This outbreak of MERS in South Korea had entirely nosocomial, human-to-human and hospital-to-hospital transmission patterns. The outbreak was initiated by a failure to identify an imported emerging infectious disease and was then amplified through the unique health care system in South Korea [13]. South Korea has a nationwide health insurance system, which controls overall medical costs en bloc and provides a flexible medical service-delivery system without barriers between small and large hospitals [11, 13]. All Koreans can be treated at a low cost and can easily visit an ED in a tertiary hospital without a referral. To reduce costs, hospital rooms generally have multiple beds per room, as did the ED in our tertiary hospital. This system provides convenient medical service to patients at low cost, but it can be vulnerable to transmission of infectious diseases between hospitals. Early in the MERS outbreak in South Korea, some infected patients visited the ED of a tertiary hospital, but this hospital failed to recognize that the patient had MERS because of delayed information for the transmission tree from the national health care ministry and rapid movement of the patient to another hospital before the recognition of MERS infection at the previous hospital [16].
MERS patients may seek a medical facility early because of serious illness, but they may expose others if the infection is not identified quickly. In the Middle East, unrecognized cases are frequently reported and are related to a sudden peak of nosocomial infection [3, 4, 17]. In South Korea, lack of awareness about this emerging infection and experience with serious outbreaks of infection may have contributed to the low compliance of HCPs for maintaining PPE and hand hygiene in the hospital [11, 13]. Therefore, the unrecognized MERS patients were easily able to transmit the infection to others during their stay in hospital. In the South Korea outbreak, a total of 186 confirmed cases were reported, 153 (83.2%) of which had derived from 5 super-spreading events [16]. In these cases, transmission occurred mainly before these patients were isolated. Two of the super-spreading events were responsible for many cases of MERS transmission in the ED space in Hospital A (2nd super-spreading), Hospital B and our hospital (index patient in this study). All 3 hospitals were located in Seoul with a population of ≈10 million (Fig. 1). The long hospital stays and crowding in these EDs contributed strongly to the higher risk of coming into contact with infected patients or exposure to infected droplets.
A study of the outbreak in the ED of Hospital A initiated from the 2nd super-spreading event revealed a high potential risk of multiple transmissions of MERS from an unrecognized patient in a crowded ED [14]. This study showed that tracing of the contact with this patient was important for predicting the attack rate of nosocomial MERS infection. Because of the close exposure of other patients, there was a high risk of contact or exposure to droplets around this patient, which may have contributed to the high attack rate. In that study, people who stayed in the same zone in the ED (close contact area) had a 20% attack rate (23 of 117). By contrast, the attack rates were only 5% for others who stayed in different zones (3 of 58) despite a time overlap with the MERS patient in the ED before that patient was isolated and 1% (4 of 500) in those with no time overlap. This study emphasizes the importance of an isolation and surveillance strategy based on contact tracing.
The epidemiological results from our hospital ED contrast with the transmission results from Hospital A. In contrast to the high transmission rate from the 2nd super-spreading event in the ED of Hospital A, in our hospital, only 1 person, who worked in the radiology suit at ED, was confirmed with MERS. Although the index patient had a mild fever (37.5 °C) and lack of respiratory symptoms, we assumed that the index patient had a sufficient risk of transmission of MERS to others when this patient visited our ED. Five infected cases were identified at another hospital, and 2 ambulance workers were confirmed as having acquired MERS during transportation of the index patient before this patient visited our ED. In our post hoc comparison between the ED and GW, the ED group had a higher overall risk of MERS than the GW group. The overlap time with the index patient was much longer in the ED than in the GW (8 h vs. 1 h), and a higher percentage (23.1%) were classified in the high-risk group in the ED group (within 2 m of the index patient). However, the overall occurrence rate was only 0.6% in the ED group and there was no transmission among the 60 people (42.0%) who stayed in the same area of the ED, including the high-risk area within 2 m of the index patient. Otherwise GW showed relative higher transmission rate than ED. One of 8 people (16.7%) who stayed in the same room as the index patient in the GW was identified as having MERS. Surprisingly, two transmissions occurred in the low-risk group (staying on the same floor but no contact), which had been thought unlikely to be infected. These epidemiological features seemed to contradict previous knowledge of MERS transmission.
Our investigation has unique characteristics. The index patient could not walk by herself because of the femur fracture, which allowed us to obtain clear information about patient’s movement and contacts during the stay. Early acquisition of all available videos and assessment of closed-looped interviews can provide useful information for the investigation of outbreaks in hospitals. Using these, we were able to obtain comprehensive information to investigate the direct and indirect transmission risks, including possible virus shedding into the environment. We also obtained objective data by observation of PPE and hand hygiene of hospital staff at the same time.
Based on these data, we propose three issues for consideration when developing a MERS transmission and prevention policy. First, a useful assumption from our analysis is that human-to-human transmission can occur even with a very brief exposure time. Generally, a shorter duration of contact time may reduce the risk of transmission because of the lower chance of contact or exposure to droplets [6, 7]. However, more cautious measures should be considered because the duration of exposure to our index patient was very brief. In our case review, all four MERS patients who were in contact with or within 2 m of the index patients had a very brief contact time (all < 5 min). The short duration did not translate to a lower risk of MERS transmission in this case. This suggests that MERS transmission can occur by brief human-to-human contact more easily than has been thought.
Second, we identified a possible pattern of human-to-human MERS transmission via the hands of medical employees who were in contact with an infected patient. In our post-hoc analysis of the tracing process, we missed two case of MERS infected form the index patient (tenth and eleventh patient). Although these two patients were admitted on the same floor, there was no exposure to the index patient. Considering the long incubation period of over 14 days, both patients may have been infected from a contaminated environment on this floor after MERS patient was isolated. However, this is seldom a possible route of action because of the following facts. When we identified index patient, we cleaned all environments of hospital. The following day, we began checking daily for presence of the MERS virus for several days and confirmed no existence of the MERS virus. The transmission routes are not easily identified under current knowledge about contact or droplet transmission or indirect transmission via a contaminated environment. An attending doctor or nurse came into contact with the index patient during the physical examination or patient care and examined other admitted patients, including touching those patients, on the same day. The possible explainable route was transmission through the hands of medical employees who had touched the index patient’s body or the virus-shedding environment. Unfortunately, we could not perform a serological evaluation of samples from the hands of the HCPs and we could not confirm this transmission route. However, we conclude that transmission via medical employees’ hands or body was the most likely explanation for MERS transmission in these patients.
Conventionally, isolation of people in response to a MERS outbreak is mainly initiated by identifying the epidemiological contact history [18]. However, considering the possibility of indirect transmission via virus shedding into the environment [19, 20], some researchers have suggested that people who share space and time with a patient should also be included in the quarantine group despite the lack of direct contact. During the early phase of the MERS outbreak in South Korea, quarantine was mainly confined to people who had come into close contact (within 2 m) with an infected person, but this has limited effects in protecting against MERS outbreaks in some hospitals [11, 12, 16]. During an outbreak, most hospitals try to isolate all people who have shared space and time with MERS patients based on this belief. However, this strategy does not include the possibility of indirect transmission via medical employees’ body or hands, which may mean that some infected people are excluded from the initial isolation process because there was no discernible contact with patients or spatial or time overlap. In contrast to the community setting, more frequent contact may occur between HCPs, patients and others in the hospital setting. Nosocomial infection may involve the transmission of a pathogen via direct contact between medical staff and other patients. We propose that during a nosocomial MERS outbreak the isolation should be extended to people who were treated by any medical employee who contacted MERS patients.
In our case, we initially missed the tenth and eleventh patients during the first isolation phase because they did not made contact with the index patient and had not shared time and space with the index patient. This had a disastrous outcome. They went around everywhere in the hospital before they were isolated. As a result, numerous people were exposed to the tenth and eleventh MERS infected patients or shared space and time with MERS patients. Although we thought that other people may seldom become infected because of the early isolation of infected patients, we should have performed extensive quarantine procedures for all people in the hospital because of the national fear of MERS transmission and the urgency of abating MERS transmission. Fortunately, among the 1019 people, there were no transmission cases. We believed that following concrete infection control measures may greatly contribute to preventing further transmission of MERS. Daily monitoring can detect these patients early and minimize the risk of MERS transmission. In-hospital campaigns of basic infection control for all people may be another contributing factor that prevented nosocomial infection of MERS. However, implementing unnecessarily broad isolations of hospital employees could cause a lack of adequate manpower and increased fatigue among non-isolated medical employees. During the national MERS outbreak, most hospitals suffering from nosocomial MERS transmission experienced the same, which may have resulted in the crisis of a lack of medical services in some regions. Unrecognized MERS patient often caused super-spreading events, especially in large volume hospitals, which can threaten not only a hospital system but also the regional medical service system.
Our study confirmed the importance of a routine basic infection policy for blocking widespread propagation of nosocomial MERS infection. Our post hoc analysis identified cases involving close contact over the long duration (8 h) of the index patient in the ED. Considering the previous report of an unrecognized case in ED [14, 17], our infection control team predicted widespread nosocomial infection at our ED. However, the outcome turned out to be quite different from what we had anticipated. During the analysis, all researchers agreed that our routine basic infection-prevention policy in the ED may have greatly contributed to the lack of MERS transmission in the ED space. Being aware of the potential for unrecognized MERS patients to enter the ED, we strengthened the initial triage in the ED to select patients at risk of MERS and encouraged all involved in the ED, including HCPs, patients and visitors, to routinely wear a surgical mask and to wash their hands frequently. Although we failed to isolate the index patient at the initial triage, high compliance with routine surgical mask wearing and hand hygiene was observed in nearly all people in the ED. In particular, we placed many hand sanitizers near beds and stations in the ED to allow all HCPs and visitors to wash their hands easily at any time. The CCTV review showed that > 95% of people in the ED washed their hands using the portable hand sanitizers. The high compliance rate of surgical mask wearing may have contributed to prevention of direct transmission of droplets into the respiratory tract and from hand to mouth or nose [21].
As overseas travel increases, the spread of emerging infections such as MERS by returning travellers is a major concern for many countries. Although the risk of encountering a patient with an emerging infection in the ED is slight, lack of recognition of emerging infections may cause serious problems for regional and national health care systems. Transmission may be extended to include hospital-to-hospital transmission, and a MERS outbreak can pose a risk to the national health care system.
Many studies have reported on the heterogenetic epidemic results of nosocomial MERS infection. Some hospitals have experienced serious nosocomial outbreaks [3, 4, 14, 17], but others [7,8,9,10, 22], mainly outside the Middle East, have reported a lack of MERS in hospital systems. We postulated that this phenomenon may result from complex interactions between the strong transmission via human-to-human contact and infection-prevention measures in each medical institution.