Outbreaks of Middle East Respiratory Syndrome in Two Hospitals Initiated by a Single Patient in Daejeon, South Korea

Abstract

Background: A Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak in South Korea in 2015 started by a single imported case and was amplified by intra- and inter-hospital transmission. We describe two hospital outbreaks of MERS-CoV infection in Daejeon caused by a single patient who was infected by the first Korean case of MERS.

Materials and methods: Demographic and clinical information involving MERS cases in the Daejeon cluster were retrospectively collected and potential contacts and exposures were assessed. The incubation periods and serial intervals were estimated. Viral RNAs were extracted from respiratory tract samples obtained from the index case, four secondary cases and one tertiary case from each hospital. The partial S2 domain of the MERS-CoV spike was sequenced.

Results: In Daejeon, a MERS patient (the index case) was hospitalized at Hospital A in the first week of illness and was transferred to Hospital B because of pneumonia progression in the second week of illness, where he received a bronchoscopic examination and nebulizer therapy. A total of 23 secondary cases (10 in Hospital A and 13 in Hospital B) were detected among patients and caregivers who stayed on the same ward with the index case. There were no secondary cases among healthcare workers. Among close hospital contacts, the secondary attack rate was 15.8% (12/76) in Hospital A and 14.3% (10/70) in Hospital B. However, considering the exposure duration, the incidence rate was higher in Hospital B (7.7/100 exposure-days) than Hospital A (3.4/100 exposure-days). In Hospital B, the median incubation period was shorter (4.6 days vs. 10.8 days), the median time to pneumonia development was faster (3 days vs. 6 days) and mortality was higher (70% vs. 30.8%) than in Hospital A. MERS-CoV isolates from 11 cases formed a single monophyletic clade, with the closest similarity to strains from Riyadh.

Conclusion: Exposure to the MERS case in the late stage (2nd week) of diseases appeared to increase the risk of transmission and was associated with shorter incubation periods and rapid disease progression among those infected. Early detection and isolation of cases is critical in preventing the spread of MERS in the hospital and decreasing the disease severity among those infected.

Keywords: Daejeon; Hospital; Middle East Respiratory Syndrome coronavirus; Outbreak; South Korea; Superspreading.

Figure 1. Epidemic curve of all cases with Middle East respiratory syndrome-coronavirus (MERS-CoV) infection linked to the index case in Daejeon, South Korea. All cases with MERS-CoV infection are plotted by the date of symptom onset, according to the hospital. The implementation of infection control measures is also shown in the graph.

Figure 2. Transmission map of outbreak of Middle East respiratory syndrome-coronavirus infection in Daejeon and chest CT scans of the index case.

Figure 3. Distributions of incubation periods of cases with Middle East respiratory syndrome-coronavirus infection in two hospitals in Daejeon. The fitted distributions of incubation periods of Hospital A (blue line) and B (red line) are plotted against the empirical cumulative density function of observed incubation periods (midpoint of exposure to symptom onset) (black line). The 95% confidence intervals for the medians of these fitted distributions are also plotted. Bootstrap estimates are shown in grey shading.

Figure 4. Phylogenetic analysis of S2 fragment sequences of Middle East respiratory syndrome-coronavirus (MERS-CoV) from 11 cases from the Daejeon cluster. The partial S2 fragment sequences of MERS-CoV spike genes were obtained from the index case (Index), 4 secondary cases (A1, A2, A3, A8) from the Hospital A cluster and 4 secondary cases (B1, B2, B6, B7) from the Hospital B cluster. The S2 fragment sequences isolated from two tertiary cases (A14, B11) were also analyzed. The new 2 sequences of spike genes identified in this study are highlighted in blue, and compared with the previously published 20 MERS-CoV genomes (Supplementary Table 2). Values on nodes correspond to posterior probability values obtained from the approximate likelihood ratio test based on a Shimodaira-Hasegawa-like procedure.