The Fight Against MERS is Not Over Yet

Despite the relatively short history of Middle East respiratory syndrome (MERS) coronavirus, researchers have made significant progress toward identifying potential medical countermeasures to both curtail its spread and enhance its treatment. Still, much work needs to be done as the virus continues to plague countries in the Arabian Peninsula—as the outbreak in South Korea last spring illustrates.

These are essentially the conclusions of a review published by MERS experts at the Centers for Disease Control and Prevention (CDC) in the July 2016 issue of the journal Emerging Infectious Diseases (EID). According to the World Health Organization, there have been more than 1,700 laboratory-confirmed cases of MERS coronavirus disease, and more than 600 deaths attributed to it, since September 2012, when the first case was identified. Approximately 75% of the confirmed cases have been in Saudi Arabia, although 27 countries have reported locally acquired or exported cases of the disease. There have been 2 reported cases in the United States, both involving healthcare personnel who worked in Saudi Arabia.

Stanley Perlman, MD, PhD, professor of microbiology and pediatrics at the University of Iowa, told Contagion that the fact that most of the cases have “occurred in Saudi Arabia… has made it difficult to obtain information and, in some instances, samples” from patients to use in testing and lab work. Dr. Perlman, who was not involved in the CDC report published in EID but has published research on MERS elsewhere, added that researchers “are not where we want to be” as a result of these and other impediments.

The CDC authors, who summarize research accomplishments and outline for future research priorities, essentially agree. As they write in EID, the identification of suitable animal models for research into potential vaccines against and drug treatments for MERS coronavirus remains very much a work in progress, although significant strides have been made recently toward the potential use of common marmosets (small animal models) as well as camels and/or alpacas (large animal models). Additionally, although reverse transcription PCR (RT-PCR) molecular assays “can measure MERS-coronavirus RNA in samples from symptomatic patients and their asymptomatic contacts,” the CDC authors write, “[a] worldwide gap exists in the lack of readily available, simple, rapid, and accurate diagnostic tests.” They note that the slow development of MERS-coronavirus assays may, at least in part, be the result of the aforementioned “limited availability of clinical specimens and isolates from infected patients.”

Similarly, the CDC authors write that “no investigational therapeutic drugs have been evaluated for treatment of MERS-coronavirus patients in prospective randomized controlled clinical trials,” although already-available, Food and Drug Administration (FDA)-approved drugs such as “immunomodulators, small-molecule drugs with broad antiviral activity, small-molecule drugs that show activity against MERS-coronavirus in vitro, and newly developed monoclonal or polyclonal antibody therapies with specific activity against MERS-coronavirus” offer possible avenues for research in the short-term. They add that vaccines against MERS are already in development at the National Institute for Allergy and Infectious Diseases as well as at privately owned pharmaceutical manufacturers.

“Although preclinical development and research on potential MERS-coronavirus medical countermeasures has achieved appreciable progress to date, such development is preliminary, and substantive challenges must be overcome before most potential countermeasures are ready for human clinical trials,” the CDC authors write. “The only clinical trials of MERS-coronavirus medical countermeasures are phase I studies of a candidate vaccine and an immunotherapeutic… Prioritization of animal models, standardization of representative virus strains, and establishment of clinical trial capabilities in areas where the virus is endemic among dromedaries are viewed as critical elements of effective MERS-coronavirus medical countermeasures development.”

Other researchers agree. “The lack of understanding regarding transmission is still a gap that needs filling,” said Darryl Falzarano, PhD, project leader at the International Vaccine Centre at the University of Saskatchewan. “We do not understand how some people get infected, we do not understand who is going to infect an inordinate number of people as a ‘super-spreader,’ and in what conditions this occurs, and I think we do not really know why nosocomial outbreaks still play such a significant role in many of the cases. We also do not know the role of asymptomatic individuals in transmission.”

Dr. Falzarano believes the lack of attention paid to “advancing MERS-related countermeasures to date is due, at least in part, to “the absence of large outbreaks outside of the endemic area, with the exception of South Korea last summer.” However, that may be changing. A study published July 7 in The Lancet has assessed the South Korea outbreak, and may help identify how MERS was transmitted from a single so-called “super-spreader” patient in an overcrowded emergency room to a total of 82 patients, visitors, and healthcare workers over 3 days. The South Korea outbreak marked the highest transmission of MERS virus from a single patient outside the Middle East; overall, 186 cases were confirmed within 2 months.

According to the authors of The Lancet paper, the “super-spreader” was a 68-year-old male who had travelled to Bahrain, the United Arab Emirates, Saudi Arabia, and Qatar in the spring of 2015 before returning to South Korea. He first visited the Samsung Medical Center in Seoul on May 17 of that year, and was isolated the next day under the suspicion of MERS. He was formally diagnosed with the virus 3 days later. Unfortunately, prior to arriving at Samsung Medical Centre, the super-spreader had already transmitted the virus to several individuals in other hospitals, including a 35-year-old male with whom he shared a ward. This second man was the source of the outbreak at the hospital.

In a retrospective investigation of the outbreak at the hospital that included a review of closed-circuit security video footage and electronic medical records, The Lancet researchers estimated that more than 1,500 people were exposed to this second patient. Patients staying in the same zone of the emergency room as the patient had the highest risk of infection (20%), while the risk was 5% among those who had brief exposure at the registration area or the radiology suite, and 1% among other patients who stayed in different zones. The risk of infection was 2% in health-care workers and 6% in visitors. There were no confirmed cases of patients or visitors who visited the emergency room after the patient had been isolated.

In contrast, the super-spreader patient had been in contact with 285 other patients and 193 health-care workers but no further transmissions occurred at the hospital during the 24-hour period before he was isolated (he had previously infected 28 other patients in another hospital). The authors of The Lancet paper say that the difference in transmissibility between the super-spreader and the second patient could be caused by a number of factors such as time from onset of disease, symptoms, duration of contact, pattern of movement, and the spread of the virus itself.

“This study is the first to document the spread of MERS-coronavirus through a hospital by providing specific infection risk depending on the proximity of patients to the infected patient,” they write. “Our results show the increased potential of MERS virus infection from a single patient in an overcrowded emergency room. Overcrowding is an important issue for this outbreak but also a common feature of modern medicine which should be of concern to governments and health-care providers in the context of future possible outbreaks. Emergency preparedness and vigilance in hospitals, laboratories, and government agencies are crucial to the prevention of further large outbreaks not only of MERS-coronavirus infections, but also other emerging infectious diseases.”

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.