Middle East respiratory syndrome (MERS)
History and exam
Key diagnostic factors
All confirmed cases have either resided in, or traveled to, the Middle East in the 14 days prior to the onset of symptoms.[98]Guery B, Poissy J, el Mansouf L, et al. Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission. Lancet. 2013;381:2265-2272. http://www.ncbi.nlm.nih.gov/pubmed/23727167?tool=bestpractice.com [99]Lee SI. Costly lessons from the 2015 Middle East respiratory syndrome coronavirus outbreak in Korea. J Prev Med Public Health. 2015;48:274-276. https://www.jpmph.org/journal/view.php?doi=10.3961/jpmph.15.064 http://www.ncbi.nlm.nih.gov/pubmed/26639740?tool=bestpractice.com [100]Reuss A, Litterst A, Drosten C, et al. Contact investigation for imported case of Middle East respiratory syndrome, Germany. Emerg Infect Dis. 2014;20:620-625. https://wwwnc.cdc.gov/eid/article/20/4/13-1375_article http://www.ncbi.nlm.nih.gov/pubmed/24655721?tool=bestpractice.com [101]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;63:431-436. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6319a4.htm http://www.ncbi.nlm.nih.gov/pubmed/24827411?tool=bestpractice.com This includes the Arabian Peninsula (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, United Arab Emirates, Yemen) and its surrounding countries (Iraq; Iran; Israel, the West Bank, and Gaza; Jordan; Lebanon; Syria).
Ninety-eight percent of cases have been reported in adults (defined as age >14 years).[102]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;13:752-761. http://www.ncbi.nlm.nih.gov/pubmed/23891402?tool=bestpractice.com
Infection in children is rare, although the reason for this is unknown.[103]Memish ZA, Al-Tawfiq JA, Assiri A, et al. Middle East respiratory syndrome coronavirus disease in children. Pediatr Infect Dis J. 2014;33:904-906. http://www.ncbi.nlm.nih.gov/pubmed/24763193?tool=bestpractice.com [104]Khuri-Bulos N, Payne DC, Lu X, et al. Middle East respiratory syndrome coronavirus not detected in children hospitalized with acute respiratory illness in Amman, Jordan, March 2010 to September 2012. Clin Microbiol Infect. 2014;20:678-682. http://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(14)61157-5/fulltext http://www.ncbi.nlm.nih.gov/pubmed/24313317?tool=bestpractice.com
Reported in 40% to 98% of cases.[105]Assiri A, McGeer A, Perl TM, et al. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med. 2013;369:407-416. http://www.nejm.org/doi/full/10.1056/NEJMoa1306742#t=article http://www.ncbi.nlm.nih.gov/pubmed/23782161?tool=bestpractice.com [102]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;13:752-761. http://www.ncbi.nlm.nih.gov/pubmed/23891402?tool=bestpractice.com [106]Al-Tawfiq JA, Hinedi K, Ghandour J, et al. Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients. Clin Infect Dis. 2014;59:160-165. https://academic.oup.com/cid/article/59/2/160/2895452/Middle-East-Respiratory-Syndrome-Coronavirus-A http://www.ncbi.nlm.nih.gov/pubmed/24723278?tool=bestpractice.com
Fever may be absent in older patients, immunocompromised patients, pregnant women, and patients with end-stage renal disease, diabetes mellitus, or hemochromatosis;[107]Shalhoub S, Farahat F, Al-Jiffri A, et al. IFN-alpha-2a or IFN-beta-1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study. J Antimicrob Chemother. 2015;70:2129-2132. http://www.ncbi.nlm.nih.gov/pubmed/25900158?tool=bestpractice.com therefore, absence of fever should not preclude workup for MERS.[108]Shalhoub S, Al-Zahrani A, Simhairi R, et al. Successful recovery of MERS CoV pneumonia in a patient with acquired immunodeficiency syndrome: a case report. J Clin Virol. 2015;62:69-71. http://www.ncbi.nlm.nih.gov/pubmed/25542475?tool=bestpractice.com
Reported in 54% to 86% of cases. It is usually dry; however, has been reported to be productive in 23% to 36% of patients.[102]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;13:752-761. http://www.ncbi.nlm.nih.gov/pubmed/23891402?tool=bestpractice.com [106]Al-Tawfiq JA, Hinedi K, Ghandour J, et al. Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients. Clin Infect Dis. 2014;59:160-165. https://academic.oup.com/cid/article/59/2/160/2895452/Middle-East-Respiratory-Syndrome-Coronavirus-A http://www.ncbi.nlm.nih.gov/pubmed/24723278?tool=bestpractice.com [109]Saad M, Omrani AS, Baig K, et al. Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia. Int J Infect Dis. 2014;29:301-306. http://www.ijidonline.com/article/S1201-9712(14)01622-1/fulltext http://www.ncbi.nlm.nih.gov/pubmed/25303830?tool=bestpractice.com
Reported in 60% to 72% of cases.[102]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;13:752-761. http://www.ncbi.nlm.nih.gov/pubmed/23891402?tool=bestpractice.com [106]Al-Tawfiq JA, Hinedi K, Ghandour J, et al. Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients. Clin Infect Dis. 2014;59:160-165. https://academic.oup.com/cid/article/59/2/160/2895452/Middle-East-Respiratory-Syndrome-Coronavirus-A http://www.ncbi.nlm.nih.gov/pubmed/24723278?tool=bestpractice.com [109]Saad M, Omrani AS, Baig K, et al. Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia. Int J Infect Dis. 2014;29:301-306. http://www.ijidonline.com/article/S1201-9712(14)01622-1/fulltext http://www.ncbi.nlm.nih.gov/pubmed/25303830?tool=bestpractice.com
Other diagnostic factors
Reported in 7% to 17% of cases.[102]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;13:752-761. http://www.ncbi.nlm.nih.gov/pubmed/23891402?tool=bestpractice.com [106]Al-Tawfiq JA, Hinedi K, Ghandour J, et al. Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients. Clin Infect Dis. 2014;59:160-165. https://academic.oup.com/cid/article/59/2/160/2895452/Middle-East-Respiratory-Syndrome-Coronavirus-A http://www.ncbi.nlm.nih.gov/pubmed/24723278?tool=bestpractice.com [109]Saad M, Omrani AS, Baig K, et al. Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia. Int J Infect Dis. 2014;29:301-306. http://www.ijidonline.com/article/S1201-9712(14)01622-1/fulltext http://www.ncbi.nlm.nih.gov/pubmed/25303830?tool=bestpractice.com
Reported in 7% to 26% of cases.[107]Shalhoub S, Farahat F, Al-Jiffri A, et al. IFN-alpha-2a or IFN-beta-1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study. J Antimicrob Chemother. 2015;70:2129-2132. http://www.ncbi.nlm.nih.gov/pubmed/25900158?tool=bestpractice.com [102]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;13:752-761. http://www.ncbi.nlm.nih.gov/pubmed/23891402?tool=bestpractice.com [106]Al-Tawfiq JA, Hinedi K, Ghandour J, et al. Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients. Clin Infect Dis. 2014;59:160-165. https://academic.oup.com/cid/article/59/2/160/2895452/Middle-East-Respiratory-Syndrome-Coronavirus-A http://www.ncbi.nlm.nih.gov/pubmed/24723278?tool=bestpractice.com
Reported in 17% to 24% of cases.[102]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;13:752-761. http://www.ncbi.nlm.nih.gov/pubmed/23891402?tool=bestpractice.com [109]Saad M, Omrani AS, Baig K, et al. Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia. Int J Infect Dis. 2014;29:301-306. http://www.ijidonline.com/article/S1201-9712(14)01622-1/fulltext http://www.ncbi.nlm.nih.gov/pubmed/25303830?tool=bestpractice.com
Reported in 7% to 21% of cases.[107]Shalhoub S, Farahat F, Al-Jiffri A, et al. IFN-alpha-2a or IFN-beta-1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study. J Antimicrob Chemother. 2015;70:2129-2132. http://www.ncbi.nlm.nih.gov/pubmed/25900158?tool=bestpractice.com [102]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;13:752-761. http://www.ncbi.nlm.nih.gov/pubmed/23891402?tool=bestpractice.com [106]Al-Tawfiq JA, Hinedi K, Ghandour J, et al. Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients. Clin Infect Dis. 2014;59:160-165. https://academic.oup.com/cid/article/59/2/160/2895452/Middle-East-Respiratory-Syndrome-Coronavirus-A http://www.ncbi.nlm.nih.gov/pubmed/24723278?tool=bestpractice.com
Usually associated with fever.
Nonspecific symptom reported in some cases.[110]WHO MERS-CoV Research Group. State of knowledge and data gaps of Middle East respiratory syndrome coronavirus (MERS-CoV) in humans. PLoS Curr. 2013;5:pii ecurrents.outbreaks.0bf719e352e7478f8ad85fa30127ddb8. http://currents.plos.org/outbreaks/article/state-of-knowledge-and-data-gaps-of-middle-east-respiratory-syndrome-coronavirus-mers-cov-in-humans-2/ http://www.ncbi.nlm.nih.gov/pubmed/24270606?tool=bestpractice.com [107]Shalhoub S, Farahat F, Al-Jiffri A, et al. IFN-alpha-2a or IFN-beta-1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study. J Antimicrob Chemother. 2015;70:2129-2132. http://www.ncbi.nlm.nih.gov/pubmed/25900158?tool=bestpractice.com [111]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;372:846-854. http://www.nejm.org/doi/full/10.1056/NEJMoa1408636#t=article http://www.ncbi.nlm.nih.gov/pubmed/25714162?tool=bestpractice.com [105]Assiri A, McGeer A, Perl TM, et al. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med. 2013;369:407-416. http://www.nejm.org/doi/full/10.1056/NEJMoa1306742#t=article http://www.ncbi.nlm.nih.gov/pubmed/23782161?tool=bestpractice.com [102]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;13:752-761. http://www.ncbi.nlm.nih.gov/pubmed/23891402?tool=bestpractice.com [106]Al-Tawfiq JA, Hinedi K, Ghandour J, et al. Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients. Clin Infect Dis. 2014;59:160-165. https://academic.oup.com/cid/article/59/2/160/2895452/Middle-East-Respiratory-Syndrome-Coronavirus-A http://www.ncbi.nlm.nih.gov/pubmed/24723278?tool=bestpractice.com
Nonspecific symptom reported in some cases.[110]WHO MERS-CoV Research Group. State of knowledge and data gaps of Middle East respiratory syndrome coronavirus (MERS-CoV) in humans. PLoS Curr. 2013;5:pii ecurrents.outbreaks.0bf719e352e7478f8ad85fa30127ddb8. http://currents.plos.org/outbreaks/article/state-of-knowledge-and-data-gaps-of-middle-east-respiratory-syndrome-coronavirus-mers-cov-in-humans-2/ http://www.ncbi.nlm.nih.gov/pubmed/24270606?tool=bestpractice.com [107]Shalhoub S, Farahat F, Al-Jiffri A, et al. IFN-alpha-2a or IFN-beta-1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study. J Antimicrob Chemother. 2015;70:2129-2132. http://www.ncbi.nlm.nih.gov/pubmed/25900158?tool=bestpractice.com [111]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;372:846-854. http://www.nejm.org/doi/full/10.1056/NEJMoa1408636#t=article http://www.ncbi.nlm.nih.gov/pubmed/25714162?tool=bestpractice.com [105]Assiri A, McGeer A, Perl TM, et al. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med. 2013;369:407-416. http://www.nejm.org/doi/full/10.1056/NEJMoa1306742#t=article http://www.ncbi.nlm.nih.gov/pubmed/23782161?tool=bestpractice.com [102]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;13:752-761. http://www.ncbi.nlm.nih.gov/pubmed/23891402?tool=bestpractice.com [106]Al-Tawfiq JA, Hinedi K, Ghandour J, et al. Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients. Clin Infect Dis. 2014;59:160-165. https://academic.oup.com/cid/article/59/2/160/2895452/Middle-East-Respiratory-Syndrome-Coronavirus-A http://www.ncbi.nlm.nih.gov/pubmed/24723278?tool=bestpractice.com
Nonspecific symptom reported in some cases.[110]WHO MERS-CoV Research Group. State of knowledge and data gaps of Middle East respiratory syndrome coronavirus (MERS-CoV) in humans. PLoS Curr. 2013;5:pii ecurrents.outbreaks.0bf719e352e7478f8ad85fa30127ddb8. http://currents.plos.org/outbreaks/article/state-of-knowledge-and-data-gaps-of-middle-east-respiratory-syndrome-coronavirus-mers-cov-in-humans-2/ http://www.ncbi.nlm.nih.gov/pubmed/24270606?tool=bestpractice.com [107]Shalhoub S, Farahat F, Al-Jiffri A, et al. IFN-alpha-2a or IFN-beta-1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study. J Antimicrob Chemother. 2015;70:2129-2132. http://www.ncbi.nlm.nih.gov/pubmed/25900158?tool=bestpractice.com [111]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;372:846-854. http://www.nejm.org/doi/full/10.1056/NEJMoa1408636#t=article http://www.ncbi.nlm.nih.gov/pubmed/25714162?tool=bestpractice.com [105]Assiri A, McGeer A, Perl TM, et al. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med. 2013;369:407-416. http://www.nejm.org/doi/full/10.1056/NEJMoa1306742#t=article http://www.ncbi.nlm.nih.gov/pubmed/23782161?tool=bestpractice.com [102]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;13:752-761. http://www.ncbi.nlm.nih.gov/pubmed/23891402?tool=bestpractice.com [106]Al-Tawfiq JA, Hinedi K, Ghandour J, et al. Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients. Clin Infect Dis. 2014;59:160-165. https://academic.oup.com/cid/article/59/2/160/2895452/Middle-East-Respiratory-Syndrome-Coronavirus-A http://www.ncbi.nlm.nih.gov/pubmed/24723278?tool=bestpractice.com
Nonspecific symptom reported in some cases.[110]WHO MERS-CoV Research Group. State of knowledge and data gaps of Middle East respiratory syndrome coronavirus (MERS-CoV) in humans. PLoS Curr. 2013;5:pii ecurrents.outbreaks.0bf719e352e7478f8ad85fa30127ddb8. http://currents.plos.org/outbreaks/article/state-of-knowledge-and-data-gaps-of-middle-east-respiratory-syndrome-coronavirus-mers-cov-in-humans-2/ http://www.ncbi.nlm.nih.gov/pubmed/24270606?tool=bestpractice.com [107]Shalhoub S, Farahat F, Al-Jiffri A, et al. IFN-alpha-2a or IFN-beta-1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study. J Antimicrob Chemother. 2015;70:2129-2132. http://www.ncbi.nlm.nih.gov/pubmed/25900158?tool=bestpractice.com [111]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;372:846-854. http://www.nejm.org/doi/full/10.1056/NEJMoa1408636#t=article http://www.ncbi.nlm.nih.gov/pubmed/25714162?tool=bestpractice.com [105]Assiri A, McGeer A, Perl TM, et al. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med. 2013;369:407-416. http://www.nejm.org/doi/full/10.1056/NEJMoa1306742#t=article http://www.ncbi.nlm.nih.gov/pubmed/23782161?tool=bestpractice.com [102]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;13:752-761. http://www.ncbi.nlm.nih.gov/pubmed/23891402?tool=bestpractice.com [106]Al-Tawfiq JA, Hinedi K, Ghandour J, et al. Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients. Clin Infect Dis. 2014;59:160-165. https://academic.oup.com/cid/article/59/2/160/2895452/Middle-East-Respiratory-Syndrome-Coronavirus-A http://www.ncbi.nlm.nih.gov/pubmed/24723278?tool=bestpractice.com
Nonspecific symptom reported in some cases.[110]WHO MERS-CoV Research Group. State of knowledge and data gaps of Middle East respiratory syndrome coronavirus (MERS-CoV) in humans. PLoS Curr. 2013;5:pii ecurrents.outbreaks.0bf719e352e7478f8ad85fa30127ddb8. http://currents.plos.org/outbreaks/article/state-of-knowledge-and-data-gaps-of-middle-east-respiratory-syndrome-coronavirus-mers-cov-in-humans-2/ http://www.ncbi.nlm.nih.gov/pubmed/24270606?tool=bestpractice.com [107]Shalhoub S, Farahat F, Al-Jiffri A, et al. IFN-alpha-2a or IFN-beta-1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study. J Antimicrob Chemother. 2015;70:2129-2132. http://www.ncbi.nlm.nih.gov/pubmed/25900158?tool=bestpractice.com [111]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;372:846-854. http://www.nejm.org/doi/full/10.1056/NEJMoa1408636#t=article http://www.ncbi.nlm.nih.gov/pubmed/25714162?tool=bestpractice.com [105]Assiri A, McGeer A, Perl TM, et al. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med. 2013;369:407-416. http://www.nejm.org/doi/full/10.1056/NEJMoa1306742#t=article http://www.ncbi.nlm.nih.gov/pubmed/23782161?tool=bestpractice.com [102]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;13:752-761. http://www.ncbi.nlm.nih.gov/pubmed/23891402?tool=bestpractice.com [106]Al-Tawfiq JA, Hinedi K, Ghandour J, et al. Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients. Clin Infect Dis. 2014;59:160-165. https://academic.oup.com/cid/article/59/2/160/2895452/Middle-East-Respiratory-Syndrome-Coronavirus-A http://www.ncbi.nlm.nih.gov/pubmed/24723278?tool=bestpractice.com
Nonspecific symptom reported in some cases.[110]WHO MERS-CoV Research Group. State of knowledge and data gaps of Middle East respiratory syndrome coronavirus (MERS-CoV) in humans. PLoS Curr. 2013;5:pii ecurrents.outbreaks.0bf719e352e7478f8ad85fa30127ddb8. http://currents.plos.org/outbreaks/article/state-of-knowledge-and-data-gaps-of-middle-east-respiratory-syndrome-coronavirus-mers-cov-in-humans-2/ http://www.ncbi.nlm.nih.gov/pubmed/24270606?tool=bestpractice.com [107]Shalhoub S, Farahat F, Al-Jiffri A, et al. IFN-alpha-2a or IFN-beta-1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study. J Antimicrob Chemother. 2015;70:2129-2132. http://www.ncbi.nlm.nih.gov/pubmed/25900158?tool=bestpractice.com [111]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;372:846-854. http://www.nejm.org/doi/full/10.1056/NEJMoa1408636#t=article http://www.ncbi.nlm.nih.gov/pubmed/25714162?tool=bestpractice.com [105]Assiri A, McGeer A, Perl TM, et al. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med. 2013;369:407-416. http://www.nejm.org/doi/full/10.1056/NEJMoa1306742#t=article http://www.ncbi.nlm.nih.gov/pubmed/23782161?tool=bestpractice.com [102]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;13:752-761. http://www.ncbi.nlm.nih.gov/pubmed/23891402?tool=bestpractice.com [106]Al-Tawfiq JA, Hinedi K, Ghandour J, et al. Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients. Clin Infect Dis. 2014;59:160-165. https://academic.oup.com/cid/article/59/2/160/2895452/Middle-East-Respiratory-Syndrome-Coronavirus-A http://www.ncbi.nlm.nih.gov/pubmed/24723278?tool=bestpractice.com
Present in some cases, including patients with acute respiratory distress.
Present in some cases, including patients with acute respiratory distress.
Present in some cases, including patients with acute respiratory distress.
May indicate pneumonia.
May indicate pneumonia.
Bronchial breath sounds may also be heard.
Risk factors
All confirmed cases have either resided in, or traveled to, the Middle East in the 14 days prior to the onset of symptoms.[17]Guery B, Poissy J, el Mansouf L, et al. Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission. Lancet. 2013;381:2265-2272. http://www.ncbi.nlm.nih.gov/pubmed/23727167?tool=bestpractice.com [19]Lee SI. Costly lessons from the 2015 Middle East respiratory syndrome coronavirus outbreak in Korea. J Prev Med Public Health. 2015;48:274-276. https://www.jpmph.org/journal/view.php?doi=10.3961/jpmph.15.064 http://www.ncbi.nlm.nih.gov/pubmed/26639740?tool=bestpractice.com [79]Reuss A, Litterst A, Drosten C, et al. Contact investigation for imported case of Middle East respiratory syndrome, Germany. Emerg Infect Dis. 2014;20:620-625. https://wwwnc.cdc.gov/eid/article/20/4/13-1375_article http://www.ncbi.nlm.nih.gov/pubmed/24655721?tool=bestpractice.com [80]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;63:431-436. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6319a4.htm http://www.ncbi.nlm.nih.gov/pubmed/24827411?tool=bestpractice.com This includes the Arabian Peninsula (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, United Arab Emirates, Yemen) and its surrounding countries (Iraq; Iran; Israel, the West Bank, and Gaza; Jordan; Lebanon; Syria).
Majority of cases are a result of human-to-human transmission (rather than camel-to-human transmission) with peaks of confirmed cases occurring during nosocomial outbreaks.[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;372:846-854. http://www.nejm.org/doi/full/10.1056/NEJMoa1408636#t=article http://www.ncbi.nlm.nih.gov/pubmed/25714162?tool=bestpractice.com [7]Assiri A, McGeer A, Perl TM, et al. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med. 2013;369:407-416. http://www.nejm.org/doi/full/10.1056/NEJMoa1306742#t=article http://www.ncbi.nlm.nih.gov/pubmed/23782161?tool=bestpractice.com [28]Alenazi TH, Al Arbash H, El-Saed A, et al. Identified transmission dynamics of Middle East respiratory syndrome coronavirus infection during an outbreak: implications of an overcrowded emergency department. Clin Infect Dis. 2017;65:675-679. http://www.ncbi.nlm.nih.gov/pubmed/28575307?tool=bestpractice.com
Transmission has been well documented in family clusters.[18]Abroug F, Slim A, Ouanes-Besbes L, et al. Family cluster of Middle East respiratory syndrome coronavirus infections, Tunisia, 2013. Emerg Infect Dis. 2014;20:1527-1530. http://www.ncbi.nlm.nih.gov/pubmed/25148113?tool=bestpractice.com [29]Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014;58:309-318. https://academic.oup.com/cid/article/58/3/309/340555/Executive-Summary-2013-IDSA-Clinical-Practice http://www.ncbi.nlm.nih.gov/pubmed/24421306?tool=bestpractice.com [30]Memish ZA, Zumla AI, Al-Hakeem RF, et al. Family cluster of Middle East respiratory syndrome coronavirus infections. N Engl J Med. 2013;368:2487-2494. http://www.nejm.org/doi/full/10.1056/NEJMoa1303729#t=article http://www.ncbi.nlm.nih.gov/pubmed/23718156?tool=bestpractice.com However, it has been reported more commonly in nosocomial outbreaks (e.g., hemodialysis units, intensive care units, medical wards).[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;372:846-854. http://www.nejm.org/doi/full/10.1056/NEJMoa1408636#t=article http://www.ncbi.nlm.nih.gov/pubmed/25714162?tool=bestpractice.com [7]Assiri A, McGeer A, Perl TM, et al. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med. 2013;369:407-416. http://www.nejm.org/doi/full/10.1056/NEJMoa1306742#t=article http://www.ncbi.nlm.nih.gov/pubmed/23782161?tool=bestpractice.com [30]Memish ZA, Zumla AI, Al-Hakeem RF, et al. Family cluster of Middle East respiratory syndrome coronavirus infections. N Engl J Med. 2013;368:2487-2494. http://www.nejm.org/doi/full/10.1056/NEJMoa1303729#t=article http://www.ncbi.nlm.nih.gov/pubmed/23718156?tool=bestpractice.com [31]Omrani AS, Matin MA, Haddad Q, et al. A family cluster of Middle East Respiratory Syndrome Coronavirus infections related to a likely unrecognized asymptomatic or mild case. Int J Infect Dis. 2013;17:e668-e672. http://www.ijidonline.com/article/S1201-9712(13)00225-7/fulltext http://www.ncbi.nlm.nih.gov/pubmed/23916548?tool=bestpractice.com [32]Memish ZA, Cotten M, Watson SJ, et al. Community case clusters of Middle East respiratory syndrome coronavirus in Hafr Al-Batin, Kingdom of Saudi Arabia: a descriptive genomic study. Int J Infect Dis. 2014;23:63-68. http://www.ijidonline.com/article/S1201-9712(14)01451-9/fulltext http://www.ncbi.nlm.nih.gov/pubmed/24699184?tool=bestpractice.com [33]Al-Abdallat MM, Payne DC, Alqasrawi S, et al. Hospital-associated outbreak of Middle East respiratory syndrome coronavirus: a serologic, epidemiologic, and clinical description. Clin Infect Dis. 2014;59:1225-1233. https://academic.oup.com/cid/article/59/9/1225/419021/Hospital-Associated-Outbreak-of-Middle-East http://www.ncbi.nlm.nih.gov/pubmed/24829216?tool=bestpractice.com
Transmission is via respiratory droplets (e.g., coughing, sneezing) from an infected patient, or close contact with an infected patient. However, airborne or fomite transmission cannot be ruled out.[65]Kim SH, Chang SY, Sung M, et al. Extensive viable Middle East respiratory syndrome (MERS) coronavirus contamination in air and surrounding environment in MERS isolation wards. Clin Infect Dis. 2016;63:363-369. https://academic.oup.com/cid/article/63/3/363/2595016/Extensive-Viable-Middle-East-Respiratory-Syndrome http://www.ncbi.nlm.nih.gov/pubmed/27090992?tool=bestpractice.com The incubation period is 2 to 14 days and transmission is thought to occur during either the symptomatic or incubation stages.[8]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;13:752-761. http://www.ncbi.nlm.nih.gov/pubmed/23891402?tool=bestpractice.com [66]Centers for Disease Control and Prevention. MERS clinical features. September 2017 [internet publication]. http://www.cdc.gov/coronavirus/mers/clinical-features.html
All patients diagnosed outside of the Middle East have been in contact with someone who has traveled from the Middle East in the preceding 14 days.[17]Guery B, Poissy J, el Mansouf L, et al. Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission. Lancet. 2013;381:2265-2272. http://www.ncbi.nlm.nih.gov/pubmed/23727167?tool=bestpractice.com [19]Lee SI. Costly lessons from the 2015 Middle East respiratory syndrome coronavirus outbreak in Korea. J Prev Med Public Health. 2015;48:274-276. https://www.jpmph.org/journal/view.php?doi=10.3961/jpmph.15.064 http://www.ncbi.nlm.nih.gov/pubmed/26639740?tool=bestpractice.com [79]Reuss A, Litterst A, Drosten C, et al. Contact investigation for imported case of Middle East respiratory syndrome, Germany. Emerg Infect Dis. 2014;20:620-625. https://wwwnc.cdc.gov/eid/article/20/4/13-1375_article http://www.ncbi.nlm.nih.gov/pubmed/24655721?tool=bestpractice.com [80]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;63:431-436. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6319a4.htm http://www.ncbi.nlm.nih.gov/pubmed/24827411?tool=bestpractice.com
Dromedary camels are thought to be the primary animal host.[39]Omrani AS, Shalhoub S. Middle East respiratory syndrome coronavirus (MERS-CoV): what lessons can we learn? J Hosp Infect. 2015;91:188-196. http://www.ncbi.nlm.nih.gov/pubmed/26452615?tool=bestpractice.com
Exact mode of transmission is unknown, but it is thought to occur from direct or indirect contact with dromedary camels (e.g., camel milking, contact with camel nasal secretions, urine, or feces) or camel products (e.g., unpasteurized camel milk, raw or undercooked camel meat).
Strongest evidence for camel-to-human transmission comes from a study in Saudi Arabia where the virus was isolated from a patient and one of his camels and the genome was found to be almost identical.[61]Memish ZA, Cotten M, Meyer B, et al. Human infection with MERS coronavirus after exposure to infected camels, Saudi Arabia, 2013. Emerg Infect Dis. 2014;20:1012-1015. https://wwwnc.cdc.gov/eid/article/20/6/14-0402_article http://www.ncbi.nlm.nih.gov/pubmed/24857749?tool=bestpractice.com [62]Azhar EI, El-Kafrawy SA, Farraj SA, et al. Evidence for camel-to-human transmission of MERS coronavirus. N Engl J Med. 2014;370:2499-2505. http://www.nejm.org/doi/full/10.1056/NEJMoa1401505#t=article http://www.ncbi.nlm.nih.gov/pubmed/24896817?tool=bestpractice.com
A case-control study identified contact with camels to be a risk factor.[64]Alraddadi BM, Watson JT, Almarashi A, et al. Risk factors for primary Middle East respiratory syndrome coronavirus illness in humans, Saudi Arabia, 2014. Emerg Infect Dis. 2016;22:49-55. https://wwwnc.cdc.gov/eid/article/22/1/15-1340_article http://www.ncbi.nlm.nih.gov/pubmed/26692185?tool=bestpractice.com
Although infection has been reported in different age groups within the adult population, the median age of patients ranges from 50 to 67 years of age.[4]WHO MERS-CoV Research Group. State of knowledge and data gaps of Middle East respiratory syndrome coronavirus (MERS-CoV) in humans. PLoS Curr. 2013;5. http://currents.plos.org/outbreaks/article/state-of-knowledge-and-data-gaps-of-middle-east-respiratory-syndrome-coronavirus-mers-cov-in-humans-2/ http://www.ncbi.nlm.nih.gov/pubmed/24270606?tool=bestpractice.com [9]Al-Tawfiq JA, Hinedi K, Ghandour J, et al. Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients. Clin Infect Dis. 2014;59:160-165. https://academic.oup.com/cid/article/59/2/160/2895452/Middle-East-Respiratory-Syndrome-Coronavirus-A http://www.ncbi.nlm.nih.gov/pubmed/24723278?tool=bestpractice.com [26]Omrani AS, Saad MM, Baig K, et al. Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study. Lancet Infect Dis. 2014;14:1090-1095. http://www.ncbi.nlm.nih.gov/pubmed/25278221?tool=bestpractice.com
Age ≥50 years is associated with more severe presentation, worse outcomes, and a higher risk of mortality.[5]Shalhoub S, Farahat F, Al-Jiffri A, et al. IFN-alpha-2a or IFN-beta-1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study. J Antimicrob Chemother. 2015;70:2129-2132. http://www.ncbi.nlm.nih.gov/pubmed/25900158?tool=bestpractice.com [27]Saad M, Omrani AS, Baig K, et al. Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia. Int J Infect Dis. 2014;29:301-306. http://www.ijidonline.com/article/S1201-9712(14)01622-1/fulltext http://www.ncbi.nlm.nih.gov/pubmed/25303830?tool=bestpractice.com In one cohort study, mortality increased with increasing age to reach 75% in patients >60 years of age.[8]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;13:752-761. http://www.ncbi.nlm.nih.gov/pubmed/23891402?tool=bestpractice.com
Reported in 65% to 87% of confirmed cases and has been associated with severe infection.[5]Shalhoub S, Farahat F, Al-Jiffri A, et al. IFN-alpha-2a or IFN-beta-1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study. J Antimicrob Chemother. 2015;70:2129-2132. http://www.ncbi.nlm.nih.gov/pubmed/25900158?tool=bestpractice.com [8]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;13:752-761. http://www.ncbi.nlm.nih.gov/pubmed/23891402?tool=bestpractice.com [9]Al-Tawfiq JA, Hinedi K, Ghandour J, et al. Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients. Clin Infect Dis. 2014;59:160-165. https://academic.oup.com/cid/article/59/2/160/2895452/Middle-East-Respiratory-Syndrome-Coronavirus-A http://www.ncbi.nlm.nih.gov/pubmed/24723278?tool=bestpractice.com [26]Omrani AS, Saad MM, Baig K, et al. Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study. Lancet Infect Dis. 2014;14:1090-1095. http://www.ncbi.nlm.nih.gov/pubmed/25278221?tool=bestpractice.com
Most common comorbid condition in one cohort of 12 critically ill patients admitted to the intensive care unit.[81]Arabi YM, Arifi AA, Balkhy HH, et al. Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Ann Intern Med. 2014;160:389-397. http://annals.org/aim/article/1817260/clinical-course-outcomes-critically-ill-patients-middle-east-respiratory-syndrome http://www.ncbi.nlm.nih.gov/pubmed/24474051?tool=bestpractice.com
Identified as a risk factor in a case-control study.[64]Alraddadi BM, Watson JT, Almarashi A, et al. Risk factors for primary Middle East respiratory syndrome coronavirus illness in humans, Saudi Arabia, 2014. Emerg Infect Dis. 2016;22:49-55. https://wwwnc.cdc.gov/eid/article/22/1/15-1340_article http://www.ncbi.nlm.nih.gov/pubmed/26692185?tool=bestpractice.com
Reported in 33% of confirmed cases (compared with 7% of patients who were initially suspected of being infected but who later tested negative).[9]Al-Tawfiq JA, Hinedi K, Ghandour J, et al. Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients. Clin Infect Dis. 2014;59:160-165. https://academic.oup.com/cid/article/59/2/160/2895452/Middle-East-Respiratory-Syndrome-Coronavirus-A http://www.ncbi.nlm.nih.gov/pubmed/24723278?tool=bestpractice.com
Patients with end-stage renal disease were reported to develop severe infection and had worse clinical outcomes.[81]Arabi YM, Arifi AA, Balkhy HH, et al. Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Ann Intern Med. 2014;160:389-397. http://annals.org/aim/article/1817260/clinical-course-outcomes-critically-ill-patients-middle-east-respiratory-syndrome http://www.ncbi.nlm.nih.gov/pubmed/24474051?tool=bestpractice.com In one case series, a mortality rate of 100% was reported in patients with chronic renal impairment, including 8 patients who were undergoing hemodialysis.[5]Shalhoub S, Farahat F, Al-Jiffri A, et al. IFN-alpha-2a or IFN-beta-1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study. J Antimicrob Chemother. 2015;70:2129-2132. http://www.ncbi.nlm.nih.gov/pubmed/25900158?tool=bestpractice.com
May be related to the immune dysregulation that occurs in patients with end-stage renal disease on hemodialysis.[82]Deenitchina SS, Ando T, Okuda S, et al. Cellular immunity in hemodialysis patients: a quantitative analysis of immune cell subsets by flow cytometry. Am J Nephrol. 1995;15:57-65. http://www.ncbi.nlm.nih.gov/pubmed/7872366?tool=bestpractice.com
Identified as a risk factor in a case-control study.[64]Alraddadi BM, Watson JT, Almarashi A, et al. Risk factors for primary Middle East respiratory syndrome coronavirus illness in humans, Saudi Arabia, 2014. Emerg Infect Dis. 2016;22:49-55. https://wwwnc.cdc.gov/eid/article/22/1/15-1340_article http://www.ncbi.nlm.nih.gov/pubmed/26692185?tool=bestpractice.com
Patients with confirmed infection had a median BMI of 32 compared with 27.8 in controls in one case-control study.[9]Al-Tawfiq JA, Hinedi K, Ghandour J, et al. Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients. Clin Infect Dis. 2014;59:160-165. https://academic.oup.com/cid/article/59/2/160/2895452/Middle-East-Respiratory-Syndrome-Coronavirus-A http://www.ncbi.nlm.nih.gov/pubmed/24723278?tool=bestpractice.com
Reported to be associated with severe infection and worse clinical outcomes in several case series.[8]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;13:752-761. http://www.ncbi.nlm.nih.gov/pubmed/23891402?tool=bestpractice.com [81]Arabi YM, Arifi AA, Balkhy HH, et al. Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Ann Intern Med. 2014;160:389-397. http://annals.org/aim/article/1817260/clinical-course-outcomes-critically-ill-patients-middle-east-respiratory-syndrome http://www.ncbi.nlm.nih.gov/pubmed/24474051?tool=bestpractice.com
Identified as a risk factor in a case-control study.[64]Alraddadi BM, Watson JT, Almarashi A, et al. Risk factors for primary Middle East respiratory syndrome coronavirus illness in humans, Saudi Arabia, 2014. Emerg Infect Dis. 2016;22:49-55. https://wwwnc.cdc.gov/eid/article/22/1/15-1340_article http://www.ncbi.nlm.nih.gov/pubmed/26692185?tool=bestpractice.com
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