The suspected transmission route for human Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection was a direct contact with the saliva of infected camels, or through consumption of unpasteurized milk or undercooked meat [2]. Kayali et al. showed that the seroprevalence of MERS-CoV was several times higher in persons with regular exposure to camels than in the general population [3]. Further, Muller et al. reported a 15- and 23-times higher seroprevalence of MERS-CoV antibodies in shepherds and in slaughterhouse workers, respectively, compared with the general population [4].

Person-to-person transmission of zoonotic disease has been reported for only a limited number of diseases [5]. The incapability of MERS-CoV to infect animal models like hamsters, mice, and ferrets, indicates the presence of a species barrier. However, an experimental study showed that human cell lines were susceptible to MERS-CoV infection [6], and the reports of human-to-human transmission have increased [789]. The modes of human-to-human MERS-CoV spread are incompletely defined [10]. However, some experts have suggested the occurrence of secondary infections through droplets, or direct contact with infected patients or fomites [11]. Furthermore, an epidemiological study reported the potential for MERS-CoV nosocomial transmission through contaminated surfaces of bed sheets, bed controllers, bedrails, medical devices, and even air-ventilation equipment [12].

Although the school-going children of the community were not initially a suspected at-risk population for virus transmission, growing public fear finally resulted in closure of more than 1,160 kindergartens, schools, and even some universities. During this time, people riding subways, buses, and other public transports while wearing face masks, was a common sight. Increasing public fear resulted in cancellation of social meetings, and the downtowns were no longer crowed [13]. However, there still are no strong evidences supporting MERS spread in community-settings, and therefore, the usefulness of these social efforts to prevent MERS spread in the community remains uncertain.

Chowell et al. suggested that a few early super-spreading events fueled the MERS outbreak in Republic of Korea [1]: the index patient who infected 30 secondary cases, and another two second generation cases who infected 80 and 23 secondary cases, respectively (Fig. 1). These cases were termed as "super-spreaders," while the vast majority of cases induced relatively few secondary infections. According to some researchers, super-spreading events follow the 20/80 rule [14], where approximately 20% of the infected individuals are responsible for 80% of the transmissions. Moreover, Lloyd-Smith et al. reported that super-spreading is a normal feature of disease transmission [15].

Stein et al. summarized the contributing factors resulting in a super-spreader as follows: pathogen's virulence factors, co-infections, decreased host immunity, misdiagnosis, delayed hospital admission, inter-hospital transfers, host behaviors such as ignoring instructions regarding infection control, and poor environmental conditions such as crowding, poor ventilation, etc. [16]. An observational, laboratory-based study of outbreaks in Jeddah and Riyadh reported that the MERS super-spreading events and the observed overdispersion of MERS transmission may similarly result from a combination of factors, including individual viral shedding and contact rates, hospital procedures and locations, as well as population structure and density [17].

Predicting super-spreading events is thus very important in infectious disease management and pandemic preparedness plans [16]. However, it may be difficult to identify the super-spreaders before the onset of an epidemic. In both the French [9] and the German MERS-CoV cases [18], which had similar findings listed above, the exposed healthcare workers did not get infected, although appropriate infection-protection measures were not in place. In the Korean outbreak as well, some non-super-spreaders had similar conditions to those favoring super-spreading events: high viral titer, delayed awareness, narrow and crowded rooms, and unprotected close contact such as intubation. Despite this, no confirmed secondary cases were found amongst thousands of exposed persons (data not published). The consequence of this discrepant transmission can be summarized in a statement by Galvani and May, "heterogeneously infectious emerging disease will be less likely to generate an epidemic, but if sustained, the resulting epidemic is more likely to be explosive" [14] (Fig. 2).

A Korean MERS outbreak epidemiological study was undertaken to estimate the case fatality rate (CFR) among senior patients [19]. The CFR for patients aged 60 years or older, with underlying diseases, was estimated at 48.2 %, as of July 31, 2015. The estimated CFR among other cases were as follows: 1.8 % in the lowest risk group (age < 60 years without any underlying diseases); 13.6 % for those aged 60 years or older, without any underlying diseases; and 11.1 % for those younger than 60 years, with underlying diseases. Senior patients were thus 9.3-fold (95 % CI, 5.3–16.9) more likely to die compared to younger patients, while presence of underlying diseases resulted in a 7.8-fold (95 % CI, 4.0–16.7) higher likelihood of fatality [19]. Although the researchers were not able to ensure a systematic and consistent review of all common comorbidities, these findings showed that enhanced hospital infection control practices, protecting the specific at-risk groups from MERS exposure, were very important to reduce associated mortality.

The health care system of Republic of Korea is a very unique structure, in which a 39 year-old universal social welfare system; the utilitarian "National Health Insurance System (NHIS)"; and competitive private clinics and hospitals miraculously co-exist. The efficiency of the Korean medical insurance system is among the highest in the world, having even numerous mega-sized hospitals running at relatively low medical costs. Although the reimbursement system of the medical costs are public, there is no limitation to hospital use in different regions, and relatively few restrictions exist in choosing from large university hospitals or tertiary care centers. Thus, patients can select a medical institution they want to visit, and move easily from one hospital to another. Further, even though accurate transfer notes are mandatory, the patient management and clinical testing information are not adequately shared by the referring hospitals. These factors may make hospital-to-hospital infection transmission more common [20]. In addition, with an aim to restrict over-charging by individual institutions, medical expenditures including institutional safety-related expenditures are strictly controlled by the Health Insurance Review & Assessment Service (HIRA). Consequently, more than 50% of the hospital rooms in Korea have more than 4 beds per room, and family members or privately hired health care aides usually stay with the patients in theses crowded hospital rooms. This situation has not been ameliorated with the recently built large-sized university hospitals, and this increased vulnerability to easier viral transmission as a result of overcrowding has long been considered a common occurrence at the larger hospitals [20].

How can Korean healthcare institutions, with high population density, be better prepared against MERS-CoV-like outbreaks? This question is even more pertinent for large well-constructed hospitals, operating in relatively resource limited settings in terms of safety issues; availability of adequate space; and number of healthcare workers, that cater to severe cases including the critically ill patients. To prevent future infectious disease outbreaks in Korea, several strategies might be adopted, and are summarized as below. These strategies should include not only individual institution-level preparedness, but also the entire healthcare system. Debates are expected on prioritization of infection safety.

Last year, struggling with an unfamiliar syndrome, the Korean healthcare system was unable to find infected cases in time, and to react quickly and accurately as the first imported case was reported. Multiple potential factors were associated with the super-spreading events: misdiagnosis, delayed hospital admission, inter-hospital transfers without accurate information, and also behaviors such as ignoring instructions regarding infection control, and poor environmental conditions. Institutional and healthcare system's preparedness is required to prevent such outbreaks. Efforts to halt transmission of infectious diseases need to be prioritized and should include: reviewing existing recommendations, improved contact tracing policy, improved public hospital facilities for critical care of severe infections, and pre-emptive isolation for unknown acute respiratory infection. These strategies are crucial to prepare for a future MERS-like epidemic in Korea.