We’ve all had that annoying sore throat and cough which we often ignore thinking it’s only a cold. But, what if it’s the sign of something more ominous than just a cold or flu? What if it’s an infection by an unknown, killer virus – a coronavirus?
That was the scenario in 2003, when around 8000 people worldwide were sickened by SARS (severe acute respiratory syndrome) – the first frightening global epidemic of the 21st century – that killed 10 percent of those infected. SARS was caused by a newly discovered coronavirus, the SARS coronavirus (SARS-CoV).
Coronaviruses, named after their crown-like spikes from their surface, are viruses that can infect both humans and animals. In humans, they usually cause upper respiratory tract illnesses, and account for 20 percent of viruses causing the common cold. Until 2003, there were only two coronaviruses known to infect humans.
During the SARS epidemic, unprecedented panic and fear gripped the public, health workers, and travelers alike. Almost everyone in Hong Kong donned face masks, which became a household necessity. Most people in Asia were, in some way or another, affected by SARS, and the thought of another SARS-like disease would spark nightmares among many of us, particularly in Asia.
Now, a decade after the SARS outbreak, the threat of another potentially deadly epidemic is looming – this time coming from the Middle East. Middle East Respiratory Syndrome or MERS first emerged in September 2012 in Saudi Arabia. Coincidentally, MERS is also caused by a coronavirus never seen before in humans. The virus, referred to as MERS-CoV – and resembles SARS-CoV1,2 – was discovered by Dutch virologists.
As of 30 September 2013, there have been a total of 130 cases of MERS, mostly in Saudi Arabia, but a few cases as far away as the UK, of which 58 died. Scientists and healthcare workers are concerned as the disease is fatal in almost half of those infected.
Initial symptoms of SARS were flu-like and seemingly innocuous. But later they got more threatening as people developed pneumonia. SARS spread from person-to-person through close contact with infected individuals and through droplets emitted from the cough of those infected. MERS also presents symptoms similar to those of SARS; but one rather menacing difference is that many MERS patients develop kidney failure.
Both viruses originate from animals; the deadly MERS virus is traced to bats that were also found to be to the culprits of SARS. But, more animals are implicated in this intricate trail from bats to humans.
Origins of SARS
Initially, civets (cat-like animals), considered a delicacy in China, were widely believed to be the source of SARS. This led to the mass-culling of thousands of civets. In fact, some of the early cases were restaurant workers who served exotic food; these restaurants kept caged civets that ended up being served to customers.3 However, scientists later learned that no wild civets or farm civets were infected; only civets that were found in live-animal markets in southern China were infected with SARS.4
So how did those civets get SARS? The focus turned to bats as they were, along with civets and many other animals, kept in cages close to each other in crowded live-animal markets in southern China. They were, like civets, sold for consumption as their meat is eaten in some parts of China. Eventually, in 2005, the mystery was solved as SARS was traced to Chinese horseshoe bats in the wild areas of southern China, from research led by Prof. KY Yuen at the University of Hong Kong.5 At the same time, another independent study by a different group also found bats as natural reservoirs of SARS-CoV.6
Scientists then learned that civets were only intermediate hosts of SARS-CoV, meaning that they caught the virus and spread it to humans. The most widely accepted scenario is that bats had infected civets with SARS in the animal markets, and these civets then transmitted the virus to people.
This finding triggered an intense hunt for coronaviruses in bats, and since then scientists have discovered many bat coronaviruses. Prior to SARS, the existence of coronaviruses in bats was largely unexplored. But the unearthing of other viruses in bats was not alarming to scientists – bats are notorious for harboring many viruses causing diseases such as Nipah, Hendra, Rabies and Ebola, without overtly displaying any symptoms.
Origins of MERS
Many questions remain unanswered about MERS-CoV: what are the origins of this virus, how did humans get infected with MERS, and what can we do to prevent infection. The finding of the novel coronavirus prompted several researchers around the world who were previously involved in SARS-related studies to once again collaborate in their quest for the origins of this virus.
The obvious suspects were bats. Upon closer examination of the virus’s genetic code, indeed, its closest relatives are two coronaviruses isolated from bats in Hong Kong, both of which were discovered by a team led by Prof. Yuen, who was earlier involved in linking bats to SARS.7 The coronaviruses are found in Lesser bamboo bat and Japanese Pipistrelle, which are prevalent in Southeast Asia. Interestingly, bats belonging to the genus Pipistrelle are also reportedly found in Saudi Arabia.
To further support the view that bats are the hosts of MERS, a separate group of researchers isolated MERS-related coronaviruses from European Pipistrelle bats and Nycteris bats from Ghana.8 Subsequently, another study identified a new coronavirus from the feces of a bat in South Africa that is genetically closer to MERS-CoV than all previous Pipistrelle coronaviruses reported.9
Recently, a six-month long study on bats in Saudi Arabia carried out by the an international team of scientists, reported MERS-CoV in an Egyptian tomb bat that is identical in genetic sequence to the virus isolated from the first infected patient.10 Notably, this bat was found only a few kilometers from the patient’s home. This was the first study so far to find an exact match of MERS-CoV in bats, and although only one bat out of more than 90 was a perfect match, it provides strong evidence of bats as the virus’s reservoir.
Scientists are investigating the prospect that other animals may have caught the virus from bats and transmitted it to humans, like civets in the case of SARS. This is because sometimes viruses require the body of another mammal for them to change or mutate enough to jump into and infect humans. Also, humans are usually not in such close contact with bats than with other mammals. In fact, many of the cases of MERS had no known contact with bats before falling sick.
Prof. Yuen suggested that there is a chance that the ancestor of MERS-CoV is in bats and may jump into intermediate hosts like camels, goats or horses. It can then evolve into another immediate ancestor-virus that may further jump into humans giving rise to MERS-CoV. Scientists are still testing camels, goats, and sheep for MERS-CoV to decipher the transmission path of the virus.
To make things even more interesting and complicated, a latest study has found compelling evidence that the most likely suspects in our MERS mystery are camels. In this study, Prof Koopman from the Netherlands, along with an international team of scientists, collected blood samples from various livestock animals including cows, sheep, goats, and dromedary or one-humped camels from different countries.11 They tested the sera (clear yellow liquid called blood plasma minus any clotting factors) samples for the presence of antibodies against MERS-CoV spike protein on the surface of the virus. The results were astonishing – all 50 of the camels tested that originated from Oman were positive, indicating previous exposure to the MERS-CoV.
Camels are a source of meat and milk in some Middle Eastern countries. They are also used to transport goods and for racing.
To unravel the origins, it is crucial to test camels in Saudi Arabia, the center of the outbreak. But, even if they are also found to contain antibodies to MERS, that may not explain how patients got infected – most had no earlier contact with camels. Could another animal be involved? We need to determine whether patients had contact with any animals or animal-derived products before falling ill.
How then did MERS-CoV transmit from animals to humans? Possible routes could be through the feces of animals or respiratory droplets produced by coughing, assuming that animals also get sick upon infection. Perhaps camels came into close contact with bat feces (guano)?
Causes of emerging diseases
Outbreaks of novel diseases are becoming increasingly frequent. In fact, over 70% of emerging infectious diseases in humans come from animals. Why are we seeing this rise in novel diseases from animals? “Human population growth, density and intrusion into wild life habitats” along with “increasing concentration of animals in markets” are to blame, said Yuen – and other scientists agree.
Even though bats may harbor potentially deadly viruses, we should not blame them as the cause of SARS or MERS. Rather, it is our quest to encroach into their habitats (in some cases an unintended consequence of urbanization) and engage in illegal wildlife trade that brings us into close contact with them.
Bats – best known for their ability to use sound waves for navigation – are the only mammals capable of flying and amazingly represent 20 percent of all mammalian species. They play crucial roles in pollinating trees and in seed dispersal.
Humans have peacefully co-existed with wildlife for millennia. Mass-culling of civets was not the answer to curb the spread of SARS. Exposing wild animals to species that they would otherwise not have come into contact with poses risks. We’re just beginning to see the consequences; SARS and MERS are only a couple of the many diseases lurking out there. Surely, we’ll be witnessing other exotic diseases in the future – it’s just a matter of time before a new virus surfaces.
Are we not somewhat responsible for the emergence of novel infectious diseases in humans? What can we do to prevent them in humans?
- Corman V.M., Eckerle I, Bleicker T, Zaki A, Landt O, Eschbach-Bludau M., van Boheemen S., Gopal R., Ballhause M,…Drosten C. (2012). Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction. Euro Surveill, 17(39): pii=20285.
- Zaki A.M., van Boheemen S., Bestebroer T.M., Osterhaus ADME, Fouchier RAM. (2012). Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med, 367:1814-182. DOI: 10.1056/NEJMoa1211721
- Wang, M., Yan, M., Xu, H., Liang, W., Kan, B., Zheng, B, Xu, J. (2005). SARS-CoV infection in a restaurant from palm civet. Emerging Infectious Diseases, 11(12), 1860-1865. DOI: 10.3201/eid1112.041293
- Tu, C., Crameri, G., Kong, X., Chen, J., Sun, Y., Yu, M.,…Wang, L.F. (2004). Antibodies to SARS coronavirus in civets. Emerging Infectious Diseases, 10(2), 2244-2248. DOI: 10.3201/eid1012.040520
- Lau, S.K.P., Woo, P.K.Y., Li, K.S.M., Huang, Y., Tsoi, H.W., Wong, B.H.L.,…Yuen, K-Y. (2005). Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats. Proceedings of the National Academy of Sciences, 102, 14040-14045. DOI: 10.1073/pnas.0506735102
- Li, W., Shi, Z., Yu, M., Ren, W., Smith, C., Epstein, J.H.,…Wang, L.F. (2005). Bats are natural reservoirs of SARS-like coronaviruses. Science, 310, 676-678.
- Chan, J.F.W., Li, K.S.M., To, K.K.W., Cheng, V.C.C., Chen, H., Yuen, K-Y. (2012). Is the discovery of the novel human betacoronavirus 2c EMC/2012 (HCoV-EMC) the beginning of another SARS-like pandemic? Journal of Infection, 65: 477-489. DOI: 10.1016/j.jinf.2012.10.002
- Annan A, Baldwin HJ, Corman VM, Klose SM, Owusu M, Nkrumah EE, et al. (2013). Human betacoronavirus 2c EMC/2012–related viruses in bats, Ghana and Europe. Emerging Infectious Diseases, 19 (3). DOI: 10.3201/eid1903.121503
- Ithete N.L., Stoffberg S., Corman V.M., Cottontail V.M., Richards L.R., Schoeman M.C.,…Preiser W. (2013). Close relative of human Middle East respiratory syndrome coronavirus in bat, South Africa [letter]. Emerg Infect Dis [Internet]. 2013 Oct. DOI: 10.3201/eid1910.130946
- Memish, Z.A., Mishra, N., Olival, K.J., Fagbo, S.F., Kapoor, V., Epstein, J.H.,…Lipkin, W.I. (2013). Middle East respiratory syndrome coronavirus in bats, Saudi Arabia. Emerg Infect Dis [Internet]. 2013 Nov. DOI: 10.3201/eid1911.131172.
- Reusken, C.B.E.M, Haagmans, B.L., Muller, M.A., Gutierrez, C., Godeke, G-J., Meyer, B.,…Koopmans, M.P.G. (2013). Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study. The Lancet Infectious Diseases. DOI: 10.1016/S1473-3099(13)70164-6.