Though Middle East Respiratory Syndrome (MERS) was stopped cold last year in the U.S. when two unrelated cases were admitted to hospitals, infection preventionists should maintain a high level of vigilance given a global situation marked by the continuing emergence of the coronavirus.
While the two cases in Indiana and Florida in May 2014 were healthcare workers who recently worked in Saudi Arabian hospitals, next time MERS may not be so obviously identified. Don’t forget that it was a sick family member of a SARS case — who therefore had no history of travel to the Hong Kong epicenter — that started a devastating outbreak in Toronto in 2003.1
“Of course we did a wonderful job in containing the two cases that were imported from the Middle East,” says Terri Rebmann, PhD, RN, CIC, associate professor in the Institute for Biosecurity at Saint Louis (MO) University. “We also got lucky because it would be very easy to import additional cases of MERS into the United States unknowingly. People could come in while they were still in the incubation period and we wouldn’t catch them on screening. We have been lucky in that regard. The sooner you identify these cases and get them isolated and start following correct infection prevention protocols, the less of an impact there should be in terms of morbidity and mortality.”
As of June 16, the MERS outbreak in Korea had reached 154 cases with 19 deaths, the World Health Organization reported. That translates to a mortality rate of 12%, considerably less than the 50%-60% death rates in hospital outbreaks after MERS emerged in Saudi Arabia in 2012. Saudi officials investigating those outbreaks said at the time they were probably missing a spectrum of milder cases, and that may explain some of the difference in the mortality rates. Saudi investigators are now starting to detect these milder cases, projecting that there may be thousands of subacute but transmissible infections in those with frequent contact with camels.2
“There is actually quite a bit more MERS disease — subclinical or very mild cases — [in Saudi Arabia] so the actual mortality rate isn’t as high as we previously thought,” Rebmann says. “So for hospitalized cases the mortality rate is still close to 60% — it’s very high. But in their general population [researchers have found] that the mortality rate was closer to 27%-30%. That is still a very high mortality rate.”
In Korea, the rapid spread of the coronavirus from a single imported case — a businessman who had traveled to the Middle East — was shocking, raising questions of whether the virus had mutated and become more transmissible. The WHO recently issued a preliminary finding based on isolates from two Koreans, noting that nothing points “conclusively to any significant biological change” in the MERS coronavirus.
“So far the virus is genetically stable; no major mutations,” says Ghazi Kayali, PhD, MPH, staff scientist in the Department of Infectious Diseases at St. Jude Children’s Research Hospital in Memphis, TN “But there is data showing that ‘super-spreaders’ — infected humans shedding a lot of virus — exist and may be the cause of the hospital-based infections we saw in the Gulf and currently in Korea.”
Concurring was Stanley Perlman, MD, PhD, a microbiology professor who studies coronavirus pathogenesis at the University of Iowa in Iowa City.
“There has been speculation that the index case and possibly others infected during the Korean outbreak have been so-called super spreaders: People who aerosolize the virus and almost have a halo of virus around them,” he says.
Credit Koreans for transparency
That said, Perlman makes an interesting observation that as bad as its infection control has been, Korea has been transparent in reporting cases.
“The reason that this is looking so bad is a combination of low vigilance; people were not ready,” he says. “Then after that the Koreans have actually been very transparent about what they are doing. They are reporting cases, doing all the testing and quarantining. This sounds very bad, but I suspect if Saudi Arabia had done this [at outbreak onset] it might have looked just as bad. But the Saudis tended to give out information less willingly, so you heard just about the severe cases. In Korea, everybody is being tested and all of the information is available.”
Based on current data there is no evidence “to suggest sustained human-to-human transmission in communities and no evidence of airborne transmission,” the WHO reports. “However, MERS is a relatively new disease and information gaps are considerable.”
In that regard, none other than Jun Byung-yool, the former director of the Korea Center for Disease Control and Prevention, said the rapid spread of MERS in Korea may be explained in part by the lack of antibodies in a population with no history of exposure to camels.
“One of the reasons [for the difference] may be that people in the Middle East have antibodies against the MERS virus from their frequent contact with camels, and South Koreans don‘t have them,” Jun said.3
A recent seroprevalence study in Saudi Arabia did find a higher level of antibodies in those frequently exposed to camels, but the vast majority of the samples taken showed no MERS antibodies present. Still, Jun’s theory is intriguing, recalling the European importation of smallpox which devastated Native Americans who had never been exposed to the disease.
Patient zero
Then again, no super spreaders or naïve immunity is really needed to explain the onset of the outbreak, which spread in the brazen absence of case identification and competent infection control measures.
The Korean outbreak was set in motion on May 4, when a 68-year-old businessman returned to Korea after a trip to Bahrain, United Arab Emirates, Saudi Arabia, and Qatar. He became symptomatic for a respiratory infection about a week later. This fits the MERS incubation period: a mean of five days to symptom onset with a range of two to 14 days.
Now suffering fever and cough, the man went to at least three different hospitals from May 8th to 20th, but MERS testing was not done until May 19. The sputum sample tested positive for MERS on May 20, after which the patient “was transferred to the nationally designated treatment facility for isolation,” Korean public health officials reported.
Meanwhile, symptoms began developing in patients, visitors, and healthcare workers at the various facilities where the index case sought care. From these cases the outbreak spread out in waves to at least a dozen healthcare facilities. One of these cases travelled from Korea to China on May 26 while symptomatic, testing positive for MERS in China on May 29 and making that Asian nation the 25th country to have at least one case of the coronavirus.
The rapidly expanding outbreak exposed the vulnerability and eccentricity of the Korean healthcare system, where it is apparently the norm to go to several different facilities in search of the best doctor and then have family members heavily involved in direct patient care.
“[Under these] circumstances you cannot possibly have rigorous infection control, particularly to the level that you need for a MERS case,” says William Schaffner, MD, chairman of preventive medicine at Vanderbilt University Medical Center in Nashville.
MERS is difficult to diagnose, particularly in the early part of an outbreak when awareness is relatively low and the coronavirus presents like many other influenza-like illnesses. The index case also did not report his recent travel history to the Middle East when he first sought treatment, the WHO reported. It is not clear whether healthcare providers asked.
“Conditions and cultural traditions specific to Korea have likely also played a role in the outbreak’s rapid spread,” the WHO noted.4 “The accessibility and affordability of healthcare in Korea encourage ‘doctor shopping.’ Patients frequently consult specialists in several facilities before deciding on a first-choice facility. Moreover, it is customary in Korea for many family members and friends to visit loved ones when they are in the emergency room or admitted to hospital. It is also customary for family members to provide almost constant bedside care often staying in the hospital room overnight, increasing the risk of close exposures in the healthcare setting.”
Perfect storm
A large outbreak of MERS under such conditions seems to fulfill the adage that “every system is perfectly designed to produce the results that it gets.” If changes are not made after the MERS outbreak, the Korean healthcare system could certainly be vulnerable to future emerging infections, possibly even amplifying the etiologic agent.
“When you look at it you think, ‘Wow, that is a good way to spread infections,” Perlman says.
In that regard, the WHO recommended that Korea should strengthen the medical facilities needed to deal with serious infectious diseases, including increased numbers of negative-pressure isolation rooms. After a thorough review of the situation, the WHO recommended that Korea:
• consider how to reduce the practice of “doctor shopping;”
• train more infection prevention and control specialists, infectious disease experts, laboratory scientists, epidemiologists, and risk communication experts;
• invest in strengthening public health capacities and leadership
Adding to this general state of confusion and misinformation were the widely dispersed images of Koreans wearing surgical masks in public and at social events. This measure would presumably not really be protective unless the person wearing the mask has MERS and is protecting others by containing their own respiratory secretions.
“First of all, that is the wrong kind of mask — those don’t do very much because they’re surgical masks and that’s not protective against respiratory spread,” Perlman says. “My take on it is that people are scared. You would have to be walking down the street and pass someone who had MERS who was really sick — was shedding a lot of virus — and then maybe talk within a foot of them. The odds of getting it are pretty slim. Closing schools also seemed like a bad idea to me.”
The WHO encouraged Korean officials to reopen schools that were closed due to fears around MERS. “Schools have not been linked to transmission of MERS in the Republic of Korea or elsewhere,” the WHO stated. “Reopening, combined with clear messages for the public on why, could start to build confidence and trust with the population in Korea. Regular communications on the evolution of the outbreak will also build confidence both in Korea and internationally.”
Even before the outbreak in Korea, MERS was increasing, with Saudi Arabia reporting twice as many cases (16) in the month of April than had occurred during the two years prior. Amid the ongoing outbreak in Korea and the substantial increase in the number of MERS cases reported worldwide since last spring, the Centers for Disease Control and Prevention recently issued both a health advisory and updated infection control guidelines on the coronavirus.5, 6
“The CDC updated their definition of a “person under investigation (PUI),’” Rebmann says. “They now indicate that recent travel within 14 days to a Korean healthcare facility is part of the definition for determining if someone should be a PUI. Travel to South Korea in and of itself is not a risk factor for exposure to MERS at this time. It’s a [history of] being in the Korean healthcare system that is the potential risk factor for exposure. This has important implications for infection preventionists, infectious disease physicians, hospital epidemiologists, and primary care providers. There needs to be increased awareness about this new potential source of exposure.”
The MERS outbreak should ultimately fade out in Korea as SARS did in Toronto, and perhaps for the same reason: the lack of an animal host (e.g, camel, civet cat) to serve as a reservoir. There are still many vexing questions about the emerging coronavirus, however, including, as noted above, exactly how it is transmitted.
“Even in the Middle East where there was a substantial period of a lot of nosocomial transmission, it never really got out into the community,” Schaffner says. “We have this great propensity for nosocomial spread, but once it gets out of the hospital environment it doesn’t spread very readily — there have been cases, but it doesn’t spread 1-2-3-4-5 in the community. This is kind of a [strange] virus and despite all of the verbiage that’s been written about it, I don’t think we really understand completely how it is transmitted.”
It would seem to require close, prolonged contact to transmit, but there have been case reports in Korea of patients acquiring MERS after being “in the same ward” as an infected patient.
“Even though the patients didn’t have direct contact, they were in the same ward,” Schaffner said. “The mode of transmission in those circumstances — could it have been airborne or was it transmitted via a healthcare worker? I don’t think that has ever been clarified.”
One of the lessons of SARS is that once you’ve lost vigilance — the bug is in the house — you’d better practice diligence with every MERS patient.
“We have great lessons about SARS from Canada,” he says. “We learned that nosocomial transmission occurred readily, had serious implications, and in order to interrupt it you had to identify patients very early and then put them in negative pressure rooms with absolute adherence to full-blown precautions. That’s where we learned that you have to have a monitor at the door to make sure everybody puts everything on and, very importantly, takes everything off carefully. The donning and doffing is done meticulously because as we have learned again with Ebola, it’s the doffing that could be potentially hazardous. I am skeptical that this level of education, training, and supervision is currently happening in South Korea. I am dubious.”
References
- Varia M, Wilson S, Sarwal S, et al. Hospital Outbreak Investigation Team. Investigation of a nosocomial outbreak of severe acute respiratory syndrome (SARS) in Toronto, Canada. CMAJ 2003; 19:285-392.
- Yang-joong, K. Professor: Lack of camel contact could be making Koreans more vulnerable to MERS. Hankyoreh June 16, 2015: http://bit.ly/1J5H1g6.
- Muller MA, Meyer B, Corman VM, et al. Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: A nationwide, cross-sectional, serological study Lancet Infect Dis 2015;15 (5)559–564.
- World Health Organization: Middle East Respiratory Syndrome (MERS) in the Republic of Korea. Situation Assessment: 15 June 2015: http://bit.ly/1IJHfGF.
- Centers for Disease Control and Prevention. Interim Infection Prevention and Control Recommendations for Hospitalized Patients with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) UPDATED June 2015: http://1.usa.gov/1sATkDQ.
- CDC. Updated Information and Guidelines for Evaluation of Patients for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection. Health Advisory Notice. June 11, 2015: http://1.usa.gov/1GROvRI.
Though MERS was stopped cold last year in the U.S. when two unrelated cases were admitted to hospitals, infection preventionists should maintain a high level of vigilance given a global situation marked by the continuing emergence of the coronavirus.
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