When MERS-CoV (Middle East Respiratory Syndrome Coronavirus) emerged in 2012, Malik Peiris, co-director of HKU-Pasteur Research Pole, along with colleagues from the School of Public Health (The University of Hong Kong) and the Centre of Influenza Research rapidly mobilized to investigate the virus. Today, keeping a close watch on the virus epidemiology, setting serological, clinical studies and immunotherapy strategies in animal models are still a main objective shared among the team in order to respond to a global situation. During the past 3 years, they published numerous papers, strong of their previous experience in studying another coronavirus, the SARS-CoV (Severe Acute Respiratory Syndrome Coronavirus).
© National Institute of Allergy and Infectious Diseases (NIAID)
Coronaviruses, the “global village”, MERS and the threat of emerging diseases
In late 2002, the emergence of SARS-CoV in Southern China came as an unexpected public health crisis as coronaviruses had not been recognized as pathogens responsible for severe diseases in humans at that time. Research conducted since the SARS epidemic has then shown that a variety of coronaviruses are circulating among various species, bats notably, revealing the risk for human health caused by theses viruses. The SARS outbreak also demonstrated that emerging infectious diseases have the potential to quickly spread from one local region to turn global illustrating that for diseases as for information, we live in a “global village”, and highlighted the need for a close surveillance of coronaviruses. Zoonotic threats also made emerge the “One Health” concept, setting the global paradigm of interdependent health in humans, animals and environment.
In this context, MERS-CoV has been first discovered in September 2012 in Saudi Arabia. Today, MERS-CoV infection has been widely exported by travelers from the Middle East to North America, North Africa, Europe and Asia. To date, 26 countries have reported cases of MERS-CoV and WHO has been notified of 1,684 laboratory-confirmed cases of infection with MERS-CoV globally and 600 deaths related to MERS-CoV since September 2012. Saudi Arabia is the most affected country, but South Korea has also known a severe outbreak in 2015.
MERS-CoV infection can cause severe acute respiratory disease, especially in people with underlying conditions such as diabetes, renal failure, chronic lung disease or immunocompromission. The mortality rate is estimated at around 30% even though it could be an over-estimation given that mild or asymptomatic cases may not be detected.
The primary source of zoonotic infection in human is complex to clarify. Highly phylogenetically similar viruses have been found in bats, which may be a natural reservoir for the precursor of MERS-CoV. Transmission of MERS-CoV between camels has been documented and more importantly, dromedary camels can transmit the virus to humans. Are they an intermediate host or the natural reservoir of the virus? This question remains to be addressed. Occasional transmissions to humans probably occurred during contact with dromedary camels or via the consumption of raw camel’s milk. Human-to-human transmission occurs during close physical contact, via respiratory secretions, particularly within healthcare facilities or family settings, but it remains limited. Sustained community transmission has not been observed so far except for the South Korea outbreak (one travel-associated patient led to 185 human MERS infections, 36 deaths). However, one should remember the emergence of SARS in 2002 that started with self-limited outbreaks of human disease before the virus finally adapted to human-to-human transmission and spread across 5 continents.
No specific treatment or vaccine is available for fighting this virus. The challenge is to contain the epidemic by preventive actions and get research efforts under way to better understand the virus pathogenesis, fill the gaps in the understanding of the transmission in animals, from animals to humans, and develop therapeutic tools.
Seroepidemiological study in Yemen. © CDC/ Awadh Mohammed Ba Saleh
Characterizing MERS-CoV and tracking transmission sources
HKU-Pasteur Research Pole researchers and their partners are involved in this challenge since the discovery of MERS-CoV. They first studied the MERS-CoV pathogenesis by experimentally infecting ex vivo cultures of the respiratory system to explore the virus tropism and the associated innate immune response. Their results showed that MERS-CoV replicates efficiently in human respiratory tissues, targeting bronchial and alveolar epitheliums, and endothelium of blood vessels in the lung. They have then conducted a lot of works to investigate the MERS-CoV seroprevalence in dromedary camels in order to have a better knowledge of the geographical distribution of MERS-CoV in its suspected animal reservoir. Seroepidemiology is a precious tool to investigate the sources of zoonotic transmission. Malik Peiris and co-workers have developed a novel pseudoparticle neutralization assay which doest not require Biosafety Level 3 containment, well adapted for large-scale seroepidemiology studies. This assay uses a replication-incompetent human immunodeficiency virus (HIV) containing a reporter gene and expressing the spike protein of MERS-CoV. With this method, they have investigated the presence of MERS in camels in countries of interest. They revealed high seroprevalence of MERS-CoV in Egypt, Saudi Arabia and Nigeria. Studies in Mongolia showed that the Bactrian camels appear to be seronegative. They also tested archived dromedary sera in Saudi Arabia and Australia. While dromedaries have been seronegative in Australia, their study revealed that MERS-CoV has been circulating in camels in the Arabian Peninsula for at least several decades: it is not a newly emerged virus from camels.
Apart from seroepidemiological investigations, HKU-Pasteur Research Pole also took part in a clinical study in collaboration with the First Affiliated Hospital of Guangzhou Medical University. They reported the case of MERS patient from South Korea infected during the outbreak who traveled to Hong Kong and China where he was hospitalized. “In this study, we provide detailed and serial data on clinical progression, viral load data in different clinical specimens, plasma cytokine levels, serum antibody responses comparing multiple serological assays and T-cell responses. Among other things, this case report highlights the importance of sputum collection that impacts on diagnostic yield and viral load, comparative serological data using conventional neutralization, pseudo-particle neutralization and ELISA assays, and potent T cell responses to the spike protein of MERS-CoV. Thus, it is one of the most intensively investigated patients with MERS so far “ says Chris Mok, principal investigator at HKU-Pasteur Research Pole who participated in the study (publication No.16 in the list below).
HKU-Pasteur Research Pole and its collaborators continue to focus their efforts on understanding MERS in a global action to be better prepared to confront the challenge of emerging diseases.
Publications on MERS (HKU-Pasteur Research Pole and the School of Public Health, HKU):
1. Tropism of and innate immune responses to the novel human betacoronavirus lineage C virus in human ex vivo respiratory organ cultures.
Chan RW, Chan MC, Agnihothram S, Chan LL, Kuok DI, Fong JH, Guan Y, Poon LL, Baric RS, Nicholls JM, Peiris JS. J Virol. 2013 Jun;87(12):6604-14. doi: 10.1128/JVI.00009-13. Epub 2013 Apr 3. PMID:23552422
2. Seroepidemiology for MERS coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in dromedary camels in Egypt, June 2013.
Perera RA, Wang P, Gomaa MR, El-Shesheny R, Kandeil A, Bagato O, Siu LY, Shehata MM, Kayed AS, Moatasim Y, Li M, Poon LL, Guan Y, Webby RJ, Ali MA, Peiris JS, Kayali G. Euro Surveill. 2013 Sep 5. PMID: 24079378
3. From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.
Hilgenfeld R, Peiris M. Antiviral Res. 2013 Oct;100(1):286-95. doi: 10.1016/j.antiviral.2013.08.015. Epub 2013 Sep 6. Review. PMID: 24012996
4. Middle East Respiratory Syndrome (MERS) coronavirus seroprevalence in domestic livestock in Saudi Arabia, 2010 to 2013.
Hemida MG, Perera RA, Wang P, Alhammadi MA, Siu LY, Li M, Poon LL, Saif L, Alnaeem A, Peiris M. Euro Surveill. 2013 Dec 12;18(50):20659. PMID:24342517
5. MERS coronaviruses in dromedary camels, Egypt.
Chu DK, Poon LL, Gomaa MM, Shehata MM, Perera RA, Abu Zeid D, El Rifay AS, Siu LY, Guan Y, Webby RJ, Ali MA, Peiris M, Kayali G. Emerg Infect Dis. 2014 Jun;20(6):1049-53. doi: 10.3201/eid2006.140299. PMID:24856660
6. Seroepidemiology of Middle East respiratory syndrome (MERS) coronavirus in Saudi Arabia (1993) and Australia (2014) and characterisation of assay specificity.
Hemida MG, Perera RA, Al Jassim RA, Kayali G, Siu LY, Wang P, Chu KW, Perlman S, Ali MA, Alnaeem A, Guan Y, Poon LL, Saif L, Peiris M. Euro Surveill. 2014 Jun 12;19(23). pii: 20828. PMID:24957744
7. MERS coronavirus in dromedary camel herd, Saudi Arabia.
Hemida MG, Chu DK, Poon LL, Perera RA, Alhammadi MA, Ng HY, Siu LY, Guan Y, Alnaeem A, Peiris M. Emerg Infect Dis. 2014 Jul;20(7):1231-4. doi: 10.3201/eid2007.140571. PMID:24964193
8. Tropism and replication of Middle East respiratory syndrome coronavirus from dromedary camels in the human respiratory tract: an in-vitro and ex-vivo study.
Chan RW, Hemida MG, Kayali G, Chu DK, Poon LL, Alnaeem A, Ali MA, Tao KP, Ng HY, Chan MC, Guan Y, Nicholls JM, Peiris JS. Lancet Respir Med. 2014 Oct;2(10):813-22. doi: 10.1016/S2213-2600(14)70158-4. Epub 2014 Aug 28. PMID:25174549
9. Sparse evidence of MERS-CoV infection among animal workers living in Southern Saudi Arabia during 2012.
Memish ZA, Alsahly A, Masri MA, Heil GL, Anderson BD, Peiris M, Khan SU, Gray GC. Influenza Other Respir Viruses. 2015 Mar;9(2):64-7. doi: 10.1111/irv.12287. Epub 2014 Dec 3. PMID:25470665
10. Lack of middle East respiratory syndrome coronavirus transmission from infected camels.
Hemida MG, Al-Naeem A, Perera RA, Chin AW, Poon LL, Peiris M. Emerg Infect Dis. 2015 Apr;21(4):699-701. doi: 10.3201/eid2104.141949. PMID:25811546
11. Passive immunotherapy with dromedary immune serum in an experimental animal model for Middle East respiratory syndrome coronavirus infection.
Zhao J, Perera RA, Kayali G, Meyerholz D, Perlman S, Peiris M. J Virol. 2015 Jun;89(11):6117-20. doi: 10.1128/JVI.00446-15. Epub 2015 Mar 18. PMID:25787284
12. Absence of MERS-Coronavirus in Bactrian Camels, Southern Mongolia, November 2014.
Chan SM, Damdinjav B, Perera RA, Chu DK, Khishgee B, Enkhbold B, Poon LL,Peiris M. Emerg Infect Dis. 2015 Jul;21(7):1269-71. doi: 10.3201/eid2107.150178. PMID:26080032
13. Dromedary Camels and the Transmission of Middle East Respiratory SyndromeCoronavirus (MERS-CoV).
Hemida MG, Elmoslemany A, Al-Hizab F, Alnaeem A, Almathen F, Faye B, Chu DK, Perera RA, Peiris M. Transbound Emerg Dis. 2015 Aug 10. doi: 10.1111/tbed.12401. PMID:26256102
14. Comparison of serological assays in human Middle East respiratory syndrome(MERS)-coronavirus infection.
Park SW, Perera RA, Choe PG, Lau EH, Choi SJ, Chun JY, Oh HS, Song KH, Bang JH, Kim ES, Kim HB, Park WB, Kim NJ, Poon LL, Peiris M, Oh MD. Euro Surveill. 2015 Oct 15;20(41). doi: 10.2807/1560-7917.ES.2015.20.41.30042. PMID:26538277
15. Molecular Epidemiology of Hospital Outbreak of Middle East Respiratory Syndrome, Riyadh, Saudi Arabia, 2014.
Fagbo SF, Skakni L, Chu DK, Garbati MA, Joseph M, Peiris M, Hakawi AM. Emerg Infect Dis. 2015 Nov;21(11):1981-8. doi: 10.3201/eid2111.150944. PMID:26484549
16. Characteristics of Traveler with Middle East Respiratory Syndrome, China, 2015.
Da Guan W, Mok CK, Chen ZL, Feng LQ, Li ZT, Huang JC, Ke CW, Deng X, Ling Y, Wu SG, Niu XF, Perera RA, Da Xu Y, Zhao J, Zhang LQ, Li YM, Chen RC, Peiris M, Chen L, Zhong NS. Emerg Infect Dis. 2015 Dec;21(12):2278-80. doi: 10.3201/eid2112.151232. PMID:26583433
17. Kinetics of Serologic Responses to MERS Coronavirus Infection in Humans, South Korea.
Park WB, Perera RA, Choe PG, Lau EH, Choi SJ, Chun JY, Oh HS, Song KH, Bang JH, Kim ES, Kim HB, Park SW, Kim NJ, Man Poon LL, Peiris M, Oh MD. Emerg Infect Dis. 2015 Dec;21(12):2186-9. doi: 10.3201/eid2112.151421. PMID:26583829
18. Asymptomatic MERS-CoV Infection in Humans Possibly Linked to Infected Dromedaries Imported from Oman to United Arab Emirates, May 2015.
Al Hammadi ZM, Chu DK, Eltahir YM, Al Hosani F, Al Mulla M, Tarnini W, Hall AJ, Perera RA, Abdelkhalek MM, Peiris JS, Al Muhairi SS, Poon LL. Emerg Infect Dis. 2015 Dec;21(12):2197-200. doi: 10.3201/eid2112.151132. PMID:26584223
19. Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels in Nigeria, 2015.
Chu DK, Oladipo JO, Perera RA, Kuranga SA, Chan SM, Poon LL, Peiris M. Euro Surveill. 2015 Dec 10;20(49). doi: 10.2807/1560-7917.ES.2015.20.49.30086. PMID:26676406
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