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MERS-CoV: the intermediate host identified?

2013; Elsevier BV; Volume: 13; Issue: 10 Linguagem: Inglês

10.1016/s1473-3099(13)70193-2

1474-4457

Emmie de Wit, Vincent J. Munster,

COVID-19 Clinical Research Studies

As of Aug 2, 2013, Middle East respiratory syndrome coronavirus (MERS-CoV) has caused 94 human cases—with most having severe respiratory disease—46 of these patients have died.1WHOGlobal Alert and Response (GAR): novel coronavirus infection.http://www.who.int/csr/don/2013_08_01/en/index.htmlGoogle Scholar Cases have been reported in Jordan, Qatar, United Arab Emirates, Saudi Arabia, France, Germany, Italy, the UK, and Tunisia. All cases detected outside the Arabian peninsula were linked to one of the Middle Eastern countries, either as a result of travel to those countries or through transmission from a person thought to have acquired the infection there. The high similarity of MERS-CoV to virus sequences detected in bats2Annan A Baldwin HJ Corman VM et al.Human betacoronavirus 2c EMC/2012-related viruses in bats, Ghana and Europe.Emerg Infect Dis. 2013; 19: 456-459Crossref PubMed Scopus (285) Google Scholar, 3Anthony SJ Ojeda-Flores R Rico-Chavez O et al.Coronaviruses in bats from Mexico.J Gen Virol. 2013; 94: 1028-1038Crossref PubMed Scopus (133) Google Scholar, 4van Boheemen S de Graaf M Lauber C et al.Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans.mBio. 2012; 3 (e00412): e00473Crossref Scopus (725) Google Scholar, 5Ithete NL Stoffberg S Corman VM et al.Close relative of human Middle East respiratory syndrome coronavirus in bat, South Africa.Emerg Infect Dis. 2013; http://dx.doi.org/10.3201/eid1910.130946PubMed Google Scholar suggests that it originates from bats. However, no one with the disease reported having direct contact with bats and bat-to-human transmission seems unlikely. The large geographical area of the MERS-CoV outbreak across the Arabian peninsula, the sequence variation between isolates, and the projected date of emergence some time before the first human cases were reported,6Cotten M Lam TT Watson SJ et al.Full-genome deep sequencing and phylogenetic analysis of novel human betacoronavirus.Emerg Infect Dis. 2013; 19 (42B): 736Crossref PubMed Scopus (121) Google Scholar, 7Drosten C Seilmaier M Corman VM et al.Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection.Lancet Infect Dis. 2013; (published online June 17.)http://dx.doi.org/10.1016/S1473-3099(13)70154-3PubMed Google Scholar suggest multiple zoonotic introductions of MERS-CoV and could indicate the involvement of an intermediate host. In The Lancet Infectious Diseases, Chantal Reusken and colleagues8Reusken CBEM Haagmans BL Muller MA et al.Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study.Lancet Infect Dis. 2013; (published online Aug 9.)http://dx.doi.org/10.1016/S1473-3099(13)70164-6PubMed Google Scholar provide some insight into one potential animal reservoir that might be involved in the emergence of MERS-CoV in people—for the first time since the discovery of the virus a year ago.9Zaki 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: 1814-1820Crossref PubMed Scopus (4187) Google Scholar They detected neutralising antibodies in 100% of serum samples from 50 dromedary camels collected in Oman in March, 2013. Surprisingly, 15 (14%) of 105 of dromedary camels from the Canary Islands (Spain) also had such antibodies. Serum samples collected from various other livestock species did not contain MERS-CoV-specific antibodies, although they were not collected in the same area as the camels, thereby potentially indicating geographical rather than host restriction. Whether the camels were infected with MERS-CoV itself or with a closely related virus is unclear. No human cases of infection have been reported in Oman so far, despite its proximity to countries with human cases and the high prevalence of neutralising antibodies against the virus in the local camel population. The detection of sequences similar to MERS-CoV in bats in Africa, the Americas, and Eurasia, and the presence of neutralising antibodies in camels from the Canary Islands suggest that MERS-CoV-like viruses have a wide geographical distribution. The absence of an association between the high prevalence of neutralising antibodies and morbidity or mortality in camels suggests that circulation of MERS-CoV-like viruses in camels might go undetected. This fact begs the question of whether the detection of MERS-CoV neutralising antibodies in camels from both Spain and Oman is a result of unrelated cross-species transmission events or whether the virus has been circulating in camels for a long time. Regardless, a change in the ecology of MERS-CoV must have occurred to enable emergence in people. This change could have been genetic, enabling the virus to efficiently replicate in the human respiratory tract, as happened with severe acute respiratory syndrome coronavirus, which acquired the ability to bind to human ACE2.10Bolles M Donaldson E Baric R SARS-CoV and emergent coronaviruses: viral determinants of interspecies transmission.Curr Opin Virol. 2011; 1: 624-634Crossref PubMed Scopus (136) Google Scholar Alternatively, an environmental or agricultural change could have enabled the introduction of MERS-CoV into a new host species, similar to the establishment of pig farming in Malaysia that enabled cross-species transmission of Nipah virus into pigs and subsequent spillover to people.11Pulliam JR Epstein JH Dushoff J et al.Agricultural intensification, priming for persistence and the emergence of Nipah virus: a lethal bat-borne zoonosis.J R Soc Interface. 2012; 9: 89-101Crossref PubMed Scopus (223) Google Scholar The report by Reusken and colleagues stresses the urgent need for an integrated, one health, approach by public and veterinary health stakeholders in all involved countries, combined with the rapid dissemination of data. Extensive serosurveys should be done across the Arabian peninsula, in people, livestock, and wild animal species, combined with virological testing where possible, to identify the potential reservoirs of MERS-CoV. In the absence of prophylactic or therapeutic treatment options for MERS-CoV,12Guery B van der Werf S Coronavirus: need for a therapeutic approach.Lancet Infect Dis. 2013; (published online June 17).http://dx.doi.org/10.1016/S1473-3099(13)70153-1PubMed Google Scholar blocking zoonotic and human-to-human transmission could be the most promising and cost-effective method to prevent further human fatalities. However, doing so requires knowledge of the virus' hosts. Although the study by Reusken and colleagues leaves many questions unanswered, it is an important step to a more comprehensive understanding of the emergence of MERS-CoV. This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. The views expressed are the authors' own and do not necessarily represent the views of the National Institutes of Health or the US Government. Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological studyMERS-CoV or a related virus has infected camel populations. Both titres and seroprevalences in sera from different locations in Oman suggest widespread infection. Full-Text PDF