Middle East Respiratory Syndrome (MERS)

Characteristics
Morphology	Coronaviruses cause infections in a wide variety of animals, resulting in respiratory, enteric, hepatic, and neurological diseases of various levels of severity. Middle East respiratory syndrome-related coronavirus (MERS-CoV) is the sixth coronavirus identified with the ability to infect humans. It was identified in 2012 in a lung sample of a 60-year-old patient who had died of respiratory failure in Jeddah, Saudi Arabia. MERS-CoV is an enveloped, positive-sense, single-stranded RNA virus that encodes 5 unique accessory proteins, two of which give it the ability to modulate interferon production. While Severe Acute Respiratory Syndrome-related coronavirus (SARS-CoV) uses angiotensin-converting enzyme 2 (ACE2) as its receptor, MERS-CoV mediates cell entry using the host receptor dipeptidyl peptidase-4 (DPP4).
Growth Conditions	Cultured in Vero, Huh7, and LLC-MK2 cells

Characteristics

Morphology

Coronaviruses cause infections in a wide variety of animals, resulting in respiratory, enteric, hepatic, and neurological diseases of various levels of severity. Middle East respiratory syndrome-related coronavirus (MERS-CoV) is the sixth coronavirus identified with the ability to infect humans. It was identified in 2012 in a lung sample of a 60-year-old patient who had died of respiratory failure in Jeddah, Saudi Arabia. MERS-CoV is an enveloped, positive-sense, single-stranded RNA virus that encodes 5 unique accessory proteins, two of which give it the ability to modulate interferon production. While Severe Acute Respiratory Syndrome-related coronavirus (SARS-CoV) uses angiotensin-converting enzyme 2 (ACE2) as its receptor, MERS-CoV mediates cell entry using the host receptor dipeptidyl peptidase-4 (DPP4).

Growth
Conditions

Cultured in Vero, Huh7, and LLC-MK2 cells

Health Hazards
Host Range	Animals such as dromedary camels and goats are intermediate hosts in nature, although it has thought to have originated in African bats. Humans have become natural hosts for MERS-CoV and can transmit between individuals. NHPs and some rodents can be susceptible in laboratory environments
Modes of Transmission	The virus can spread through respiratory secretions, such as saliva or mucous, of infected animals or people. Contact with infected camels can lead to transmission to humans. People infected through contact with camels can then spread the virus to other people. Large outbreaks from person-to-person spread have occurred in healthcare facilities treating patients with MERS.
Signs and Symptoms	Illnesses have ranged from asymptomatic to severe. Symptoms can include: Fever, Cough, and Shortness of Breath. Some people may also have diarrhea, nausea, or vomiting. In a majority of cases, patients develop pneumonia. Additional complications such as kidney failure have also occurred. About 35% of patients reported with a MERS-CoV infection have died. People with diabetes, renal failure, or chronic lung diseases are at high risk of severe disease.
Infectious Dose	Unknown, but it is thought to be highly infectious with 10 TCID50 being an LD50 dose
Incubation Period	Median range of 5-7 days for symptoms to arise (1-14 day range), shedding of virus occurs for 2-4 weeks in patients who experience MERS-CoV pneumonia

Medical Precautions/Treatment
Prophylaxis	No commonly used prophylaxis exists. Avoid contact with infected animals and self-isolate during outbreaks. 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
Vaccines	None publically available
Treatment	Most MERS-CoV infections require only care to help relieve symptoms. Infected individuals should isolate to prevent transmission to others.
Surveillance	Monitor for symptoms. Confirmation is via detection of MERS-CoV viral RNA in respiratory tract specimens during the acute phase of illness using qRT-PCR or through detection of antibodies through ELISA. MERS-CoV may be detected in blood, urine, or stool specimens.
GWU Requirements	Report all incidents to the Office of Risk Management as well as the Office of Research Safety (ORS) IMMEDIATELY FOLLOWING THE OCCURRENCE.

Containment
BSL-3	Risk Group 3 classification is applied to MERS-CoV. Containment Level 3 facilities, equipment, and operational practices for work involving infectious or potentially infectious material. All activities with infectious material should be conducted in a HEPA-filtered biological safety cabinet (BSC) or other appropriate primary containment device in combination with personal protective equipment. Centrifugation of infected materials must be carried out in closed containers placed in sealed safety cups, or in rotors that are unloaded in a biological safety cabinet. Open wounds, cuts, scratches, and grazes should be covered with waterproof dressings.
ABSL-3	All work involving infectious or potentially infectious material should follow the same guidelines as stated above. Additional precautions should be considered with work involving animals.

Containment

BSL-3

Risk Group 3 classification is applied to MERS-CoV. Containment Level 3 facilities, equipment, and operational practices for work involving infectious or potentially infectious material. All activities with infectious material should be conducted in a HEPA-filtered biological safety cabinet (BSC) or other appropriate primary containment device in combination with personal protective equipment. Centrifugation of infected materials must be carried out in closed containers placed in sealed safety cups, or in rotors that are unloaded in a biological safety cabinet. Open wounds, cuts, scratches, and grazes should be covered with waterproof dressings.

ABSL-3

All work involving infectious or potentially infectious material should follow the same guidelines as stated above. Additional precautions should be considered with work involving animals.

Spill Procedures
Small Spills (<1 liter)	If the spill occurred inside a biological safety cabinet, close the sash and allow the cabinet to operate for 15 minutes before continuing with the spill cleanup. MERS-CoV is primarily transmitted via aerosols, so spills present an increased risk of exposure. Leave the room immediately and allow the aerosols to dissipate for 15 minutes. Notify others working in the lab. Don appropriate PPE. Cover area of the spill with paper towels or any absorbent material and apply an EPA registered disinfectant effective against enveloped viruses (ethanol, bleach, povidone‐iodine, and chlorhexidine), working from the perimeter towards the center. Allow 30 minutes of contact time before disposal and cleanup of spill materials.
Large Spills	Alert lab personnel in the laboratory to the spill and keep people out of the area to prevent spread of the contamination. Check if you have been contaminated or if any of your PPE has been breached. If so follow exposure procedures. Remove any contaminated clothing and place it the biohazard waste. Wash your hands and post a sign on the door. Notify your supervisor of the incident and call ORS (4-8258) for assistance. If the situation involves an imminently life-threatening injury or has catastrophic potential, call 911.

Spill Procedures

Small Spills (<1 liter)

If the spill occurred inside a biological safety cabinet, close the sash and allow the cabinet to operate for 15 minutes before continuing with the spill cleanup.

MERS-CoV is primarily transmitted via aerosols, so spills present an increased risk of exposure. Leave the room immediately and allow the aerosols to dissipate for 15 minutes. Notify others working in the lab. Don appropriate PPE. Cover area of the spill with paper towels or any absorbent material and apply an EPA registered disinfectant effective against enveloped viruses (ethanol, bleach, povidone‐iodine, and chlorhexidine), working from the perimeter towards the center. Allow 30 minutes of contact time before disposal and cleanup of spill materials.

Large Spills

Alert lab personnel in the laboratory to the spill and keep people out of the area to prevent spread of the contamination. Check if you have been contaminated or if any of your PPE has been breached. If so follow exposure procedures. Remove any contaminated clothing and place it the biohazard waste. Wash your hands and post a sign on the door. Notify your supervisor of the incident and call ORS (4-8258) for assistance. If the situation involves an imminently life-threatening injury or has catastrophic potential, call 911.

Exposure Procedures
Mucus Membrane	Flush eyes, mouth or nose for 15 minutes at eyewash station.
Other Exposure	Wash area with soap and water for 15 minutes.
Reporting	Report ALL injuries to the PI immediately and reported to the Office of Risk Management at [email protected] IMMEDIATELY FOLLOWING THE OCCURRENCE. Exposures that involve a bloodborne-pathogen or recombinant DNA also need to be reported to the Office of Research Safety at [email protected]. If the injury requires immediate medical attention, call GWPD at 202-994-6111 or call 911.
Medical Monitoring	Seek immediate medical evaluation, treatment, and post exposure follow-up at the Employee Health Office at GWU Hospital (900 23rd St., NW, Suite G-1090, Phone: 202-715-4275). Students should go to the Students Health Office at Marvin Center. After hours treatment can be received at the GWU hospital emergency room.

Stability
Disinfection	Susceptible to 10% bleach and moderately susceptible to 70% ethanol. In addition 7.5% povidone‐iodine, 0.05% chloroxylenol, 0.05% chlorhexidine, and 0.1% benzalkonium chloride are thought to also be effective since SARS-CoV-2 is also susceptible
Inactivation	Inactivation of virus can occur using temperatures above 56°C for 30 minutes
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%. The virus is stable in camel breast milk for up to 72 hours at 4°C

Personal Protective Equipment (PPE)
Minimum PPE Requirements	At minimum, personnel are required to don gloves, closed toed shoes, lab coat, and appropriate face and eye protection prior to working with MERS-CoV. Additional PPE may be required depending on lab specific SOPs and biosafety level
Additional Precautions	Additional protection may be worn over laboratory clothing when infectious materials are directly handled, such as solid-front gowns with tight fitting wrists, gloves, and respiratory protection.

References
CDC (https://www.cdc.gov/mers/about/index.html) Genomic Characterization of a Newly Discovered Coronavirus Associated with Acute Respiratory Distress Syndrome in Humans (https://pmc.ncbi.nlm.nih.gov/articles/PMC3509437/) The Middle East Respiratory Syndrome (MERS) (https://pmc.ncbi.nlm.nih.gov/articles/PMC7127753/) Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS-coronavirus infection in a mouse model (https://www.sciencedirect.com/science/article/pii/S0168170216305524) WHO (https://www.who.int/health-topics/middle-east-respiratory-syndrome-coro…) Canadian PHAC (https://www.canada.ca/en/public-health/services/laboratory-biosafety-bi…)

References