Middle East respiratory syndrome coronavirus: current situation and travel-associated concerns

Abstract

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 brought back memories of the occurrence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002. More than 1500 MERS-CoV cases were recorded in 42 months with a case fatality rate (CFR) of 40%. Meanwhile, 8000 cases of SARS-CoV were confirmed in six months with a CFR of 10%. The clinical presentation of MERS-CoV ranges from mild and non-specific presentation to progressive and severe pneumonia. No predictive signs or symptoms exist to differentiate MERS-CoV from community-acquired pneumonia in hospitalized patients. An apparent heterogeneity was observed in transmission. Most MERS-CoV cases were secondary to large outbreaks in healthcare settings. These cases were secondary to community-acquired cases, which may also cause family outbreaks. Travel-associated MERS infection remains low. However, the virus exhibited a clear tendency to cause large outbreaks outside the Arabian Peninsula as exemplified by the outbreak in the Republic of Korea. In this review, we summarize the current knowledge about MERS-CoV and highlight travel-related issues.

Keywords

coronavirus / MERS / Middle East respiratory syndrome

References

[1] Al-Tawfiq JA, Zumla A, Memish ZA. Travel implications of emerging coronaviruses: SARS and MERS-CoV. Travel Med Infect Dis 2014; 12(5): 422–428

[2] Al-Tawfiq JA, Zumla A, Memish ZA. Coronaviruses: severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus in travelers. Curr Opin Infect Dis 2014; 27(5): 411–417

[3] Word Health Organization. Middle East respiratory syndrome coronavirus (MERS-CoV) — Kuwait.

[4] Drosten C, Muth D, Corman VM, Hussain R, Al Masri M, HajOmar W, Landt O, Assiri A, Eckerle I, Al Shangiti A, Al-Tawfiq JA, Albarrak A, Zumla A, Rambaut A, Memish ZA. 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): 369–377

[5] Oboho IK, Tomczyk SM, Al-Asmari AM, Banjar AA, Al-Mugti H, Aloraini MS, Alkhaldi KZ, Almohammadi EL, Alraddadi BM, Gerber SI, Swerdlow DL, Watson JT, Madani TA. 2014 MERS-CoV outbreak in Jeddah—a link to health care facilities. N Engl J Med 2015; 372(9): 846–854

[6] WHO. Middle East respiratory syndrome coronavirus (MERS-CoV) — Republic of Korea.

[7] FluTrackers. South Korea Coronavirus MERS Case List—including imported and exported cases.

[8] World Health Organization. Middle East respiratory syndrome coronavirus (MERS-CoV): summary and risk assessment of current situation in the Republic of Korea and China —as of 19 June 2015.

[9] World Health Organization. Middle East respiratory syndrome coronavirus (MERS-CoV): WHO statement on the tenth meeting of the IHR Emergency Committee regarding MERS, 3 September 2015.

[10] Wolfe ND, Dunavan CP, Diamond J. Origins of major human infectious diseases. Nature 2007; 447(7142): 279–283

[11] The Economic and Social Impact of Emerging Infectious Disease. Mitigation through Detection, Research, and Response.

[12] Memish ZA, Alhakeem R, Stephens GM. Saudi Arabia and the emergence of a novel coronavirus. East Mediterr Health J 2013; 19(Suppl 1): S7–S11

[13] Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 2012; 367(19): 1814–1820

[14] Al-Tawfiq JA, Memish ZA. An update on Middle East respiratory syndrome: 2 years later. Expert Rev Respir Med 2015; 9(3): 327–335

[15] Hall AJ, Tokars JI, Badreddine SA, Saad ZB, Furukawa E, Al Masri M, Haynes LM, Gerber SI, Kuhar DT, Miao C, Trivedi SU, Pallansch MA, Hajjeh R, Memish ZA. Health care worker contact with MERS patient, Saudi Arabia. Emerg Infect Dis 2014; 20(12): 2148–2151

[16] Memish ZA, Mishra N, Olival KJ, Fagbo SF, Kapoor V, Epstein JH, Alhakeem R, Durosinloun A, Al Asmari M, Islam A, Kapoor A, Briese T, Daszak P, Al Rabeeah AA, Lipkin WI. Middle East respiratory syndrome coronavirus in bats, Saudi Arabia. Emerg Infect Dis 2013; 19(11): 1819–1823

[17] Memish ZA, Al-Tawfiq JA, Makhdoom HQ, Al-Rabeeah AA, Assiri A, Alhakeem RF, AlRabiah FA, Al Hajjar S, Albarrak A, Flemban H, Balkhy H, Barry M, Alhassan S, Alsubaie S, Zumla A. Screening for Middle East respiratory syndrome coronavirus infection in hospital patients and their healthcare worker and family contacts: a prospective descriptive study. Clin Microbiol Infect 2014; 20(5): 469–474

[18] World Health Organization. Middle East respiratory syndrome coronavirus case definition for reporting to WHO: interim case definition 14 July 2015.

[19] Al-Tawfiq JA, Memish ZA. Middle East respiratory syndrome coronavirus: epidemiology and disease control measures. Infect Drug Resist 2014; 7: 281–287

[20] Müller MA, Meyer B, Corman VM, Al-Masri M, Turkestani A, Ritz D, Sieberg A, Aldabbagh S, Bosch BJ, Lattwein E, Alhakeem RF, Assiri AM, Albarrak AM, Al-Shangiti AM, Al-Tawfiq JA, Wikramaratna P, Alrabeeah AA, Drosten C, Memish ZA. Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: a nationwide, cross-sectional, serological study. Lancet Infect Dis 2015; 15(5): 559–564

[21] Memish ZA, Zumla AI, Al-Hakeem RF, Al-Rabeeah AA, Stephens GM. Family cluster of Middle East respiratory syndrome coronavirus infections. N Engl J Med 2013; 368(26): 2487–2494

[22] Omrani AS, Matin MA, Haddad Q, Al-Nakhli D, Memish ZA, Albarrak AM. 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(9): e668–e672

[23] Memish ZA, Cotten M, Watson SJ, Kellam P, Zumla A, Alhakeem RF, Assiri A, Rabeeah AA, Al-Tawfiq JA. 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

[24] Cotten M, Watson SJ, Zumla AI, Makhdoom HQ, Palser AL, Ong SH, Al Rabeeah AA, Alhakeem RF, Assiri A, Al-Tawfiq JA, Albarrak A, Barry M, Shibl A, Alrabiah FA, Hajjar S, Balkhy HH, Flemban H, Rambaut A, Kellam P, Memish ZA. Spread, circulation, and evolution of the Middle East respiratory syndrome coronavirus. MBio 2014; 5(1): e01062–e13

[25] Cotten M, Watson SJ, Kellam P, Al-Rabeeah AA, Makhdoom HQ, Assiri A, Al-Tawfiq JA, Alhakeem RF, Madani H, AlRabiah FA, Al Hajjar S, Al-nassir WN, Albarrak A, Flemban H, Balkhy HH, Alsubaie S, Palser AL, Gall A, Bashford-Rogers R, Rambaut A, Zumla AI, Memish ZA. Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study. Lancet 2013; 382(9909): 1993–2002

[26] Assiri A, McGeer A, Perl TM, Price CS, Al Rabeeah AA, Cummings DA, Alabdullatif ZN, Assad M, Almulhim A, Makhdoom H, Madani H, Alhakeem R, Al-Tawfiq JA, Cotten M, Watson SJ, Kellam P, Zumla AI, Memish ZA; KSA MERS-CoV Investigation Team. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med 2013; 369(5): 407–416

[27] Memish ZA, Al-Tawfiq JA. Middle East respiratory syndrome coronavirus infection control: the missing piece? Am J Infect Control 2014; 42(12): 1258–1260

[28] Al-Tawfiq JA, Memish ZA. Middle East respiratory syndrome coronavirus: transmission and phylogenetic evolution. Trends Microbiol 2014; 22(10): 573–579

[29] Hijawi B, Abdallat M, Sayaydeh A, Alqasrawi S, Haddadin A, Jaarour N, Alsheikh S, Alsanouri T. Novel coronavirus infections in Jordan, April 2012: epidemiological findings from a retrospective investigation. East Mediterr Health J 2013; 19(Suppl 1): S12–S18

[30] Al-Abdallat MM, Payne DC, Alqasrawi S, Rha B, Tohme RA, Abedi GR, Al Nsour M, Iblan I, Jarour N, Farag NH, Haddadin A, Al-Sanouri T, Tamin A, Harcourt JL, Kuhar DT, Swerdlow DL, Erdman DD, Pallansch MA, Haynes LM, Gerber SI, Sabri N, Al Azhari M, Khazali H, Al Maayah M, Bilbeisi A, Dawood N, Al Zubi B, Meflih J, Mounds T, Fitzner J, Eltom A, Mafi A, Miao C, Caidi H, Trivedi S, Kamili S, Hall AJ, Curns A, Moore J, Pham H, Zimmerman C, Farnon E, Giorgi G, Gerber R; Jordan MERS-CoV Investigation Team. Hospital-associated outbreak of Middle East respiratory syndrome coronavirus: a serologic, epidemiologic, and clinical description. Clin Infect Dis 2014; 59(9): 1225–1233 PMID:24829216

[31] MERS-Coronavirus Molecular Epidemiology and Genetic Analysis— Origin and Evolution.

[32] Lau SK, Li KS, Tsang AK, Lam CS, Ahmed S, Chen H, Chan KH, Woo PC, Yuen KY. Genetic characterization of Betacoronavirus lineage C viruses in bats reveals marked sequence divergence in the spike protein of pipistrellus bat coronavirus HKU5 in Japanese pipistrelle: implications for the origin of the novel Middle East respiratory syndrome coronavirus. J Virol 2013; 87(15): 8638– 8650

[33] World Health Organization. Middle East respiratory syndrome coronavirus (MERS-CoV) summary and literature update as of 9 May 2014.

[34] World health organization. Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV in Republic of Korea at a glance.

[35] Cowling BJ, Park M, Fang VJ, Wu P, Leung GM, Wu JT. Preliminary epidemiological assessment of MERS-CoV outbreak in South Korea, May to June 2015. Euro Surveill 2015; 20(25): 7–13

[36] Saad M, Omrani AS, Baig K, Bahloul A, Elzein F, Matin MA, Selim MA, Al Mutairi M, Al Nakhli D, Al Aidaroos AY, Al Sherbeeni N, Al-Khashan HI, Memish ZA, Albarrak AM. 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

[37] Al-Tawfiq JA, Hinedi K, Ghandour J, Khairalla H, Musleh S, Ujayli A, Memish ZA. Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients. Clin Infect Dis 2014; 59(2): 160–165

[38] Arabi YM, Arifi AA, Balkhy HH, Najm H, Aldawood AS, Ghabashi A, Hawa H, Alothman A, Khaldi A, Al Raiy B. Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Ann Intern Med 2014; 160(6): 389–397

[39] Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, Al-Rabiah FA, Al-Hajjar S, Al-Barrak A, Flemban H, Al-Nassir WN, Balkhy HH, Al-Hakeem RF, Makhdoom HQ, Zumla AI, Memish ZA. 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(9): 752–761

[40] Shalhoub S, Farahat F, Al-Jiffri A, Simhairi R, Shamma O, Siddiqi N, Mushtaq A. IFN-α2a or IFN-β1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study. J Antimicrob Chemother 2015; 70(7): 2129–2132

[41] Who Mers-Cov Research Group. Stat e of Knowledge and Data Gaps of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Humans. PLoS Curr 2013 Nov 12; 5. pii: ecurrents.outbreaks.0bf719e352e7478f8ad85fa30127ddb8

[42] World Health Organization. Middle East respiratory syndrome coronavirus (MERS-CoV) summary and literature update–as of 20 January 2014.

[43] Memish ZA, Al-Tawfiq JA, Makhdoom HQ, Assiri A, Alhakeem RF, Albarrak A, Alsubaie S, Al-Rabeeah AA, Hajomar WH, Hussain R, Kheyami AM, Almutairi A, Azhar EI, Drosten C, Watson SJ, Kellam P, Cotten M, Zumla A. Respiratory tract samples, viral load, and genome fraction yield in patients with Middle East respiratory syndrome. J Infect Dis 2014; 210(10): 1590–1594

[44] World Health Organization. Revised case definition for reporting to WHO— Middle East respiratory syndrome coronavirus.

[45] European CDC. Severe respiratory disease associated with Middle East respiratory syndrome coronavirus (MERS-CoV) 21^st update, 21 October 2015.

[46] World Health Organization. IHR Emergency Committee concerning Middle East respiratory syndrome coronavirus.

[47] World Health Organization. Report on Sep 2, 2015 meeting

[48] Soliman T, Cook AR, Coker RJ. Pilgrims and MERS-CoV: what’s the risk? Emerg Themes Epidemiol 2015; 12(1): 3

[49] Lessler J, Rodriguez-Barraquer I, Cummings DA, Garske T, Van Kerkhove M, Mills H, Truelove S, Hakeem R, Albarrak A, Ferguson NM; MERS-CoV Scenario Modeling Working Group. Estimating Potential Incidence of MERS-CoV Associated with Hajj Pilgrims to Saudi Arabia, 2014. PLoS Curr 2014 Nov 24; 6. pii: ecurrents.outbreaks.c5c9c9abd636164a9b6fd4dbda974369

[50] Sridhar S, Brouqui P, Parola P, Gautret P. Imported cases of Middle East respiratory syndrome: an update. Travel Med Infect Dis 2015; 13(1): 106–109

[51] Zumla A, Mwaba P, Bates M, Al-Tawfiq JA, Maeurer M, Memish ZA. The Hajj pilgrimage and surveillance for Middle East Respiratory syndrome coronavirus in pilgrims from African countries. Trop Med Int Health 2014; 19(7): 838–840

[52] Annan A, Owusu M, Marfo KS, Larbi R, Sarpong FN, Adu-Sarkodie Y, Amankwa J, Fiafemetsi S, Drosten C, Owusu-Dabo E, Eckerle I. High prevalence of common respiratory viruses and no evidence of Middle East respiratory syndrome coronavirus in Hajj pilgrims returning to Ghana, 2013. Trop Med Int Health 2015; 20(6): 807–812

[53] Gautret P, Charrel R, Benkouiten S, Belhouchat K, Nougairede A, Drali T, Salez N, Memish ZA, Al Masri M, Lagier JC, Million M, Raoult D, Brouqui P, Parola P. Lack of MERS coronavirus but prevalence of influenza virus in French pilgrims after 2013 Hajj. Emerg Infect Dis 2014; 20(4): 728–730

[54] Memish ZA, Assiri A, Almasri M, Alhakeem RF, Turkestani A, Al Rabeeah AA, Al-Tawfiq JA, Alzahrani A, Azhar E, Makhdoom HQ, Hajomar WH, Al-Shangiti AM, Yezli S. Prevalence of MERS-CoV nasal carriage and compliance with the Saudi health recommendations among pilgrims attending the 2013 Hajj. J Infect Dis 2014; 210(7): 1067–1072

[55] Gierer S, Hofmann-Winkler H, Albuali WH, Bertram S, Al-Rubaish AM, Yousef AA, Al-Nafaie AN, Al-Ali AK, Obeid OE, Alkharsah KR, Pöhlmann S. Lack of MERS coronavirus neutralizing antibodies in humans, eastern province, Saudi Arabia. Emerg Infect Dis 2013; 19(12): 2034–2036

[56] Drosten C, Meyer B, Müller MA, Corman VM, Al-Masri M, Hossain R, Madani H, Sieberg A, Bosch BJ, Lattwein E, Alhakeem RF, Assiri AM, Hajomar W, Albarrak AM, Al-Tawfiq JA, Zumla AI, Memish ZA. Transmission of MERS-coronavirus in household contacts. N Engl J Med 2014; 371(9): 828–835

[57] van Doremalen N, Bushmaker T, Munster VJ. Stability of Middle East respiratory syndrome coronavirus (MERS-CoV) under different environmental conditions. Euro Surveill 2013; 18(38): 20590

[58] Leclercq I, Batéjat C, Burguière AM, Manuguerra JC . Heat inactivation of the Middle East respiratory syndrome coronavirus. Influenza Other Respi Viruses 2014; 8(5): 585–586

[59] WHO. Infection prevention and control of epidemic-and pandemic prone acute respiratory infections in health care.

[60] ECDC.

[61] CDC. Interim infection prevention and control recommendations for hospitalized patients with Middle East respiratory syndrome coronavirus. MERSCoV 15 May 2014.

[62] Coleman CM, Frieman MB. Treating MERS-CoV during an outbreak. Lancet Infect Dis 2014; 14(11): 1030–1031

[63] Momattin H, Mohammed K, Zumla A, Memish ZA, Al-Tawfiq JA. Therapeutic options for Middle East respiratory syndrome coronavirus (MERS-CoV)—possible lessons from a systematic review of SARS-CoV therapy. Int J Infect Dis 2013; 17(10): e792–e798

[64] Al-Tawfiq JA, Momattin H, Dib J, Memish ZA. Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study. Int J Infect Dis 2014; 20: 42–46

[65] Omrani AS, Saad MM, Baig K, Bahloul A, Abdul-Matin M, Alaidaroos AY, Almakhlafi GA, Albarrak MM, Memish ZA, Albarrak AM. Ribavirin and interferon α-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study. Lancet Infect Dis 2014; 14(11): 1090–1095

[66] Zumla A, Memish ZA, Maeurer M, Bates M, Mwaba P, Al-Tawfiq JA, Denning DW, Hayden FG, Hui DS. Emerging novel and antimicrobial-resistant respiratory tract infections: new drug development and therapeutic options. Lancet Infect Dis 2014; 14(11): 1136–1149

[67] Falzarano D, de Wit E, Rasmussen AL, Feldmann F, Okumura A, Scott DP, Brining D, Bushmaker T, Martellaro C, Baseler L, Benecke AG, Katze MG, Munster VJ, Feldmann H. Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat Med 2013; 19(10): 1313–1317

[68] Chan JF, Chan KH, Kao RY, To KK, Zheng BJ, Li CP, Li PT, Dai J, Mok FK, Chen H, Hayden FG, Yuen KY. Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus. J Infect 2013; 67(6): 606–616

[69] Falzarano D, de Wit E, Martellaro C, Callison J, Munster VJ, Feldmann H. Inhibition of novel coronavirus replication by a combination of interferon-α2b and ribavirin. Sci Rep 2013; 3: 1686

[70] Chan JF, Chan KH, Kao RY, To KK, Zheng BJ, Li CP, Li PT, Dai J, Mok FK, Chen H, Hayden FG, Yuen KY. Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus. J Infect 2013; 67(6): 606–616

[71] Chan JF, Yao Y, Yeung ML, Deng W, Bao L, Jia L, Li F, Xiao C, Gao H, Yu P, Cai JP, Chu H, Zhou J, Chen H, Qin C, Yuen KY. Treatment with lopinavir/ritonavir or interferon-β1b improves outcome of MERS-CoV infection in a nonhuman primate model of common marmoset. J Infect Dis 2015; 212(12): 1904–1913

[72] Kim UJ, Won EJ, Kee SJ, Jung SI, Jang HC. Combination therapy with lopinavir/ritonavir, ribavirin and interferon-α for Middle East respiratory syndrome: a case report. Antivir Ther 2015 Oct 22. [Epub ahead of print]

Compliance with ethics guidelines

Jaffar A. Al-Tawfiq, Ali S. Omrani, and Ziad A. Memish declare that they have no conflict of interest. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

RIGHTS & PERMISSIONS

2016 Higher Education Press and Springer-Verlag Berlin Heidelberg