Setting

Hospital A is a 300-bed general hospital in Daejeon. The outbreak occurred in ward 51 on the fifth floor, where 13 rooms (5 with 7 beds, 6 with 4 beds, 1 with 2 beds, and 1 with 1 bed) are located. Hospital B is an 800-bed university hospital in Daejeon. The main outbreak occurred in ward 101 on the ninth floor, where 16 rooms (7 with 6 beds, 1 with 4 beds, 1 with 2 beds, and 7 with 1 bed) are located.

Data Collection and Exposure Assessment

Epidemiologic investigators of the Korea Centers for Disease Control and Prevention started their outbreak investigation with face-to-face interviews of the index case-patient in Daejeon and the 25 additional case-patients with confirmed MERS-CoV infection. We collected data on the demographic characteristics and the clinical, contact, and MERS-CoV exposure histories and thoroughly reviewed the medical records of the case-patients to identify symptoms, underlying concurrent medical conditions, laboratory findings, and clinical courses of illness. Clinical outcome was classified as recovery or death, and the ambulation status of the inpatients at the time of admission was clarified.

We collected the names of inpatients, their room numbers, medical staff, and caregivers (family members or professionals hired by the family or hospital) exposed to MERS-CoV in each hospital. The duration and route of exposure were further determined by reviewing recordings from closed-circuit televisions placed in the hospitals. Moreover, we used the floor plan of each hospital to estimate the spatial distributions and transmission routes of the virus within the hospitals. These estimates enabled us to identify a possible location of exposure and a transmission route for each confirmed case. When a patient with a confirmed case had experienced several possible exposures, we determined the most probable exposure by author consensus. Persons who had had face-to-face contact with patients with confirmed cases were considered the closest contacts. When the data were ambiguous, the following were reviewed independently by the Korea Centers for Disease Control and Prevention and the Daejeon In-Depth team: all potential exposures by symptom onset; disease duration; physical distance from a patient with a confirmed case; and infector factors including ambulation status, symptoms (including a productive cough), and sharing of caregivers. When a patient with a confirmed case had been subjected to several potential exposures, the most probable exposure was determined by consensus of the 2 teams. An expert member of the Korean Society of Epidemiology reviewed all decisions. The process was repeated until a final consensus was obtained.

Laboratory Diagnoses

Sputum samples from the persons suspected of having MERS were collected in sterile cups and sent to qualified local or national laboratories for confirmation. As a confirmatory test, a real-time reverse transcription PCR of nucleic acid extracted from sputum specimens was performed (5). Cycle threshold values were also measured to quantify viral loads. For each patient with a confirmed case, the Korea Centers for Disease Control and Prevention assigned a case number according to the order of confirmation during the 2015 MERS outbreak in South Korea. For example, the case number of the index case-patient in Daejeon was 16.

Data and Statistical Analyses

The cases were described in case-series form. Attack rates were calculated as the number of cases per number of exposed persons (defined as persons who had experienced face-to-face contact with a symptomatic MERS case-patient in either hospital or as persons who had been in the same hospital ward as the symptomatic case-patients). Such persons were identified from the outbreak investigation reports and the lists of those undergoing cohort or home quarantine. To assess differences in attack rates and case-fatality rates according to independent variables, we performed χ² and Fisher exact tests by using SAS software version 9.3 (SAS Institute, Inc., Cary, NC, USA). Comparisons were considered significant at p<0.05 and marginally significant at p<0.1 (both p values were 2-tailed).

We defined the incubation period as the time from exposure to onset of MERS-associated symptoms, including nonspecific signs and symptoms such as fever, chills, cough, sore throat, sputum production, dyspnea, myalgia, headache, nausea, vomiting, diarrhea, and abdominal discomfort. If the exposure period was >2 days, a single interval-censored estimate of the incubation period was computed by using the earliest and latest dates of exposure and the date of symptom onset for each case-patient (coarseDataTools package in R statistical software version 3.2.2) (7). To construct cumulative fraction curves of all cases by incubation period, we calculated the log-normal density function by fitting the interval-censored data on incubation periods. To do this, we used the maximum-likelihood method and calculated the medians and 5th and 95th percentiles of the incubation periods.

Description of the Daejeon Index Case-Patient

The Daejeon index case-patient (case-patient 16), a 41-year-old man, lived in Daejeon and was a former smoker (10 to 20 pack-years). He had undergone colon surgery in August 2014 at hospital P. The index case-patient of the MERS outbreak in South Korea (case-patient 1) was in hospital P during May 15–17, 2015. The Daejeon index case-patient was admitted to hospital P at the same time (May 15–18, 2015) for a follow-up colonoscopy. After discharge on May 20, the Daejeon index case-patient felt feverish and had chills, cough, general weakness, and diarrhea. Because of these symptoms, he was hospitalized in hospital A in Daejeon during May 22–28; the room was shared by 3 inpatients and 1 caregiver. Because his symptoms did not improve, he was transferred to the emergency department at hospital B. After hospitalization in ward 101 in hospital B, he was suspected of having MERS and was isolated in a negative-pressure room on May 30. Ultimately, he became the 16th confirmed MERS patient of 186 total case-patients during the 2015 outbreak.

Before the Daejeon case-patient was isolated, those around him did not use protective equipment. Therefore, virus was spread from him during his first 10 days of illness, before MERS diagnosis and isolation. When we checked the closed-circuit television recordings from hospital A to estimate how many persons could have been in contact with the Daejeon index case-patient, we found that he had been in several sections of the hospital ward, in particular those located on the left side of the nurse station. These sections included his admission room, a restroom, the nurse station, the foyer, and the hall in front of the elevators. The Daejeon index case-patient had potentially contacted every inpatient in the same hospital ward. Therefore, we classified all patients and caregivers in that ward as possible contacts.

Description of Patients with Confirmed Cases

A total of 26 cases (including the index case) were confirmed in the 2 hospitals, and 11 case-patients died of MERS (4 in hospital A and 7 in hospital B) (Technical Appendix). Other than the index case, 14 cases occurred in hospital A and 11 in hospital B. Case-patients 30, 38, and 128 were admitted to the same room in hospital A as the Daejeon index case-patient. Case-patient 85 was a caregiver hired by case-patient 128, so she was in the same hospital room in hospital A during May 22–28. Case-patients 23, 24, 31, 36, and 95 were admitted to the same room in hospital B as the Daejeon index case-patient. Case-patient 82 was the wife of case-patient 36; case-patient 106 was a caregiver hired by case-patient 36; and case-patient 127 was the wife of case-patient 24. Therefore, when caregiving, they were in the same room as the Daejeon index case-patient.

The median age of the case-patients was 71 (interquartile range 38–86) years; 13 (52.0%) were male; 6 (24.0%) were commercial caregivers; and 3 (12.0%) were family caregivers. A total of 18 (72.0%) case-patients had underlying diseases; 7 (28.0%) had pulmonary diseases, such as asthma, chronic obstructive pulmonary disease, idiopathic pulmonary disease, lung cancer, and pulmonary tuberculosis.

All patients reported fever. Other signs and symptoms included chills (10 patients, 38.5%), cough (8, 30.8%), sputum (6, 23.1%), myalgia (9, 34.6%), headache (4, 15.4%), dyspnea (6, 23.1%), nausea (3, 11.5%), diarrhea (6, 23.1%), sore throat (3, 11.5%), rhinorrhea (2, 7.7%), hemoptysis (1, 3.8%), and abdominal discomfort (1, 3.8%)

Quarantine

To prevent the spread of MERS-CoV to the local community, on June 1, 2015, the government of South Korea ordered cohort quarantine, which hospitals A and B followed (Table 1). Persons with a history of exposure to patients with confirmed MERS were isolated in the same hospital ward.

Epidemic Curve

Figure 1

Figure 1. Epidemic curves for the Middle East respiratory syndrome outbreak in Daejeon, South Korea, 2015. The cases are numbered in the order in which they were confirmed in the context of all...

After the index case-patient in Daejeon spread MERS-CoV in Daejeon, the first case occurred on May 30, 2015, and the last on June 15, 2015 (total outbreak duration 17 days) (Figure 1). The epidemic curve for hospital A suggested a relatively sporadic pattern compared with that for hospital B. The peak in hospital B comprised mostly patients who shared a hospital room with the index case-patient. Most MERS cases appeared later in professional or family caregivers rather than in inpatients.

Figure 2

Figure 2. Estimated incubation periods for the Middle East respiratory syndrome outbreak in Daejeon, South Korea, 2015. Curves indicate estimated cumulative fractions of cases corresponding to the incubation periods, estimated by creating log-normal...

The estimated median incubation period for confirmed cases was 6.1 (95% CI 4.7–7.5) days (Figure 2). Incubation periods were 8.8 (95% CI 7.2–10.4) days for hospital A and 4.6 (95% CI 2.9–6.2) days for hospital B.

Figure 3

Figure 3. Locations of Middle East respiratory syndrome case-patients in hospitals A and B, Daejeon, South Korea, 2015, showing where case-patients were exposed to presumed infectors. Not shown are case-patient 143, an engineer...

In hospital A, the index case-patient was admitted to room 5101, in sector A (Figure 3). Thereafter, 12 case-patients were in sector A, and 1 was in sector B. However, the case-patient in sector B had a history of contact with case-patient 85, who was transferred to sector B from sector A for quarantine. Most case-patients were presumed to have been infected by the Daejeon index case-patient (case-patient 16). However, 3 instances of other transmission were noted: case-patient 85 to case-patient 130, case-patient 54 to case-patient 172, and several case-patients to case-patient 129. For this last instance of transmission, we could not identify the most probable source, because many possible exposures were evident (case-patients 54, 84, 86, 87, 107, and 149).

In hospital B, the index case-patient was admitted to room 1007, located on the upper side of ward 101 (sector C). Eight case-patients were in sector C. Case-patient 83 was in room 1013 on the opposite side of ward 101 (sector D). Case-patient 45 was in the emergency room and ward 101 with the index case-patient. Case-patient 148 was presumed to have been infected by case-patient 36 during performance of cardiopulmonary resuscitation in the intensive care unit.

Attack Rate and Case-Fatality Rate

A total of 14 cases developed among 301 persons exposed in hospital A (attack rate 4.7%) and 11 among 371 persons exposed in hospital B (attack rate 3.0%) (Table 2). The attack rates for the sectors hosting the index case-patients (sector A of hospital A, sector C of hospital B; Figure 3) were higher than those for other sectors (sector B of hospital A, sector D of hospital B; Figure 3) (31.6% vs. 2.4% in hospital A, p<0.05; 18.2% vs. 6.5% in hospital B; Table 3). The probability of infection for a person admitted to the same rooms as the index case-patient was 75.0%. In both hospitals, attack rates were somewhat higher for caregivers (22.5%) than for inpatients (12.3%), although statistical significance was not attained.

The overall case-fatality rate was 44% (Table 4). This rate was higher for patients in hospital B (63.6%) than for those in hospital A (28.6%), although statistical significance was not attained.