Middle East respiratory syndrome coronavirus: risk factors and determinants of primary, household, and nosocomial transmission

David S Hui, Esam I Azhar, Yae-Jean Kim, Ziad A Memish, Myoung-Don Oh, Alimuddin Zumla, David S Hui, Esam I Azhar, Yae-Jean Kim, Ziad A Memish, Myoung-Don Oh, Alimuddin Zumla

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonosis that causes death in 35·7% of cases. As of Feb 28, 2018, 2182 cases of MERS-CoV infection (with 779 deaths) in 27 countries were reported to WHO worldwide, with most being reported in Saudi Arabia (1807 cases with 705 deaths). MERS-CoV features prominently in the WHO blueprint list of priority pathogens that threaten global health security. Although primary transmission of MERS-CoV to human beings is linked to exposure to dromedary camels (Camelus dromedarius), the exact mode by which MERS-CoV infection is acquired remains undefined. Up to 50% of MERS-CoV cases in Saudi Arabia have been classified as secondary, occurring from human-to-human transmission through contact with asymptomatic or symptomatic individuals infected with MERS-CoV. Hospital outbreaks of MERS-CoV are a hallmark of MERS-CoV infection. The clinical features associated with MERS-CoV infection are not MERS-specific and are similar to other respiratory tract infections. Thus, the diagnosis of MERS can easily be missed, unless the doctor or health-care worker has a high degree of clinical awareness and the patient undergoes specific testing for MERS-CoV. The largest outbreak of MERS-CoV outside the Arabian Peninsula occurred in South Korea in May, 2015, resulting in 186 cases with 38 deaths. This outbreak was caused by a traveller with undiagnosed MERS-CoV infection who became ill after returning to Seoul from a trip to the Middle East. The traveller visited several health facilities in South Korea, transmitting the virus to many other individuals long before a diagnosis was made. With 10 million pilgrims visiting Saudi Arabia each year from 182 countries, watchful surveillance by public health systems, and a high degree of clinical awareness of the possibility of MERS-CoV infection is essential. In this Review, we provide a comprehensive update and synthesis of the latest available data on the epidemiology, determinants, and risk factors of primary, household, and nosocomial transmission of MERS-CoV, and suggest measures to reduce risk of transmission.

Copyright © 2018 Elsevier Ltd. All rights reserved.

Figures

Figure
Figure
Global cases of MERS-CoV infection reported to WHO Reproduced from WHO by permission of World Health Organization. MERS CoV=Middle East respiratory syndrome coronavirus.

References

    1. Peiris JS, Yuen KY, Osterhaus AD, Stöhr K. The severe acute respiratory syndrome. N Engl J Med. 2003;349:2431–2441.
    1. WHO Severe acute respiratory syndrome. (accessed March 28, 2018).
    1. Hui DS, Memish ZA, Zumla A. Severe acute respiratory syndrome vs the Middle East respiratory syndrome. Curr Opin Pulm Med. 2014;20:233–241.
    1. WHO Middle East respiratory syndrome coronavirus (MERS-CoV) (accessed Jan 16, 2018).
    1. Zumla A, Hui DS, Perlman S. Middle East respiratory syndrome. Lancet. 2015;386:995–1007.
    1. Lee JY, Kim YJ, Chung EH. The clinical and virological features of the first imported case causing MERS-CoV outbreak in South Korea, 2015. BMC Infect Dis. 2017;17:498.
    1. Majumder MS, Brownstein JS, Finkelstein SN, Larson RC, Bourouiba L. Nosocomial amplification of MERS-coronavirus in South Korea, 2015. Trans R Soc Trop Med Hyg. 2017;111:261–269.
    1. Korea Centers for Disease Control and Prevention Middle East respiratory syndrome coronavirus outbreak in the Republic of Korea, 2015. Osong Public Health Res Perspect. 2015;6:269–327.
    1. WHO WHO statement on the ninth meeting of the IHR Emergency Committee regarding MERS-CoV. June 17, 2015. (accessed Oct 15, 2017).
    1. WHO List of blueprint priority diseases. (accessed March 28, 2018).
    1. Zaki AM, van Boheemen S, Bestebroer TM. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012;367:1814–1820.
    1. Arabi YM, Balkhy HH, Hayden FG. Middle East respiratory syndrome. N Engl J Med. 2017;376:584–594.
    1. Saudi Arabia Ministry of Health MERS-CoV daily update. (accessed March 19, 2018).
    1. Memish ZA, Mishra N, Olival KJ. Middle East respiratory syndrome coronavirus in bats, Saudi Arabia. Emerg Infect Dis. 2013;19:1819–1823.
    1. Reusken CB, Farag EA, Jonges M. Middle East respiratory syndrome coronavirus (MERS-CoV) RNA and neutralising antibodies in milk collected according to local customs from dromedary camels, Qatar, April 2014. Euro Surveill. 2014;19:20829.
    1. Ali MA, Shehata MM, Gomaa MR. Systematic, active surveillance for Middle East respiratory syndrome coronavirus in camels in Egypt. Emerg Microbes Infect. 2017;6:e1.
    1. van Doremalen N, Bushmaker T, Munster VJ. Stability of Middle East respiratory syndrome coronavirus (MERS-CoV) under different environmental conditions. Euro Surveill. 2013;18:20590.
    1. Sikkema RS, Farag EA, Himatt S. Risk factors for primary Middle East respiratory syndrome coronavirus infection in camel workers in Qatar during 2013–2014: a case-control study. J Infect Dis. 2017;215:1702–1705.
    1. Alraddadi BM, Watson JT, Almarashi A. Risk factors for primary Middle East respiratory syndrome coronavirus illness in humans, Saudi Arabia, 2014. Emerg Infect Dis. 2016;22:49–55.
    1. Arwady MA, Alraddadi B, Basler C. Middle East respiratory syndrome coronavirus transmission in extended family, Saudi Arabia, 2014. Emerg Infect Dis. 2016;22:1395–1402.
    1. Müller MA, Meyer B, Corman VM. Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: a nationwide, cross-sectional, serological study. Lancet Infect Dis. 2015;15:559–564.
    1. Azhar EI, El-Kafrawy SA, Farraj SA. Evidence for camel-to-human transmission of MERS coronavirus. N Engl J Med. 2014;370:2499–2505.
    1. Memish ZA, Cotten M, Meyer B. Human infection with MERS coronavirus after exposure to infected camels, Saudi Arabia, 2013. Emerg Infect Dis. 2014;20:1012–1015.
    1. Al Hammadi ZM, Chu DK, Eltahir YM. Asymptomatic MERS-CoV infection in humans possibly linked to infected dromedaries imported from Oman to United Arab Emirates, May 2015. Emerg Infect Dis. 2015;21:2197–2200.
    1. Kasem S, Qasim I, Al-Hufofi A. Cross-sectional study of MERS-CoV-specific RNA and antibodies in animals that have had contact with MERS patients in Saudi Arabia. J Infect Public Health. 2017 doi: 10.1016/j.jiph.2017.09.022. published online Oct 6.
    1. Hemida MG, Al-Naeem A, Perera RA, Chin AW, Poon LL, Peiris M. Lack of Middle East respiratory syndrome coronavirus transmission from infected camels. Emerg Infect Dis. 2015;21:699–701.
    1. Dudas G, Carvalho LM, Rambaut A, Bedford T. MERS-CoV spillover at the camel-human interface. ELife. 2018 doi: 10.7554/eLife.31257. published online Jan 16.
    1. Al-Abdallat MM, Payne DC, Alqasrawi S. Hospital-associated outbreak of Middle East respiratory syndrome coronavirus: a serologic, epidemiologic, and clinical description. Clin Infect Dis. 2014;59:1225–1233.
    1. Assiri A, McGeer A, Perl TM. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med. 2013;369:407–416.
    1. Memish ZA, Zumla AI, Assiri A. Middle East respiratory syndrome coronavirus infections in health care workers. N Engl J Med. 2013;369:884–886.
    1. Memish ZA, Al-Tawfiq JA, Assiri A. Hospital-associated Middle East respiratory syndrome coronavirus infections. N Engl J Med. 2013;369:1761–1762.
    1. Memish ZA, Zumla AI, Al-Hakeem RF. Family cluster of Middle East respiratory syndrome coronavirus infections. N Engl J Med. 2013;368:2487–2494.
    1. Garbati MA, Fagbo SF, Fang VJ. A comparative study of clinical presentation and risk factors for adverse outcome in patients hospitalised with acute respiratory disease due to MERS coronavirus or other causes. PLoS One. 2016;11:e0165978.
    1. Mohd HA, Memish ZA, Alfaraj SH. Predictors of MERS-CoV infection: a large case control study of patients presenting with ILI at a MERS-CoV referral hospital in Saudi Arabia. Travel Med Infect Dis. 2016;14:464–470.
    1. Oh MD, Park WB, Choe PG. Viral load kinetics of MERS coronavirus infection. N Engl J Med. 2016;375:1303–1305.
    1. Memish ZA, Assiri AM, Al-Tawfiq JA. Middle East respiratory syndrome coronavirus (MERS-CoV) viral shedding in the respiratory tract: an observational analysis with infection control implications. Int J Infect Dis. 2014;29:307–308.
    1. Zhou J, Li C, Zhao G. Human intestinal tract serves an alternative infection route for Middle East respiratory syndrome coronavirus. Sci Adv. 2017;3:eaao4966.
    1. Ahmed AE. The predictors of 3- and 30-day mortality in 660 MERS-CoV patients. BMC Infect Dis. 2017;17:615.
    1. Rivers CM, Majumder MS, Lofgren ET. Risks of death and severe disease in patients with Middle East respiratory syndrome coronavirus, 2012–2015. Am J Epidemiol. 2016;184:460–464.
    1. Yang YM, Hsu CY, Lai CC. Impact of comorbidity on fatality rate of patients with Middle East respiratory syndrome. Sci Rep. 2017;7:11307.
    1. Hong KH, Choi JP, Hong SH. Predictors of mortality in Middle East respiratory syndrome (MERS) Thorax. 2017 doi: 10.1136/thoraxjnl-2016-209313. published online July 19.
    1. Seys LJ, Widagdo W, Verhamme FM. DPP4, the MERS coronavirus receptor, is upregulated in lungs of smokers and COPD patients. Clin Infect Dis. 2018;66:45–53.
    1. Lee JY, Kim YJ, Chung EH. The clinical and virological features of the first imported case causing MERS-CoV outbreak in South Korea, 2015. BMC Infect Dis. 2017;17:498.
    1. Al-Gethamy M, Corman VM, Hussain R. A case of long-term excretion and subclinical infection with Middle East respiratory syndrome coronavirus in a healthcare worker. Clin Infect Dis. 2015;60:973–974.
    1. Drosten C, Meyer B, Müller MA. Transmission of MERS-coronavirus in household contacts. N Engl J Med. 2014;371:828–835.
    1. Omrani AS, Matin MA, Haddad Q. 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.
    1. Nam HS, Park JW, Ki M. High fatality rates and associated factors in two hospital outbreaks of MERS in Daejeon, the Republic of Korea. Int J Infect Dis. 2017;58:37–42.
    1. Oboho IK, Tomczyk SM, Al-Asmari AM. 2014 MERS-CoV outbreak in Jeddah—a link to health care facilities. N Engl J Med. 2015;372:846–854.
    1. Alenazi TH, Al Arbash H, El-Saed A. 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.
    1. Al Hosani FI, Pringle K, Al Mulla M. Response to emergence of Middle East respiratory syndrome coronavirus, Abu Dhabi, United Arab Emirates, 2013–2014. Emerg Infect Dis. 2016;22:1162–1168.
    1. Alfaraj SH, Al-Tawfiq JA, Altuwaijri TA. Middle East respiratory syndrome coronavirus transmission among health care workers: implication for infection control. Am J Infect Control. 2017 doi: 10.1016/j.ajic.2017.08.010. published online Sept 25.
    1. Kim SW, Park JW, Jung HD. Risk factors for transmission of Middle East respiratory syndrome coronavirus infection during the 2015 outbreak in South Korea. Clin Infect Dis. 2017;64:551–557.
    1. Bin SY, Heo JY, Song MS. Environmental contamination and viral shedding in MERS patients during MERS-CoV outbreak in South Korea. Clin Infect Dis. 2016;62:755–760.
    1. Kang CK, Song KH, Choe PG. Clinical and epidemiologic characteristics of spreaders of Middle East respiratory syndrome coronavirus during the 2015 outbreak in Korea. J Korean Med Sci. 2017;32:744–749.
    1. Kim SH, Chang SY, Sung M. 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.
    1. Hunter JC, Nguyen D, Aden B. Transmission of Middle East respiratory syndrome coronavirus infections in healthcare settings, Abu Dhabi. Emerg Infect Dis. 2016;22:647–656.
    1. Cho SY, Kang J-M, Ha YE. MERS-CoV outbreak following a single patient exposure in an emergency room in South Korea: an epidemiological outbreak study. Lancet. 2016;388:994–1001.
    1. WHO WHO MERS-CoV global summary and assessment of risk. 21 July 2017. (accessed Nov 5, 2017).
    1. Alraddadi BM, Al-Salmi HS, Jacobs-Slifka K. Risk factors for Middle East respiratory syndrome coronavirus infection among healthcare personnel. Emerg Infect Dis. 2016;22:1915–1920.
    1. Majumder MS, Brownstein JS, Finkelstein SN, Larson RC, Bourouiba L. Nosocomial amplification of MERS-coronavirus in South Korea, 2015. Trans R Soc Trop Med Hyg. 2017;111:261–269.
    1. Choi S, Jung E, Choi BY, Hur YJ, Ki M. High reproduction number of Middle East respiratory syndrome coronavirus in nosocomial outbreaks: mathematical modelling in Saudi Arabia and South Korea. J Hosp Infect. 2017 doi: 10.1016/j.jhin.2017.09.017. published online Sept 25.
    1. Song JY, Cheong HJ, Choi MJ. Viral shedding and environmental cleaning in Middle East respiratory syndrome coronavirus infection. Infect Chemother. 2015;47:252–255.
    1. Corman VM, Albarrak AM, Omrani AS. Viral shedding and antibody response in 37 patients with Middle East respiratory syndrome coronavirus infection. Clin Infect Dis. 2016;62:477–483.
    1. Park GE, Ko JH, Peck KR. Control of an outbreak of Middle East respiratory syndrome in a tertiary hospital in Korea. Ann Intern Med. 2016;165:87–93.
    1. Moon SY, Son JS. Infectivity of an asymptomatic patient with Middle East respiratory syndrome coronavirus infection. Clin Infect Dis. 2017;64:1457–1458.
    1. WHO . World Health Organization; Geneva: 2015. Infection prevention and control during health care for probable or confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection Interim guidance. (accessed Jan 17, 2018).
    1. WHO . World Health Organization; Geneva: 2009. WHO guidelines on natural ventilation for infection control in health-care settings. (accessed Nov 11, 2017).
    1. WHO Management of asymptomatic persons who are RTPCR positive for Middle East respiratory syndrome coronavirus (MERS-CoV) Interim Guidance. Updated Jan 3, 2018. (accessed Jan 16, 2018).
    1. WHO Middle East respiratory syndrome coronavirus (MERS-CoV) Fact sheet. Updated May 2017. (accessed Jan 16, 2018).
    1. Chu DK, Chan SM, Perera RA. MERS-CoV in Arabian camels in Africa and Central Asia. Virus Evol. 2017;3(suppl 1) vew036.045.
    1. Miguel E, Perera RA, Baubekova Absence of Middle East respiratory syndrome coronavirus in camelids, Kazakhstan, 2015. Emerg Infect Dis. 2016;22:555–557.
    1. Tran K, Cimon K, Severn M, Pessoa-Silva CL, Conly J. Aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review. PLoS One. 2012;7:e35797.
    1. 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;27:411–417.
    1. Hui DS, Perlman S, Zumla A. Spread of MERS to South Korea and China. Lancet Respir Med. 2015;3:509–510.
    1. Memish ZA, Zumla A, Alhakeem RF. Hajj: infectious disease surveillance and control. Lancet. 2014;383:2073–2082.
    1. Zumla A, Rustomjee R, Ntoumi F. Middle East respiratory syndrome—need for increased vigilance and watchful surveillance for MERS-CoV in sub-Saharan Africa. Int J Infect Dis. 2015;37:77–79.
    1. Zumla A, Hui DS. Infection control and MERS-CoV in health-care workers. Lancet. 2014;383:1869–1871.
    1. Zumla A, Chan JF, Azhar EI, Hui DS, Yuen KY. Coronaviruses—drug discovery and therapeutic options. Nat Rev Drug Discov. 2016;15:327–347.
    1. Hui DS, Zumla A. Advancing priority research on the Middle East respiratory syndrome coronavirus. J Infect Dis. 2014;209:173–176.

Source: PubMed

3
Abonnieren