Pathogen Safety Data Sheet: Infectious substances - Middle east respiratory syndrome (MERS)-related Coronavirus
On this page
- More information
- Section I - Infectious agent
- Section II - Hazard identification
- Section III - Dissemination
- Section IV - Stability and viability
- Section V - First aid/medical
- Section VI - Laboratory hazards
- Section VII - Exposure controls/personal protection
- Section VIII - Handling and storage
- Section IX - Regulatory and other information
For more information on MERS-CoV, see the following:
- Biosafety advisories/notifications/directives: MERS-CoV Biosafety Advisory July 7, 2015
- Infection Control Guideline Series: Infection Prevention and Control Guidance for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Acute Care Settings
- Travel Health and Safety: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Middle East
- 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
Species: Middle East respiratory syndrome-related coronavirus
Synonym or cross reference: Formerly Human coronavirus Erasmus medical centre (HCoV-EMC/2012) Footnote 1Footnote 2. Also known as MERS-CoV, MERS, Footnote 2 and novel coronavirus (nCoV) Footnote 3.
Brief Description: MERS-CoV is the sixth coronavirus identified with the ability to infect humans. 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 coronaviruses HKU4 and HKU5, which were isolated from Tylomycteris pachypus and Pipistrellus abramus bats Footnote 1. MERS-CoV is an enveloped, positive-sense, single-stranded RNA virus that encodes 5 unique accessory proteins, including 4A and 4b, which modulate interferon production. In contrast to Severe Acute Respiratory Syndrome-related coronavirus (SARS-CoV), which uses angiotensin-converting enzyme 2 (ACE2) as its receptor, MERS-CoV mediates cell entry using the host receptor dipeptidyl peptidase 4 (DPP4). Whereas SARS-CoV underwent extensive mutation to adapt to the human ACE2 protein, there is no evidence to suggest that MERS-CoV has adapted to human DPP4. The DPP4 receptor is expressed in respiratory tract cells but, due to the low abundance in the upper respiratory tract, human-to-human transmission of the virus may be limited. Consequently, MERS-CoV is not considered to be as infectious in humans relative to SARS-CoV Footnote 2.
Properties: 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 4.
Section II - Hazard identification
Pathogenicity and toxicity: Clinical symptoms of MERS-CoV infection in humans range from asymptomatic or mild respiratory illness in the upper respiratory tract to severe acute pneumonia. A rapid progression to acute lung injury and acute respiratory distress syndrome, followed by septic shock, multi-organ failure and death has been reported. Patients experience flu-like symptoms such as fever, sore throat, non-productive cough, chills, chest pain, headache, muscle pain, and difficulty breathing. Gastrointestinal symptoms, including abdominal pain, vomiting, and diarrhea, may also occur Footnote 2Footnote 5. Other extrapulmonary manifestations may present, such as acute kidney injury, liver enzyme malfunctions, or reduced lymphocyte and/or platelet count Footnote 6.
Since MERS-CoV infection was first reported to the World Health Organization in September 2012, there have been more than 2000 cases, with a case fatality rate (CFR) of approximately 35% Footnote 7. Numbers continue to increase. The CFR is known to increase with age.
Camels can develop mild rhinitis from natural MERS-CoV infection, but in most cases, they remain asymptomatic Footnote 5. Camels experimentally inoculated with a human isolate of MERS-CoV have also displayed rhinorrhea, but no other clinical signs were apparent Footnote 8.
Experimentally infected rhesus macaques may develop pneumonia, but most often experience self-limiting mild clinical disease Footnote 9Footnote 10. In contrast, experimentally inoculated marmosets (Callithrix jacchus) can develop severe interstitial pneumonia, some of which also experience frothy hemorrhagic discharge from the mouth. Systemic dissemination of MERS-CoV was suggested in these animal models based on the detection of viral RNA in the blood. In marmosets, viral loads in the lungs were up to 1000 times higher than those in rhesus macaques and the duration of illness was longer. In certain marmosets, euthanization was necessary due to disease severity Footnote 11.
Males account for almost 2/3 of all MERS cases seen to date, but case fatality rates (CFR) between males and females are comparable Footnote 12. Increased cases in males may be attributed to higher exposure rates Footnote 2.
Both primary and secondary hospital-acquired cases have occurred in older individuals, with the average MERS patient around 50 years old. Primary cases account for more than half of all MERS-CoV infections. The elderly have an increased likelihood of dying following infection; the CFR is higher in the elderly and lower in those 20 years and younger Footnote 2. In contrast, secondary-acquired infections are more gender- and age-balanced Footnote 13.
Individuals with diabetes, chronic renal and cardiac disease, obesity, hypertension, asthma, and chronic obstructive pulmonary disease are at higher risk of infection. Approximately 75% of all MERS-CoV cases have occurred in patients with comorbidities Footnote 2Footnote 5.
Communicability: MERS-CoV human-to-human transmission is not sustained; however, the virus can be shed during coughing and from excretions from the lower respiratory tract and has been shown to spread between humans in health care facilities Footnote 3Footnote 14Footnote 15. Spreading of the virus between patients and health care workers in nosocomial settings, or between family members, is likely to occur via large droplet aerosols and direct contact, but airborne or fomite transmission is also possible since the virus can persist on inanimate surfaces Footnote 16. MERS-CoV viral RNA can also persist in nasal discharge, blood, urine, vomit or saliva, feces, and urine, suggesting that direct intimate or casual contact may lead to transmission of the virus Footnote 5Footnote 14.
Direct casual contact with a sick camel may lead to human transmission by the respiratory route, but transmission is considered inefficient. Consumption of contaminated camel milk, meat, or urine (a traditional custom in the Arabian Peninsula and East Africa) may lead to infection but is unlikely Footnote 2Footnote 13Footnote 17.
Camel-to-camel spread is believed to contribute to maintenance of MERS-CoV infection in these animals Footnote 5. Infected calves can excrete MERS-CoV in their feces and saliva which can lead to surface contamination and spread to other camels through direct or indirect contact Footnote 13. Based on experimentally infected alpacas, spreading of MERS-CoV in animals is thought to occur mainly through intimate contact as opposed to aerosol transmission Footnote 18.
Epidemiology: MERS-CoV is a novel coronavirus believed to have originated in bats, and then spread to camels, which represent the primary source of infection for humans Footnote 2. The index case occurred on June 13, 2012 in Jeddah, Saudi Arabia, in a 60 year old man with a 7 day history of fever, cough, expectoration, and shortness of breath Footnote 1Footnote 2. A second case of MERS-CoV was reported 3 months later on September 22, 2012 in London, United Kingdom, in a 49 year old man who had travelled to Saudi Arabia and Qatar, where he had direct contact with camels and sheep Footnote 19. Retrospective studies confirmed that MERS-CoV was also responsible for an outbreak of respiratory disease in Zarqa, Jordan in April, 2012. Since then, the virus caused a 2015 outbreak in South Korea, involving 186 cases, as well as several outbreaks throughout the years in the Arabian Peninsula and Middle East, where the disease is considered endemic. Most cases (~75%) occur in Saudi Arabia, with other occurrences being traced to patients travelling from the Middle East Footnote 2Footnote 20. Nosocomial outbreaks of MERS-CoV have been reported in Saudi Arabian health care facilities. In these settings, the risk for person-to-person transmission is elevated Footnote 15.
A total of 27 countries have reported cases of MERS-CoV Footnote 7. Secondary cases of MERS-CoV predominated during the early stages of the outbreak, but have been significantly reduced due to improved infection-control practices Footnote 2. The disease 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; however, cases are reported throughout the year Footnote 5Footnote 13.
MERS-CoV is maintained in camels, which typically remain asymptomatic. Humans can become infected through direct exposure to camels but the virus is transmitted inefficiently among humans Footnote 2; however, only a small proportion of primary cases report having had direct contact with camels or camel products Footnote 13. Approximately 45,000 people in Saudi Arabia are believed to be infected by MERS-CoV without clinical illness and may play a role in the spread of disease to other humans Footnote 17. Adult dromedary camels have increased seropositivity compared to juvenile camels, likely due to higher exposure Footnote 21.
Natural host(s): Dromedary camels may experience mild respiratory symptoms from MERS-CoV infection but they are typically asymptomatic despite exhibiting a high titer of neutralizing antibodies to the virus. Serological evidence suggests that over 90% of adult dromedaries are infected with MERS-CoV and have been infected for at least 30 years Footnote 22. Camels are considered intermediate hosts for MERS-CoV Footnote 23. Goats have also been suggested as potential intermediate hosts given that cell lines derived from these animals can effectively replicate the virus. Goats are more likely to use DPP4 as a receptor for MERS-CoV entry compared to mice, cats, dogs, hamsters and ferrets Footnote 16. Natural susceptibility to MERS-CoV infection has also been observed in alpacas, although the animals were asymptomatic Footnote 24.
Other host(s): Mice transduced with human DPP4 Footnote 25Footnote 26, rabbits Footnote 27, rhesus macaques, African bats Footnote 16, and marmosets Footnote 28 are susceptible to MERS-CoV experimental infection Footnote 2. Intranasal inoculation of MERS-CoV in llamas and pigs resulted in mucus secretion from the nose Footnote 29.
Infectious dose: Unknown. MERS-CoV has an estimated ID50 of <1 TCID50 and a LD50 of 10 TCID50 Footnote 30.
Incubation period: The incubation period ranges from 1 to 14 days, with a median of 5 to 7 days Footnote 2Footnote 3Footnote 15. Patients with MERS-CoV pneumonia experience viral shedding for 2 to 4 weeks Footnote 31Footnote 32.
In experimentally infected dromedary camels, shedding of infectious virus from nasal swab specimens was detected through 7 days post-infection (dpi) and RNA was detected through 35 dpi, but the infectious period is believed to be short. In experimentally infected alpacas, shedding was detectable up to 10 dpi Footnote 18. Shedding is believed to occur predominantly in juvenile camels Footnote 8.
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 to no overt symptoms of infection Footnote 16. Camels in Africa and the Arabian Peninsula have displayed seropositive rates as high as 80 to 90% Footnote 2Footnote 22Footnote 33.
Zoonosis/Reverse zoonosis: Yes, from dromedary camels to humans Footnote 34. Bats are considered an unlikely source of zoonosis due to their limited exposure to humans Footnote 2.
Section IV - Stability and viability
Drug susceptibility: There are no existing drugs that specifically target MERS-CoV; however, in vitro and in vivo combination interferon-α2b and ribavirin have reduced inflammation and disease during MERS-CoV infection in rhesus macaques Footnote 35. Lopinavir/ritonavir treatment has shown anti-MERS activity and a combination of interferon-β1b and mycophenolate mofetil has demonstrated synergistic effects in vitro Footnote 36; however, these drugs have proven ineffective in randomized controlled trials Footnote 37. Resveratrol may also inhibit MERS-CoV infection in humans, but this compound has only been tested in vitro Footnote 38.
Drug resistance: Unknown.
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 31.
Given the comparable genetic characteristics 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 39, ice-cold acetone (90 seconds), ice-cold acetone/methanol mixture (40:60, 10 minutes), 70% ethanol (10 minutes), 100% ethanol (5 minutes), paraformaldehyde (2 minutes), and glutaraldehyde (2 minutes) Footnote 40. Commonly used brands of hand disinfectants also inactivate SARS-CoV (30 seconds) Footnote 40. Disinfection methodologies should be validated to ensure efficacy for MERS-CoV.
Physical inactivation: A 30 minute heat treatment at 63°C removed all infectious virus from dromedary camel milk samples containing MERS-CoV Footnote 41. 65°C for 15 minutes or 56°C for 30 minutes completely inactivates the virus Footnote 42.
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. 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 Footnote 14Footnote 31. 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 41.
Human coronavirus (HCoV) 229E, one of the 6 coronaviruses known to infect humans, has been shown to persist on high-touch environmental surfaces (polyvinylchloride, laminate, wood, stainless steel) in a university classroom despite daily cleaning with a commercial cleaning solution containing alcohol ethoxylates and sodium xylene sulfonate. Swab specimens collected from these surfaces remained infectious for at least 7 days at ambient temperature (24°C) and RH conditions (~50%) Footnote 43. Aerosolized HCoV 229E can better survive at 50% RH than at 30% RH at 20°C. In general, coronaviruses survive well in suspension. Up to 80% of HCoV 229E can survive in PBS over 3 days Footnote 44.
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. The virus can also survive as an aerosol with a reduction of 7% over 10 minutes at 40% RH Footnote 45.
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 qRT-PCR. MERS-CoV can be identified using ELISA to detect virus-specific antibodies in serum samples collected 2 to 3 weeks after disease onset. This method requires two different specific genomic segments for diagnosis. MERS-CoV can also be identified using a positive immunofluorescence and/or microneutralization test Footnote 2.
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 (CBH).
First aid/treatment: Supportive care is used for MERS-CoV patients since there are no specific therapies that currently exist Footnote 46; however, if administered early on during infection, interferon-α2b, interferon-α2 and ribivarin may reduce viral load titer in patient lungs and lessen damage Footnote 2. Passive immunotherapy with convalescent patient plasma or MERS-CoV specific antibodies has also been suggested as a possible therapeutic option based on its ability to reduce the odds of mortality by 75% when administered to patients suffering from severe acute respiratory infections Footnote 47. Certain antiviral drugs are under review for possible clinical use, including Lopinavir, chloroquine, chlorpromazine, mycophenolic acid, and nitazoxanide Footnote 2.
No treatment for infected animals has been reported.
Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which should be developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the CBH.
Immunization: There are no MERS-CoV vaccines currently approved for human use Footnote 46; however, inactivated, live attenuated virus, viral vector, protein subunit, and DNA vaccines are all in various stages of preclinical development Footnote 2Footnote 48. One DNA vaccine based on the full length viral Spike (S) protein of the virus has reached Phase I clinical trials Footnote 20.
Note: More information on the medical surveillance program can be found in the CBH, and by consulting the Canadian Immunization Guide.
Prophylaxis: The use of monoclonal antibodies (LCA60) isolated from memory B cells of patients infected with MERS-CoV may prove effective as both a pre- and post-exposure prophylaxis Footnote 49. A neutralizing human antibody (m336) may also help prevent MERS-CoV infection when given before exposure Footnote 50. These treatments are not yet approved for clinical use Footnote 46.
Note: More information on prophylaxis as part of the medical surveillance program can be found in the CBH.
Section VI - Laboratory hazards
Laboratory-acquired infections: There are no known cases of MERS-CoV laboratory-acquired infections Footnote 51.
Please consult the Canadian Biosafety Standard (CBS) and Handbook (CBH) for additional details on requirements and guidelines for reporting exposure incidents.
Sources/specimens: MERS-CoV RNA has been detected in the human respiratory tract (tracheal aspirates and sputum), nasal discharge, serum, blood, urine, vomit, saliva, feces, and urine Footnote 5Footnote 52.
In infected animals, the virus has been recovered from nasal swabs, oropharyngeal swabs, blood samples, raw camel milk and bronchoalveolar lavage Footnote 2Footnote 9Footnote 53.
Primary hazards: The primary route of exposure to MERS-CoV is not well-defined but inhalation of airborne or aerosolized infectious material, either from infected humans or animals, is believed to be the main source of infection Footnote 16. Exposure to infectious material on fomites has also been considered likely Footnote 13Footnote 45.
Camels can become naturally infected through direct contact with large droplets or fomite transmission Footnote 8. Camels are believed to have originally become infected by bats, and have had the virus circulating between them for over 20 years Footnote 54.
Special hazards: None.
Section VII - Exposure controls/personal protection
Risk group classification: MERS-CoV is considered to be a Risk Group 3 Human Pathogen and Risk Group 3 Animal Pathogen.
MERS-CoV is also classified as an Emerging Animal Disease (EAD), requiring CFIA oversight.
Containment requirements: The applicable CL3 or CL3-Ag requirements outlined in the CBS and in the MERS-CoV Biosafety Advisory for all in vitro propagative and in vivo activities. Non-propagative diagnostic or clinical activities can be conducted at CL2 with additional biosafety requirements, as specified in the MERS-CoV Biosafety Advisory.
Protective clothing: The applicable CL3 requirements for personal protective equipment and clothing outlined in the CBS and MERS-CoV Biosafety Advisory should be followed.
Based on a local risk assessment, appropriate hand, foot, head, body, eye/face, and respiratory protection should be identified, and the PPE requirements for the containment zone should be documented in Standard Operating Procedures.
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.
Section VIII - Handling and storage
Spills: Allow aerosols to settle. Wearing protective clothing, 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 before clean up Footnote 55.
Disposal: All materials/substances that have come in contact with the infectious agent should be completely decontaminated before they are removed from the containment zone. This can be achieved by using a decontamination method that has been demonstrated to be effective against the infectious material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination Footnote 55.
Storage: The applicable CL3 or CL3-Ag requirements for storage outlined in the CBSshould be followed. Containers of infectious material or toxins stored outside the containment zone should be labelled, leakproof, impact resistant, and kept in locked storage equipment and within an area with limited access Footnote 56.
Section IX - Regulatory and other information
Regulatory information: The import, transport, and use of pathogens in Canada is regulated under many regulatory bodies, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment Canada, and Transport Canada. Users are responsible for ensuring they are compliant with all relevant acts, regulations, guidelines, and standards.
Work with MERS-CoV requires a Human Pathogens and Toxins Licence, issued by the Public Health Agency of Canada. Import of MERS-CoV requires a Health of Animals Act import permit, issued by the Canadian Food Inspection Agency.
Prepared by: Centre for Biosecurity, Public Health Agency of Canada.
Although the information, opinions, and recommendations contained in this Pathogen Safety Data Sheet are compiled from sources believed to be reliable, we accept no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information. Newly discovered hazards are frequent and this information may not be completely up to date.
Public Health Agency of Canada, 2019
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- Footnote 29
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- Footnote 30
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