In 2015, the Republic of Korea (ROK) experienced a public health crisis due to Middle East respiratory syndrome (MERS), which exposed the weaknesses of the national health disaster response system. Since January 2020, the ROK has been experiencing the coronavirus disease 2019 (COVID-19) epidemic caused by a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). MERS and COVID-19 share common characteristics: both are emerging novel coronaviruses with a zoonotic origin and can be fatal, particularly in both older adults and people with chronic medical conditions [1,2]; superspreading events (SSEs) form the overall epi-curve of both outbreaks [3]; and both pose global health threats in the absence of therapeutics or vaccines [4,5]. However, SARS-CoV-2 is more difficult to contain than MERS-coronavirus (MERS-CoV) because of faster human-to-human transmission. Thus, it has spread globally and become a pandemic (Table 1) [1,2,6–19].

MERS-CoV has circulated in the Middle East since 2012, but the ROK is the only country outside of the Middle East that has ever become heavily impacted by the virus [20]. The explosive MERS outbreak in May to June of 2015 revealed many issues in the nation’s public health crisis response [21], before its eventual containment within about 2 months. Since then, improvements have been made at different levels and across the public and private health sectors to protect society against threats from emerging infectious diseases (EIDs). Five years after the MERS outbreak, the COVID-19 pandemic occurred. The country was very successful in quickly flattening the epidemic curve at the early phase of the pandemic without the draconian control measures adopted in most countries [22]. The number of new daily COVID-19 cases reached its lowest level (fewer than 10) in late April 2020. After easing restrictions such as strict social distancing in early May, community transmissions with unknown sources of infection and an inflow of cases from foreign countries have continuously occurred. Furthermore, there have been a series of outbreaks at several mass gatherings that have spread to provincial cities. In this review, we review the lessons from the MERS-CoV outbreak that made the ROK’s response to the COVID-19 pandemic different from that of other countries during early 2020. We also discuss the next steps the ROK can take to further improve control of the virus.

On 20 May 2015, a 68-year-old Korean man returning from travel in the Middle East was confirmed as the first MERS case in the ROK [23]. Since the identification of the causative agent in Saudi Arabia in September 2012, 98% of MERS cases have occurred in the Middle East [20]. The propagation of MERS cases from the index case was driven mainly by transmission in one of the hospitals where the index case was admitted [23]. The outbreak resulted in a total of 186 confirmed cases and 38 deaths, with the last case confirmed on July 4, 2015, the 46th day after the first confirmation (Fig. 1) [23]. The outbreak and response affected the entire country and had a detrimental impact in various areas. The socioeconomic impact from the outbreak was estimated to be 9 billion US dollars (1 US dollar equals 1,200 Korean won) [24].

The epidemiology of the MERS outbreak in the ROK in 2015 was characterized by predominantly nosocomial transmissions and hospital clusters related to several SSEs [23,25]. The majority of confirmed cases (93%, 173/186) were infected in healthcare-associated settings (12 hospitals, three clinics, and two ambulances) [25], which is a much higher proportion compared to Middle East countries, where ongoing animal-to-human transmission is occurring [20]. Approximately 80% of transmission events were attributed to five SSEs, which were characterized by more intimate contacts, unprotected visits in crowded emergency rooms or general wards, and “doctor shopping” than non-SSEs [26]. A highly overdispersed pattern of MERS transmission increased the potential for large SSEs, although the overall R₀ was less than 1 [27,28].

The ROK learned the hard way from the MERS outbreak. During and after the outbreak, the country developed a national containment infrastructure against EIDs. The master plans for reform of the national infectious disease prevention and management system were announced by the Ministry of Health and Welfare (MOHW) in September 2015, and its implementation was closely tracked [43]. The pillars of the plan included early detection of EIDs, increased surge capacity to handle outbreaks, reform of national infectious disease control systems, and improvement of hospital IPC systems.

The Korean government implemented active monitoring of communicable diseases outbreak situations outside of the country implementing entry screening at airports and seaports, and immediate isolation of suspected cases at a quarantine station in the port of entry [43]. The Emergency Operation Center (EOC) in the Korea Centers for Diseases Control and Prevention (KCDC) was established in January 2016 and has run 24/7 since then. The legislation was amended for a rapid response team to be organized and deployed in case of an incident, and EIS officers are to lead the management of the situation [43]. To enhance the epidemic investigation workforce, the number of central EIS officers was increased from 34 in 2015 to 77 in 2020, and local governments were encouraged to recruit 2 local EIS officers per province [43].

Laboratory capacity was enhanced to accommodate large-scale diagnostic testing in emergency situations. The Korean government has invested in diagnostics research and development, and many private molecular diagnostic companies have also responded. In 2017, the Centre for Laboratory Control of Infectious Diseases in KCDC and the Ministry of Food and Drug Safety adopted the Emergency Use Authorization (EUA) system, which facilitates the rapid approval of diagnostic test kits in response to an EID outbreak [44]. The Center also established a quality assessment program for molecular diagnostics for EIDs in collaboration with the Korean Society for Laboratory Medicine [45].

The KCDC director position was elevated to a Vice-Minister level, and the coordination between central and local governments was improved. The number of regional centers for disease control increased from one in 2015 to five in 2016. The number of staff for infectious disease response at the subnational level increased by more than 360 [46]. Standard operating procedures for crisis management were renewed in June 2016 [46].

During the MERS outbreak in 2015, hospitals learned that insufficient IPC could significantly impact hospital management and finance. They gained institutional knowledge about how to set up MERS-CoV screening stations [47], the importance of proper training for putting on and taking off personal protective equipment, the need for an increasing number of AIIRs, improved room layouts to separate infectious disease patients from non-infectious disease patients, and well-trained healthcare personnel to care for patients with EIDs [48]. Some hospital IPC activities became eligible for financial support from National Health Insurance in July 2016. The Korean Society of Infectious Diseases published the Guidelines on MERS Prevention and Control for Health Facilities in December 2015 [49]. Hospitals were encouraged to limit the number of caregivers and visitors by keeping a logbook or issuing visitor passes. Systems were put in place to encourage hospitals to improve their visitor policies, and those that followed best practices were provided with a certificate [43].

Practices in IPC at emergency departments were improved. More AIIRs and general rooms were created at Emergency Medical Centers [43]. Legislation was introduced in December 2015 requiring Regional Emergency Medical Centers to be equipped with AIIRs [43]. In addition, in 2016, financial support was provided for the establishment and maintenance of AIIRs. The out-of-pocket payment for mild or non-urgent diseases at emergency departments was increased in 2016 to discourage unnecessary visits and reduce crowding. Hospitals were also encouraged to redesign emergency removes to create separate spaces and enable physical distancing between patients.

The 2015 MERS outbreak provided a foundation for amendments to the Infectious Disease Prevention and Control Act that enabled the MOHW and KCDC to collect, and share extensive personal data during serious infectious disease outbreaks [50,51]. In the early stage of the outbreak, detailed movements of individuals were withheld for fear of reidentification and lost business. Later (June 2015), high demand from the public and health professionals justified increased information sharing to alert individuals who may have come into contact with an infected person or contaminated environment [21,33,50].

A joint external evaluation in 2017 concluded that the overall International Health Regulation (2005) core capacities of the ROK were fulfilled, with the majority of indicators in 19 technical areas reflecting a sustainable capacity (60.4%) or demonstrated capacity (31.3%) [52]. It also noted that the country’s impressive preparedness was derived from its recent experience with the MERS outbreak in 2015, and that continued multisectoral effort and stable investment would enable the country to sustain such a high level of capacity.

The country had an opportunity to test and further refine its preparedness soon after the first MERS outbreak. On September 9, 2018, the first MERS-CoV case after the 2015 outbreak was detected in the ROK [46]. The patient, who arrived from the Middle East, visited a hospital on the day he arrived at the airport. The case was immediately confirmed as MERS-CoV infection at the hospital. The government immediately convened a press conference and coordinated a nationwide response. The rapid response team identified 21 close contacts and 487 casual contacts, all of whom were quarantined and monitored. There were no secondary transmissions reported.

After China, the ROK was one of the first countries to experience a massive surge in COVID-19 cases in the early 2020. The first confirmed COVID-19 case in the country was reported on January 20, 2020; as of June 12, 2020, 12,003 cases and 277 deaths had been reported, with daily new laboratory-confirmed cases peaking at 909 on 28 February 2020 (Fig. 1) [53]. A cluster of cases related to a large religious sect congregation in late February to early March dominated the outbreak, accounting for nearly half of the total number of cases in the ROK (43%). As most cases related to the cluster were young, more than one-third of the total confirmed cases in the entire country (38%) were in their 20s or 30s. As of June 12, 2020, the overall case-fatality rate was 2.3%, ranging from 0 among people under 30 years old to 26% among those aged 80 years or older. Nosocomial transmissions, as well as various community clusters, such as households, nursing homes, call centers, fitness dance classes, churches, and clubs, have been reported [54–56].

SARS-CoV-2 seems unlikely to follow the course of SARS-CoV, which suddenly disappeared after strong public health countermeasures were implemented across different parts of the world [77]. Instead, it is likely to continue circulating for an extended period of time, causing periodic resurgences depending on factors such as countermeasures, human behavior, and environmental variables [78]. The virus may even persist for some time after a safe and effective vaccine becomes available. In the entire history of mankind, only once has an infectious disease been eliminated by a vaccine. However, in the meantime SARS-CoV-2 may be controlled by self-hygiene, social distancing, and therapeutics.

SARS-CoV-2 was an “unknown unknown”: most governments have struggled to control it in the initial phase. However, the role of government is critical in preparing for subsequent waves of the COVID-19 pandemic. Both central and local governments should develop contingency plans for worst-case scenarios. The pandemic may worsen later in 2020, as COVID-19 and influenza circulate simultaneously [79]. Government agencies should develop strategies to progressively increase healthcare surge capacity to meet peak demand, so-called “raising the bar,” including measures to protect healthcare workers.

Until either vaccine administration or natural infection result in sufficient population immunity, infectious disease control measures should be modified and implemented on a country-specific basis, leveraging the most recent knowledge about the virus to reduce its incidence. These measures include surveillance, quarantine, laboratory testing, case management and isolation, contact tracing, and physical distancing. At the same time, to alleviate response fatigue in the population due to the prolonged emergency situation, the government should carefully select the most appropriate and flexible COVID-19 response activities.

The ROK attracted global attention for its early surge in COVID-19 cases in early 2020, and later for its aggressive interventions (the Korean 3T strategy), which other countries were skeptical about for their perceived non-sustainability and breach of human rights. Rigorous testing, the first element of the strategy, is based on the maintenance of a large number of testing facilities and high testing capacity. The financial sustainability of the strategy and its cost-benefit ratio require further review. Extensive IT-supported epidemic investigation and tracing, followed by strict restriction of mobility for every case and contact, are considered additional elements of the 3T strategy to interrupt transmission. However, human rights controversies have been raised, particularly by Western countries, because such investigation requires the collection of extensive personal medical and nonmedical data [51], and GPS and quarantine tracker wristbands are used to limit the movement of contacts. Broader stakeholder discussions are needed to reach an agreement on the balance between the effectiveness of the interventions and the protection of human privacy rights. Finally, although CTCs have helped reduce the burden of COVID-19, the facility isolation/treatment policy has put a heavy workload on healthcare workers. Because SARS-CoV-2 is transmitted relatively silently and rapidly, and a substantial proportion of COVID-19 cases among vulnerable people can become critical, healthcare systems may be quickly overburdened in the absence of appropriate control measures. Therefore, urgent actions are needed to improve IPC practices in nursing homes and LTCFs [80], repurpose and reshape hospitals [75], increase critical care capacity, and stockpile enough personal protective equipment for healthcare workers. Strategies to prevent burnout among healthcare workers should be established before subsequent waves to support the healthcare system while implementing the 3T strategy.

As the COVID-19 pandemic evolves, false or misleading information has created unnecessary panic in the population. Some serious incidents related to this “infodemic” have been reported in the ROK. For example, a religious group leader unknowingly inoculated his congregation with SARS-CoV-2 by serially spraying saltwater contaminated with the virus into their mouths [81]. Another example is methanol intoxication after using methanol spray for disinfection in an enclosed room. Most scientists are inexperienced in communicating with the public rather than other scientists. To counteract the infodemic, scientists and experts should be proactive in delivering science-based facts and correcting false or misleading information.

Although public health preparedness and health system resilience have improved throughout the responses to EIDs in the ROK, further efforts are needed to better prepare for preventing and managing EIDs. To the greatest extent possible, these efforts need to be based on science. Innovation and global solidarity may help with this. One good example is an ongoing project funded by the Gates Foundation utilizing artificial intelligence-based information and communication technology to enhance surveillance and outbreak forecasting [82]. Successful innovations and local experience must be quickly and widely shared at the global level to help overcome common challenges.

Prompt development of diagnostic tests, as well as effective and safe therapeutics and vaccines, is a critical factor for controlling EIDs. Drug repurposing, new drug screening, the use of convalescent plasma, and monoclonal antibody development have been proposed for use as prophylactics or treatments for critical patients [83]. Effective therapeutics may be more easily identified through drug repurposing, which would not require new safety reviews, and therapeutics for very ill require less rigorous safety reviews than vaccines given to large, healthy populations. However, investing in vaccine development remains necessary, because a vaccine is needed to achieve population immunity while avoiding the negative impact of high infection rates [84]. Rapid, mass production of COVID-19 vaccines, distribution of the vaccines to vulnerable or marginalized populations in middle- and low-income countries, low vaccine immunogenicity among older adults, and vaccine safety issues will remain challenges even after vaccines are authorized for use [85].

Rigorous research should be conducted to determine the optimal combination of countermeasures for each country, taking into account sustainability and direct health costs as well as social burden. For example, the health and social benefits of maintaining in-school education should be carefully balanced against the increased risk for SARS-CoV-2 infections. School closures do not only interrupt learning, but may also aggravate inequity and malnutrition for socially disadvantaged children and increase dropout rates, which in turn have long-term economic and social consequences [86]. School closures may create additional child-care obligations [87], and there is not yet robust epidemiological evidence that children are significant drivers of community transmission [88].

The ROK can figuratively be said to have been “vaccinated” against EIDs by the major MERS-CoV outbreak in 2015, which enabled the country to swiftly scale up its EID response systems. Hong Kong, Singapore, and Taiwan, the countries hit hardest by SARS in 2003, responded well to the COVID-19 pandemic during the early phase. They strengthened their EID outbreak response capacity based on lessons learned from past failures, and thereby responded aggressively and promptly to COVID-19 from the beginning. They learned how an unknown infectious disease can disrupt the integrity of society with massive health and economic consequences, and that over-reaction is better than under-reaction.

EIDs will continue to emerge, sometimes with catastrophic economic consequences. Deforestation has resulted in human exposure to various pathogens silently residing in wildlife. Viruses can evolve to infect novel hosts, thus increasing their chances of reproducing. Certain high-risk human activities, such as maintaining live animal markets, increase the likelihood of exposure to animal viruses with zoonotic potential, and globalization and massive international traffic have caused more rapid global EID transmission. The ROK, a major hub for international travel and trade, must be comprehensively prepared for future EIDs.

The 2015 MERS-CoV outbreak in the ROK served as a stress test to expose weaknesses in healthcare systems and infectious disease control and management systems. Significant progress in response to that outbreak enabled a rapid and aggressive response to the COVID-19 pandemic in early 2020 in the country. The massive epidemic curve has been successfully flattened through the cooperation of the population, the medical community, and the government. In general, the public has adhered well to social distancing, wearing masks, and handwashing. Hospitals responded proactively against the epidemic by enhancing IPC and healthworkers worked hard to diagnose and treat COVID-19 patients. The KCDC has coordinated actions from central and local governments to implement the 3T strategy while mobilizing IT, a major legacy of the 2015 MERS outbreak. However, there is currently a window of opportunity to further increase the surveillance system’s vigilance and strengthen healthcare capacities, particularly in critical care. In the middle of 2020, before a potential second wave, we must rapidly develop functional and comprehensive national preparedness and response plans, in parallel with accelerating the development of vaccines and therapeutics.