Volume 10, Issue 1: 01-11; January 25, 2020  
ISSN 2228-7701  
REVIEW ON CORONAVIRUS, A MIDDLE EAST  
RESPIRATORY SYNDROME (MERS-CoV)  
Berhanu KASSAHUN1 , Tilahun BERHANU2 and Berhanu DAMTEW3  
1Jigjiga University, College of Veterinary Medicine, P.O.box 1030 jigjiga, Ethiopia  
2Haramaya University,College of veterinary medicine, P.O.Box 138 Diredawa , Ethiopia  
3 Shirka veterinary clinic, Arsi, Ethiopia  
Email: kassahunberhanu110@gmail.com  
Supporting Information  
ABSTRACT: Human coronaviruses (HCoVs) have long been considered in consequential pathogens, causing the  
―common cold‖ in otherwise healthy people. However, in the 21st century, 2 highly pathogenic HCoVssevere  
acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-  
CoV)emerged from animal reservoirs to cause global epidemics with alarming morbidity and mortality. In  
December 2019, yet another pathogenic HCoV, 2019 novel coronavirus (2019-nCoV), was recognized in  
Wuhan, China, and has caused serious illness and death. The ultimate cope and effect of this outbreak is  
unclear at present as the situation is rapidly evolving. Middle East respiratory syndrome coronavirus (MERS-  
CoV) is zoonotic diseases causing severe respiratory illness emerged in 2012 in Saudi Arabia. Phylogenetic  
studies and viral sequencing results strongly suggest that MERS-CoV originated from bat ancestors after  
evolutionary recombination process, primarily in dromedary camels in Africa. The prevalence of MERS-CoV  
antibodies, the identification of MERS-CoV RNA and viable virus from dromedary camels of Eastern Africa and  
the Arabian Peninsula are the suggestive evidence for inter-transmission of the virus, primarily from camels to  
humans and its public health risks. However, the infection in camel is mostly asymptomatic. In contrast to the  
camel case, the clinical signs and symptoms of MERS-CoV infection in humans ranges from an asymptomatic  
or mild respiratory illness to severe pneumonia and multi-organ failure with an overall mortality rate of about  
35%. Though inter-human spread within health care settings is responsible for the majority of reported MERS-  
CoV human cases, the virus is currently incapable of causing sustained human-to-human transmission  
(pandemic occurrence). Currently, there is no specific drug or vaccine available for treatment and prevention of  
MERS-CoV. The important measures to control MERS-CoV spread are strict regulation of camel movement,  
regular herd screening and isolation of infected camels, use of personal protective equipment by camel  
handlers and awareness creation on the public where consumption of unpasteurized camel milk is common.  
Therefore, urgent global epidemiological studies are required, to understand the transmission patterns and the  
human cases of MERS-CoV and also for the proper implementation of the above-mentioned control measures.  
Keywords: Bats, Dipeptidyl peptidase 4, Dromedary camels, MERS-CoV, SARS-CoV, Transmission  
Abbreviations  
COV  
Coronavirus  
MERS-CoV  
SARS-CoV  
DPP4  
WHO  
Middle East respiratory syndrome coronavirus  
Severe respiratory syndrome corona virus  
Dipeptyl peptidase 4  
World Health Organization  
ICTV  
PCR  
International Committee on Taxonomy of Virus  
Polymerase Chain Reaction  
Rt-PCR  
Hcov  
Real Time Polymerase Chain Reaction  
Human Coronaviruses  
ORF  
Open Reading Frame  
CDC  
Centers for Disease Control and Prevention  
European Centre for Disease Prevention and Control  
Enzyme-linked immune sorbent assay  
Upstream of the envelope gene  
Bat coronaviruses  
ECDC  
ELISA  
UpE  
BtCOV  
INTRODUCTION  
Coronaviruses (CoV) are enveloped, positive-sense RNA viruses with large genomes (2932 kb) packaged in particles with  
corona-like morphology (Lai et al., 2007). They can infect humans, as well as a variety of animals, such as bats, mice,  
birds, dogs, pigs, and cattle, causing mainly respiratory and enteric diseases (Perlman and Net land, 2009).  
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Citation: Kassahun B, Berhanu T and Damtew B (2020). Review on coronavirus, a middle east respiratory syndrome (MERS-CoV). Online J. Anim. Feed Res., 10(1): 01-  
Before the 21st century, it was believed that human corona viruses, represented by the virus‘s hCoV-OC43 and hCoV-  
229E, can only cause mild respiratory symptoms (Saif, 2004). This notion changed after the outbreak of the severe acute  
respiratory syndrome (SARS) in 2002-2003, when a previously unknown human corona virus, named severe acute  
respiratory syndrome corona virus (SARS-CoV), caused the first corona virus-associated human epidemic, infecting  
approximately 8000 and killing 774 people (Peiris et al., 2004). In the years that followed, two additional human corona  
viruses were discovered, namely hCoV-NL63 and hCoV-HKU1 (Woo et al., 2005). All known human corona viruses are  
believed to have a zoonotic origin, with bats playing a major role in the interspecies transmission (To et al., 013).  
MERS-CoV is the second newly discovered Beta corona virus lineage 2C and initially recognized in the Kingdom of  
Saudi Arabia in June 2012, when an elderly Saudi Arabian man was admitted to a local hospital with acute pneumonia  
and later died of progressive severe respiratory illness and renal failure (Zaki et al., 2012). The World Health Organization  
(WHO) global case count for MERS was 1952 laboratory-confirmed cases, including at least 693 deaths (case fatality rate  
36%) from September 2012 to 3 April 2017 (WHO, 2017).  
MER-CoV previously called human corona virus-Erasmus Medical Center was discovered by Zaki et al. (2012) in  
Saudi Arabia in 2012. In May 2013, the Corona Virus Study Group of the International Committee on Taxonomy of Viruses  
renamed the virus ―Middle East respiratory syndrome corona virus (Murphy et al., 2012; Degroot, 2013). MERS-CoV marks  
the second known zoonotic introduction of a highly pathogenic corona virus, probably originating from bats (Sharif and  
Kanj, 2014). Three lines of evidence currently support this theory: Firstly, the very close phylogenetic similarity with the bat  
Beta corona viruses: BtCoV-HKU4 and BtCoV-HKU5 (Van bohemeen et al., 2012). Secondly closely related corona virus  
sequences have been recovered from bats in Africa, Asia, the Americas, and Eurasia; and thirdly MERS-CoV uses the  
evolutionary conserved dipeptidylpeptidase 4 (DPP4) protein in Pipistrellus pipistrellus bats for cell entry (Raj et al.,  
Since human-bat contact is limited, camels have been implicated as probable intermediate hosts. MERS-CoV  
appears to have been circulating in dromedary camels for over 20 years (Corman et al., 2014). Many studies have now  
identified dromedary camels (Camelus dromedarius) as a natural host for MERS-CoV, and there appears to be ample  
evidence of wide spread infection in dromedaries in the Middle East and in many parts of Africa (Reusken et al., 2014a,  
Hamid et al., 2015). MERS-CoV strains isolated from dromedaries are genetically and phenotypically very similar or  
identical to those infecting humans (Farag et al., 2015).  
While corona viruses affect wide animal species (Woo et al., 2012a), MERS-CoV have affects limited host ranges. In  
the last few years, a large spectrum of domestic species has been negative after MERS-CoV serology tests, including  
horses, cattle, water buffalo, chickens, goats, and Bactrian camels (hemida et al., 2013). An exception was published  
recently when antibodies were detected in Alpaca (Vicugna pacos) in Qatar (Reusken et al., 2016) and susceptibility of  
pigs and llamas to MERS-CoV infection (Vergera et al., 2017).  
In the case of MERS-CoV transmission, there is a large uncertainty about the various exposure pathways associated  
with new dromedary camel or human cases, and, although published research on MERS-CoV is actively increasing (Zyoud  
et al., 2016), few transmission risks have yet been quantified.  
Therefore, the objective of this paper was to review the public health risk and transmission of Middle East  
Respiratory Syndrome.  
ETIOLOGY AND TAXONOMY  
Middle East respiratory syndrome (MERS), an emerging infectious disease, is caused by the MERS-corona virus (MERS-  
CoV) (Zaki et al., 2012). CoVs taxonomically belong to the subfamily Coronavirine, family Coronaviridae, in the order  
Nidoviales, and can be further classified into four genera: Alpha corona virus, Beta-corona virus, Gamma corona virus and  
Delta corona virus (De Groot, 2011).  
The genus Beta corona virus contains four different lineages, A, B, C and D. The human corona virus‘s hCoV-229 and  
hCoV-NL63 belong to the genus Alpha corona virus, while hCoV-OC43 and hCoV-HKU1 belong to the lineage A of the genus  
Beta corona virus. SARS-CoV belongs to the genus Beta corona virus of lineage B while MERS-CoV grouped under lineage c  
beta corona virus. The genera Gamma and Delta corona virus contain only viruses that infect animals (ICTV, 2012).  
Phylogenetic analysis performed by Zaki et al. (2012) after the isolation of MERS-CoV from the Saudi patient  
suggested that the virus belongs to the lineage C of the genus Beta coronavirus, together with the bat coronaviruses  
BtCoV-HKU4 and BtCoV-HKU5, which have been isolated from the species Tylony cterispachypus and Pipistrellus abramus,  
As stated by the ICTV, viruses that present greater than 90% sequence identity in their replicase domains belong to  
the same species. To investigate whether the newly identified virus is the prototype of a novel virus species, the amino  
acid sequence of the replicase gene obtained by sequencing of the PCR fragments that the pan-coronavirus PCR yielded  
was aligned with the respective sequences of its closest relatives, BtCoV-HKU4 and BtCoV-HKU5 (ICTV, 2012).  
The comparison showed that the identity the viruses shared was greater than 80%, suggesting that the discovered  
virus represents a novel Beta corona virus species, the first human coronavirus described in lineage C of this genus. These  
results were repeated by the study of Van Boheemen et al. (2012), after they obtained the complete genome sequence of  
the the virus.  
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Citation: Kassahun B, Berhanu T and Damtew B (2020). Review on coronavirus, a middle east respiratory syndrome (MERS-CoV). Online J. Anim. Feed Res., 10(1): 01-  
EPIDEMIOLOGY OF THE DISEASE  
Geographic distribution  
According to WHO report, MERS cases reported from 27 countries including Arabian peninsula (Jordan, Kuwait,  
Lebanon, Oman, Qatar, Saudi Arabia, the United Arab Emirates, Iran, Yemen), Europe (Austria, France, Germany, Greece,  
Italy, Netherland Turkey and UK), Asia (China, Philippines, Malaysia, Thailand, Republic of Korea), Africa (Algeria, Egypt,  
Tunisia) and USA. In the European and Asian countries as well as in Algeria, Egypt, Tunisia, and the United States, patients  
developed illness after returning from the Arabian Peninsula (WHO, 2019). In the United Kingdom, France, Italy, and  
Tunisia, limited human-to-human transmission occurred among close contacts of the index cases (WHO, 2015). MERS  
outbreak is ongoing in South Korea since May 2015; the index case was a man who had traveled to Bahrain, the United  
Arab Emirates, Saudi Arabia, and Qatar. All of the cases outside of the Middle East have had a direct or indirect  
connection to the Middle East.  
Figure 1 - Map showing confirmed global cases of MERS-CoV. Source: WHO (2017).  
Virus replication on cyclophilin A  
CypA is one of the most abundant cytosolic proteins constituting 0.10.4% of the total cellular protein content  
(Harding et al., 1986). Data from different labs suggest that relatively low levels of CypA may suce to support ecient  
coronavirus replication. Cyclophilins were initially implicated as host factors in coronavirus replication during studies with  
general Cyp inhibitors such as cyclosporine A (CsA). In cell culture, the replication of a variety of coronaviruses was found  
to be strongly inhibited by low micromolar concentrations of cyclosporine A and the non-immunosuppressive Cs A analogs  
Alisporivir. The cyclosporine A dependence of the replication corona viruses in the same cell line (Huh7), in which CypA  
expression was knocked-out using CRISPR/Cas9 gene editing technology (de wilde et al , 2017).  
Reservoirs and host susceptibility  
Dipeptidyl peptidase 4 (DPP4; also, known as CD26) has been identified as the receptor for the MERS-CoV spike  
protein and is required for viral binding and entry into host cells (Raj et al., 2013). DPP4 is a type II Transmembrane  
glycoprotein that is expressed on epithelial and endothelial cells throughout the body (Lambeir et al., 2003). Although  
DPP4 is evolutionarily conserved, differences in the amino acids present in its extracellular domain, which interacts with  
MERS-CoV spike protein, have been noted among various animal species and humans. Specifically, 14 amino acids in  
DPP4 appear to be critical in determining whether the MERS-CoV spike protein can bind to DPP4 (Wang et al., 2013).  
Bats  
Bats are known natural reservoirs for several emerging viral infections in humans including rabies, Nipah virus,  
Hendra virus and Ebola virus (Han et al., 2015). Several features enable bats to be efficient sources of emerging human  
viral infections. As an extremely diverse species with a long evolutionary history, bats have co-evolved with a variety of  
viruses. Their lack of B-cell-mediated immune responses allows them to carry viruses without showing overt signs of  
illness (Brook and Dobson, 2015). Low metabolic rate and suppressed immune response during bats‘ hibernation result in  
delayed viral clearance (George et al., 2011). Bats live closely together in extremely large numbers facilitating stable  
circulation of viruses amongst them (Calisher et al., 2008).  
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Citation: Kassahun B, Berhanu T and Damtew B (2020). Review on coronavirus, a middle east respiratory syndrome (MERS-CoV). Online J. Anim. Feed Res., 10(1): 01-  
Furthermore, bats are capable of flying and hence carrying potentially infectious pathogens over considerable  
distances (Drexler et al., 2014). A pertinent feature of bats is that they chew fruits to absorb their sugars and spit out the  
remains. The discarded fruits can be contaminated with viruses from the oral cavity, urine and feces providing a ready  
source for transmission to other potential hosts such animals and humans (Brook and Dobson, 2015).  
Bats have been implicated as the main reservoir of members of the genera Alpha corona virus and Beta corona virus  
(Woo et al., 2012b) and play pivotal roles in interspecies transmission of CoVs. This is best exemplified by SARS-CoV,  
which was shown to originate from Chinese horseshoe bats (Lau et al., 2005), and was probably transmitted directly to  
humans (Ge et al., 2013) or through an intermediate host, such as the palm civet (Guan et al., 2004). MERS-CoV, together  
with bat CoV-HKU4 and HKU5, phylogenetically belongs to lineage C in the genus Beta corona virus (Van Boheemen et al.,  
2012). Thus, it is suspected that the emerging MERS-CoV might also originate from bats.  
A large screening study for beta corona viruses was conducted on fecal specimens taken from 4758 bats of ten  
different species in Ghana, and 272 Pipistrellus bats from four European countries showed that a bat derived corona virus  
that has a very close phylogenetic relationship to MERS-CoV (Annan et al., 2013).  
A report from South Africa and Saudi Arabia identified a bat derived corona virus that has a very close phylogenetic  
relationship to MERS-CoV (Ithete et al., 2013; Memish et al., 2013c). An experimental study conducted on Jamaican fruit  
bat (Artibeusja maicensis) showed evidence of infection as they shed the virus from their respiratory and intestinal tract  
(Munster et al., 2014). Therefore MERS-CoV, like many other coronaviruses, originated in bats. This is based on the  
isolation of other lineage C beta-corona viruses that are very closely related to MERS-CoV on phylogenetic analysis (De  
Dromedary camels  
The close phylogenetic relationship of human MERS-CoV isolates with those obtained from bats initially suggested  
that MERS-CoV might have originated from bats. However, bats were unlikely to be the direct source of the MERS  
outbreak, since MERS cases were rarely found to have a history of contact with bats. Therefore, other animals were  
searched as direct sources of zoonotic transmission of MERS-CoV (Han et al., 2016). Multiple lines of evidence implicate  
dromedary camels in the emergence and transmission of MERS CoV.  
MERS-CoV antibodies are highly prevalent in dromedary camels from across the Arabian Peninsula, North Africa and  
Eastern Africa (Nowotny and Kolodziejek, 2014). The high prevalence of MERS-CoV seropositivity in Africa and the Middle  
East suggests that animal movement has facilitated the transmission and circulation of MERS-CoV amongst dromedary  
camels in these regions. MERS-CoV antibodies have neither been found in Mongolian or Dutch Bactrian camels nor in  
South American camelids such as ilamas, alpacas and guanacos (Reusken et al., 2013a).  
MERS-CoV reported by RT-PCR in oro-nasal and faecal samples from dromedary camels in multiple locations in the  
Arabian Peninsula (Hemida et al., 2013). The four of 110 dromedary camels in which MERS-CoV RNA was detected in  
Egypt were all imported from Sudan or Ethiopia for slaughter (Chu et al., 2014). MERS-CoV was also detected by RT-PCR  
in symptomatic camels. Dromedaries with active MERS-CoV infection exhibited symptoms such muco-purulent nasal and  
lachrymal discharge, cough, sneezing, fever and loss of appetite (Memish et al., 2013b).  
The potential infectiousness of MERS-CoV recovered from dromedary camels was evident its capability to cause ex-  
vivo infection in human respiratory cells and human hepatoma cells. Successful MERS-CoV cultures usually coincide with  
corresponding high viral loads in the same specimens (Chan et al., 2014). Experimental MERS-CoV infection of dromedary  
camels with result mild clinical infection manifesting as fever and rhinorhea also implicate dromedary camels in the  
emergence and transmission of MERS CoV (Adney et al., 2014a,b).  
Other animal species  
Differences in virus susceptibility and pathogenicity between animals of different species could be explained by a  
distinct tissue distribution of DPP4, the MERS-CoV receptor. Species with few or no differences in the 14 amino acids  
seem to be susceptible to MERS-CoV, including rhesus macaques, common marmosets and result cytopathic cellular  
changes and mild to severe respiratory illness (Munster et al., 2013; Falzarano et al., 2014). Macaques and marmosets  
have already proved useful animal models for the investigation of MERS-CoV (Eckerle et al., 2014).  
Dromedary camels seems to be the only domestic animal reservoir for MERS-CoV until a recent study by Reusken et  
al. (2016) and Vergera et al. (2017). Reusken et al. (2016) investigated the MERS-CoV infection status of 15 healthy  
alpacas (Vicugnapacos) in a herd of 20 that shared a barn complex with dromedaries. All tested alpacas were seropositive  
to MERS-CoV.  
Recent study on livestock susceptibility conducted in 2017 indicate that pigs and llamas are susceptible to MERS-  
CoV infection (Vergera et al., 2017), but the level of MERS-CoV excreted in the nose of dromedaries seems to be much  
higher than that of other animal species described so far (Adney et al., 2014a,b). On the other hands the study showed  
that sheep did not show clinical sign. These results are in concordance with those reported by Adney et al. (2016) that  
MERS-CoV experimentally inoculated sheep showed no clinical disease and that only small amounts of virus were  
detected in nasal swab samples. Even though the receptor binding domain, and in particular key amino acids on the  
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Citation: Kassahun B, Berhanu T and Damtew B (2020). Review on coronavirus, a middle east respiratory syndrome (MERS-CoV). Online J. Anim. Feed Res., 10(1): 01-  
negative for MERS-CoV (Meyer et al., 2015). These results highlight that other mechanisms, such as epithelial cell  
permissibility or strong innate immune responses, may influence the establishment of infection. Differences in the  
number of goblet cells in the lining epithelium and mucus covering epithelial surfaces, which may have impeded the  
binding of the virus to the respiratory epithelium of horses (Vergera et al., 2017). Serological study, conducted in Saudi  
Arabia and Europe from sheep, goats, cattle, and chickens representing different geographical areas within the country  
were resulted sero negative for MERS-CoV (Hemida et al., 2013; Reusken et al., 2013a). In addition ferrets, hamsters, and  
mice are resistant to infection (Van et al., 2014).  
Source of infection and transmission  
There is growing evidences that the dromedary camel is host species for MERS-CoV and plays an important role in  
the transmission of the viruses to human (Azhar et al., 2014). In August 2013, for the first time, dromedary camels were  
implicated as a possible source of virus causing human infection because of the presences of MERS-CoV specific  
neutralizing antibodies in dromedary camels from Oman and other countries in the Arabian Peninsula and North Africa.  
An analysis of an outbreak of MERS-CoV infection in humans in Qatar in October 2013 found that dromedary camels  
and humans were infected with a nearly identical strain of MERS-CoV (Hemida et al., 2013). Widespread circulation of  
different genetic variants of MERS-CoV has been found in camels and the presence of MERS-CoV specific antibodies in  
samples taken from camels, years earlier. Although dromedary camels are suspected to be the primary source of MERS-  
CoV leading to human infections, the true routes of zoonotic transmission remain to be determined (Azhar et al., 2014).  
Chu et al. (2014) reported that Middle East respiratory syndrome corona virus from Egypt has been fully genetically  
sequenced and biologically characterized. While this virus was genetically diverse from viruses causing zoonotic infections  
in the Arabian Peninsula, the receptor binding domain of the Egyptian viruses is conserved, indicating that these viruses  
would be able to infect the human respiratory tract. This contention is supported by the finding that tropism and virus  
replication competence of MERS-CoV from Egypt in ex vivo cultures of the human bronchial and lung is comparable to that  
of camel of human virus isolates in the Arabian Peninsula (Chu et al., 2014).  
Camel to human transmission  
Whole MERS-CoV genome sequences obtained from viral cultures of the human and camel isolates were 100%  
identical. Importantly, 4-fold rise in MERS-CoV antibody titres was documented in the camels, indicating that active MERS-  
CoV infection was probably circulating in the dromedary herd. Later, rising MERS-CoV antibodies were documented in the  
asymptomatic men, aged 29 and 33 years, who were in contact with the camels, were found to be positive for MERS-CoV  
RNA in their respiratory samples. Partial sequences of MERS-CoV spike and nucleocapsid regions from the human and  
linked camels were identical. Within 48 days from diagnosis, both patients had undetectable MERS-CoV RNA (Al  
MERS-CoV sequences have been detected more commonly in nasal swabs than in rectal specimens of camels  
(Hemida et al., 2014). Infection of camels in the laboratory also confirmed susceptibility, with a large quantity of virus  
shedding from the upper respiratory tract (Adney et al., 2014a,b). Therefore, droplet transmission or direct contact with  
infected camels may be the most likely mode of camel-to-human transmission of MERS-CoV. Direct contact with camels  
can only explain some of the primary cases, since some MERS cases did not report any direct contact with camels (Han et  
Other possible routes for camel-to-human transmission include food-borne transmission through consumption of  
unpasteurized camel milk, raw meat and the camel urine. Camels are an important source of milk in some Middle East  
countries and parts of Africa, and more than half of the camel milk is sold as unpasteurized fresh or fermented milk to  
local and urban consumers in Saudi Arabia (Faye et al., 2014). A survey found the presence of MERS-CoV RNA in the milk  
of camels actively shedding the virus (Reusken et al., 2014b).  
An experimental study of the stability of MERS-CoV in milk showed that viable viruses could still be recovered after  
48 h regardless of reduction in virus titre, indicating that infection could happen by consumption of unpasteurized fresh  
raw milk (Van Doremalen et al., 2014). Consumption of undercooked meat from infected camels and handling of infected  
raw camel meat without proper protective equipment may also pose risks for getting MERS CoV from camel. An oral–  
faecal transmission mode was also suspected. Using protein intrinsic disorder prediction, MERS-CoV was placed into  
disorder group C and was likely to persist in the environment for a rather long period of time, and showed high oralfaecal  
transmission chances (Goh et al., 2013).  
The single study, by Van Doremalen et al. (2013), on Plastic or steel surfaces inoculated with MERS-CoV at different  
temperature and relative humidity (RH) shows that the virus remained viable for 24 h. The study reported that MERS-CoV  
was more stable under low-temperature/low-humidity conditions, suggesting the potential for MERS-CoV to be  
transmitted via contact or fomite transmission due to prolonged environmental presence. By comparison, a well-known  
and efficiently transmitted respiratory virus, influenza A virus, could not be recovered in culture beyond four hours under  
any conditions. Aerosol experiments found MERS-CoV viability only decreased 7% at low relative humidity at 20 °C. In  
comparison, influenza A virus decreased by 95 % (Van Doremalen et al., 2013).  
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Citation: Kassahun B, Berhanu T and Damtew B (2020). Review on coronavirus, a middle east respiratory syndrome (MERS-CoV). Online J. Anim. Feed Res., 10(1): 01-  
Enter-human transmission  
While the introduction of MERS-CoV to the human species from an animal reservoir seems to be the reason for the  
initial infections, the occurrence of clusters suggests that the virus hasadapted to human-to-human transmission. Person-  
to-person transmission of MERS-CoV has been documented in several human clusters associated with healthcare  
facilities, households and workplace (Assiri et al., 2013a; Memish et al., 2013a).  
Nosocomial outbreak is a distinct hallmark in MERS-CoV transmission involving hospitalized patients, healthcare  
workers and close family contacts in healthcare facilities in affected countries in the Middle East and in some countries  
where the disease had been exported to, the most recent being the Republic of Korea (RoK). Droplet spread between  
humans is considered the mechanism of human-to-human transmission and the need for droplet precautions was  
emphasized after the Al-Ahsa hospital, the KSA (Khalafalla et al., 2015) and the South Korean outbreaks (Assiri et al.,  
MERS-CoV‘s ability to remain viable over long time periods gives it the capacity to thoroughly contaminate a room‘s  
surfaces when occupied by an infected and symptomatic patient (Van Doremalen et al., 2013). Whether MERS-CoV can  
remain a drift and infectious for extended periods (truly airborne) remains unknown. Such findings expand our  
understanding of the possibilities for droplets to transmit respiratory viruses in many settings, including hospital waiting  
rooms, emergency departments, treatment rooms, open intensive care facilities and private patient rooms. The nature  
and quality of air exchange, circulation and filtration are important variables in risk measurement and reduction as is the  
use of negative pressure rooms to contain known cases (Assiri et al., 2013a).  
Furthermore, given the high concentration of the virus in the lower respiratory tract of infected patients, airway  
suctions or use of bronchoscopes could also serve as a source of transmission (Guberina, 2014). The infectiousness of  
urine and stool is currently under investigation, since the virus has been detected in urine and stool samples of patients  
and based on the fact that cluster patients had been sharing toilet rooms during hospitalization. Transmission via blood  
should also be considered a possible route, since scientists claim that the virus might be present in blood (Guery, 2013).  
This could be correlated to the reported person-to-person transmission in hem dialysis units of a hospital in Saudi Arabia  
Generally, corona viruses are transmitted among humans via aerosol droplets and/or through direct contact with  
other secretions (stool, urine etc.) (Danielsson, 2012). Currently, the pathways used by MERS-CoV for inter human  
transmission remain unknown. Several case investigations have suggested that airborne transmission seems to be the  
most likely route (Memish et al., 2013a).  
Figure 2 - Reported Infection sources and transmission routes of MERS-CoV between bats, camels and human (Source:  
Omrani et al., 2015).  
Public health importance  
This novel virus can cause severe acute respiratory disease, mainly in patient with immunosuppressant condition  
and underlying disease including diabetes, heart disease, renal failure, hypertension, chronic lung disease, including  
asthma and cystic fibrosis. Moreover, history of travel in at risk countries and smoking might have considered as a risk  
factors of severe disease (Al Barrak et al., 2012). Washing hands, face and hair in camel urine is a traditional custom  
among Bedouins and camel-herding peoples in the Arabian Peninsula and East Africa. There are currently no published  
data about MERS-CoV in the urine of infected camels, but the virus has been found in low concentration in human urine  
samples (Drosten et al., 2013), and therefore, consumption of camel urine may represent a risk factor for infection.  
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Citation: Kassahun B, Berhanu T and Damtew B (2020). Review on coronavirus, a middle east respiratory syndrome (MERS-CoV). Online J. Anim. Feed Res., 10(1): 01-  
Dromedary camel meat represents 0.45% of the red meat produced worldwide (Faye, 2013). While there is no  
evidence of MERS-CoV in camel meat, by analogy with what is known about other viruses like Rift Valley fever virus, we  
can assume that the fall in pH of meat with maturation could inactivate the virus (Food and Agriculture Organization) and  
that proper cooking would kill the virus. However, handling of raw meat and slaughtering of animals should not be  
excluded as a risk factor. The list of at-risk countries, as defined in European Centre for Disease Prevention and Control  
(ECDC) rapid risk assessment included Iraq, Israel, Jordan, Qatar, Saudi Arabia, Syria, Kuwait, Lebanon, Palestine, Oman,  
UAE, Yemen, Bahrain and Iran (ECDC, 2013). People working closely with camels (e.g. farm workers, slaughterhouse  
workers and veterinarians) may be at higher risk of MERS-CoV infection than people who do not have regular close  
contacts with camels and also health care workers (WHO, 2014).  
PATHOGENESIS  
MERS-CoV pathogenicity is based on the extent pathogen-host interaction. It elicits maximum pathogenic potential  
especially in humans. This is due to the fact that MERS-CoV shows a strong tropism for bronchial non-ciliated epithelia.  
Furthermore, the virus arrests host bronchial interferon synthesis. It should be noted that most of other viruses causing  
respiratory diseases attack and damage epithelial cilia, including Influenza type A.  
Molecular studies revealed that cellular receptors for MERS-CoV are exopeptidase (angiotensin converting enzyme  
2) (Coleman et al., 2014). Moreover, it was found that neutralization of angiotensin converting enzyme 2 by specific  
antibodies did not arrest the spread of infection into bronchus and lung alveolus. Extensive investigations showed that  
another functional cellular receptor called DDP4 was also involved in the severity of MERS-CoV disease spread into the  
lungs (de Wit et al., 2013). Of note, receptors for DDP4 are also located in nephrons of kidneys and heart.  
During the acute stage of the MERS-CoV infection, there is a severe viremia, leading o spread of MERS-CoV viral  
particles in the bloodstream. Hence, MERS-CoV leads not only to the damage of lungs but also kidneys and heart, thereby  
resulting in respiratory, renal and cardiac failure, ultimately ending to coma and death (Van Boheemen et al., 2012). The  
severity is worsened by concurrent secondary bacterial infections. Recent research showed that bacterial infections due to  
Staphylococcus aureus, Group A Streptococcus, Streptococcus pneumonia and Haemophilus influenzae type b augment  
the pathogenic potential of MERS-CoV, particularly in humans. These bacteria particularly dwell in the oral cavities, tonsils  
and pharynx of humans (Lau et al., 2013).  
CLINICAL FEATURES  
The median incubation period of a MERS-CoV infection is 5 days. The clinical manifestations in patients of MERS-CoV  
range from subclinical infection to severe respiratory disease. Symptomatic patients often present with fever, myalgia,  
and sore throat, shortness of breath, cough, and occasionally hemoptysis. Gastrointestinal symptoms such as diarrhea  
and vomiting are also common. Hematological abnormalities reported for clinical cases include thrombocytopenia,  
lymphopenia, lymphocytosis, and neutrophilia (Assiriet al., 2013a; Gueryet al., 2013). Radiographs with a spectrum of  
lower pulmonary infiltrates and consolidation consistent with viral pneumonia (Zakiet al., 2012; Assiriet al., 2013b).  
In contrast to the human cases, camel showed minor clinical signs of the disease, including of rhinorrhea and a mild  
increase in body temperature but no other clinical signs were observed (Khalafalla et al., 2013) and the nasal discharge  
drained from both nostrils varied in character from serous to purulent (Daniella et al., 2014). In humans, after the entry of  
MERS-CoV viral particles in to lung alveoles, alveolar macrophages fail to contain the spread of infection. The strong host  
cellular immune response and cytokine release leads to inflammation and fluid accumulation in lungs.  
DIAGNOSIS  
Sputum from lower respiratory tract, nasopharyngeal swab, whole blood, tissue from biopsy or autopsy including from  
lung and serum for serology are important for virus detection. Lower respiratory tract specimens (such as tracheal  
aspirates and Broncho alveolar lavage) appear to have the highest virus titre. Upper respiratory tract specimens are also  
recommended, especially when lower respiratory tract specimens cannot be collected (Guery et al., 2013).  
Rapid verification of cases of novel corona virus infection will be based on detection of unique sequences of viral  
RNA by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and immune fluorescence. However,  
antibodies against beta corona viruses are identified to cross react within the genus. Therefore, immunofluorescence  
effectively limits their use to confirmatory applications (Corman et al., 2012b). However, for detection of MERS-CoV in  
particular, alternative RT-PCR assays are required, detecting certain targets that have been described to be specific for  
Corman (2012a) proposed two RT-PCR assays for the detection of the virus, each one targeting different parts of the  
viral genome. The first assay targets a region upstream of the envelope (E) gene (upE assay), while the second assay  
targets part of ORF1b (ORF1b assay), which does not overlap with the target of pan-coronavirus assay. The upE assay was  
found to be more sensitive in comparison to the ORF1b assay. Thus, the use of the upE assay is recommended for  
screening, while the ORF1b assay can be used for confirmation (Corman et al., 2012b).The specificity of both assays was  
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Citation: Kassahun B, Berhanu T and Damtew B (2020). Review on coronavirus, a middle east respiratory syndrome (MERS-CoV). Online J. Anim. Feed Res., 10(1): 01-  
confirmed by excluding cross-reactivity with the other known human corona viruses. A third assay, optimized for  
sensitivity, was described by the same group, this time targeting ORF1a. Overall, a combination of the upE and ORF1a  
assay seems to be the optimal approach for MERS-CoV detection (Corman et al., 2012a).  
Several serology assays have been developed for the detection of MERS-CoV antibodies, including immuno-  
fluorescence assays and a protein microarray assay (Reusken et al., 2013b). The Center of Disease Control and  
Prevention (CDC) has developed a two-stage approach, which uses an enzyme-linked immune sorbent assay (ELISA) for  
screening followed by an indirect immunofluorescence test or micro neutralization test for confirmation.  
PREVENTION AND CONTROL  
Since there are currently no effective drug therapies to treat or prevent the infection, clinical management of patients with  
severe disease largely relies on meticulous intensive care support and prevention of complications. This includes  
hydration, antipyretic, analgesics, respiratory support, and antibiotics, if needed, for bacterial super infection. Current  
treatment is based on previous experience with the Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV), in vitro  
studies, and case series. Various agents have been tried, including those that block virus entry, inhibit viral replication, or  
interfere with host immune response (Al-Tawfiq and Memish, 2014).  
Monoclonal antibodies that efficiently block the interaction between the MERS-CoV envelope spike glycoprotein and  
a human protein DDP4 have been developed using a humanized mouse (transgenic mouse). These researchers are now  
working to move the antibodies into human trials. Based on experience with SARS-CoV, the use of convalescent plasma,  
hyper-immune globulin, or human monoclonal antibodies that contain neutralizing antibodies may be efficacious and is  
recommended as first-line treatment when available (Jiang et al., 2014).  
Understanding the zoonotic sources of MERS-CoV might guide control and prevention of the disease. The WHO  
advises people at risk of MERS-CoV infection to avoid contact with camels, to practice good hand hygiene, and to avoid  
drinking raw milk or eating contaminated food unless it is properly washed, peeled or cooked (WHO, 2014). Since most of  
the cases occur in the health care setting, it is thoughtful that all health care workers practice appropriate infection  
control measures when taking care of patients with suspected or confirmed MERS-CoV (WHO, 2015).Currently, there is no  
specific drug or vaccine available for treatment of infection caused by MERS-CoV. Even though, a number of antiviral  
medicines are currently under study (Zumla et al., 2015), there is no licensed vaccine to prevent MERS-CoV infection.  
However, one company has developed an experimental candidate MERS-CoV vaccine (Novavax, 2013). 0 also developed  
other candidate vaccines which are being studied as full-length infectious DNA clone of the MERS-CoV genome in a  
bacterial artificial chromosome.  
CONCLUSION  
Middle East respiratory syndrome is zoonotic diseases causing severe lower respiratory illness and now considered a  
threat to global public health. The current knowledge about virus is limited, since many important epidemiological and  
clinical aspects remain unknown. Transmission of MERS-CoV from camel to human is well documented and studied by  
different researchers but is generally not very efficient because transmission route of the virus back from human to camel  
is still hypothetical.  
The exact mechanism of transmission is not clear, including whether other intermediate hosts are involved, which  
will be a risk for new incidence of the disease, especially for those countries in which infection cases were not reported.  
Although MERS-CoV displays lower transmissibility among humans than SARS-CoV, the possibility that future mutations  
will render the virus highly transmittable, with a devastating outcome, cannot be discarded.  
In the light of aforementioned conclusions the following general and specific points are recommended.  
Urgent epidemiologic investigations through surveillance on environmental, animal and testing around sporadic  
unexplained cases are needed to find other animal reservoirs.  
Extensive efforts are required to speed up the development of an effective therapy and vaccine.  
Camels may play important role in transmission of the virus, and the common practices in pastoral areas of  
consuming unpasteurized camels‘ milk and raw meat should be avoided.  
Health care workers caring for patients under investigation for MERS-CoV or confirmed cases should exercise  
standard precautions including hand hygiene, as well as contact or air borne precautions.  
DECLARATION  
Corresponding author  
E-mail:kassahunberhanu110@gmail.com  
Acknowledgement  
The authors would wish to acknowledge Haramaya University, college of veterinary medicine staff for their valuable  
and constructive comments on preparation of this review.  
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Citation: Kassahun B, Berhanu T and Damtew B (2020). Review on coronavirus, a middle east respiratory syndrome (MERS-CoV). Online J. Anim. Feed Res., 10(1): 01-  
Authors‘ contribution  
Dr. Birhanu and Dr. Kassahun participate in design the topic of the review. Dr. Damtew performed by gathering the  
data. In addition, Dr. kassahun carefully revised and write the manuscript. Finally, all authors read and approved the final  
manuscript.  
Availability of data  
The data can be availed to the journal upon request.  
Conflict of interest  
The authors declare they have no competing of interests.  
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