key: cord-1002144-rh88lod0
authors: Shim, Eunha; Tariq, Amna; Choi, Wongyeong; Lee, Yiseul; Chowell, Gerardo
title: Transmission potential and severity of COVID-19 in South Korea
date: 2020-03-18
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2020.03.031
sha: 1aed8cc899c77553312d72e2ec022fd77e50b4fb
doc_id: 1002144
cord_uid: rh88lod0

OBJECTIVES: Since the first case of 2019 novel coronavirus (COVID-19) identified on Jan 20, 2020 in South Korea, the number of cases rapidly increased, resulting in 6,284 cases including 42 deaths as of March 6, 2020. To examine the growth rate of the outbreak, we aimed to present the first study to report the reproduction number of COVID-19 in South Korea. METHODS: The daily confirmed cases of COVID-19 in South Korea were extracted from publicly available sources. By using the empirical reporting delay distribution and simulating the generalized growth model, we estimated the effective reproduction number based on the discretized probability distribution of the generation interval. RESULTS: We identified four major clusters and estimated the reproduction number at 1.5 (95% CI: 1.4-1.6). In addition, the intrinsic growth rate was estimated at 0.6 (95% CI: 0.6, 0.7) and the scaling of growth parameter was estimated at 0.8 (95% CI: 0.7, 0.8), indicating sub-exponential growth dynamics of COVID-19. The crude case fatality rate is higher among males (1.1%) compared to females (0.4%) and increases with older age. CONCLUSIONS: Our results indicate early sustained transmission of COVID-19 in South Korea and support the implementation of social distancing measures to rapidly control the outbreak.

A novel coronavirus (SARS-CoV-2) that emerged out of the city of Wuhan, China in December 2019 has already demonstrated its potential to generate explosive outbreaks in confined settings and cross borders following human mobility patterns (Mizumoto et al., 2020) . While COVID-19 frequently induces mild symptoms common to other respiratory infections, it has also exhibited an ability to generate severe disease among certain groups including older populations and individuals with underlying health issues such as cardiovascular disease and diabetes (Adler, 2020) . Nevertheless, a clear picture of the epidemiology of this novel coronavirus is still being elucidated.

The number of cases of COVID-19 in the province of Hubei, the disease epicenter, quickly climbed following an exponential growth trend. The total number of COVID-19 cases is at 80,859 including 3,100 deaths in China as of March 8, 2020 (WHO, 2020 . Fortunately, by February 15, 2020 the daily number of new reported cases in China started to decline across the country although Hubei Province reported 128 cases on average per day in the week of March 2-8, 2020 (WHO, 2020) . While the epidemic continues to decline in China, 24,727 COVID-19 cases have been reported in more than 100 countries outside of China including South Korea, Italy, Iran, Japan, Germany, and France (WHO, 2020).

In particular, South Korea quickly became one of the hardest hit countries with COVID-19, exhibiting a steadily increasing number of cases over the last few days. Hence, it is crucial to monitor the progression of these outbreaks and assess the effects of various public health measures including the social distancing measures in real time.

The first case in South Korea was identified on January 20, 2020 followed by the detection of one or two cases on average in the subsequent days. However, the number of confirmed cases of SARS-CoV-2 infection started to increase rapidly on February 19, 2020 with a total of 6,284 confirmed COVID-19 cases including 42 deaths reported as of March 6, 2020 according to the Korea Centers for Disease Control and Prevention (KCDC) (KCDC, 2020) ( Table 1 ). The epicenter of the South Korean COVID-19 outbreak has been identified in Daegu, a city of 2.5 million people, approximately 150 miles South East of Seoul. The rapid spread of COVID-19 in South Korea has been attributed to one case linked to a superspreading event that has led to more than 3,900 secondary cases stemming from church services in the city of Daegu (Kuhn, 2020 , Ryall, 2020 . This has led to sustained transmission chains of COVID-J o u r n a l P r e -p r o o f 19, with 55% of the cases associated with the church cluster in Daegu (Bostock, 2020) . Moreover, three other clusters have been reported including one set in Chundo Daenam hospital in Chungdo-gun, Gyeongsanggbuk-do (118 cases), one set in the gym in Cheonan, Chungcheongnam-do (92 cases), and one Pilgrimage to Israel cluster in Gyeongsanggbuk-do (49 cases). These few clusters have become the major driving force of the infection. A total of 33 cases were imported while the four major clusters are composed of local cases as described in Table 2 .

Transmission of SARS-CoV-2 in Korea has been exacerbated by amplified transmission in confined settings including a hospital and a church in the city of Daegu. The hospital-based outbreak alone involves 118 individuals including 9 hospital staff (News, 2020) , which is reminiscent of past outbreaks of SARS and MERS (Chowell et al., 2015) . To respond to the mounting number of cases of COVID-19, the Korean government has raised the COVID-19 alert level to the highest (Level 4) on February 23, 2020 to facilitate the implementation of comprehensive social distancing measures including enhanced infection control measures in hospitals, restricting public transportation, cancelling social events, and delaying the start of school activities (Kim, 2020) .

While the basic reproduction number, denoted by R0, applies at the outset of an exponentially growing epidemic in the context of an entirely susceptible population and in the absence of public health measures and behavior changes, the effective reproduction number (Rt) quantifies the time-dependent transmission potential. This key epidemiological parameter tracks the average number of secondary cases generated per case as the outbreak progresses over time. Steady values of Rt above 1 indicate sustained disease transmission, whereas values of Rt <1 do not support sustained transmission and the number of new cases is expected to follow a declining trend. In this report, using a mathematical model parameterized with cases series of the COVID-19 outbreak in Korea, we investigate the transmission potential and severity of COVID-19 in Korea using early data of local and imported cases reported up until February 26, 2020.

We obtained the daily series of confirmed cases of COVID-19 in South Korea from January 20, 2020

to February 26, 2020 that are publicly available from the Korea Centers for Disease Control and Prevention (KCDC) (KCDC, 2020). Our data includes the dates of reporting for all confirmed cases, the dates of symptom onsets for the first 28 reported cases, and whether the case is autochthonous (local transmission) or imported. We also summarize the case clusters comprising one or more cases according to the source of infection according to the field investigations conducted by the KCDC (KCDC, 2020).

Accordingly, four major clusters were identified. The total number of confirmed and suspected cases as of March 6, 2020 as well as the crude case and fatality rate distribution by gender and age are presented in Table 1 .

To estimate the growth rate of the epidemic, it is ideal to characterize the epidemic curve according to dates of symptoms onset rather than according to dates of reporting. For the COVID-19 data in Korea, the symptom onset dates are available for only the first 28 reported cases. Moreover, all of the dates of symptoms onset are available for the imported cases. Therefore, we utilize this empirical distribution of reporting delays from the onset to diagnosis to impute the missing dates of onset for the remainder of the cases with missing data. For this purpose, we reconstruct 300 epidemic curves by dates of symptoms onset from which we derive a mean incidence curve of local case incidence and drop the last three data points from the analysis to adjust for reporting delays in our real-time analysis (Tariq et al., 2019) .

We assess the effective reproduction number, , which quantifies the time dependent variations in the average number of secondary cases generated per case during the course of an outbreak due to intrinsic factors (decline in susceptible individuals) and extrinsic factors (behavior changes, cultural factors, and the implementation of public health measures) (Anderson and May, 1991 , Chowell et al., 2015 . Using the Korean incidence curves for imported and local cases, we estimate the evolution of Rt for COVID-19 in Korea. First, we characterize daily local case incidence using the generalized growth model (GGM) (Viboud et al., 2016) . This model characterizes the growth profile via two parameters: the growth rate parameter ( ) and the scaling of the growth rate parameter ( ). The model captures diverse epidemic profiles ranging from constant incidence ( = 0 ), sub-exponential or polynomial growth (0 < < 1), and exponential growth ( = 1) (Viboud et al., 2016) . The generation interval is assumed to follow a gamma distribution with a mean of 4.41 days and a standard deviation of 3.17 days (Nishiura et al., 2020 , You et al., 2020 .

Next, to estimate the most recent estimate of Rt, we simulate the progression of incident cases from GGM, and apply the discretized probability distribution ( ) of the generation interval using the renewal equation (H. Nishiura, 2009 , Nishiura and Chowell, 2014 , Paine et al., 2010 given by

In the renewal equation we denote the local incidence at calendar time by , and the raw incidence J o u r n a l P r e -p r o o f of imported cases at calendar time by . The parameter 0 ≤ ≤ 1 quantifies the relative contribution of imported cases to the secondary disease transmission (Nishiura and Roberts, 2010) . The denominator represents the total number of cases that contribute to the incidence cases at time . Next, we estimate for 300 simulated curves assuming a Poisson error structure to derive the uncertainty bounds around the curve of (Chowell, 2017) .

The reconstructed daily incidence curve of COVID-19 after the imputing the onset dates for the Korean cases is shown in Figure 1 . Between January 20 and February 18, 2020 an average of 2 new cases were reported each day, whereas between February 19-26, 2020, 154 new cases were reported on average each day.

Under the empirical reporting delay distribution from early Korean cases with available dates of onset, the intrinsic growth rate (r) was estimated at 0.6 (95% CI: 0.6, 0.7) and the scaling of growth parameter (p) was estimated at 0.8 (95% CI: 0.7, 0.8), indicating sub-exponential growth dynamics of COVID-19

in Korea (Figure 2 , Table 3 ). The mean reproduction number was estimated at 1.5 (95% CI: 1.4, 1.6) as of February 26, 2020. Our estimates of are not sensitive to the changes to the parameter that modulates the contribution of the imported cases to transmission ( ).

The crude case fatality rate is higher among males (1.1%) compared to females (0.4%) and increases with older age, from 0.1% among those 30-39 yrs to 6% among those >=80 yrs as of March 6, 2020.

Spatial distribution of the Korean clusters is shown in Figure 3 and the characteristics of each cluster are presented in Table 2 as of March 8, 2020.

As 

In the central cities of Cheonan, 92 COVID-19 patients were associated with to a Zumba dance class after an instructor became the 5th confirmer of Cheonan on February 25, 2020. According to the provincial government of South Chungcheong Province, everyone who attended the class in Cheonan was tested, and 27 cases were confirmed on February 28, 2020, with most of the cases being women in their 30's and 40's (KCDC, 2020). As of March 8, 2020, a total of 92 individuals were infected including Zumba instructors and students as well as their families and acquaintances (KCDC, 2020) .

This cluster is comprised of 49 cases as of March 8, 2020. This cluster was identified when 31 Catholic pilgrims visited Israel between February 8, 2020 and February 16, 2020 and were subsequently confirmed for COVID-19 (2020). Amongst these, 11 individuals were diagnosed on February 17, 2020, while 20 others were confirmed positive between February 21-25, 2020 and quarantined immediately.

Of the 31 infected pilgrims, 19 belong to the Euiseong County, North Gyeongsang Province, while one patient, a tour guide belongs to Seoul. Health authorities have traced multiple contacts from the cases of this cluster, and additional cases were confirmed thereafter, raising concerns about the potential risk of secondary infections.

This is the first study to report estimates of the transmission potential of COVID-19 in Korea based on J o u r n a l P r e -p r o o f the trajectory of the epidemic, which was reconstructed by using the dates of onset of the first reported cases in Korea. The estimates of R clearly indicate sustained transmission of the novel coronavirus in Korea and the case fatality rate appears to be higher among males and older populations (Table 1) .

Moreover, the imported cases contribute little to the secondary disease transmission in Korea, as majority of these cases occurred in the early phase of the epidemic, with the most recent imported case reported on February 9, 2020. These findings support the range of social distancing interventions that the Korean government put in place in order to bring the outbreak under control as soon as possible.

Our estimates of the reproduction number can be compared with earlier estimates reported for the epidemic in China where the estimates of R lie in the range 2-7.1 (Lai et al., 2020 , Li et al., 2020 , Mizumoto et al., 2020 , Read et al., 2020 Group for Control of the Epidemic of Novel

Coronavirus Pneumonia of the Chinese Preventive Medicine, 2020, Wu et al., 2020 , Zhang et al., 2020 . Moreover, the mean R reached values as high as ~11 for the outbreak that unfolded aboard the Princess Cruises Ship during January-February 2020 (Mizumoto and Chowell, 2020) . In contrast, a recent study on Singapore's COVID-19 transmission dynamics reported lower estimates for

(1.1, 95% CI: 1.1, 1.3) as of February 19 th , 2020, reflecting a significant impact of the control interventions that have been implemented in Singapore (Tariq et al., 2020) . The estimates of the scaling of growth parameter (p) in our study indicate sub-exponential growth dynamics of COVID-19 in Korea.

This aligns well with the sub-exponential growth patterns of COVID-19 in Singapore and all Chinese provinces except Hubei , Tariq et al., 2020 .

Since the first COVID-19 case was reported on January 20, 2020, the epidemic's trajectory showed a rapid upturn until February 18, 2020, when a super spreader (Case 31) was identified in the Shincheonji (Cowling et al., 2015) . Amplification of MERS in the hospital setting has been associated with diagnostic delays, which increase the window of opportunity for the generation of secondary cases (Chowell et al., 2015) . This underscores the need for rapid testing, case detection and active contact tracing to isolate infectious individuals.

Beyond Korea, substantial COVID-19 transmission has been reported in Italy, Iran, Germany, France, and aboard the Diamond cruise ship (Marcus, 2020 , Woods, 2020 Contributions: ES, AT and GC analyzed the data. YS and WC retrieved and managed the data. ES, AT, and GC wrote the first draft of the paper. All authors contributed to the writing of the paper. 

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