While the disease du jour remains Zika, another virus with a much greater ability to spread in hospitals continues to simmer in an arid region a plane ride away: Middle East Respiratory Syndrome (MERS) coronavirus.
Though eclipsed by Zika virus, MERS is still causing infections in hospitals, some of them begun by “super spreaders” that cause explosive outbreaks. The quasi-medical term was coined to describe a single person who infects an unusually large number of contacts, including other patients and healthcare workers.
WHO recently reported an outbreak of MERS in a hospital in Riyadh, Saudi Arabia, where a single patient infected 24 contacts — 13 patients and 11 healthcare workers.1 A WHO report on June 22, 2016, stated the index patient was admitted to a Saudi hospital in critical condition with MERS undiagnosed because it was “masked by other predominant symptoms.” She was admitted through the ED and began showing signs of respiratory illness before death. MERS symptoms commonly include fever, cough, and shortness of breath. Pneumonia develops in many cases, and gastrointestinal symptoms like diarrhea have also been reported.
“Following admission, the patient showed signs of respiratory illness and MERS was suspected,” the WHO states. “The hospital diagnosed and confirmed MERS on June 12, 2016, within 48 hours of her original admission.”
Investigators of a 2015 outbreak of MERS in Samsung Medical Center in Seoul, South Korea, recently published a study that revealed one patient exposed hundreds of patients, visitors, and healthcare workers while in the ED between May 27 and May 29.2 MERS infection was confirmed in 33 patients, 41 visitors, and eight healthcare workers.
“Our results showed increased transmission potential of MERS from a single patient in an overcrowded emergency room and provide compelling evidence that healthcare facilities worldwide need to be prepared for emerging infectious diseases,” the authors concluded.
These transmissions to numerous contacts from a single infected case reopened discussions of super-spreaders, a phenomenon also observed in the 2003 outbreak of a similar coronavirus, Severe Acute Respiratory Syndrome (SARS). The concept goes back at least to “Typhoid Mary,” a food server in the early 20th century, but was popularized during the 2003 SARS outbreak. Indeed, the global outbreak of SARS began when a Chinese doctor infected more than a dozen other people staying on the ninth floor of the Metropole Hotel in Hong Kong. They departed to their home countries with SARS in tow.
A patient with undiagnosed SARS was admitted to one hospital and then transferred to another in Singapore in 2003. A total of 62 people with probable SARS, including 37 additional patients, were linked to this single case.3
“With respiratory infections, TB included, the concept of a super-spreader being extremely dangerous in terms of transmission has some real credence,” says William Schaffner, MD, an epidemiologist in the department of preventive medicine at Vanderbilt University Medical Center in Nashville, TN. “I think the general infectious disease community is very accepting of that, though it is not as well-documented as we would like. Of course, in addition to that, the longer a patient goes undiagnosed — ‘super-spreader’ or not — and they have the opportunity to have face-to-face contact with more and more people, that obviously increases the risk of transmission.”
Super-spreaders are related to a variety of factors, from the viral titer in the patient’s system, the frequency and type of contacts, and the air currents in the room where they are awaiting or receiving care.
“I think it is a perfectly valid concept, but there is still a little bit of controversy about them,” says Allison McGeer, MD, a microbiologist and infectious disease consultant at Mount Sinai Hospital in Toronto. “I think the events themselves are a combination of [factors influencing] transmission from individual patients and the environmental space, airflow, and infection control practices. I don’t think there is any question that they are real, but a lot of the time they are really complex events.”
The number of newly infected patients resulting from a single infected patient over a defined period of time is found in some variety for most infectious diseases, she adds. With SARS, maps of transmission showed most infections resulting in few, if any, additional cases, and then one or two patients who infect 20 other people.
WHO and individual epidemiologists have cited “doctor shopping” and other practices of the Korean healthcare system by way of explanation of the large outbreak after importation of MERS by a returning traveler.
“That was a big part of it — not only that patient’s visit to a lot of institutions and individual providers, but the entire structure and tradition of infection control simply was not as robust in Korea as it was in other parts of the world,” Schaffner says. “This was true also initially in Saudi Arabia and the Middle East, and those countries have been working very hard to introduce the kind of infection control that we are used to in the U.S. into those countries. They have still not been entirely successful. It takes a very sustained effort.”
Having experienced the 2003 SARS outbreak in Toronto firsthand, McGeer is unconvinced that the Korean MERS outbreak was an anomaly.
“It’s fine to say people in South Korea shop for hospitals, but we do the same thing,” she says. “I think South Korea with MERS looked a lot like Toronto with SARS: a competent healthcare system that just wasn’t paying enough attention to the possibility [of a MERS introduction]. Things can go wrong.”
‘It Ain’t Over Yet’
In that regard, some complacency may have set in at U.S. facilities, as MERS was contained in 2014 when two unrelated cases were admitted to hospitals in Indiana and Florida. Those cases involved healthcare workers who had recently worked in Saudi Arabian hospitals, but next time MERS may not be so obviously identified. Crowded EDs in the U.S. could certainly be vulnerable to an undiagnosed MERS patient, thus a familiar colloquialism applies to the situation.
“It’s true it ain’t over till it’s over — and MERS ain’t over yet,” says Schaffner. “We can all use a reminder that it is not over and to stay alert.”
Camels in Saudi Arabia are the likely reservoir host for the virus, which appears to be originally of bat origin. MERS does not spread effectively in the community, but can cause hospital outbreaks that endanger other patients and often include transmission to healthcare workers. It is striking that MERS has emerged in the Middle East but has not been able to really establish an endemic foothold in another region in the absence of its camel reservoir. That said, as we have seen with Zika virus, the longer the MERS coronavirus is loose in the world and causing infections, the greater the likelihood that it could eventually mutate to become more transmissible between humans.
“There is no question that primary cases are continuing to occur at a steady rate,” McGeer says. “I think there are far fewer secondary cases and that there are presumably fewer exported cases. There is still a risk of travel-associated cases and there is no evidence that that risk is going to go away. All of us around the world are still at risk of a travel-associated case triggering an outbreak.”
MERS Travels to 27 Countries
As of Sept. 8, 2016, the WHO reported that MERS has caused 1,800 laboratory-confirmed cases of infection with 640 deaths related to MERS-CoV since September 2012. The pathogen remains primarily in Saudi Arabia, though 27 countries have reported cases via travelers from the region. The overall case count translates to a mortality rate of 35%, with deaths occurring primarily in those with underlying medical conditions.
“I think even with a really good healthcare system, you can miss an index case and then detect a case as part of a nosocomial outbreak,” McGeer says. “Twenty-five years ago, detecting dengue in my hospital was not an issue, but now it is. Detecting things like MERS has been helpful, because travel history is not just something needed in terms of infection control — it is helpful in terms of individual-level diagnosis [and treatment].”
Complicating the situation, a study published last year raised the possibility of transmission from those with asymptomatic MERS. There appear to be thousands of asymptomatic or mild MERS cases — primarily young men who have frequent contact with camels — who may be transmitting the virus to those with underlying medical conditions in Saudi Arabia, according to a seroprevalence study.4 That said, U.S. hospitals may have to run that risk as long as they can at least pick up incoming symptomatic MERS cases.
“In North America you just have to pick up the travelers to get the people at risk, but in Saudi Arabia you have to treat everybody who might have a respiratory infection as if they had a MERS infection — that it is a huge burden,” says McGeer, who has traveled to the kingdom to investigate the hospital outbreaks. “From my perspective, it has been really hard for Saudi Arabia to get this far, but the good news in this latest outbreak is that less than a week from what appeared to be the index case, there was a report to WHO [disclosing that a case was missed and transmission occurred]. That’s as good as it is going to get in Saudi Arabia. They are going to miss cases.”
Though no transmission has occurred in the U.S., the 2014 MERS introductions caused considerable chaos and concern. The CDC initially reported that an Indiana man with MERS transmitted it via handshake to a man from Illinois, but more refined testing revealed the suspected secondary case did not have the coronavirus. No other patients were infected, but healthcare workers exposed to the first two MERS cases were subject to rapid follow-up and home quarantine policies following the exposures.
The emotional toll on healthcare workers during a MERS outbreak can be considerable. A hospital outbreak of MERS caused emotional turmoil and stress in healthcare workers, particularly after some of their own colleagues became so seriously infected they had to be put on ventilator support, a recent study reports.5
The unusual study looked at the emotional toll and stress on healthcare workers during a 2014 MERS outbreak in King Faisal Specialist Hospital & Research Center, a 420-bed tertiary care hospital in Jeddah, Saudi Arabia. The three severely infected workers survived, but seeing their condition with the knowledge that healthcare workers had died of MERS in other outbreaks was unsettling to staff, Imran Khalid, MD, a pulmonary and critical care physician at the hospital and lead author of the study, said via email.
“The healthcare workers were really disturbed to see that MERS is able to cause fatal infections in previously healthy people and transmit from asymptomatic patients,” Khalid said. “However, fears were eased once the outbreak came under control in 2014, and also since then, no more cases have been seen in our hospital. There were 12 healthcare workers who were infected with MERS. Three required ICU [treatment] but all survived and are back to work.”
The three severely infected workers suffered respiratory failure, leading to intubation and mechanical ventilation to keep them alive.
How deadly can MERS be? Eight patients infected with coronavirus developed pneumonia and died during the outbreak.
Keep up Index of Suspicion
The 2014 U.S. introductions certainly raised MERS awareness, as hospitals like Vanderbilt follow-up rapidly when they identify a suspect case, Schaffner says. The travel piece is critical because the initial onset of MERS can be virtually indistinguishable from other severe respiratory infections.
“We have not had any MERS, but we have had several ‘alerts’ on patients who have been evaluated as possible MERS introductions,” he says. “That system has worked very well. The patient immediately gets put into isolation, infection control is notified, and they are on the scene. Specimens are obtained and the state health department laboratory is notified, and the specimens are sent to the state lab and are managed with appropriate security. We get answers pretty darn quick.”
Likewise, McGeer sees about one case a month of a patient with severe respiratory symptoms and a travel or contact history that would raise the possibility of MERS infections.
“The screening question in our emergency department is, ‘Have you or any of your close contacts traveled?’” she says. “That testing gets done in six hours and the second that testing result is available, every hospital in the province will know what’s going on in my hospital. I would say we send testing for MERS once a month.”
Of course, many patients and healthcare workers may already be exposed by the time a MERS case is diagnosed. To prevent these exposures from the outset, the CDC recommends respiratory “etiquette” signs and posters, reminding patients to adhere to respiratory hygiene and cover coughs while practicing hand disinfection and following triage procedures.6
“Instructions should include how to use face masks or tissues to cover nose and mouth when coughing or sneezing, to dispose of tissues and contaminated items in waste receptacles, and how and when to perform hand hygiene,” CDC recommends. “Implement respiratory hygiene and cough etiquette (i.e., placing a face mask over the patient’s nose and mouth) and isolate those at risk for MERS-CoV infection in an airborne infection isolation room.”
- WHO. Update and clarification on recent MERS cases reported by the Kingdom of Saudi Arabia. Geneva, Switzerland. 23 June 2016: http://bit.ly/2azKtF5.
- Sun YC, Kang JM, Young EH, et al. MERS-CoV outbreak following a single patient exposure in an emergency room in South Korea: an epidemiological outbreak study. Lancet. Published online July 8, 2016: http://bit.ly/2aS1nvS.
- CDC. Severe Acute Respiratory Syndrome — Singapore, 2003. MMWR 2003;52(18):405-411.
- 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.
- Khalid I, Khalid TJ, Qabajah MR, et al. Healthcare Workers’ Emotions, Perceived Stressors and Coping Strategies During a MERS-CoV Outbreak. Clinical Medicine & Research 2016;14:7-14.
- CDC. Interim Infection Prevention and Control Recommendations for Hospitalized Patients with Middle East Respiratory Syndrome Coronavirus (MERS-CoV): http://bit.ly/2aGpwWQ.