In 2012, a zoonotic coronavirus was identified as the causative agent of Middle East respiratory syndrome and was named MERS coronavirus (MERS-CoV). As of August 11, 2016, the virus has infected 1,791 patients, with a mortality rate of 35.6%. Although MERS-CoV generally causes subclinical or mild disease, infection can result in serious outcomes, including acute respiratory distress syndrome and multi-organ failure in patients with comorbidities. The virus is endemic in camels in the Arabian Peninsula and Africa and thus poses a consistent threat of frequent reintroduction into human populations. Disease prevalence will increase substantially if the virus mutates to increase human-to-human transmissibility. No therapeutics or vaccines are approved for MERS; thus, development of novel therapies is needed. Further, since many MERS cases are acquired in healthcare settings, public health measures and scrupulous attention to infection control are required to prevent additional MERS outbreaks.


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Literature Cited

  1. Zaki AM, van Boheemen S, Bestebroer TM. 1.  et al. 2012. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. New Engl. J. Med. 367:1814–20 [Google Scholar]
  2. de Groot RJ, Baker SC, Baric RS. 2.  et al. 2013. Middle East respiratory syndrome coronavirus (MERS-CoV): announcement of the Coronavirus Study Group. J. Virol. 87:7790–92 [Google Scholar]
  3. Lee SS, Wong NS. 3.  2015. Probable transmission chains of Middle East respiratory syndrome coronavirus and the multiple generations of secondary infection in South Korea. Int. J. Infect. Dis. 38:65–67 [Google Scholar]
  4. Masters PS, Perlman S. 4.  2013. Coronaviridae. Fields Virology DM Knipe, PM Howley 6825–58 Philadelphia: Lippincott Williams & Wilkins, 6th ed.. [Google Scholar]
  5. Yang Y, Zhang L, Geng H. 5.  et al. 2013. The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists. Protein Cell 4:951–61 [Google Scholar]
  6. Raj VS, Mou H, Smits SL. 6.  et al. 2013. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature 495:251–54 [Google Scholar]
  7. Li W, Moore MJ, Vasilieva N. 7.  et al. 2003. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426:450–54 [Google Scholar]
  8. Sabir JS, Lam TT, Ahmed MM. 8.  et al. 2016. Co-circulation of three camel coronavirus species and recombination of MERS-CoVs in Saudi Arabia. Science 351:81–84 [Google Scholar]
  9. Kim Y, Cheon S, Min CK. 9.  et al. 2016. Spread of mutant Middle East respiratory syndrome coronavirus with reduced affinity to human CD26 during the South Korean outbreak. mBio 7:e00019–16 [Google Scholar]
  10. 10. Chinese SARS Molecular Epidemiology Consortium 2004. Molecular evolution of the SARS coronavirus during the course of the SARS epidemic in China. Science 303:1666–69 [Google Scholar]
  11. 11. Korean Society of Infectious Diseases, Korean Society for Healthcare-associated Infection Control and Prevention 2015. An unexpected outbreak of Middle East respiratory syndrome coronavirus infection in the Republic of Korea, 2015. Infect. Chemother. 47:120–22 [Google Scholar]
  12. Alsahafi AJ, Cheng AC. 12.  2016. The epidemiology of Middle East respiratory syndrome coronavirus in the Kingdom of Saudi Arabia, 2012–2015. Int. J. Infect. Dis. 45:1–4 [Google Scholar]
  13. van Doremalen N, Bushmaker T, Munster VJ. 13.  2013. Stability of Middle East respiratory syndrome coronavirus (MERS-CoV) under different environmental conditions. Eurosurveillance 18:3820590 [Google Scholar]
  14. Cotten M, Watson SJ, Zumla AI. 14.  et al. 2014. Spread, circulation, and evolution of the Middle East respiratory syndrome coronavirus. mBio 5:1e01062–13 doi: 10.1128/mBio.01062-13 [Google Scholar]
  15. Drosten C, Meyer B, Muller MA. 15.  et al. 2014. Transmission of MERS-coronavirus in household contacts. New Engl. J. Med. 371:828–35 [Google Scholar]
  16. Poletto C, Pelat C, Levy-Bruhl D. 16.  et al. 2014. Assessment of the Middle East respiratory syndrome coronavirus (MERS-CoV) epidemic in the Middle East and risk of international spread using a novel maximum likelihood analysis approach. Eurosurveillance 19:2320824 [Google Scholar]
  17. Muller MA, Meyer B, Corman VM. 17.  et al. 2015. Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: a nationwide, cross-sectional, serological study. Lancet Infect. Dis. 15:5559–64 [Google Scholar]
  18. Assiri A, Al-Tawfiq JA, Al-Rabeeah AA. 18.  et al. 2013. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. Lancet Infect. Dis. 13:752–61 [Google Scholar]
  19. Meyerholz DK, Lambertz AM, McCray PB Jr. 19.  2016. Dipeptidyl peptidase 4 distribution in the human respiratory tract: implications for the Middle East respiratory syndrome. Am. J. Pathol. 186:78–86 [Google Scholar]
  20. Widagdo W, Raj VS, Schipper D. 20.  et al. 2016. Differential expression of the Middle East respiratory syndrome coronavirus receptor in the upper respiratory tracts of humans and dromedary camels. J. Virol. 90:4838–42 [Google Scholar]
  21. Boonacker E, Van Noorden CJ. 21.  2003. The multifunctional or moonlighting protein CD26/DPPIV. Eur. J. Cell Biol. 82:53–73 [Google Scholar]
  22. Ng DL, Al Hosani F, Keating MK. 22.  et al. 2016. Clinicopathologic, immunohistochemical, and ultrastructural findings of a fatal case of Middle East respiratory syndrome coronavirus infection in the United Arab Emirates, April 2014. Am. J. Pathol. 186:652–58 [Google Scholar]
  23. Zielecki F, Weber M, Eickmann M. 23.  et al. 2013. Human cell tropism and innate immune system interactions of human respiratory coronavirus EMC compared to those of severe acute respiratory syndrome coronavirus. J. Virol. 87:5300–4 [Google Scholar]
  24. Chan JF, Chan KH, Choi GK. 24.  et al. 2013. Differential cell line susceptibility to the emerging novel human betacoronavirus 2c EMC/2012: implications for disease pathogenesis and clinical manifestation. J. Infect. Dis. 207:1743–52 [Google Scholar]
  25. Dijkman R, Jebbink MF, Koekkoek SM. 25.  et al. 2013. Isolation and characterization of current human coronavirus strains in primary human epithelial cell cultures reveal differences in target cell tropism. J. Virol. 87:6081–90 [Google Scholar]
  26. Hocke AC, Becher A, Knepper J. 26.  et al. 2013. Emerging human Middle East respiratory syndrome coronavirus causes widespread infection and alveolar damage in human lungs. Am. J. Respir. Crit. Care Med. 188:882–86 [Google Scholar]
  27. Chan RW, Chan MC, Agnihothram S. 27.  et al. 2013. Tropism of and innate immune responses to the novel human betacoronavirus lineage C virus in human ex vivo respiratory organ cultures. J. Virol. 87:6604–14 [Google Scholar]
  28. Menachery VD, Eisfeld AJ, Schafer A. 28.  et al. 2014. Pathogenic influenza viruses and coronaviruses utilize similar and contrasting approaches to control interferon-stimulated gene responses. mBio 5:e01174–14 [Google Scholar]
  29. Lau SK, Lau CC, Chan KH. 29.  et al. 2013. Delayed induction of proinflammatory cytokines and suppression of innate antiviral response by the novel Middle East respiratory syndrome coronavirus: implications for pathogenesis and treatment. J. Gen. Virol. 94:2679–90 [Google Scholar]
  30. Tynell J, Westenius V, Ronkko E. 30.  et al. 2016. Middle East respiratory syndrome coronavirus shows poor replication but significant induction of antiviral responses in human monocyte-derived macrophages and dendritic cells. J. Gen. Virol. 97:344–55 [Google Scholar]
  31. Zhou J, Chu H, Li C. 31.  et al. 2014. Active replication of Middle East respiratory syndrome coronavirus and aberrant induction of inflammatory cytokines and chemokines in human macrophages: implications for pathogenesis. J. Infect. Dis. 209:1331–42 [Google Scholar]
  32. Chu H, Zhou J, Wong BH. 32.  et al. 2015. Middle East respiratory syndrome coronavirus efficiently infects human primary T lymphocytes and activates the extrinsic and intrinsic apoptosis pathways. J. Infect. Dis. 213:6904–14 [Google Scholar]
  33. Law HK, Cheung CY, Ng HY. 33.  et al. 2005. Chemokine up-regulation in SARS-coronavirus-infected, monocyte-derived human dendritic cells. Blood 106:2366–74 [Google Scholar]
  34. Cheung CY, Poon LL, Ng IH. 34.  et al. 2005. Cytokine responses in severe acute respiratory syndrome coronavirus-infected macrophages in vitro: possible relevance to pathogenesis. J. Virol. 79:7819–26 [Google Scholar]
  35. Scheuplein VA, Seifried J, Malczyk AH. 35.  et al. 2015. High secretion of interferons by human plasmacytoid dendritic cells upon recognition of Middle East respiratory syndrome coronavirus. J. Virol. 89:3859–69 [Google Scholar]
  36. Faure E, Poissy J, Goffard A. 36.  et al. 2014. Distinct immune response in two MERS-CoV-infected patients: Can we go from bench to bedside?. PLOS ONE 9:e88716 [Google Scholar]
  37. Zumla A, Hui DS, Perlman S. 37.  2015. Middle East respiratory syndrome. Lancet 386:995–1007 [Google Scholar]
  38. Al-Tawfiq JA, Hinedi K, Ghandour J. 38.  et al. 2014. Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients. Clin. Infect. Dis. 59:160–65 [Google Scholar]
  39. Arabi YM, Arifi AA, Balkhy HH. 39.  et al. 2014. Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Ann. Intern. Med. 160:389–97 [Google Scholar]
  40. Assiri A, McGeer A, Perl TM. 40.  et al. 2013. Hospital outbreak of Middle East respiratory syndrome coronavirus. New Engl. J. Med. 369:407–16 [Google Scholar]
  41. Saad M, Omrani AS, Baig K. 41.  et al. 2014. 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. 29:301–6 [Google Scholar]
  42. Virlogeux V, Park M, Wu JT, Cowling BJ. 42.  2016. Association between severity of MERS-CoV infection and incubation period. Emerg. Infect. Dis. 22:3526–28 [Google Scholar]
  43. Poissy J, Goffard A, Parmentier-Decrucq E. 43.  et al. 2014. Kinetics and pattern of viral excretion in biological specimens of two MERS-CoV cases. J. Clin. Virol. 61:275–78 [Google Scholar]
  44. Memish ZA, Al-Tawfiq JA, Makhdoom HQ. 44.  et al. 2014. Respiratory tract samples, viral load, and genome fraction yield in patients with Middle East respiratory syndrome. J. Infect. Dis. 210:1590–94 [Google Scholar]
  45. Ajlan AM, Ahyad RA, Jamjoom LG. 45.  et al. 2014. Middle East respiratory syndrome coronavirus (MERS-CoV) infection: chest CT findings. Am. J. Roentgenol. 203:782–87 [Google Scholar]
  46. Corman VM, Ithete NL, Richards LR. 46.  et al. 2014. Rooting the phylogenetic tree of Middle East respiratory syndrome coronavirus by characterization of a conspecific virus from an African bat. J. Virol. 88:11297–303 [Google Scholar]
  47. Omrani AS, Al-Tawfiq JA, Memish ZA. 47.  2015. Middle East respiratory syndrome coronavirus (MERS-CoV): animal to human interaction. Pathog. Glob. Health 109:354–62 [Google Scholar]
  48. Reusken CB, Raj VS, Koopmans MP, Haagmans BL. 48.  2016. Cross host transmission in the emergence of MERS coronavirus. Curr. Opin. Virol. 16:55–62 [Google Scholar]
  49. Adney DR, van Doremalen N, Brown VR. 49.  et al. 2014. Replication and shedding of MERS-CoV in upper respiratory tract of inoculated dromedary camels. Emerg. Infect. Dis. 20:1999–2005 [Google Scholar]
  50. Hemida MG, Al-Naeem A, Perera RA. 50.  et al. 2015. Lack of Middle East respiratory syndrome coronavirus transmission from infected camels. Emerg. Infect. Dis. 21:699–701 [Google Scholar]
  51. Reusken CB, Farag EA, Jonges M. 51.  et al. 2014. Middle East respiratory syndrome coronavirus (MERS-CoV) RNA and neutralising antibodies in milk collected according to local customs from dromedary camels, Qatar, April 2014. Eurosurveillance 19:2320829 [Google Scholar]
  52. Corman VM, Muller MA, Costabel U. 52.  et al. 2012. Assays for laboratory confirmation of novel human coronavirus (hCoV-EMC) infections. Eurosurveillance 17:4920334 [Google Scholar]
  53. 53. World Health Organization. 2015. Laboratory testing for Middle East respiratory syndrome coronavirus: interim guidance http://www.who.int/csr/disease/coronavirus_infections/mers-laboratory-testing/en/
  54. Alshukairi AN KI, Ahmed WA, Dada AM. 54.  et al. 2016. Antibody response and disease severity in healthcare worker MERS survivors. Emerg. Infect. Dis. 22:6 http://wwwnc.cdc.gov/eid/article/22/6/16-0010_article [Google Scholar]
  55. Graham RL, Donaldson EF, Baric RS. 55.  2013. A decade after SARS: strategies for controlling emerging coronaviruses. Nat. Rev. Microbiol. 11:836–48 [Google Scholar]
  56. Perlman S, Vijay R. 56.  2016. Middle East respiratory syndrome vaccines. Int. J. Infect. Dis. 16:31021–29 [Google Scholar]
  57. Haagmans BL, van den Brand JM, Raj VS. 57.  et al. 2016. An orthopoxvirus-based vaccine reduces virus excretion after MERS-CoV infection in dromedary camels. Science 351:77–81 [Google Scholar]
  58. Kindler E, Jonsdottir HR, Muth D. 58.  et al. 2013. Efficient replication of the novel human betacoronavirus EMC on primary human epithelium highlights its zoonotic potential. mBio 4:e00611–12 [Google Scholar]
  59. Falzarano D, de Wit E, Rasmussen AL. 59.  et al. 2013. Treatment with interferon-alpha2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat. Med. 19:1313–17 [Google Scholar]
  60. Omrani AS, Saad MM, Baig K. 60.  et al. 2014. Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study. Lancet Infect. Dis. 14:1090–95 [Google Scholar]
  61. Al-Tawfiq JA, Momattin H, Dib J, Memish ZA. 61.  2014. Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study. Int. J. Infect. Dis. 20:42–46 [Google Scholar]
  62. Mair-Jenkins J, Saavedra-Campos M, Baillie JK. 62.  et al. 2015. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J. Infect. Dis. 211:80–90 [Google Scholar]
  63. Corti D, Zhao J, Pedotti M. 63.  et al. 2015. Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus. PNAS 112:10473–78 [Google Scholar]
  64. Tang XC, Agnihothram SS, Jiao Y. 64.  et al. 2014. Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution. PNAS 111:E2018–26 [Google Scholar]
  65. Ying T, Du L, Ju TW. 65.  et al. 2014. Exceptionally potent neutralization of Middle East respiratory syndrome coronavirus by human monoclonal antibodies. J. Virol. 88:7796–805 [Google Scholar]
  66. Luke T, Wu H, Zhao J. 66.  et al. 2016. Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo. Sci. Transl. Med. 8:326ra21 [Google Scholar]
  67. Zumla A, Chan JF, Azhar EI. 67.  et al. 2016. Coronaviruses—drug discovery and therapeutic options. Nat. Rev. Drug Discov. 15:5327–47 [Google Scholar]
  68. 68. Public Health England, ISARIC 2015. Treatment of MERS-CoV: information for clinicians. Clinical decision-making support for treatment of MERS-CoV patients. http://www.gov.uk/government/uploads/system/uploads/attachment_data/file/360424/MERS_COV_information_for_clinicians_17_July.pdf
  69. Channappanavar R, Lu L, Xia S. 69.  et al. 2015. Protective effect of intranasal regimens containing peptidic Middle East respiratory syndrome coronavirus fusion inhibitor against MERS-CoV infection. J. Infect. Dis. 212:1894–903 [Google Scholar]
  70. Lan J, Yao Y, Deng Y. 70.  et al. 2015. Recombinant receptor binding domain protein induces partial protective immunity in rhesus macaques against Middle East respiratory syndrome coronavirus challenge. EBioMedicine 2:1438–46 [Google Scholar]
  71. Zhao J, Li K, Wohlford-Lenane C. 71.  et al. 2014. Rapid generation of a mouse model for Middle East respiratory syndrome. PNAS 111:4970–75 [Google Scholar]
  72. Agrawal AS, Garron T, Tao X. 72.  et al. 2015. Generation of a transgenic mouse model of Middle East respiratory syndrome coronavirus infection and disease. J. Virol. 89:3659–70 [Google Scholar]
  73. Li K, Wohlford-Lenane C, Perlman S. 73.  et al. 2016. Middle East respiratory syndrome coronavirus causes multiple organ damage and lethal disease in mice transgenic for human dipeptidyl peptidase 4. J. Infect. Dis. 213:712–22 [Google Scholar]
  74. Haagmans BL, van den Brand JM, Provacia LB. 74.  et al. 2015. Asymptomatic Middle East respiratory syndrome coronavirus infection in rabbits. J. Virol. 89:6131–35 [Google Scholar]
  75. Houser KV, Gretebeck L, Ying T. 75.  et al. 2016. Prophylaxis with a Middle East respiratory syndrome coronavirus (MERS-CoV)-specific human monoclonal antibody protects rabbits from MERS-CoV infection. J. Infect. Dis. 213:1557–61 [Google Scholar]
  76. Baseler LJ, Falzarano D, Scott DP. 76.  et al. 2016. An acute immune response to Middle East respiratory syndrome coronavirus replication contributes to viral pathogenicity. Am. J. Pathol. 186:630–38 [Google Scholar]
  77. Johnson RF, Bagci U, Keith L. 77.  et al. 2016. 3B11-N, a monoclonal antibody against MERS-CoV, reduces lung pathology in rhesus monkeys following intratracheal inoculation of MERS-CoV Jordan-n3/2012. Virology 490:49–58 [Google Scholar]
  78. 78. Scientific Advisory Council Mininstry of Health, Saudi Arabia. 2014. Infection prevention/control and management guidelines for patients with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection, 2nd. http://www.moh.gov.sa/en/CCC/StaffRegulations/Corona/Documents/GuidelinesforCoronaPatients.pdf
  79. 79. World Health Organization 2014. Middle East respiratory syndrome coronavirus (MERS-CoV). Update on MERS-CoV transmission from animals to humans, and interim recommendations for at-risk groups http://www.who.int/csr/disease/coronavirus_infections/MERS_CoV_RA_20140613.pdf

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