Alarm bells over MERS coronavirus.

Middle East coronavirus is causing alarm among researchers and international health officials. Neil Bennet looks at the unfolding situation.

Middle East coronavirus is causing alarm among researchers and international health officials. Neil Bennet looks at the unfolding situation.

Speaking at the close of the 66th World Health Assembly in Geneva, Switzerland, on May 27, WHO Director General Margaret Chan said: “Looking at the overall world health situation, my greatest concern right now is the novel coronavirus.”

The virus, which has now been named the Middle East respiratory syndrome (MERS) coronavirus, is the first lineage-C β coronavirus known to infect human beings. It is related to bat coronaviruses, but although an animal reservoir is suspected as the source of the infections, none has been identified. As of June 11, 55 confirmed infections and 31 deaths have been reported to WHO since the first case was identified in September last year. Most of the infections and deaths have occurred in Saudi Arabia, where a recent outbreak has centred on one health-care facility in the Al-Hasa region.

“When the first case was detected in Saudi Arabia, the initial suspicion was that we were dealing with an isolated zoonotic event”, Ron Fouchier (Erasmus MC, Rotterdam, Netherlands) told TLID. Fouchier's team characterised the virus isolated from the first reported case—a patient from Jeddah, Saudi Arabia.

Cases have since been reported in three other countries in the region—Jordan, Qatar, and the United Arab Emirates (UAE). Infections associated with travel or contact with a returned traveller have been reported in France, Germany, Italy, Tunisia, and the UK.

The second case was in London, UK, in a man who had recently travelled from Qatar. “Alarm bells went off, as the two cases were separated in time and space”, Fouchier continued. “With the cases imported into European hospitals, the retrospectively identified outbreak in Jordan, and the outbreak in Al-Hasa, this MERS outbreak starts to look like SARS more and more.”

According to WHO, all patients with laboratory-confirmed MERS coronavirus infection have had respiratory disease as part of their illness, with cough, fever, and breathing difficulties reported. Presentation can range from mild symptoms to severe pneumonia. Other reported clinical features include acute respiratory distress syndrome, renal failure, pericarditis, consumptive coagulopathy, and gastrointestinal symptoms. Infection can present atypically—without initial respiratory symptoms—in immunocompromised patients. No virus-specific treatment exists, although WHO has noted that general care can be life saving.

The existence of clusters of infections was suggestive of person-to-person transmission, and recent reports have shown that such transmission has taken place, albeit only in health-care settings and among close family contacts. A report in of two cases in France described probable person-to-person transmission from a 64-year-old man who had recently visited Dubai, UAE, to a 51-year-old man with whom he had shared a hospital room for 3 days.

“The virus's incubation period in the second patient appears to have been 9–12 days, which is somewhat longer than what was previously observed”, said Benoit Guery (University of Lille, Lille, France), one of the investigators of the report. “This finding has important implications for the duration of the quarantine required to rule out infection among contacts”, he added.

Another important finding of the investigation was that the virus could be reliably detected only in samples taken from the lower respiratory tract, with nasopharyngeal samples weakly positive or inconclusive. The authors also recommended that initial negative results should be confirmed by a further sample a few days later to rule out infection with the coronavirus.

Most cases have been in men, and many have been in individuals with comorbidities. “Many of the reported cases, including those believed to have been infected through nosocomial transmission, had underlying conditions and were associated with a degree of immunosuppression”, Andrew Amato-Gauci (European Centre for Disease Prevention and Control [ECDC], Stockholm, Sweden) told TLID. “These underlying conditions may be an important factor increasing vulnerability and the risk of transmission.”

However, uncertainty about possible risk factors for infection emphasises the many substantial gaps in our knowledge about the virus. “We do not know where the virus hides in nature”, Chan noted in her speech. “We do not know how people are getting infected. Until we answer these questions, we are empty-handed when it comes to prevention. These are alarm bells. And we must respond.”

Margaret Chan during a meeting on the SARS-like virus coronavirus on May 23, 2013 at the World Health Assembly, Geneva

Sylvie van der Werf (Institut Pasteur, Paris, France) agreed, saying that “identification of the exact source of the virus is critical to be able to act to prevent new human infections. Although this virus is genetically closely related to those in bats, there might be an intermediate host in which the virus evolves and may acquire increased ability to transmit to humans.”

“The exact mechanism of transmission is unclear and much remains to be learned in that respect”, van der Werf also noted. “The more human cases there are with so-far limited person-to-person transmission, the more opportunities for the virus to fully adapt to humans and establish efficient human-to-human transmission, as was the case for SARS in 2003.”

In the SARS epidemic of 2002–03, WHO documented more than 8000 cases and 774 deaths. Case-fatality for MERS coronavirus seems higher (estimated at about 50%) than for SARS, although whether this is caused by higher virulence, under-reporting of mild disease, or a larger proportion of patients with immunosuppressive comorbidities is unknown.

Although no evidence exists for sustained transmission of MERS coronavirus in the community so far, that possibility remains a serious concern. The ECDC has done a risk assessment on the basis of available data. “At this stage, it is not possible to exclude a SARS-like scenario”, warned Marc Sprenger (ECDC), “especially in the light of the hospital-related outbreaks in Jordan and Al-Hasa.”

One major difference from the SARS outbreak is that, so far, very few health-care workers have been infected. Although this difference could result from differences between the two viruses, WHO speculated that improvements in infection control in response to the SARS outbreak might have had a substantial effect.

WHO has been working closely with affected countries, and a joint mission with Saudi Arabia concluded that the country has done “an excellent job in investigating and controlling the outbreaks”. Steps taken have included implementation of infection control in hospitals, increased surveillance, public awareness campaigns, epidemiological investigations, and collaboration with international experts. More generally, WHO is encouraging all countries to intensify surveillance and increase awareness among medical workers and travellers.

Although similarities with SARS sound bad the disease was stoppable, Fouchier reasons. “There is no evidence that MERS coronavirus spreads more efficiently between humans than SARS coronavirus did, and we should thus use the lessons from the SARS outbreak to stop this one.”