Middle East respiratory syndrome (MERS)-related coronavirus: Infectious substances pathogen safety data sheet

For more information on MERS-CoV, see the following:

• Government of Canada diseases and conditions facts: Middle East respiratory syndrome (MERS)
• Other: Summary of Assessment of Public Health Risk to Canada Associated with Middle East Respiratory Syndrome Coronavirus (MERS-CoV), July 13, 2017

Section I – Infectious agent

Name

Middle East Respiratory syndrome (MERS)-related coronavirus

Agent type

Virus

Taxonomy

Family

Coronaviridae

Genus

Betacoronavirus

Species

cameli^{Footnote 1Footnote 2}

Synonym or cross-reference

Formerly Human coronavirus Erasmus medical centre (HCoV-EMC) and novel coronavirus (CoV)^{Footnote 3Footnote 4}. Also known as MERS-CoV, or MERS^{Footnote 5}.

Characteristics

Brief description

MERS-CoV is the sixth coronavirus identified with the ability to infect humans^{Footnote 4}. First isolated in 2012, the virus was recognized as the first human coronavirus in lineage C of the Betacoronavirus genus. The closest genetic relatives to MERS-CoV are bat coronaviruses HKU4 and HKU5, which were isolated from Tylomycteris pachypus and Pipistrellus abramus bats^{Footnote 4}. MERS-CoV virions are enveloped, approximately 100 nm spheres with surface projections formed by the surface spike (S) proteins^{Footnote 3Footnote 6}. MERS-CoV has positive-sense, single-stranded RNA genome consisting of approximately 30 kb, and encoding for 10 proteins in total^{Footnote 5Footnote 6Footnote 7}. These 10 proteins comprise of two replicase polyproteins (ORF1ab and ORF1a), four structural proteins (envelope [E], nucleocapsid [N], membrane [M], and spike [S]), and four non-structural proteins (ORFs, 3, 4a, 4b, and 5)^{Footnote 7}. Additionally, MERS-CoV's G+C content varies between 32-43 %^{Footnote 8}.

Properties

The non-structural proteins aid in viral replication and interfere with the host innate immune system in infected hosts^{Footnote 7}. Specifically both 4a and 4b non-structural proteins modulate interferon production for the virus^{Footnote 5}.

The viral particle can enter via the endosomal pathway (the virion induces endocytosis of the host cell), or by direct fusion (the virion fuses with the plasma membrane of the host cell following S protein cleavage by human proteases)^{Footnote 6}. In the endosomal pathway, MERS-CoV mediates cell entry using the host receptor dipeptidyl peptidase 4 (DPP4), which is expressed in respiratory epithelial cells such as type I and II pneumocytes, non-ciliated bronchial epithelial cells, endothelial cells, and some hematopoietic cells^{Footnote 5}. Then the S protein binds to DPP4, which induces endocytosis of the viral particle and a change in the S protein that then mediates virus-host membrane fusion and uncoating of virus RNA^{Footnote 6}. Virions are then assembled at the endoplasmic reticulum membrane as viral proteins and genomic RNA are grouped together and then bud into the lumen of the endoplasmic reticulum^{Footnote 6}.

The evolutionary rate for the coding region of the MERS-CoV viral genome is estimated to be 1.12 X 10-³ substitutions per site per year; however, there is limited evidence of adaptation to human transmission in MERS-CoV lineages^{Footnote 9}.

Section II – Hazard identification

Pathogenicity and toxicity

The MERS-CoV infection in humans ranges from asymptomatic to mild respiratory illness to severe acute pneumonia, which can rapidly progress to acute lung injury and acute respiratory distress syndrome (ARDS), multi-organ failure, septic shock, and death^{Footnote 5Footnote 8}.

Patients experience flu-like symptoms such as fever, sore throat, non-productive cough, chills/rigours, chest pain, headache, muscle pain (myalgia), joint pain (arthralgia), and difficulty breathing/shortness of breath^{Footnote 5}. Those with milder disease often present with manifestations confined to the upper respiratory tract. In addition to the lungs, the infection may also damage other organs or tissues, including the gastrointestinal tract, spleen, lymph nodes, brain, skeletal muscles, thyroid, and heart^{Footnote 5Footnote 7Footnote 10}. Other extrapulmonary manifestations that have been reported for MERS-CoV include acute kidney injury, liver enzyme malfunctions, reduced lymphocyte (lymphocytopenia) and/or platelet (thrombocytopenia) count, as well as gastrointestinal symptoms, including abdominal pain, vomiting, and diarrhea^{Footnote 5Footnote 7Footnote 10}.

Documented MERS-CoV infection in camels typically remains asymptomatic or mild with rare cases involving mild rhinitis, conjunctivitis, coughing/honking, and diarrhea^{Footnote 10}. In experimental settings, camels inoculated with a human isolate of MERS-CoV have also displayed rhinorrhea, but no other clinical signs were apparent^{Footnote 11}.

Epidemiology

MERS-CoV is believed to have originated in bats, and then spread to camels, which represent the primary source of infection for humans^{Footnote 12}.

The first case of MERS-CoV, occurred in June of 2012 in Jeddah, Saudi Arabia, in a 60 year old man who succumbed to the illness^{Footnote 4Footnote 5Footnote 6}. In September of the same year, another case of a severe respiratory infection related to a novel coronavirus was reported in the United Kingdom following travel to the Middle East^{Footnote 6}. Retrospective studies confirmed that MERS-CoV was also responsible for an outbreak of respiratory disease in Zarqa, Jordan in April of 2012^{Footnote 5}. Since then, the virus caused an outbreak in 2015 in South Korea, involving 186 cases, which was as a result of travel from the Middle East as well as a number of MERS-CoV cases/outbreaks occurring in hospitals/healthcare facilities (nosocomial) throughout the years in the Arabian Peninsula and Middle East, typically as a result of inadequate infection-control practices^{Footnote 5}.

All cases of MERS-CoV have been geographically linked to the Middle East, and cases that occurred outside of the Middle East involved travelers from the region^{Footnote 5}. From September 2012 to June 2020, a total of 2450 cases were confirmed, of which 2048 occurred in Saudi Arabia^{Footnote 13}.

MERS-CoV infection is considered seasonal due to an increase in the number of cases observed in April/May/June, coinciding with the weaning of camel calves in the spring but cases are reported throughout the year^{Footnote 10Footnote 14}.

Males account for almost 2/3 of all MERS-CoV cases, however, this sex-based difference is believed to reflect a difference in MERS-CoV exposure^{Footnote 5}. Notably, mortality is seen to be highest in elderly, male patients with comorbidities, especially diabetes^{Footnote 6}. Age is also a risk factor for developing a severe MERS-CoV infection with the average patient age being 50 years old^{Footnote 5}. The case fatality rate is higher in the elderly (90%) and lower in those 20 years and younger (~10%)^{Footnote 5}. Additionally, individuals with diabetes, chronic renal and cardiac disease, obesity, hypertension, asthma, and chronic obstructive pulmonary disease are at higher risk of developing severe disease^{Footnote 5Footnote 10}. Approximately 75% of all MERS-CoV cases have occurred in patients with comorbidities^{Footnote 5}.

Host range

Natural host(s)

Humans^{Footnote 5}, dromedary camels^{Footnote 5Footnote 15Footnote 16}, alpacas^{Footnote 15}, sheep^{Footnote 16}, cows, goats, donkeys, and possibly bats^{Footnote 5}.

Other host(s)

Other hosts in experimental settings are mice^{Footnote 17Footnote 18Footnote 19}, llamas^{Footnote 15Footnote 20}, rabbits^{Footnote 21Footnote 22}, rhesus macaques^{Footnote 23Footnote 24}, marmosets^{Footnote 24}, horses^{Footnote 20}, cats^{Footnote 22}, dogs, and primates.

Infectious dose

Unknown. However, a study involving the administration of viral doses of MERS-CoV to mice had estimated ID₅₀ of <1 TCID₅₀ and a LD₅₀ of 10 TCID₅₀^{Footnote 17}.

Incubation period

The incubation period ranges from 1 to 14 days, with a median of 5 to 7 days^{Footnote 5Footnote 10}. Patients with MERS-CoV pneumonia experience viral shedding for 2 to 4 weeks^{Footnote 25Footnote 26}.

Communicability

The preferred route of transmission for MERS-CoV is inhalation of droplets or aerosols from infected hosts^{Footnote 7}. Transmission is also possible via contact with mucous membranes or contact with damage skin (respiratory droplets)^{Footnote 12Footnote 22}, as well as ingestion (camel products such as milk, meat or urine used medicinally)^{Footnote 5Footnote 10Footnote 12Footnote 27Footnote 28}. Furthermore, transmission of MERS-CoV can also occur through both direct contact, specifically casual direct contact, and indirect contact with fomites since the virus can persist on inanimate surfaces^{Footnote 5Footnote 12}.

Section III – Dissemination

Reservoir

MERS-CoV is believed to have originated in African bats, and then subsequently infected dromedary camels, both of which display little or no overt symptoms of infection^{Footnote 12}. Additionally, camels in Africa and the Arabian Peninsula have seropositivity rates as high as 80-90%^{Footnote 5}.

Zoonosis

MERS-CoV is spread from infected hosts, specifically dromedary camels to humans (direct zoonosis)^{Footnote 5}. Bats are considered an unlikely source for direct zoonosis due to their limited exposure to humans^{Footnote 5}.

Vectors

None.

Section IV – Stability and viability

Drug susceptibility/resistance

There are no existing drugs that specifically target MERS-CoV^{Footnote 5Footnote 10Footnote 29}. However, in experimental settings, both in vitro and in vivo, combinations of drugs have shown some effectiveness for treatment. A combination of interferon-α2b and ribavirin have shown to reduce virus replication, moderate the host response, and improve clinical outcomes in rhesus macaques^{Footnote 30}. Lopinavir/ritonavir treatment has also shown anti-MERS-CoV activity, and a combination of interferon-β1b and mycophenolate mofetil (MMF) has demonstrated synergistic effects in vitro^{Footnote 31}; however, these drugs have proven ineffective in randomized controlled trials^{Footnote 32}. Additionally, resveratrol may also inhibit MERS-CoV infection in humans, but this compound has only been tested in vitro^{Footnote 33}.

In experimental studies, the developed human monoclonal antibodies, REGN3048 and REGN3051, are able to target the spike protein, and the administration of both has been shown to be substantially more effective for reducing viral titer, lung inflammation, and pathology in human DPP4 mice compared with control antibodies, and to each antibody monotherapy^{Footnote 29}.

Susceptibility to disinfectants

MERS-CoV is moderately susceptible to 70% alcohol, but bleach (1:100 dilution of 5% sodium hypochlorite) is effective against the virus^{Footnote 25}. Additionally, the usage of monophasic solution of phenol and guanidinium isothiocyanate (1:3 ratio of virus stock to solution), completely inactivated MERS-CoV^{Footnote 34}.

Given the genetic similarities between SARS-CoV and MERS-CoV, MERS-CoV may also be susceptible to the following disinfection measures known to inactivate SARS-CoV: 5 minute contact with household bleach^{Footnote 35}, ice-cold acetone for 90 seconds^{Footnote 36}, ice-cold acetone/methanol mixture (40:60) for 10 minutes, 70% ethanol for 10 minutes, 100% ethanol for 5 minutes, paraformaldehyde for 2 minutes, and glutaraldehyde for 2 minutes. Commonly used brands of hand disinfectants also inactivate SARS-CoV in 30 seconds^{Footnote 36}.

Physical inactivation

A 30 minute heat treatment at 63°C removed all infectious virus from dromedary camel milk samples containing MERS-CoV^{Footnote 14}. Moreover, a treatment of supernatant fluid at 65°C for 15 minutes or 56°C for 30 minutes completely inactivates the virus in the fluid^{Footnote 37}. In experimental settings, MERS-CoV has shown to be inactivated by UV-C (ultraviolet light which is in the range of 200-280 nm) within a 10 minute treatment^{Footnote 38}. Gamma irradiation (dose of at least 3 mrad), and viral lysis buffer treatments showed complete inactivation^{Footnote 34}.

Survival outside host

MERS-CoV can persist in the environment for 24 to 48 hours under temperature and relative humidity (RH) conditions ranging from 20-30°C and 30-80%, respectively^{Footnote 39}. Viability of aerosolized MERS-CoV at 20°C and 40% RH decreases slightly by 7%, but has been shown to drop by 89% at 70% RH. Additionally, the virus is stable in camel breast milk for up to 72 hours at 4°C, but viral titers rapidly lose infectivity when stored at 22°C for 48 hours^{Footnote 12Footnote 40}.

Human coronavirus (HCoV) 229E, one of the 6 coronaviruses known to infect humans besides MERS-CoV, has been shown to persist on high-touch environmental surfaces (polyvinylchloride, laminate, wood, stainless steel) despite daily cleaning with a commercial cleaning solution containing alcohol ethoxylates and sodium xylene sulfonate^{Footnote 41}. Swab specimens collected from these surfaces remained infectious for at least 7 days at ambient temperature of 24°C and RH conditions of ~50%. As a human coronavirus with comparable genetic characteristics, MERS-CoV may also survive outside the host under similar conditions; however, compared to other human coronaviruses, MERS-CoV may survive on dry surfaces for longer time periods^{Footnote 42}.

Section V – First aid/medical

Surveillance

There are no specific symptoms that can accurately confirm a MERS-CoV infection; however, MERS-CoV viral RNA can be detected in respiratory tract specimens during the acute phase of illness using quantitative reverse transcription polymerase chain reaction (qRT-PCR)^{Footnote 5}. MERS-CoV can also be identified using enzyme-linked immunosorbent assay (ELISA) to detect virus-specific antibodies in serum samples collected 2 to 3 weeks after disease onset or by using a positive immunofluorescence and/or microneutralization test.

Note : The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook.

First aid/treatment

Supportive care is primarily used for MERS-CoV patients since there are no specific therapies that currently exist^{Footnote 5}. Available therapies include the usage of interferons, specifically type I^{Footnote 5Footnote 7Footnote 22} (IFN-α and IFN-β), and type III^{Footnote 22}, and antiviral agents such as ribavirin^{Footnote 5Footnote 7} or lopinavir/ritonavir^{Footnote 7} have shown effectiveness. However, the use of convalescent plasma or MERS-CoV-specific antibodies is a promising approach, but requires further testing^{Footnote 5Footnote 7}. In addition, certain antiviral drugs are under review for possible clinical use, including chloroquine, chlorpromazine, mycophenolic acid, and nitazoxanide^{Footnote 5}.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the Canadian Biosafety Handbook.

Immunization

There are no MERS-CoV vaccines currently approved for human use^{Footnote 5}. However, inactivated, live attenuated virus, viral vector, protein subunit, and DNA vaccines are all in various stages of preclinical development.

A vaccine candidate for MERS-CoV, referred to as ChAdOx1 was found to be safe, well tolerated, and successful at creating an immune response in phase 1 clinical trials^{Footnote 43Footnote 44}. The safety and immunogenicity data from phase 1b trial and additional data from a trial in the UK for the ChAdOx1 vaccine support the advancement into phase 2 clinical evaluation^{Footnote 45Footnote 46}. Other vaccine candidates include MVA-MERS-S which has undergone phase 1 clinical trials^{Footnote 47}, the BVRS-GamVac which has undergone phases 1 and 2 clinical trials^{Footnote 48}, and the GLS-5300 which has completed phases 1 and 2a clinical trials^{Footnote 49}.

Note: More information on the medical surveillance program can be found in the Canadian Biosafety Handbook, and by consulting the Canadian Immunization Guide.

Prophylaxis

None available.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the Canadian Biosafety Handbook.

Section VI – Laboratory hazard

Laboratory-acquired infections

There are no known cases of MERS-CoV laboratory-acquired infections.

Note: Please consult the Canadian Biosafety Standard and Canadian Biosafety Handbook for additional details on requirements for reporting exposure incidents.

Sources/specimens

MERS-CoV RNA has been detected in the human lower respiratory tract (tracheal or tracheobronchial aspirates, bronchoalveolar lavage fluid and sputum)^{Footnote 22Footnote 50}; upper respiratory tract (pharyngeal or endotracheal aspirates, oronasal swabs, and nasal discharge)^{Footnote 50}; blood (specifically serum)^{Footnote 5Footnote 10}; urine^{Footnote 5Footnote 10Footnote 22}; vomit^{Footnote 10}; and stool^{Footnote 5Footnote 10Footnote 22}.

Additionally, in infected animals, the virus has been recovered from nasal swabs^{Footnote 12Footnote 23Footnote 51}, nasal discharge^{Footnote 5}, rectal swabs^{Footnote 12Footnote 51}, urogenital swabs^{Footnote 23}, oropharyngeal swabs^{Footnote 12Footnote 23}, conjunctival swabs^{Footnote 12}, lymph node tissue, lung tissue, whole blood samples (including serum)^{Footnote 11Footnote 12Footnote 23Footnote 51}, raw camel milk^{Footnote 5}, stool^{Footnote 12}, and bronchoalveolar lavage^{Footnote 23}.

Primary hazards

The primary hazard associated with exposure to MERS-CoV is inhalation of airborne or aerosolized infectious material, either from infected humans or animals^{Footnote 7}. Other hazards include contaminated fomites^{Footnote 12}, ingestion^{Footnote 5Footnote 27} of contaminated products, and contact of mucous membranes with contaminated respiratory secretions^{Footnote 28}.

Special hazards

Working with naturally or experimentally infected animals in experimental settings can present a special hazard^{Footnote 11Footnote 23}.

Section VII – Exposure controls/personal protection

Risk group classification

MERS-CoV is a Risk Group 3 Human Pathogen and Risk Group 3 Animal Pathogen, and is a Security Sensitive Biological Agent (SSBA)^{Footnote 2Footnote 52}.

Containment requirements

The applicable CL3 or CL3-Ag requirements outlined in the Canadian Biosafety Standard for all for work involving infectious or potentially infectious materials, animals, or cultures.

Note that there are additional security requirements, such as obtaining a Human pathogens and Toxins Act Security Clearance, for work involving SSBAs.

Protective clothing

The applicable CL3 requirements for personal protective equipment and clothing outlined in the Canadian Biosafety Standard are to be followed. At minimum, use of full body coverage dedicated protective clothing, dedicated protective footwear and/or additional protective footwear, gloves when handling infectious materials or animals, face protection when there is a known or potential risk of exposure to splashes or flying objects, respirators when there is a risk of exposure to infectious aerosols, and an additional layer of protective clothing prior to work with infectious materials or animals.

Note : A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone must be documented.

Other precautions

All activities involving open vessels of infectious material or toxins to be performed in a certified BSC or other appropriate primary containment device.

The use of needles, syringes, and other sharp objects are to be strictly limited. Additional precautions must be considered with work involving animals or large scale activities.

Section VIII – Handling and storage

Spills

Allow aerosols to settle. Wearing personal protective equipment, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time with the disinfectant before clean up (Canadian Biosafety Handbook).

Disposal

Regulated materials, as well as all items and waste to be decontaminated at the containment barrier prior to removal from the containment zone, animal room, animal cubicle, or post mortem room. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the infectious material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (Canadian Biosafety Handbook).

Storage

The applicable Containment Level 3 requirements for storage outlined in the Canadian Biosafety Standard are to be followed. Primary containers of regulated materials removed from the containment zone to be stored in a labelled, leak-proof, impact-resistant secondary container, and kept either in locked storage equipment or within an area with limited access.

SSBA: Containers of security sensitive biological agents (SSBA) stored outside the containment zone must be labelled, leakproof, impact resistant, and kept in locked storage equipment that is fixed in place (i.e., non-movable) and within an area with limited access.

An inventory of RG3 and SSBA toxins in long-term storage, to be maintained and to include:

• specific identification of the regulated materials
• a mechanism that allows for the detection of a missing or stolen sample in a timely manner

Section IX – Regulatory and other information

Canadian regulatory information

Controlled activities with MERS-CoV require a Pathogen and Toxin licence issued by the Public Health Agency of Canada. MERS-CoV is an emerging animal disease pathogen in Canada; therefore, its importation requires an import permit under the authority of the Health of Animals Regulations (HAR), issued by the Canadian Food Inspection Agency.

Note that there are additional security requirements, such as obtaining a Human Pathogens and Toxins Act Security Clearance, for work involving SSBAs.

The following is a non-exhaustive list of applicable designations, regulations, or legislations:

• Human Pathogens and Toxins Act and Human Pathogens and Toxins Regulations
• Health of Animals Act and Health of Animals Regulations
• Non-Indigenous Animal Pathogen or WOAH (OIE)-listed disease (please contact the Canadian Food Inspection Agency)

Last file update

July 2024

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, directives and standards applicable to the import, transport, and use of pathogens and toxins in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

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