere and nonspecific clin- disease, was used for the treatment of the
ical findings resembling other cases of viral first US case of 2019-nCoV.41 An ongoing
pneumonia, early detection of those infect- randomized controlled trial evaluating the

68 www.theijoem.com  Vol 11, Num 2; April, 2020

 review

P. Habibzadeh, E. K. Stoneman

efficacy and safety of lopinavir-ritonavir coronavirus associated with severe acute respira-
and interferon-α 2b in patients infected tory syndrome. N Engl J Med 2003;348:1953-66.
with the novel coronavirus was launched 4. Zhong NS, Zheng BJ, Li YM, et al. Epidemiology and
on January 10, 2020.42 However, isola- cause of severe acute respiratory syndrome (SARS)
in Guangdong, People's Republic of China, in Febru-
tion and supportive care including oxygen
ary, 2003. Lancet 2003;362:1353-8.
therapy, fluid management, and adminis-
tration of antimicrobials for treatment of 5. Zaki AM, van Boheemen S, Bestebroer TM, et
al. Isolation of a novel coronavirus from a man
secondary bacterial infections to allevi- with pneumonia in Saudi Arabia. N Engl J Med
ate the symptoms and prevent end-organ 2012;367:1814-20.
dysfunction is currently recommended by
6. Zhu N, Zhang D, Wang W, et al. A novel coronavirus
WHO for suspected and confirmed cases from patients with pneumonia in China, 2019. N
requiring hospital admission.43 Engl J Med 2020. doi: 10.1056/NEJMoa2001017
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Conclusion ogy. John Wiley & Sons, 2016.
8. Su S, Wong G, Shi W, et al. Epidemiology, genetic
The novel coronavirus, which comes from recombination, and pathogenesis of coronaviruses.
a viral family that was thought to be rather Trends Microbiol 2016;24:490-502.
benign before the turn of the century, has
9. Paules CI, Marston HD, Fauci AS. Coronavirus
led to a public health emergency of inter- infections---more than just the common cold. JAMA
national concern according to WHO.44 2020. doi: 10.1001/jama.2020.0757
Outbreaks like this highlight the impor- 10. de Wilde AH, Snijder EJ, Kikkert M, van Hemert MJ.
tance of effective public health strategies Host factors in coronavirus replication. Curr Top
to counteract the never-ending threats Microbiol Immunol 2018;419:1-42.
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Acknowledgments SARS coronavirus. Nature 2003;426:450-4.
12. Qian Z, Travanty EA, Oko L, et al. Innate immune re-
We would like to thank Dr. Mohammad sponse of human alveolar type II cells infected with
Sajadi from the Institute of Human Virol- severe acute respiratory syndrome-coronavirus. Am
ogy, University of Maryland for his invalu- J Respir Cell Mol Biol 2013;48:742-8.
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and its receptor CD26. Nature 2013;500:227-31.
Conflicts of Interest: None declared.
14. Raj VS, Mou H, Smits SL, et al. Dipeptidyl peptidase
4 is a functional receptor for the emerging human
coronavirus-EMC. Nature 2013;495:251-4.
Financial Support: None.
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