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MERS Coronavirus in dromedary camel herd, Saudi Arabia

July 2014
Emerging Infectious Diseases 20(7)

July 2014
20(7)

DOI:10.3201/eid2007.140571

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PubMed

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CC BY

Authors:

Maged Hemida

Long Island University

Daniel Chu

The University of Hong Kong

Leo L. M. Poon

The University of Hong Kong

Ranawaka A.P.M Perera

University of Pennsylvania

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A prospective study of a dromedary camel herd during the 2013-14 calving season showed Middle East respiratory syndrome coronavirus infection of calves and adults. Virus was isolated from the nose and feces but more frequently from the nose. Preexisting neutralizing antibody did not appear to protect against infection.

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 EmergingInfectiousDiseases•www.cdc.gov/eid•Vol.20,No.7,July2014 1231

MERS Coronavirus

in Dromedary

Camel Herd,

Saudi Arabia

Maged G. Hemida,1 Daniel K.W. Chu,1

Leo L.M. Poon, Ranawaka A.P.M. Perera,

Mohammad A. Alhammadi, Hoi-yee Ng,

Lewis Y. Siu, Yi Guan, Abdelmohsen Alnaeem,

and Malik Peiris

A prospective study of a dromedary camel herd during

the2013–14calving seasonshowedMiddle East respira-

tory syndrome coronavirus infection of calves and adults.

Viruswasisolatedfrom the nose andfeces but more fre-

quentlyfromthenose.Preexistingneutralizingantibodydid

not appear to protect against infection.

Ongoing transmission of Middle East respiratory syn-

drome coronavirus (MERS-CoV) to humans under-

scores the need to understand the animal sources of zoonot-

ic infection (1,2). MERS-CoV RNA has been detected in

dromedary camels (3,4), and dromedary infection precedes

human infection (5). We conducted a prospective study in

dromedary herds in Al-Hasa, Saudi Arabia, through the

peak calving season (December 2013–February 2014) to

document virologic features of MERS-CoV infection in

these animals.

The Study

We studied dromedaries at 2 farms in Al-Hasa, 4–5

km apart. Farm A had 70 animals; 4 were 1 month of

age, 8 were ≈1 year of age, and the rest were adults (>2

years of age). The herd did not go to pasture in the des-

ert (“zero-grazing”; type of grazing may inuence types

of potential exposures). The animals were sampled on 5

occasions during November 2013–February 2014. Farm

B (“semi–zero-grazing”) had 17 adults and 3 calves; its

herd was sampled in February 2014. Nasal, oral, or rectal

swab samples and blood samples were collected (Table 1;

online Technical Appendix Table, http://wwwnc.cdc.gov/

EID/article/20/7/14-0571-Techapp1.pdf). Swab and serum

samples were stored frozen at −80°C until testing.

Hydrolysis probe–based real-time reverse transcrip-

tion PCR (RT-PCR) targeting MERS-CoV upstream of

E (UpE) and open reading frame (ORF) 1a genes and a

broad-range RT-PCR reacting across the CoV family to

detect other CoVs were used as described (4). Specimens

initially positive for MERS-CoV were re-extracted and re-

tested to conrm the positive results.

The full genome of MERS-CoV was obtained directly

from the clinical specimens with 3–4 times coverage by se-

quencing PCR amplicons with overlapping sequence reads

and sequence assembly (4). Dromedary MERS-CoV full

genomes obtained in this study (GenBank accession nos.

KJ650295–KJ650297) were aligned with human MERS-

CoV genomes retrieved from GenBank. We constructed

full-genome phylogenies using MEGA5 with neighbor-

joining and bootstrap resampling of 500 replicates (6).

Virus isolation was attempted in Vero E6 cells. We tested

serum samples for neutralizing antibody titers using a vali-

dated MERS-CoV spike pseudoparticle neutralization test

(7) (online Technical Appendix).

At farm A, we detected MERS-CoV in 1 of 4 drom-

edaries sampled on November 30, none of 11 sampled on

December 4, nine of 11 sampled on December 30, and none

of 9 sampled on February 14 (Table 1). Of the 10 drom-

edaries that tested positive for MERS-CoV, 9 had parallel

nasal and fecal specimens tested, with virus detected in the

nasal swab specimens from 8 and the fecal specimen from

1. At the December 30 sampling, 7 of 8 calves and 2 of 3

adults tested positive for MERS-CoV, indicating that when

MERS-CoV circulates on a farm, both calves and adults

can be infected (online Technical Appendix Table). Be-

cause all 12 adults with serum collected before December

30 were seropositive (titers >320), it is likely, though not

certain, that the MERS-CoV infections in the 2 adults (nos.

21, 19Dam) sampled on December 30 were reinfections,

as has been reported for other CoVs (8). The seronegative

1-year-old calves, nos. 13 and 14, had the highest nasal vi-

ral loads (UpE assay 1.3 × 108 to 1.78 × 108/mL specimen),

and a 2-week-old calf, no. 22, with (presumably passively

acquired) titers of 1,280 became infected but had a much

lower viral load. Overall, these data suggest that prior in-

fection or passively acquired maternal antibody might not

provide complete protection from infection (online Techni-

cal Appendix Table).

Four MERS-CoV–positive calves had mild respiratory

signs (cough, sneezing, respiratory discharge), abnormally

elevated body temperature, and loss of appetite at the De-

cember 30 sampling, which resolved over a few days. Three

calves from which paired serum samples were available

(Table 2; nos. 13, 15, 17) demonstrated >4-fold rising anti-

body titers to MERS-CoV. Calf no. 13 (1 year of age) had

Author afliations: King Faisal University,Al Hofuf, Saudi Arabia

(M.G. Hemida, M.A. Alhammadi, A. Alnaeem); Kafrelsheikh

University,KafrElsheikh,Egypt(M.G.Hemida);andTheUniversity

of Hong Kong, Hong Kong, China (D.K.W. Chu, L.L.M. Poon,

R.A.P.M.Perera,H.-y.Ng,L.Y.Siu,Y.Guan,M.Peiris)

DOI:http://dx.doi.org/10.3201/eid2007.140571 1These authors contributed equally to this article.

DISPATCHES

1232 EmergingInfectiousDiseases•www.cdc.gov/eid•Vol.20,No.7,July2014

a high viral load and was seronegative at the rst MERS-

CoV–positive result (indicating that it had been recently

infected) but was MERS-CoV RNA negative 6 weeks

later, suggesting that virus shedding is not prolonged. We

did not detect virus RNA by RT-PCR in the 3 acute-phase

serum samples from infected dromedaries (nos. 1, 16, 17),

suggesting that acute infection is not associated with pro-

longed viremia. Dromedaries from farm B were sampled

once on February 11; all results were negative.

The full genomes of MERS-CoV sequenced directly

from a nasal swab specimen collected on November 30

were identical to those from a nasal swab specimen and a

fecal specimen collected on December 30. In addition, the

complete spike gene was sequenced from 4 other MERS-

CoV–positive nasal swab specimens, and these spike genes

were genetically identical.

Virus isolation in Vero E6 cells was attempted from

7 positive nasal swab and fecal specimens that had >106

copies/mL in the original sample in the UpE RT-PCR. Vi-

ruses were isolated from 2 nasal swab (nos. 13, 14) and

1 fecal swab (no. 19Dam) specimens collected on De-

cember 30; these were the specimens with high numbers

of MERS-CoV copies (9.27 × 107 to 1.78 × 108 copies/

mL). The full-genome sequence of 1 virus culture isolate

was obtained in parallel with that of the original virus in

the original clinical specimen. We observed 3 nucleotide

changes in ORF1b, spike, and membrane protein genes

in the isolates after 2 passages in Vero E6 cells, of which

2 were nonsynonymous, leading to changes in spike

(S1251F) and membrane proteins (T8I). This nding

highlights the importance of sequencing the viral genome

directly from clinical specimens.

MERS-CoVs circulating in dromedaries on farm A

during a 1-month period were genetically identical over the

full 30,100-nt genome in 3 viruses and the spike protein of

4 more viruses, giving a mutation rate of 0 nt substitutions

per site per day (95% credible interval 0 to 2.7 × 10−6). The

estimated mutation rate for epidemiologically unlinked hu-

man MERS-CoV was 3.1 × 10−6 (95% CI 2.4 × 10−6 to 3.8

× 10−6) (9).

Conclusions

The unusual genetic stability of MERS-CoV in

dromedaries, taken together with its high seroprevalence

(7,10–13), raises the hypothesis that dromedaries might be

the natural host for this virus. Further longitudinal stud-

ies of MERS-CoVs in dromedaries are needed to conrm

this hypothesis.

Genome organization of the dromedary MERS-CoV

detected in this study was identical to that of the virus in

humans. The virus strains clustered phylogenetically with-

in clade B (9) and were most closely related to the strain

MERS-CoV_FRA/UAE and to MERS-CoV detected in

Buraidah (Saudi Arabia) and Al-Hasa (Figure). The farm

is ≈300 km from United Arab Emirates and 600 km from

Buraidah. Dromedaries move between Al-Hasa and Burai-

dah and, more limitedly, between Al-Hasa and United

Arab Emirates.

The full-genome sequence of MERS-CoV from drom-

edaries in this study is 99.9% similar to genomes of hu-

man clade B MERS-CoV. The spike gene is the major

determinant for virus host specicity. In comparison with

other publically available human MERS-CoV sequences,

we found 6-nt mutations in the spike gene unique to these

dromedary viruses. Of these, 3 (S457G, L773F, and V810I)

were nonsynonymous. These amino acid changes are lo-

cated outside the binding interface between MERS-CoV

spike protein and human DPP4 receptor, suggesting these

amino acid differences are unlikely to affect receptor bind-

ing. Thus, these dromedary viruses may retain capacity

to infect humans, as Chu et al. suggested for dromedary

MERS-CoV in Egypt (4).

MERS-CoV may be isolated from nasal swab speci-

mans and feces, indicating that both could be possible sourc-

es of virus transmission to humans and other animals, but

virus detection rates were higher in nasal swab specimens.

Table 1. RT-PCRofdromedarycamelsamplesforMERS-CoV,

Al-Hasa, Saudi Arabia*

Farm,samplingdate

Age†/no.

sampled

No.specimens

positive/no.tested

Nasal Oral Fecal

FarmA

2013Nov30

Calf, 0

Adult, 4 1/1 0/2 0/4

2013Dec4

Calf, 9

0/9

0/7

Adult,2

0/2

2013Dec30

Calf,8

7/8

0/1

0/6

Adult, 3

1/3‡

2014Feb14 Calf,7 0/7 ND 0/7

Adult,2

0/2

FarmB:2014Feb11 Calf, 3 0/3 ND 0/3

Adult, 3

0/3

*Data on individual d romedaries are providedinonlineTechnicalAppendix

Table, http://wwwnc.cdc.gov/EID/article/20/7/14-0571-Techapp1.pdf. RT-

PCR,reversetranscriptionPCR;MERS-CoV,MiddleEastrespiratory

syndromecoronavirus;ND,notdone.

†Adults are 6–14yofage;calvesare40dto2yofage.

‡Two different dromedaries were positive in nasal and fecal swabs.

Table2.LongitudinalsamplingofMERS-CoV–positive dromedary

camel calves on farm A, Al-Hasa, Saudi Arabia*

Calf no.

Sample collection

date

Sex/age

RT-PCR

result

Titer

13 2013Dec30 F/1y Positive <20

2014Feb14

F/1y

Negative

640

2013Dec30

F/1y

Positive

2014Feb14 F/1y Negative 160

2013Dec30

F/40d

Positive

2014Feb14 F/3mo Negative 1,280

2013Dec30

F/1y

Positive

2014Feb14

F/1y

Negative

320

*MERS-CoV,MiddleEastrespiratorysyndromecoronavirus;RT-PCR,

reverse transcription PCR.

 EmergingInfectiousDiseases•www.cdc.gov/eid•Vol.20,No.7,July2014 1233

MERS-CoVinCamelHerd

Our preliminary data suggest that preexisting MERS-CoV

antibody might not completely protect against re-infection;

however, this question needs more investigation.

We thank the King Faisal University Deanship of Scientif-

ic Research for their support (grant no. 143011). This research

was funded by a research contract from the National Insti-

tute of Allergy and Infectious Diseases, National Institutes of

Health (contract no. HHSN266200700005C), and a grant

from the European Community Seventh Framework Program

(FP7/2007-2013) under project European Management Platform

for Emerging and Re-emerging Disease entities (grant agreement

no. 223498) (EMPERIE).

Dr Hemida is an assistant professor of molecular virology at

King Faisal University, Saudi Arabia. His primary research inter-

ests are virus–host interactions and the molecular biology of CoVs.

References

1. World Health Organization. Middle East respiratory syndrome

coronavirus (MERS‐CoV). Summary and literature update—as of

27 March 2014 [cited 2014 Apr 11]. http://www.who.int/csr/disease/

coronavirus_infections/MERS_CoV_Update_27_March_2014.

pdf?ua=1

2. The WHO MERS-CoV Research Group. State of knowledge and

data gaps of Middle East respiratory syndrome coronavirus (MERS-

CoV) in humans. PLoS Curr. 2013;5:pii:ecurrents.outbreaks.0bf719

e352e7478f8ad85fa30127ddb8.

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Zeid DA, et al. MERS coronaviruses in dromedary camels, Egypt.

[Internet]. Emerg Infect Dis. 2014 Jun [cited 2014 Mar 31].

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eid2006.140402

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molbev/msr121

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8. Addie DD, Dennis JM, Toth S, Callanan JJ, Reid S, Jarrett O.

Long-term impact on a closed household of pet cats of natural

infection with feline coronavirus, feline leukaemia virus and feline

immunodeciency virus. Vet Rec. 2000;146:419–24. http://dx.doi.

org/10.1136/vr.146.15.419

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Ong SH, et al. Spread, circulation, and evolution of the Middle

East respiratory syndrome coronavirus. MBio. 2014;5:e01062-13.

http://dx.doi.org/10.1128/mBio.01062-13

10. Reusken CB, Haagmans BL, Müller MA, Gutierrez C, Godeke GJ,

Meyer B, et al. Middle East respiratory syndrome coronavirus

Figure. Phylogenetic tree of

Middle East respiratory syndrome

coronavirus (MERS-CoV) full

genomes (29,901 nt after trimming

the ends) or near–full genomes

from humans and dromedary

camels. The tree was constructed

by using neighbor-joining methods

with bootstrap resampling of 500

replicates. The most divergent

MERS-CoV,EgyptNRCE-HKU205,

was used as outgroup. Bold

type indicates camel MERS-CoV

genomes from this study. GenBank

accession numbers of genome

sequences included in this study are

KJ477102, KF600652, KF600630,

KF600651, KF186567, KF600627,

KF186564, KF600634, KF600632,

KF600644, KF600647, KF600645,

KF186565, KF186566, KF745068,

KF600620, KF600612, KC667074,

KC164505, KF192507, KF600613,

KF600628, KF961222, KF961221,

KC776174, and JX869059.

Scale bar indicates nucleotide

substitutions per site.

DISPATCHES

1234 EmergingInfectiousDiseases•www.cdc.gov/eid•Vol.20,No.7,July2014

neutralising serum antibodies in dromedary camels: a comparative

serological study. Lancet Infect Dis. 2013;13:859–66. http://dx.doi.

org/10.1016/S1473-3099(13)70164-6

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Address for correspondence; Malik Peiris, School of Public Health,

The University of Hong Kong, 21 Sassoon Rd, Pokfulam, Hong

Kong Special Administrative Region; email: malik@hku.hk; or

Abdelmohsen Alnaeem, Department of Clinical Studies, College of

Veterinary Medicine, King Faisal University, Saudi Arabia; email:

aaalnaeem@kfu.edu.sa

Middle East respiratory syndrome coronavirus isolate KFU-HKU 1, complete genome

Nucleotide Sequence

April 2014

Maged Hemida · Daniel Chu · Leo L. M. Poon · Ranawaka A.P.M Perera · Joseph S Malik Peiris

Middle East respiratory syndrome coronavirus isolate KFU-HKU 13, complete genome

Nucleotide Sequence

April 2014

Maged Hemida · Daniel Chu · Leo L. M. Poon · Ranawaka A.P.M Perera · Joseph S Malik Peiris

Middle East respiratory syndrome coronavirus isolate KFU-HKU 19Dam, complete genome

Nucleotide Sequence

April 2014

Maged Hemida · Daniel Chu · Leo L. M. Poon · Ranawaka A.P.M Perera · Joseph S Malik Peiris

Technical Appendix

Data

July 2014

Maged Hemida · Daniel Chu · Leo L. M. Poon · Ranawaka A.P.M Perera · Joseph S Malik Peiris

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Bat coronaviruses cause a wide range of illnesses in humans and animals. Bats are known to harbor a wide diversity of Alphacoronaviruses and Betacoronaviruses. Betacoronaviruses have been linked to Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and other diseases such as gastroenteritis, bronchiolitis, and pneumonia. In the last 20 years, three betacoronaviruses emerged and caused widespread outbreaks in humans, including two deadly betacoronavirus epidemics, SARS-CoV, with mortality rate of 10%, and MERS-CoV, with mortality rate of 34.7%, and SARS-CoV-2, which caused the COVID-19 pandemic, with mortality rate of 3.4%. Studies have shown that bats are the main natural reservoirs for these viruses or their ancestral viruses. Observed variations in bat coronavirus genomes indicate that these viruses may have a potential to transmit to other hosts in close contact with humans and subsequently transmit to humans. As of today, there are no reported cases of direct coronavirus transmission from bats to humans. One reason for this might be that intermediate hosts are required for the transmission of bat coronaviruses to humans. Further studies are needed to map the amino acids and genomic regions responsible for the interactions between the spike of coronavirus and its receptors.

Classification, replication, and transcription of Nidovirales

Article

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Jan 2024

Nidovirales is one order of RNA virus, with the largest single-stranded positive sense RNA genome enwrapped with membrane envelope. It comprises four families (Arterividae, Mesoniviridae, Roniviridae, and Coronaviridae) and has been circulating in humans and animals for almost one century, posing great threat to livestock and poultry，as well as to public health. Nidovirales shares similar life cycle: attachment to cell surface, entry, primary translation of replicases, viral RNA replication in cytoplasm, translation of viral proteins, virion assembly, budding, and release. The viral RNA synthesis is the critical step during infection, including genomic RNA (gRNA) replication and subgenomic mRNAs (sg mRNAs) transcription. gRNA replication requires the synthesis of a negative sense full-length RNA intermediate, while the sg mRNAs transcription involves the synthesis of a nested set of negative sense subgenomic intermediates by a discontinuous strategy. This RNA synthesis process is mediated by the viral replication/transcription complex (RTC), which consists of several enzymatic replicases derived from the polyprotein 1a and polyprotein 1ab and several cellular proteins. These replicases and host factors represent the optimal potential therapeutic targets. Hereby, we summarize the Nidovirales classification, associated diseases, “replication organelle,” replication and transcription mechanisms, as well as related regulatory factors.

Identification of the host reservoir of SARS-CoV-2 and determining when it spilled over into humans

Preprint

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Nov 2023

Since the emergence of SARS-CoV-2 in Wuhan in 2019 its host reservoir has not been established. Phylogenetic analysis was performed on whole genome sequences (WGS) of 71 coronaviruses and a Breda virus. A subset comprising two SARS-CoV-2 Wuhan viruses and 8 of the most closely related coronavirus sequences were used for host reservoir analysis using Bayesian Evolutionary Analysis Sampling Trees (BEAST). Within these genomes, 20 core genome fragments were combined into 2 groups each with similar clock rates (5.9x10 -3 and 1.1x10 -3 subs/site/year). Pooling the results from these fragment groups yielded a most recent common ancestor (MRCA) shared between SARS-COV-2 and the bat isolate RaTG13 around 2007 (95% HPD: 2003, 2011). Further, the host of the MRCA was most likely a bat (probability 0.64 - 0.87). Hence, the spillover into humans must have occurred at some point between 2007 and 2019 and bats may have been the most likely host reservoir.

Severe Acute Respiratory Syndrome Coronaviruses-2 (SARS-CoV-2)

Chapter

Oct 2023

Review on Middle East Respiratory Syndrome Coronavirus disease (MERS-COV) in Dromedary camel and Its public health importance

Article

Jan 2022

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) that was first identified in Saudi Arabia in 2012 is caused by a virus of 2C beta Corona virus lineage that expresses the dipeptidyl peptidase 4 (DPP4) receptor and is densely endemic in dromedary camels of East Africa and the Arabian Peninsula. The first case of MERS-CoV was detected from a 60-year-old man from Saudi Arabia, who died of severe respiratory distress and renal failure. The virus spread over 27 countries with high fatality rate of 35.4% making an ongoing public health threat. Extensive works performed on origin of MERS-CoV indicated that, bats are ancestral host due to their huge species variations, long time fly, and unique behavior of multispecies coexistence. Strong evidence of human-to-human transmission was obtained from epidemiological and genomic studies investigating clustering of cases in hospitals and among household contacts. Zoonotic transmission in human results clinical symptoms ranging from mild to severe respiratory symptoms. Similarly, humans can be infected through direct contact with infected camels or their milk, urine or other body fluids. For identification and characterization of the virus, diagnostic methods such as serological tests, molecular methods and neutralizing assays are used. Studies indicated that, MERS-CoV entrenched in the Arabian Peninsula has acquired increased pathogenic potential for humans due to mutation in their spike protein. Although human cases are yet not detected in Africa, if pathogenic clade B viruses from the Arabian Peninsula are introduced into Africa, they are likely to become dominant and increases public health risks. Therefore, the purpose of this review is to highlight MERS-CoV in dromedary camel and its public health importance.

International Journal of Advanced Research in Biological Sciences Review on Middle East Respiratory Syndrome Coronavirus disease (MERS-COV) in Dromedary camel and Its public health importance

Article

Jan 2022

Middle East Respiratory Syndrome Coronavirus Infection in Dromedary Camels in Saudi Arabia

Article

Full-text available

Mar 2014

The Middle East respiratory syndrome (MERS) is proposed to be a zoonotic disease; however, the reservoir and mechanism for transmission of the causative agent, the MERS coronavirus, are unknown. Dromedary camels have been implicated through reports that some victims have been exposed to camels, camels in areas where the disease has emerged have antibodies to the virus, and viral sequences have been recovered from camels in association with outbreaks of the disease among humans. Nonetheless, whether camels mediate transmission to humans is unresolved. Here we provide evidence from a geographic and temporal survey of camels in the Kingdom of Saudi Arabia that MERS coronaviruses have been circulating in camels since at least 1992, are distributed countrywide, and can be phylogenetically classified into clades that correlate with outbreaks of the disease among humans. We found no evidence of infection in domestic sheep or domestic goats.

Human Infection with MERS Coronavirus after Exposure to Infected Camels, Saudi Arabia, 2013

Article

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Jun 2014

Abdullah M Assiri

MERS Coronaviruses in Dromedary Camels, Egypt

Article

Full-text available

Jun 2014
EMERG INFECT DIS

We identified the near-full-genome sequence (29,908 nt, >99%) of Middle East respiratory syndrome coronavirus (MERS-CoV) from a nasal swab specimen from a dromedary camel in Egypt. We found that viruses genetically very similar to human MERS-CoV are infecting dromedaries beyond the Arabian Peninsula, where human MERS-CoV infections have not yet been detected.

Human Infection With MERS Coronavirus After Exposure to Infected Camels

Article

Full-text available

Jun 2014

We investigated a case of human infection with Middle East respiratory syndrome coronavirus (MERS-CoV) after exposure to infected camels. Analysis of the whole human-derived virus and 15% of the camel-derived virus sequence yielded nucleotide polymorphism signatures suggestive of cross-species transmission. Camels may act as a direct source of human MERS-CoV infection.

Antibodies against MERS Coronavirus in Dromedary Camels, United Arab Emirates, 2003 and 2013

Article

Full-text available

Apr 2014

Middle East respiratory syndrome coronavirus (MERS-CoV) has caused an ongoing outbreak of severe acute respiratory tract infection in humans in the Arabian Peninsula since 2012. Dromedary camels have been implicated as possible viral reservoirs. We used serologic assays to analyze 651 dromedary camel serum samples from the United Arab Emirates; 151 of 651 samples were obtained in 2003, well before onset of the current epidemic, and 500 serum samples were obtained in 2013. Recombinant spike protein-specific immunofluorescence and virus neutralization tests enabled clear discrimination between MERS-CoV and bovine CoV infections. Most (632/651, 97.1%) camels had antibodies against MERS-CoV. This result included all 151 serum samples obtained in 2003. Most (389/651, 59.8%) serum samples had MERS-CoV-neutralizing antibody titers >1,280. Dromedary camels from the United Arab Emirates were infected at high rates with MERS-CoV or a closely related, probably conspecific, virus long before the first human MERS cases.

Middle East Respiratory Syndrome Coronavirus Infection in Dromedary Camels in Saudi Arabia

Article

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Feb 2014

Spread, Circulation, and Evolution of the Middle East Respiratory Syndrome Coronavirus

Article

Full-text available

Feb 2014

Unlabelled: The Middle East respiratory syndrome coronavirus (MERS-CoV) was first documented in the Kingdom of Saudi Arabia (KSA) in 2012 and, to date, has been identified in 180 cases with 43% mortality. In this study, we have determined the MERS-CoV evolutionary rate, documented genetic variants of the virus and their distribution throughout the Arabian peninsula, and identified the genome positions under positive selection, important features for monitoring adaptation of MERS-CoV to human transmission and for identifying the source of infections. Respiratory samples from confirmed KSA MERS cases from May to September 2013 were subjected to whole-genome deep sequencing, and 32 complete or partial sequences (20 were ≥ 99% complete, 7 were 50 to 94% complete, and 5 were 27 to 50% complete) were obtained, bringing the total available MERS-CoV genomic sequences to 65. An evolutionary rate of 1.12 × 10(-3) substitutions per site per year (95% credible interval [95% CI], 8.76 × 10(-4); 1.37 × 10(-3)) was estimated, bringing the time to most recent common ancestor to March 2012 (95% CI, December 2011; June 2012). Only one MERS-CoV codon, spike 1020, located in a domain required for cell entry, is under strong positive selection. Four KSA MERS-CoV phylogenetic clades were found, with 3 clades apparently no longer contributing to current cases. The size of the population infected with MERS-CoV showed a gradual increase to June 2013, followed by a decline, possibly due to increased surveillance and infection control measures combined with a basic reproduction number (R0) for the virus that is less than 1. Importance: MERS-CoV adaptation toward higher rates of sustained human-to-human transmission appears not to have occurred yet. While MERS-CoV transmission currently appears weak, careful monitoring of changes in MERS-CoV genomes and of the MERS epidemic should be maintained. The observation of phylogenetically related MERS-CoV in geographically diverse locations must be taken into account in efforts to identify the animal source and transmission of the virus.

Middle East Respiratory Syndrome (MERS) coronavirus seroprevalence in domestic livestock in Saudi Arabia, 2010 to 2013

Article

Full-text available

Dec 2013
Euro Surveill

In Saudi Arabia, including regions of Riyadh and Al Ahsa, pseudoparticle neutralisation (ppNT) and microneutralisation (MNT) tests detected no antibodies to Middle East Respiratory Syndrome coronavirus (MERS-CoV) in sheep (n= 100), goats (n= 45), cattle (n= 50) and chickens (n= 240). Dromedary camels however, had a high prevalence of MERS-CoV antibodies. Bovine coronavirus (BCoV) infected sera from cattle had no cross-reactivity in MERS-CoV ppNT or MNT, while many dromedary camels’ sera reacted to both BCoV and MERS-CoV. Some nevertheless displayed specific serologic reaction profiles to MERS-CoV.

Middle East Respiratory Syndrome coronavirus (MERS-CoV) serology in major livestock species in an affected region in Jordan, June to September 2013

Article

Full-text available

Dec 2013
Euro Surveill

Between June and September 2013, sera from 11 dromedary camels, 150 goats, 126 sheep and 91 cows were collected in Jordan, where the first human Middle-East respiratory syndrome (MERS) cluster appeared in 2012. All sera were tested for MERS-coronavirus (MERS-CoV) specific antibodies by protein microarray with confirmation by virus neutralisation. Neutralising antibodies were found in all camel sera while sera from goats and cattle tested negative. Although six sheep sera reacted with MERS-CoV antigen, neutralising antibodies were not detected.

State of Knowledge and Data Gaps of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Humans

Article

Full-text available

Nov 2013

Full text available at: http://currents.plos.org/outbreaks/article/state-of-knowledge-and-data-gaps-of-middle-east-respiratory-syndrome-coronavirus-mers-cov-in-humans-2/ Between September 2012 and 22 October 2013, 144 laboratory-confirmed and 17 probable MERS-CoV cases from nine countries were notified to WHO. We summarize what is known about the epidemiology, virology, phylogeny and emergence of MERS-CoV to inform public health policies. The median age of patients (n=161) was 50 years (range 14 months to 94 years), 64.5% were male and 63.4% experienced severe respiratory disease. 76.0% of patients were reported to have ≥1 underlying medical condition and fatal cases, compared to recovered or asymptomatic cases were more likely to have an underlying condition (86.8% vs. 42.4%, p<0.001). Analysis of genetic sequence data suggests multiple independent introductions into human populations and modelled estimates using epidemiologic and genetic data suggest R<sub>0</sub> is <1, though the upper range of estimates may exceed 1. Index/sporadic cases (cases with no epidemiologic-link to other cases) were more likely to be older (median 59.0 years vs. 43.0 years, p<0.001) compared to secondary cases, although these proportions have declined over time. 80.9% vs. 67.2% of index/sporadic and secondary cases, respectively, reported ≥1 underlying condition. Clinical presentation ranges from asymptomatic to severe pneumonia with acute respiratory distress syndrome and multi-organ failure. Nearly all symptomatic patients presented with respiratory symptoms and 1/3 of patients also had gastrointestinal symptoms. Sustained human-to-human transmission of MERS-CoV has not been observed. Outbreaks have been extinguished without overly aggressive isolation and quarantine suggesting that transmission of virus may be stopped with implementation of appropriate infection control measures.

MERS Coronavirus in dromedary camel herd, Saudi Arabia

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