Middle-East respiratory syndrome coronavirus: Is it worth a world panic?

Abstract

In 2012 Middle-East respiratory syndrome coronavirus (MERS-CoV) was evolved in the Arabian Peninsula. Tremendous and successful efforts have been conducted to discover the genome structure, epidemiology, clinical signs, pathogenesis, diagnosis and antiviral therapy. Taphozous perforatus bats are the incriminated reservoir host and camels are the currently confirmed animal linker. The virus resulted in less than 1000 infected cases and 355 deaths. The case fatality rate of the MERS-CoV is high, however, many survivors of MERS-CoV infection showed inapparent infections and, in several cases, multiple co-infecting agents did exist. Although MERS-CoV appears to be a dangerous disease, it is argued here that a full assessment of current knowledge about the disease does not suggest that it is a truly scary killer.

Key Words: Coronavirus; Camels; Disease threat to humans; Middle-East respiratory syndrome coronavirus; Mortality rate

Core tip: Middle-East respiratory syndrome coronavirus (MERS-CoV) emerged as a novel human coronavirus in 2012. Although it induces a high level of case fatality, fatal infections were recorded mainly in immune compromised patients and co-infections were frequently recorded. Camels are the currently known natural animal host and are susceptible to mild non-fatal infections. There is a growing evidence that the virus has been circulating in camels for decades in the Middle East, Africa and possibly other areas where camel herds are present. The fact that the virus has existed for decades, together with the absence of large-scale human mortalities from unknown respiratory infections, gives a first indication that MERS-CoV is not a particularly dangerous virus.

TEXT

As of March 31, 2015, 1102 laboratory-confirmed cases of Middle-East respiratory syndrome coronavirus (MERS-CoV) infection have been reported by WHO with the case fatality rate reaching 37.7% (416/1102). Most cases (973/1102; 88%) were reported in Saudi Arabia and other countries of the Arabian Peninsula. Cases reported outside the Arabian Peninsula have been reported to have a direct or indirect link to the Arabian Peninsula, mostly through recent travel. MERS-CoV belongs to the C lineage of the genus Betacoronavirus. The Taphozous perforatus is a probable natural reservoir of MERS-CoV. Bat guano, saliva and/or urine are assumed to contaminate food and water resources of animals in areas with palm orchards and this may constitute an indirect source of transmission to camels, people and possibly to other animals. Dipeptidyl peptidase 4 (DPP4) (or so-called CD26) has been proved to be the functional receptor for MERS-CoV reviewed in[1].

Although all ages are affected, the most severe cases of MERS-CoV infection have generally been recorded in aged patients with underlying conditions. Mild and asymptomatic cases have also increased recently[2]. Co-infection with other pathogens including influenza A, parainfluenza, herpes simplex and pneumococcus was reported[3]. The clinical epidemiology of MERS-CoV cases has some similarities to human seasonal flu. Like seasonal flu, MERS-CoV infections resulted in respiratory illness in the majority of patients, with the disease affecting all ages, but being most severe in the elderly and immuno-compromised people. The fact that approximately half of the lethal cases of MERS-CoV involved mixed infections and/or immuno-compromised patients, and the fact that many subclinical and inapparent infections have been reported, suggest that the virus may not lead to catastrophic consequences.

Additionally, the annual mortalities associated with MERS-CoV are surprisingly lower than many other viruses that induce acute viral infections, e.g., seasonal influenza, 250000 to 500000 deaths[4]; rotavirus, 453000 child deaths[5]; measles, 145700 deaths[4]; rabies, 55000 deaths[6]; yellow fever virus, 30000 deaths (mostly in Africa)[4]; dengue fever virus, 25000 deaths mostly among children[7]; respiratory syncytial virus (RSV), 66000 to 199000 deaths in children less than 5 years old[8]; Lassa fever, 5000 deaths (in West Africa)[9].

It is worth mentioning that MERS-CoV has been isolated from camels in Saudi Arabia, Qatar, Oman, UAE and Egypt and the presence of MERS-CoV antibodies have been reported in camels from Saudi Arabia, Qatar, Oman, UAE, Egypt, Kenya, Nigeria, Ethiopia and the Canary Islands-Spain. Sera from sheep, goats, cattle, buffaloes, pigs, chicken and wild birds have all been found to be negative for MERS-CoV. It is interesting to note that the virus is prone to replicate efficiently in primate, pig and goat cell cultures, a finding which necessitates the screening of large numbers of these types of animals[1]. Overall, however, people in direct contact with camels are at most risk of contracting MERS-CoV infection, other possible indirect contact includes the consumption of of unpasteurized camel milk, even though only a few primary cases of MERS-CoV can be linked to an established direct contact with camels. The detection of MERS-CoV in camel serum samples archived over a period of decades is reassuring. MERS-CoV positive sera has been found in samples from 1983 in Somalia and Sudan[10], from 1993 in Saudi Arabia[11], from 1997 in Egypt[10], from 1996 in Kenya[12] and from 2003 in the UAE[13]. These findings imply that the MERS-CoV has been circulating for at least 31 years in the Horn of Africa countries and for at least 21 years in Saudi Arabia, without causing large-scale fatalities in humans. This conclusion can be further supported since, even in the absence of knowledge about MERS-CoV there have not been hundreds or thousands of cases of patients dying from unknown respiratory infections during this period. There is some hope, therefore that MERS-CoV may not be as a dangerous virus as was first feared. The ancestral virus strain might has been experienced mutations during this long period, which have rendered it able to cross the species barrier. It is not clear, however, whether the currently circulating virus strains have acquired additional mutations which have render them able to be easily transmissible from human to human.

Most viral diseases that affect cloven-hooved animals appear to be less virulent to camels, which typically develop only inapparent or mild clinical signs. This may be due to the camels’ robust immune system. It is also worth mentioning that coronavirus infection in camels leads to mild respiratory symptoms that may reflect restricted virus proliferation and consequently low virus shedding. The possibility that there is another animal linker needs to be investigated. Taking into consideration that palm dates are consumed extensively in the Arabian Peninsula, the role of an animal linker that may harbour the MERS-CoV and contaminate palm dates needs to be investigated.

A small cohort serosurvey that was conducted in Saudi Arabia did not report MERS-CoV antibodies in slaughterhouse workers who were in close contact with camels, sheep, goat and cattle[14]. Further large scale MERS-CoV serosurveys in a range of populations such as those who have no contact with animals, health-care workers, people with close contact with camels in countries where camels are bred and traded, especially in the Arabian Peninsula, Eastern Africa and Asia, are needed to explore the exact morbidity rate of MERS-CoV.

Coronaviruses are continuously evolving, but major genetic differences have not yet been recorded among human cases. Nonetheless, elucidation of the genetic diversity of MERS-CoV strains from camels in Africa, and other parts of the world where camels are found, should be undertaken as a matter of urgency. MERS-CoV is assumed currently to constitute only a mild to moderate risk to human health, but it remains important not to underestimate the potential risk of the virus.