key: cord-1043602-7mbmtegy
authors: Lee, Ji yeon; Hong, Seung Wan; Hyun, Miri; Park, Jae Seok; Lee, Jae Hyuck; Suh, Young Sung; Kim, Dae Hyun; Han, Seong-Wook; Cho, Chi-Heum; Kim, Hyun ah
title: Epidemiological and Clinical Characteristics of Coronavirus Disease 2019 in Daegu, South Korea
date: 2020-07-21
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2020.07.017
sha: 2e93e8a3cfc1f6748de749239fe891121f72cf4c
doc_id: 1043602
cord_uid: 7mbmtegy

Abstract Objectives The Coronavirus Disease 2019 (COVID-19) outbreak simultaneously occurred at a church and a long-term care facility in Daegu. This study aimed to investigate the epidemiological characteristics of COVID-19 and factors related to severe outcomes. Methods We enrolled all inpatients diagnosed with COVID-19 between February 21 and April 2, 2020 in Daegu Dongsan Hospital, South Korea. We analyzed their clinical and demographic data, laboratory parameters, radiological findings, symptoms, and treatment outcomes. Results Of 694 patients, severe cases accounted for 19.7% (137 patients). No severe case was observed among patients aged ≤19 years. Hypertension was the most common co-morbidity (27%), and cough was the most common symptom (59%). Besides, asymptomatic patients accounted for 14.4% of cases. Lymphopenia, lactate dehydrogenase, C-reactive protein, and albumin were associated with severe outcomes. The first outbreak was mostly associated with younger age groups, and asymptomatic patients mostly showed mild progression. In the second outbreak involving a long-term care facility, both the number of severe patients and the mortality rate were high. Conclusions The overall mortality in Daegu was low, which might have resulted from large scale mass screening to detect patients and starting appropriate treatment, including hospitalization for severe cases, and quarantine for asymptomatic patients.

The coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a new emerging coronavirus, currently named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first case of COVID-19 was reported in Wuhan, Hubei Province, China, in December 2019. Now, COVID-19 has spread to over 200 countries within only four months (Hui et al., 2020; World Health Organization, 2020a) . In South Korea, the first case infected with SARS-CoV-2, a Chinese visitor from Wuhan, was reported on January 20, 2020 . On February 18, 2020, the COVID-19 outbreak in South Korea started in Daegu, and it is worth noting that the coronavirus had spread mainly among a religious group called Shincheonji . As of Jun 30, 2020, the number of confirmed cases increased rapidly, reaching a total of 12,757 cases, including 282 deaths (The Korea Centers for Disease Control & Prevention, 2020) . Daegu was at the hub of the COVID-19 outbreak, with the largest number of cases in South Korea (6,906 out of 12,757 cases nationwide (54.1%).

Investigating the epidemiological characteristics of patients with COVID-19 in Daegu plays an important role in gaining an insight into the situation and characteristics of the disease in J o u r n a l P r e -p r o o f South Korea. Unlike the other regions nationwide, Daegu was hit by two COVID-19 outbreaks at the same time, of which the major outbreak was related to a specific religion, and the other one to a long-term care facility. Therefore, epidemiological characteristics of COVID-19 in Daegu may differ from those in other regions.

Moreover, SARS-CoV-2 is a new emerging virus, and its epidemiological characteristics remain inadequately described (Wang Dawei et al., 2020) . Therefore, it is vital to examine these aspects and factors related to severe outcomes to enable appropriate treatment and prevention.

This study was approved by the institutional ethics board of Keimyung University Dongsan Hospital (No. 2020-03-027). After receiving the approval, we retrospectively collected data from all inpatients who were diagnosed with SARS-CoV-2 infection from February 21, 2020

to April 2, 2020 in Daegu Dongsan Hospital. The requirement for informed consent was waived due to the retrospective nature of the study. The clinical manifestations and outcomes of the patients had also been monitored as of April 2, 2020. During the outbreak, this hospital was designated as a specialized hospital with 465 beds for COVID-19 patients.

In this study, we used real-time reverse transcription polymerase chain reaction (RT-PCR), which has been widely used to diagnose COVID-19. Protocols used to diagnose COVID-19 vary according to country, and in Korea, RT-PCR is used to detect severe acute respiratory virus syndrome coronavirus-2 (SARS-CoV-2) through identification of RdRp, E, and N genes (Corman et al., 2020) .

We collected different types of data, including clinical and demographic information, laboratory parameters, radiological findings, and outcomes from patients' medical records and attending doctors. Symptoms during hospitalization were collected daily, and all data were collected retrospectively.

We investigated whether oxygen supply, mechanical ventilation, or extra corporeal membrane oxygenation (ECMO) were prescribed. We also collected patients' treatment outcomes using retrospective chart reviews, i.e., whether they died or were discharged alive. As recommended by the World Health Organization (WHO), a severe case was defined as the patient who met at least one of the following criteria: (1) Shortness of breath, respiratory rate ≥ 30 breaths/min; (2) oxygen saturation at rest ≤ 93%; or (3) partial pressure of arterial oxygen (PaO2)/fraction of inspiration oxygen (FiO2) ≤ 300 mmHg or requirement of mechanical ventilation (World Health Organization, 2020b). All the other cases, including those with simple upper respiratory tract disease and pneumonia, were classified into the mild group.

Data on symptoms were collected daily during the patients' hospital stay, and those who manifested the largest number of symptoms on a given day were selected for analysis.

Chest computed tomography (CT) findings were divided into two categories: positive and negative CT scans. A patient was classified as a positive CT scan if he or she had any consolidation or ground glass opacity (GGO) in CT findings during the hospitalization.

Meanwhile, the patient with no consolidations or GGO in his/her CT findings during the hospitalization was classified to have a negative CT scan.

Categorical variables were analyzed using the Fisher's exact test and presented as frequencies J o u r n a l P r e -p r o o f and percentages. Continuous variables were analyzed using the independent t-test if the data were normally distributed, otherwise the Mann-Whitney test was used. Continuous variables were then expressed as means and standard deviations. Two-sided p values of ≤ 0.05 were considered to indicate statistical significance. All statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) version 23.0 software (IBM Corp., Armonk, NY, USA).

In our study, 694 cases infected with SARS-CoV-2 were enrolled, including 137, 14, and 3 patients who required oxygen therapy, ventilation therapy, and ECMO therapy, respectively, for hypoxia. In total, 18 patients died due to COVID-19 while 137 patients were classified as severe cases.

The age of all patients ranged from 19 months to 98 years, with the age group of ≥ 60 years being the most affected. No patients aged under 19 years were identified as severe cases.

Meanwhile, in the age group of over 80 years, severe cases constituted 74.5% (41/55) of the cases ( Figure 1 ).

Hypertension was the most common comorbid disease (131 cases). The number of severe cases was significantly higher among patients with hypertension, diabetes, stroke, dementia, and chronic kidney disease. More comorbid diseases were found in the severe cases group.

No patients in the group of severe cases were asymptomatic. Cough was the most prevalent symptom, occurring in 328 cases. The proportions of fever, chill, cough, sore throat, and dyspnea were higher in severe cases than those in mild cases. Eighty patients in the group of mild cases were asymptomatic.

The most common source of transmission consisted of 280 cases who were believers of the religious group at the Shincheonji Church of Jesus. The proportion of hospital-transmitted SARS-CoV-2 infections was higher in severe cases (19.7%) than that in mild cases (4.3%).

The actual proportion could have been higher as the source of transmission was not clearly identified (Table 1) .

The white blood cell count, neutrophil count, C-reactive protein (CRP), procalcitonin, aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), and albumin were correspondingly higher in severe cases than those in mild cases. However, the lymphocyte count and estimated glomerular filtration rate (eGFR) were correspondingly lower in severe cases than those in mild cases (Table 2) .

CT scans were performed for 369 patients. Both, symptoms, and CT scans were surveyed in 300 cases. Among those with positive CT scans, 22.7% and 57.3% suffered from fever and cough, respectively, while 13.8% did not have any symptoms (Table 3 ).

In our study, the mortality rate among COVID-19 patients was 2.6% (18 cases), which almost resembles the pooled mortality rate in South Korea (2.3%) (The Korea Centers for Disease

Control & Prevention, 2020). Compared to the global mortality rates, this low mortality rate might have resulted from large scale mass screening to detect patients and start appropriate treatment. In the beginning, all confirmed cases were hospitalized for medical treatment, regardless of the severity of the disease. However, after the large outbreak began, only patients whose conditions were severe and therefore in dire need of hospital treatment were admitted to the hospital. Meanwhile, to prevent transmission, asymptomatic patients or mild J o u r n a l P r e -p r o o f cases were referred to dormitories where they were managed in groups. Among these patients, those with severe symptoms were hospitalized after they were identified by using simple tests and questionnaires.

In line with a previous study , our study found no severe case in the pediatric age group. The number of overall patients and those with serious outcomes increased beyond the age of 45 years. This implies that careful monitoring should be performed among patients The comorbidities that contributed to increasing the severity of COVID-19 in our study included hypertension, diabetes, stroke, chronic kidney disease, dementia, and the comorbidity counts. Comorbidities are known as a risk factor for severe outcomes in patients with COVID-19 (Huang et al., 2020; Wang Dawei et al., 2020) .

Cough was the most common symptom among patients with COVID-19 in our study (55.2% among mild cases and 81.5% among severe cases). The proportion of patients with fever was not as high as that reported in studies from China (20% vs. 90%) (Huang et al., 2020; Wang Dawei et al., 2020) . According to a report from Europe, this rate was 45.4%, with headache (70.3%) and loss of smell (70.2%) as the most common symptoms (Lechien et al., 2020).

Our present study included 80 asymptomatic cases, accounting for 14.4% of all cases. During J o u r n a l P r e -p r o o f each day of quarantine, all asymptomatic patients were checked for the development of symptoms; no patients showed symptoms until their release from the quarantine. This might have resulted from the higher proportion of mild cases being identified by the relatively broad-based screening tests for SARS-CoV-2 in South Korea. By June 30, in total 1,273,766 PCR tests were conducted for the diagnosis of SARS-CoV-2. In addition, due to the epidemic associated with sincheonji, the government conducted large-scale screening tests for more than 10,000 shincheonji church members, regardless of symptoms. Here, several asymptomatic confirmed cases were found early and were isolated in facilities and hospitals to suppress transmission.

Asymptomatic patients are crucial factors in controlling the COVID-19 outbreak.

Furthermore, in the early stage of this outbreak in South Korea, everyone who had close contact with confirmed cases received a SARS-CoV-2 test. Therefore, we believe that the relatively large number of asymptomatic patients were included our data compared to other studies. In addition, it is thought that antibody-based follow-up studies would be needed to determine the extent to which asymptomatic patients potentially contributed to the transmission in this COVID-19 pandemic.

In our study, patients with in-hospital exposure to SARS-CoV-2 were more likely to have severe outcomes, which might be because they had poor general conditions, suffered from comorbidities, and belonged to older age groups. This highlights the need for preventing inhospital transmission. Patients who were not aware of infection sources also reported more severe outcomes, which might have been possibly affected by the time until diagnosis.

However, the efficacy of mass SARS-CoV-2 screening requires further research.

More patients with lymphopenia were observed in the severe cases group. This may be a characteristic of SARS-CoV-2 infection as this was also reported in two previous studies J o u r n a l P r e -p r o o f (Huang et al., 2020; Wang Fan et al., 2020) . Similarly, lactate dehydrogenase, CRP, and albumin were also correlated with severe outcomes in this study.

We contrasted the patients' symptoms with CT scan results and found that 31 patients were asymptomatic although they had positive CT scan results (13.8% of all patients with CT scans). Therefore, these patients might have a potential role in SARS-CoV-2 transmission, as also reported by several other studies (Bai et al., 2020; Chan et al., 2020; Wang Yanrong et al., 2020) . Therefore, we speculate that a careful approach toward asymptomatic individuals is required to prevent the further upsurge in the outbreak.

This study has several limitations that need to be addressed. First, it was a retrospective study with missing data, possibly leading to errors regarding the multivariable analysis. Second, we only collected initial laboratory data while there might be certain deviations in laboratory findings due to temporal differences. Finally, certain symptoms might not have been documented because we only collected data on symptoms during the patients' hospital stays.

This means that if certain symptoms might have occurred before the patients were hospitalized, the proportion of asymptomatic patients might not reflect the actual one.

The strength of this study lies in its large sample of patients (694 cases). Moreover, as data collection was conducted at an early stage of the outbreak, we collected clinical data of all types of cases, including severe, mild, and asymptomatic cases.

In conclusion, compared to the global mortality rates, the mortality rate in Daegu was low, which might have resulted from large scale mass screening to detect patients and starting appropriate treatment, including hospitalization for severe cases, and quarantine for asymptomatic patients who were regularly screened for severe disease using simple tests and questionnaires. Our study findings help provide an insight into COVID-19 and inform its future prevention. Besides, severe cases were more often observed beyond the age of 45 J o u r n a l P r e -p r o o f 11 years. This indicates that careful observations should be performed in this age group. We also suggest that future studies should investigate the role of asymptomatic patients in transmission and factors associated with them for prevention of the outbreak.

All authors declare to have no conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

This study was approved by the institutional ethics board of Keimyung University Dongsan Hospital (No. 2020-03-027). J o u r n a l P r e -p r o o f 

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All data are presented as means (standard deviations). The estimated glomerular filtration rate is calculated using the Chronic Kidney Disease-Epidemiology Collaboration equation

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