Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

Paul G. Auwaerter, M.D., Jaffar A. Al-Tawfiq, M.D.

PATHOGENS

  • MERS-CoV is a coronavirus, that was described initially and isolated in 2012.
    • β-coronavirus: not the same virus as SARS, but related.
    • Similar to other coronavirus described in bats.
    • MERS-CoV: dromedary camels clearly established as a host; positive specimens are known dating at least to the early 1990s.
      • Also seen in bats.
  • Believed to be mostly a respiratory pathogen in humans, as a group, coronaviruses cause disease ranging from the common cold to rarely severe pulmonary illness.

CLINICAL

  • All cases (WHO reported cases = 2,468, as of Dec 2019) traced to regions in or near Arabian Peninsula.
    • Countries in Arabian Peninsula with confirmed cases: Saudi Arabia, United Arab Emirates (UAE), Qatar, Oman, Jordan, Kuwait, Iran, Egypt, Yemen, Lebanon.
      • Countries with travel-related cases (imported): U.S. (2 cases), UK, France, Tunisia, Italy, Malaysia, S. Korea (also indigenous transmission), Germany, Netherlands, Greece, Turkey, Austria, China, Philippines, Thailand, Algeria.
      • Human-human spread, likely requiring close contact; nosocomially acquired cases reflect inadequate infection control practices, overcrowding and failure to recognize.
      • Asymptomatic infections are increasingly recognized and those patients have fewer comorbidities and may contribute to transmission.
  • Symptoms: nonspecific: fever, cough and dyspnea.
    • The clinical picture is variable.
      • Most fatalities have been described in hospitalized patients with comorbidities.
      • Spectrum of illness: ranges from asymptomatic or mildly symptomatic to severe cases requiring hospitalization and those may develop multiorgan failure.
    • Gastrointestinal symptoms: diarrhea, vomiting and abdominal pain (up to 30%).
    • Case fatality rate: 34% in cases reported to WHO.
  • Consider to place patient(s) under investigation: guidance from the CDC[18].
    • An acute respiratory infection, which may include fever (≥ 38°C, 100.4°F) and cough; AND
    • Suspicion of pulmonary parenchymal disease (e.g., pneumonia or acute respiratory distress syndrome based on clinical or radiological evidence of consolidation) AND
      • History of travel from the Arabian Peninsula (or neighbors, plus Korea) within 14d AND
      • No explanation by another infection or etiology, including all clinically indicated tests for community-acquired pneumonia
    • Also, the following people may be considered for evaluation:
      • People who develop severe acute lower respiratory illness of known etiology within 14 days after travel from the Arabian Peninsula or neighboring countries but do not respond to appropriate therapy; OR
      • People who develop severe acute lower respiratory illness who are close contacts of a symptomatic traveler who developed fever and acute respiratory illness within 14 days after travel from the Arabian Peninsula or neighboring countries.
    • U.S. reporting short form (link): http://www.cdc.gov/coronavirus/mers/interim-guidance.html

DIAGNOSIS

  • Laboratory: molecular diagnostics are the method of choice for MERS-CoV.
    • Real-time reverse transcription–PCR assay:
      • May test respiratory, blood and stool specimens. Lower respiratory samples yield better results than upper respiratory samples.
      • 2 to 3 nasopharyngeal samples produce the highest yield of positive results.
      • Available through U.S. state health departments.
    • Serology: developed, but not yet widely used for clinical care or diagnosis.
    • Viral culture: should only be performed in specialized laboratories.
  • Additional details regarding updated information and evaluation from the CDC.

TREATMENT

General

  • Potential cases should be reported immediately to the local and/or state health department.
  • Antiviral therapy: none known to be effective.
    • Convalescent serum with high neutralizing antibody titer against MERS-CoV may be of use as well as any specific monoclonal antibodies (not available).
    • There is no consensus on the optimal therapy for MERS-CoV.
    • One randomized clinical trial is being conducted.
  • Supportive care advised, including mechanical ventilation.
  • The use of antivirals is non-conclusive.

Special Considerations

  • All contacts of potential or confirmed MERS-CoV infected patients should be monitored for the development of respiratory symptoms.
    • There is no consensus on the frequency and number of samples for testing contacts.
  • Infection control:

Prevention

  • Given the lack of therapeutics or vaccines so far, prevention is critical since MERS-CoV appears endemic with ongoing cases.
  • No specific travel recommendations currently (as of Dec 2019): http://www.cdc.gov/coronavirus/mers/travel.html
  • Respiratory prevention (general)
    • Hand washing: soap and water for 20 seconds. If soap/water unavailable, use alcohol-based sanitizers.
    • Avoid touching face with unwashed hands.
    • Avoid close contact such as kissing, sharing cups, or sharing eating utensils with sick people.
    • Clean and disinfect frequently touched surfaces, such as toys and doorknobs.
    • Practice cough etiquette.
  • See the infection control section above.

FOLLOW UP

  • Mortality 34% in cases reported to WHO.
    • High rates seen especially in older patients and those with comorbidities.
      • Death usually due to multiorgan failure.
      • Higher mortality in those requiring ICU admission.

OTHER INFORMATION

Basis for recommendation

  1. Bialek SR, Allen D, Alvarado-Ramy F, et al. First Confirmed Cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection in the United States, Updated Information on the Epidemiology of MERS-CoV Infection, and Guidance for the Public, Clinicians, and Public Health Authorities - May 2014. MMWR Morb Mortal Wkly Rep. 2014;63(19):431-6.  [PMID:24827411]

    Comment: Report of first two cases of imported MERS-CoV into US. Report also summarizes current recommendations regarding case description/patient evaluation, specimen procurement and testing.

  2. Centers for Disease Control and Prevention; Coronavirus--Middle East Respiratory Syndrome (MERS); http://www.cdc.gov/coronavirus/mers/ (Dec 2019)

    Comment: Guidance from the CDC Visit URL link for most up to date information.

  3. World Health Organization. Coronavirus infections; Global Alert and Response.http://www.who.int/csr/disease/coronavirus_infections/en/index.html (accessed 12/29/2019)

    Comment: Coordinating site including MERS-CoV, SARS and other coronaviruses with public health implications. Includes link to interim case definition for MERS-CoV infection.

References

  1. Al-Tawfiq JA, Auwaerter PG. Healthcare-associated infections: the hallmark of Middle East respiratory syndrome coronavirus with review of the literature. J Hosp Infect. 2019;101(1):20-29.  [PMID:29864486]

    Comment: A review compiling outbreaks and likely reasons why they occurred. Most would be likely prevented with simple isolation and infection control measures.

  2. Alfaraj SH, Al-Tawfiq JA, Memish ZA. Middle East respiratory syndrome coronavirus intermittent positive cases: Implications for infection control. Am J Infect Control. 2019;47(3):290-293.  [PMID:30352694]

    Comment: Based on data from outbreaks, 2 to 3 nasopharyngeal samples are needed to produce the highest yield of positive results for MERS-CoV. In addition, 2 negative results 48 hours apart with clinical improvement or stabilization are needed to clear patients from MERS-CoV.

  3. Alfaraj SH, Al-Tawfiq JA, Altuwaijri TA, et al. Middle East respiratory syndrome coronavirus transmission among health care workers: Implication for infection control. Am J Infect Control. 2018;46(2):165-168.  [PMID:28958446]

    Comment: As isolation and infection control is the best way to prevent spread, simple procedures and protocols are important to limit spread in healthcare facilities.

  4. Corman VM, Albarrak AM, Omrani AS, et al. Viral Shedding and Antibody Response in 37 Patients With Middle East Respiratory Syndrome Coronavirus Infection. Clin Infect Dis. 2016;62(4):477-483.  [PMID:26565003]

    Comment: First report of a large patient population summarizing MERS-CoV kinetics and antibody response. The study shows the kinetics of the virus in the upper and lower respiratory tract, stool, urine and blood samples.

  5. Zumla A, Hui DS, Perlman S. Middle East respiratory syndrome. Lancet. 2015;386(9997):995-1007.  [PMID:26049252]

    Comment: Mortality among cases reported so far = ~ 40% including both community- and hospital-acquired cases. More severe cases seen especially in patients with co-morbidities. Now into the third year, it appears to be endemic and therefore a low-level but persistent public health threat.

  6. Oboho IK, Tomczyk SM, Al-Asmari AM, et al. 2014 MERS-CoV outbreak in Jeddah--a link to health care facilities. N Engl J Med. 2015;372(9):846-54.  [PMID:25714162]

    Comment: Of 2014 cases in KSA, most had links to hospital care implicating transmission in an arena where opportunities for prevention exist.

  7. Drosten C, Muth D, Corman VM, et al. An observational, laboratory-based study of outbreaks of middle East respiratory syndrome coronavirus in Jeddah and Riyadh, kingdom of Saudi Arabia, 2014. Clin Infect Dis. 2015;60(3):369-77.  [PMID:25323704]

    Comment: Report from the Kingdom of Saudi Arabia with the most cases, and an uptick in Spring 2014 (and again ongoing 2015). Viral studies don’t suggest the virus is mutating and appear consistent in outbreaks and nosocomial transmission.

  8. Al-Tawfiq JA, Memish ZA. Infection control measures for the Prevention of MERS Coronavirus Transmission in Healthcare settings. Expert Rev Anti Infect Ther. 2015.  [PMID:26687211]

    Comment: This is a summary of infection control and prevention of MERS transmission in healthcare settings.

  9. Al-Tawfiq JA, Memish ZA. Managing MERS-CoV in the healthcare setting. Hosp Pract (1995). 2015;43(3):158-63.  [PMID:26224424]

    Comment: This is a concise review summarizing different aspects of MERS in a healthcare setting including clinical presentation and management.

  10. Al-Tawfiq JA, Memish ZA. Middle East respiratory syndrome coronavirus: transmission and phylogenetic evolution. Trends Microbiol. 2014;22(10):573-9.  [PMID:25178651]

    Comment: This review shed lights on the different aspects of the transmission and phylogenetic evolution of MERS-CoV.

  11. Al-Tawfiq JA, Hinedi K, Ghandour J, et al. Middle East Respiratory Syndrome-Coronavirus (MERS-CoV): a case-controlstudy of hospitalized patients. Clin Infect Dis. 2014.  [PMID:24723278]

    Comment: Report from the Kingdom of Saudi Arabia examines 17 cases and 82 controls. Cases were more likely to have high BMI, normal WBC count on admission and interstitial infiltrates along with high moratligy rate (76% v. 15%, p < 0.001).

  12. Briese T, Mishra N, Jain K, et al. Middle East Respiratory Syndrome Coronavirus Quasispecies That Include Homologues of Human Isolates Revealed through Whole-Genome Analysis and Virus Cultured from Dromedary Camels in Saudi Arabia. MBio. 2014;5(3).  [PMID:24781747]

    Comment: Sequence data from human cases and samples from dromedary camels are identical (in Saudi Arabia), suggesting that camels are indeed a reservoir (known from other studies) and source of some spread to humans.

  13. Al-Tawfiq JA, Memish ZA. Middle East respiratory syndrome coronavirus: epidemiology and disease control measures. Infect Drug Resist. 2014;7:281-7.  [PMID:25395865]

    Comment: This review summarizes the epidemiology and different strategies for the control of the virus.

  14. Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, et al. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. Lancet Infect Dis. 2013.  [PMID:23891402]

    Comment: Most patients diagnosed to date have had healthcare involvement and hence co-morbidities. Patients were mostly adults in the 47 described (46 adults, one child) with laboratory-confirmed MERS-CoV disease were identified; 36 (77%) were male (male:female ratio 3·3:1). 28 patients died, a 60% case-fatality rate. The case-fatality rate rose with increasing age. Only two of the 47 cases were previously healthy; most patients (45 [96%]) had underlying co-morbid medical disorders, including diabetes (32 [68%]), hypertension (16 [34%]), chronic cardiac disease (13 [28%]), and chronic renal disease (23 [49%]).
    Gastrointestinal symptoms were noted in a significant minority including diarrhea, vomiting and abdominal pain.

  15. Centers for Disease Control and Prevention (CDC). Update: Recommendations for Middle East respiratory syndrome coronavirus (MERS-CoV). MMWR Morb Mortal Wkly Rep. 2013;62(27):557.  [PMID:23842446]

    Comment: Initial recommendations for investigating potential cases.
    Rating: Important

  16. Assiri A, McGeer A, Perl TM, et al. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med. 2013;369(5):407-16.  [PMID:23782161]

    Comment: Clearly implicating the potential for MERS to cause a serious spread of disease in closer quarters such as hospitals, an outbreak in an eastern province of Saudi Arabia (spring 2013) with 21/23 cases due to person-person spread in healthcare environments. The mortality rate was 65% which may speak to patients with pre-existing illness acquiring.

  17. Perlman S, McCray PB. Person-to-person spread of the MERS coronavirus--an evolving picture. N Engl J Med. 2013;369(5):466-7.  [PMID:23902487]

    Comment: An outbreak in Al-Hasa, part of eastern Saudi Arabia implicates direct person-to-person spread.

  18. Zaki AM, van Boheemen S, Bestebroer TM, et al. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012;367(19):1814-20.  [PMID:23075143]

    Comment: The first description of virus, first called HCoV-EMC but now referred to as MERS-CoV, and related but not the cause of SARS, a related coronavirus.

  19. Müller MA, Raj VS, Muth D, et al. Human coronavirus EMC does not require the SARS-coronavirus receptor and maintains broad replicative capability in mammalian cell lines. MBio. 2012;3(6).  [PMID:23232719]

    Comment: Investigators help confirm that this is a sister virus to SARS, and that virus appears to efficiently replicate in cell lines of human, pig and bat origin.

  20. Memish ZA, Al-Tawfiq JA, Alhakeem RF, et al. Middle East respiratory syndrome coronavirus (MERS-CoV): A cluster analysis with implications for global management of suspected cases. Travel Med Infect Dis. 2015;13(4):311-4.  [PMID:26211569]

    Comment: This study summarizes the implication of global MERS cases with links between cases in Saudi Arabia and Qatar.

  21. Al-Tawfiq JA, Zumla A, Memish ZA. Travel implications of emerging coronaviruses: SARS and MERS-CoV. Travel Med Infect Dis. 2014;12(5):422-8.  [PMID:25047726]

    Comment: This is a nice review of travel implications with comparisons between SARS and MERS-CoV.

  22. Al-Tawfiq JA, Gautret P. Asymptomatic Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection: Extent and implications for infection control: A systematic review. Travel Med Infect Dis. 2019;27:27-32.  [PMID:30550839]

    Comment: As with other respiratory viral infections, it seems that asymptomatic patients shedding virus may contribute to spread. This makes control more difficult.

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Last updated: January 12, 2020