Middle East respiratory syndrome coronavirus infection

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Epidemiology and Demographics

• The Middle East respiratory syndrome coronavirus (MERS-CoV) was first reported to cause human infection in September 2012. In July 2013, the World Health Organization (WHO) International Health Regulations Emergency Committee determined that MERS-CoV did not meet criteria for a "public health emergency of international concern," but was nevertheless of "serious and great concern".

• As of September 20, 2013, a total of 130 cases from eight countries have been reported to WHO; 58 (45%) of these cases have been fatal. All cases have been directly or indirectly linked through travel to or residence in four countries: Saudi Arabia, Qatar, Jordan, and the United Arab Emirates (UAE).

• The median age of persons with confirmed MERS-CoV infection is 50 years (range: 2–94 years).

• The male-to-female ratio is 1.6 to 1.0.

• Twenty-three (18%) of the cases occurred in persons who were identified as health-care workers.

• Although most reported cases involved severe respiratory illness requiring hospitalization, at least 27 (21%) involved mild or no symptoms.

• Despite evidence of person-to-person transmission, the number of contacts infected by persons with confirmed infections appears to be limited. No cases have been reported in the United States, although 82 persons from 29 states have been tested for MERS-CoV infection.

Pathophysiology

Potential animal reservoirs and mechanism(s) of transmission of MERS-CoV to humans remain unclear. A zoonotic origin for MERS-CoV was initially suggested by high genetic similarity to bat coronaviruses , and some recent reports have described serologic data from camels and the identification of related viruses in bats. However, more epidemiologic data linking cases to infected animals are needed to determine if a particular species is a host, a source of human infection, or both.

History and Symptoms

History

Suspect MERS-CoV infection in case of:

• Fever (≥38°C, 100.4°F) and pneumonia or acute respiratory distress syndrome (based on clinical or radiological evidence);
  

AND EITHER

• History of travel from countries in or near the Arabian Peninsula1 within 14 days before symptom onset;
  

OR

• Close contact2 with a symptomatic traveler who developed fever and acute respiratory illness (not necessarily pneumonia) within 14 days after traveling from countries in or near the Arabian Peninsula;
  

OR

• Is a member of a cluster of patients with severe acute respiratory illness (e.g. fever and pneumonia requiring hospitalization) of unknown etiology in which MERS-CoV is being evaluated, in consultation with state and local health departments.

Symptoms

• Fever (98%)
• Cough (83%)
• Shortness of breath (72%)
• Gastrointestinal symptoms
  • Diarrhea (26%)
  • Vomiting (21%)

All but two patients (96%) had one or more chronic medical conditions, including diabetes (68%), hypertension (34%), heart disease (28%), and kidney disease (49%). Thirty-four (72%) had more than one chronic condition.

Diagnosis

CDC has changed its guidance to indicate that testing for MERS-CoV and other respiratory pathogens can be conducted simultaneously and that positive results for another respiratory pathogen should not necessarily preclude testing for MERS-CoV. Health-care providers in the United States should continue to evaluate patients for MERS-CoV infection if they develop fever and pneumonia or acute respiratory distress syndrome (ARDS) within 14 days after traveling from countries in or near the Arabian Peninsula. Providers also should evaluate patients for MERS-CoV infection if they have ARDS or fever and pneumonia, and have had close contact§ with a recent traveler from this area who has fever and acute respiratory illness.

CDC continues to recommend that clusters¶ of patients with severe acute respiratory illness (e.g., fever and pneumonia requiring hospitalization) be evaluated for common respiratory pathogens and reported to local and state public health departments. If the illnesses remain unexplained, particularly if the cluster includes health-care providers, testing for MERS-CoV should be considered, in consultation with state and local health departments. In this situation, testing should be considered even for patients without travel-related exposure.

Confirmed Case

A confirmed case is a person with laboratory confirmation of MERS-CoV infection.

Probable Case

A probable case is a PUI with absent or inconclusive laboratory results for MERS-CoV infection who is a close contact of a laboratory-confirmed MERS-CoV case.

Laboratory Tests

Confirmatory laboratory testing now requires a positive polymerase chain reaction of at least two, instead of one, specific genomic targets or a single positive target with sequencing of a second.

Collecting, Handling, and Testing Clinical Specimens

Respiratory Specimens

Lower respiratory tract Broncheoalveolar lavage, tracheal aspirate, pleural fluid

Collect 2-3 mL into a sterile, leak-proof, screw-cap sputum collection cup or sterile dry container. Refrigerate specimen at 2-8°C up to 72 hours; if exceeding 72 hours, freeze at -70°C and ship on dry ice.

Sputum

Have the patient rinse the mouth with water and then expectorate deep cough sputum directly into a sterile, leak-proof, screw-cap sputum collection cup or sterile dry container. Refrigerate specimen at 2-8°C up to 72 hours; if exceeding 72 hours, freeze at -70°C and ship on dry ice.

Upper respiratory tract

Nasopharyngeal AND oropharyngeal swabs (NP/OP swabs)

Use only synthetic fiber swabs with plastic shafts. Do not use calcium alginate swabs or swabs with wooden shafts, as they may contain substances that inactivate some viruses and inhibit PCR testing. Place swabs immediately into sterile tubes containing 2-3 ml of viral transport media. NP/OP specimens can be combined, placing both swabs in the same vial. Refrigerate specimen at 2-8°C up to 72 hours; if exceeding 72 hours, freeze at -70°C and ship on dry ice.

Nasopharyngeal swabs

Insert a swab into the nostril parallel to the palate. Leave the swab in place for a few seconds to absorb secretions. Swab both nasopharyngeal areas.

Oropharyngeal swabs

Swab the posterior pharynx, avoiding the tongue.

Nasopharyngeal wash/aspirate or nasal aspirates

Collect 2-3 mL into a sterile, leak-proof, screw-cap sputum collection cup or sterile dry container. Refrigerate specimen at 2-8°C up to 72 hours; if exceeding 72 hours, freeze at -70°C and ship on dry ice.

Blood Components

Serum (for serologic testing)

For serum antibody testing: Serum specimens should be collected during the acute stage of the disease, preferably during the first week after onset of illness, and again during convalescence, ≥ 3 weeks after the acute sample was collected. However, since we do not want to delay detection at this time, a single serum sample collected 14 or more days after symptom onset may be beneficial. Serologic testing is currently available at CDC upon request and approval. Please be aware that the MERS-CoV serologic test is for research/surveillance purposes and not for diagnostic purposes - it is a tool developed in response to the MERS-CoV outbreak. Contact CDC’s Emergency Operations Center (EOC) (770-488-7100) for consultation and approval if serologic testing is being considered.

Serum (for rRT-PCR testing)

• For rRT-PCR testing (i.e., detection of the virus and not antibodies), a single serum specimen collected optimally during the first week after symptom onset, preferably within 3-4 days, after symptom onset, may be also be beneficial.

• Children and adults: Collect 1 tube (5-10 mL) of whole blood in a serum separator tube. Allow the blood to clot, centrifuge briefly, and separate sera into sterile tube container. The minimum amount of serum required for testing is 200 µL. Refrigerate the specimen at 2-8°C and ship on ice- pack; freezing and shipment on dry ice is permissible.

• Infants: A minimum of 1 mL of whole blood is needed for testing of pediatric patients. If possible, collect 1 mL in an EDTA tube and in a serum separator tube. If only 1 mL can be obtained, use a serum separator tube.

EDTA blood (plasma)

Collect 1 tube (10 mL) of heparinized (green-top) or EDTA (purple-top) blood. Refrigerate specimen at 2-8°C and ship on ice-pack; do not freeze.

Standard, Contact, and Airborne Precautions

Standard, contact, and airborne precautions are recommended for management of hospitalized patients with known or suspected MERS-CoV infection

Patient Placement in Airborne Infection Isolation Room (AIIR)

• If an AIIR is not available, the patient should be transferred as soon as is feasible to a facility where an AIIR is available. Pending transfer, place a facemask on the patient and isolate him/her in a single-patient room with the door closed. The patient should not be placed in any room where room exhaust is recirculated without high-efficiency particulate air (HEPA) filtration.
• Once in an AIIR, the patient’s facemask may be removed; the facemask should remain on if the patient is not in an AIIR.
• When outside of the AIIR, patients should wear a facemask to contain secretions
• Limit transport and movement of the patient outside of the AIIR to medically-essential purposes.
• Implement staffing policies to minimize the number of personnel that must enter the room.

Personal Protective Equipment (PPE) for Healthcare Personnel (HCP)

• PPE include:
  • Gloves
  • Gowns
  • Eye protection (goggles or face shield)
  • Respiratory protection that is at least as protective as a fit-tested NIOSH-certified disposable N95 filtering facepiece respirator.
    • If a respirator is unavailable, a facemask should be worn. In this situation respirators should be made available as quickly as possible.
• Recommended PPE should be worn by HCP upon entry into patient rooms or care areas.
• Upon exit from the patient room or care area, PPE should be removed and either
  • Discarded, or
  • For re-useable PPE, cleaned and disinfected according to the manufacturer’s reprocessing instructions

Environmental Infection Control

Follow standard procedures, per hospital policy and manufacturers’ instructions, for cleaning and/or disinfection of:

• Environmental surfaces and equipment
• Textiles and laundry
• Food utensils and dishware

Interim Home Care and Isolation Guidance for MERS-CoV

This guidance is for local and state health departments, infection prevention and control professionals, healthcare providers, and healthcare workers who are coordinating the home care and isolation of ill people who are being evaluated for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. The guidance is based on what is currently known about viral respiratory diseases and MERS-CoV. CDC will update this guidance as needed.

Ill people who are being evaluated for MERS-CoV infection and do not require hospitalization for medical reasons may be cared for and isolated in their home. Isolation is defined as the separation or restriction of activities of an ill person with a contagious disease from those who are well.

Before the ill person is isolated at home, the healthcare professional should:

• Assess whether the home is suitable and appropriate for isolating the ill person. You can conduct this assessment by phone or direct observation.
  • The home should have a functioning bathroom that only the ill person and household members use. If there are multiple bathrooms, one should be designated solely for the ill person.
  • The ill person should have his or her own bed and preferably a private room for sleeping.
  • Basic amenities, such as heat, electricity, potable and hot water, sewer, and telephone access, should be available.
  • If the home is in a multiple-family dwelling, such as an apartment building, the area in which the ill person will stay should use a separate air-ventilation system, if one is present.
  • There should be a primary caregiver who can follow the healthcare provider’s instructions for medications and care. The caregiver should help the ill person with basic needs in the home and help with obtaining groceries, prescriptions, and other personal needs.

• Contact your local or state health department if you have not already done so.

Prevention

• Enhancing infection prevention and control awareness and measures is critical to prevent the possible spread of MERS‐CoV in health care facilities. Health‐care facilities that provide care for patients suspected or confirmed to be infected with MERS‐CoV infection should take appropriate measures to decrease the risk of transmission of the virus from an infected patient to other patients, health‐care workers and visitors. It is not always possible to identify patients with MERS‐CoV early because some have mild or unusual symptoms. For this reason, it is important that health‐care workers apply standard precautions consistently with all patients – regardless of their diagnosis – in all work practices all the time.
• Urgent investigations are required to better understand the transmission pattern of this virus. The most urgent include detailed outbreak investigations, case‐control studies to understand risk factors for infection, enhancing community studies and surveillance of community‐acquired pneumonia to assess whether significant numbers of mild cases resulting from human to human transmission are being missed, and identifying risk factors for infection in the hospital setting. Detailed information on the surveillance strategy and contact tracing would help understand limitations of current data.
• Although the immediate focus should be on clarifying the magnitude of the human‐to‐human transmission, no control will be possible until the transmission from the animal/environment source to humans is understood and interrupted. Based on current information, it is prudent for people at high risk of severe disease due to MERS‐CoV, including those with diabetes, chronic lung disease, pre‐existing renal failure, or those who are immunocompromised, to take appropriate precautions when visiting farms, barn areas or market environments where camels are present. These measures might include avoiding contact with camels, good hand hygiene, and avoiding drinking raw milk or eating food that may be contaminated with animal secretions or products unless they are properly washed, peeled, or cooked. For the general public, when visiting a farm or a barn, general hygiene measures, such as regular hand washing before and after touching animals, avoiding contact with sick animals, and following food hygiene practices, should be adhered to.
• WHO recommends increasing efforts to raise awareness of MERS among travelers going to and traveling from MERS‐affected countries but otherwise does not advise special screening at points of entry with regard to this event nor does WHO currently recommend the application of any travel or trade restrictions.

Travel Guidance

The peak travel season to Saudi Arabia is July through November, coinciding with the religious pilgrimages of Hajj and Umrah. CDC encourages pilgrims to consider recommendations from the Saudi Arabia Ministry of Health regarding persons who should postpone their pilgrimages this year, including persons aged ≥65 years, children, pregnant women, and persons with chronic diseases, weakened immune systems, or cancer. WHO advises that persons with preexisting medical conditions consult a health-care provider before deciding whether to make a pilgrimage.

CDC continues to recommend that U.S. travelers to countries in or near the Arabian Peninsula protect themselves from respiratory diseases, including MERS-CoV, by washing their hands often and avoiding contact with persons who are ill. If travelers to the region have onset of fever with cough or shortness of breath during their trip or within 14 days of returning to the United States, they should seek medical care. They should tell their health-care provider about their recent travel.

Infection Control

With multiple health-care–associated clusters identified (8,10), infection control remains a primary means of preventing and controlling MERS-CoV transmission. CDC has recently made checklists available that highlight key actions that health-care providers and facilities can take to prepare for MERS-CoV patients. CDC's infection control guidance has not changed. Standard, contact, and airborne precautions are recommended for management of hospitalized patients with known or suspected MERS-CoV infection.