Literature DB >> 32797094

Containment of a healthcare-associated COVID-19 outbreak in a university hospital in Seoul, Korea: A single-center experience.

Sei Won Kim1, Sung Jin Jo2, Heayon Lee1, Jung Hwan Oh3, Jihyang Lim2, Sang Haak Lee1, Jung Hyun Choi4, Jehoon Lee2.   

Abstract

BACKGROUND: Our hospital experienced the first healthcare-associated COVID-19 outbreak in Seoul at the time the first COVID-19 cases were confirmed in Korea. The first confirmed COVID-19 patient was a hospital personnel who was in charge of transferring patients inside our hospital. To contain the virus spread, we shutdown our hospital, and tested all inpatients, medical staff members, and employees.
METHODS: We retrospectively analyzed the results of SARS-CoV-2 RT-PCR testing according to the contact history, occupation, and presence of respiratory symptoms. Closed-circuit television (CCTV) was reviewed in the presence of an epidemiologist to identify individuals who came into contact with confirmed COVID-19 patients.
RESULTS: A total of 3,091 respiratory samples from 2,924 individuals were obtained. Among 2,924 individuals, two inpatients, and one caregiver tested positive (positivity rate, 0.1%). Although all confirmed cases were linked to a general ward designated for pulmonology patients, no medical staff members, medical support personnel, or employees working at the same ward were infected. Contact with confirmed COVID-19 cases was frequent among inpatients and medical support personnel. The most common contact area was the general ward for pulmonology patients and medical support areas, including clinical and imaging examination rooms. Finally, the total number of hospital-associated infections was 14, consisting of four diagnosed at our hospital and ten diagnosed outside the hospital.
CONCLUSIONS: The robust control of the COVID-19 outbreak further minimized the transmission of SARS-CoV-2 in the hospital and local communities. However, there was also a debate over the appropriate period of hospital shutdown and testing of all hospital staff and patients. Future studies are required to refine and establish the in-hospital quarantine and de-isolation guidelines based on the epidemiological and clinical settings.

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Mesh:

Year:  2020        PMID: 32797094      PMCID: PMC7428087          DOI: 10.1371/journal.pone.0237692

Source DB:  PubMed          Journal:  PLoS One        ISSN: 1932-6203            Impact factor:   3.240


Introduction

In December 2019, a novel coronavirus disease (COVID-19) was first reported in Wuhan, Hubei Province, China [1, 2]. Since then, human-to-human transmission of the novel coronavirus has been confirmed [3] and has caused serious illness and death [4]. Following the COVID-19 outbreak in China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, has spread in many countries across the world, including Korea, Iran, European countries, and the USA [5]. In Korea, the number of COVID-19 patients who were confirmed with real-time reverse-transcription polymerase chain reaction (RT-PCR) assay was 10,564, while 222 deaths were reported until April 14, 2020 [6]. Among the COVID-19 patients, 14 patients were linked to a single university hospital. These were the first COVID-19 cases resulting from healthcare-associated infections (HAI) in Seoul. Hence, the Seoul government announced the closure of the hospital. Moreover, outpatient admission was temporarily stopped for approximately two weeks. Inpatients who had come into contact with confirmed COVID-19 patients were isolated inside the hospital. A total of 2,924 people, including hospitalized patients, medical/paramedical staff, employees, and caregivers, were all tested for SARS-CoV-2 using RT-PCR assay. In this study, we report our experience from our COVID-19 cases, as well as discuss the necessity of widespread SARS-CoV-2 RT-PCR testing and hospital shut down, particularly in major hospitals, to prevent HAI.

Materials and methods

Hospital overview and study setting

Our hospital (Eunpyeong St. Mary’s hospital, The Catholic University of Korea) is an 808-bed university hospital located in Eunpyeong District, northwest Seoul, Korea. The hospital opened in April 2019. The main building of the hospital has 17 floors above ground and seven floors below ground. The hospital receives approximately 2000 to 3000 outpatient visits and 150 to 200 patient visits to the emergency room daily. The hospital has nine floors for inpatients, which contains two general wards. Each general ward has nine rooms with four beds each, and two rooms with a single bed. The 4-bed rooms have 2 m space between beds, which are separated by curtains for privacy (Fig 1).
Fig 1

Schematic diagram of the general ward located on the 9th floor and location of confirmed COVID-19 patients.

In this study, we retrospectively analyzed the results of SARS-CoV-2 RT-PCR testing, contact history, and presence of respiratory symptoms in a single center with a healthcare-associated COVID-19 outbreak. We also reviewed data from epidemiological surveys, from the Korea Centers for Disease Control and Prevention (KCDC) and the infection control unit of our hospital. The COVID-19 prevention measures before and after the healthcare-associated outbreak were also reviewed. This study was approved by the Institutional Review Board of Eunpyeong St. Mary’s hospital (PC20RASI0040).

Hospital COVID-19 prevention measures before the healthcare-associated outbreak

We reviewed the history of patients to assess whether they visited China or other high-risk countries within two weeks prior to the outbreak of healthcare-associated COVID-19, or if they came into contact with confirmed COVID-19 cases. After the initial assessment, patients without fever or respiratory symptoms had no specific restrictions inside the hospital. Patients with fever (>37.5 °C) or respiratory symptoms were transferred to the triage room, which is located in a different part of the hospital to that of the infectious diseases department and the emergency room. After obtaining samples for RT-PCR testing, patients were sent home for self-isolation until the results were made available. If the results were positive, patients were referred to government-designated hospitals. Medical staff in the triage room used level-D personal protective equipment (PPE) and everyone in the hospital was encouraged to wear masks and follow hand hygiene practices.

The first confirmed COVID-19 case in the hospital

The first confirmed COVID-19 case was a 35-year-old man who was in charge of transferring patients inside our hospital between February 2 and 17. On February 17, 2020, he visited the clinic due to a one-week history of fever, cough, and myalgia. Although he had no history of travel or close contact with confirmed COVID-19 cases, chest X-ray showed ground-glass opacities in both lower lobes. Considering the possibility of COVID-19, RT-PCR confirmation testing was performed on February 20, 2020. After SARS-CoV-2 infection was confirmed, the Seoul city government announced the closure of the hospital on February 21, 2020, to prevent a healthcare-associated outbreak. Outpatient clinics and the emergency room were also closed, and new patient admissions were stopped. Individuals inside the hospital who had contact history, fever, or respiratory symptoms, were closely monitored.

Samples collection and test systems

In total, 3,091 respiratory samples from 2,924 people were obtained from February 21 to February 28. Two thousand one hundred seventy-one samples were processed and tested in the department of Laboratory Medicine of our hospital, while 920 samples were analyzed by a commercial laboratory (SamKwang Medical Laboratories, Korea). Sputum and combined nasopharyngeal (NP) and oropharyngeal (OP) swabs were collected from patients with acute respiratory symptoms and purulent manifestations. Combined NP and OP swabs were also collected from asymptomatic individuals. NP and OP swabs were collected in the T-SWAB TRANSPORT™ UTM (Noble Biosciences, Korea) while sputum specimens were collected in 50cc Falcon tubes. Sputum samples were prepared in phosphate buffer solution. QIAamp DSP viral RNA mini kit (Qiagen GmbH, Hilden, Germany) with QIAcube system (Qiagen), as well as NX-48 viral NA kit (Genolution, Korea) with Nextractor NX-48 system (Genolution) were used for RNA extraction. Nucleic acid was extracted according to the manufacturer’s instructions. SARS-CoV-2 nucleic acid was amplified by real-time RT-PCR using the PowerCheckTM 2019-nCoV Real-time PCR Kit (Kogenebiotech, Korea). ABI 7500 (Applied Biosystems, USA) real-time PCR system was used for the amplification of E and RdRp genes of the SARS-CoV-2 virus. In SamKwang Medical Laboratories, the NX-48 viral NA kit (Genolution) with Nextractor NX-48 system (Genolution) was used for RNA extraction, while PowerCheckTM 2019-nCoV Real-time PCR Kit (Kogenebiotech) and CFX96 (Bio-Rad, USA) were used for the amplification of viral genes. The RT-PCR included 40 cycles of amplification. SARS-CoV-2 infection was defined as the detection of both target RNAs under 35.0 cycles of threshold (CT).

Contact history

The results of SARS-CoV-2 RT-PCR were analyzed according to occupation, presence of the respiratory symptoms, and contact history. The admission department, floor, and room location were also assessed. Contact was defined as presence in the same room with COVID-19 confirmed patients, or in the same outpatient clinic or examination room, 30 minutes before and after COVID-19 confirmed patients. Moreover, closed-circuit television (CCTV) was reviewed in the presence of an epidemiologist, and people who had been within 2 m of confirmed patients were considered individuals with contact history.

Results

Patients with healthcare-associated COVID-19 infection

After the hospital staff member responsible for transporting patients was confirmed as the first COVID-19 case, people with contact history, fever, or respiratory symptoms were tested for SARS-CoV-2 infection with RT-PCR (Fig 2). Among the admitted patients, patient with pneumonia who was receiving treatment was confirmed as the 2nd COVID-19 patient (Fig 3). Chest CT showed that the patient had multiple, ground-glass opacities in both lungs. This patient was not previously tested for COVID-19, as the patient had no history travel to China or other high-risk countries, and had no close contact with confirmed patients. Due to a contact history with this inpatient, the first diagnosed medical staff was considered as nosocomial COVID-19 infection. Additionally, one caregiver who was in the same room with the 2nd COVID-19 patient also tested positive for SARS-CoV-2. The caregiver confirmed as COVID-19 was also considered as nosocomial COVID-19 infection. As the nosocomial COVID-19 infection continued to be discovered, the hospital started complete enumeration survey of all patients (Fig 2). The fourth COVID-19 patient was also an inpatient with pneumonia such as the second COVID-19 patient. On February 25, the hospital decided to perform a complete enumeration survey of all medical staff and employees to help control the healthcare-associated COVID-19 outbreak.
Fig 2

Timeline of healthcare-associated COVID-19 outbreak and number of SARS-CoV-2 RT-PCR tests performed.

Fig 3

Estimated transmission routes of 14 cases of healthcare-associated SARS-CoV-2 infection.

Quarantine after the healthcare-associated COVID-19 outbreak and complete enumeration survey of all inpatients, medical staff, and employees

As this was the first major healthcare-associated transmission cluster reported in Seoul, the city government imposed strict measures to control the spread of the virus. The entire outpatient clinic and emergency rooms were temporarily closed for two weeks, as per the guidelines set during the 2015 Middle East Respiratory Syndrome (MERS) outbreak [7]. The entire hospital was thoroughly cleaned and disinfected. Inpatients who had had no contact with confirmed COVID-19 patients and had no symptoms were discharged, while inpatients who had had contact with confirmed COVID-19 patients were quarantined in single rooms for two weeks. A complete enumeration survey was conducted from January 23 to January 28 to prevent further spread of the healthcare-associated infection by eliminating the possibility of asymptomatic transmission [8]. Two thousand nine hundred twenty-four inpatients and employees (213 doctors, 901 nurses, 271 medical support staff, 952 hospital employees, 494 inpatients, 87 guardians and caregivers, and 11 volunteers) had undergone SARS-CoV-2 testing by real-time RT-PCR (Table 1). The employees who had contact with confirmed COVID-19 patients self-isolated for two weeks. Two patients and one caregiver tested positive for SARS-CoV-2. The overall COVID-19 positivity rate in the complete enumeration survey (100 × positive tests/total number of tests conducted) was 0.1%. Fifty-one individuals were re-tested more than twice to monitor the progression of respiratory symptoms.
Table 1

Clinical characteristics of individuals who underwent SARS-CoV-2 real-time RT-PCR testing during Feb. 21 –Feb. 28, 2020, in Eunpyeong St. Mary’s Hospital after the 1st COVID-19 patient was confirmed.

GroupsNo.AgeSex (male/female)No. of COVID-19 patients (RT-PCR confirmed)No. of people resampled and re-testedNo. of people with respiratory symptoms
Doctors21340.9 ± 8.8129 / 840262
Nurses90131.0 ± 7.842 / 859047
Medical support personnel27134.1 ± 8.5130 / 141003
Employees95244.4 ± 12.1368 / 584015
Inpatients48961.8 ± 19.2229 / 260220104
Guardians and caregivers8759.4 ± 11.820 / 67102
Volunteers1147.7 ± 9.82 / 9000
Total2,92442.5 ± 16.3920 / 2,004351123

SARS-CoV-2 real-time RT-PCR: Severe acute respiratory syndrome-coronavirus-2 real-time reverse transcriptase polymerase chain reaction, COVID-19: Coronavirus disease 2019

SARS-CoV-2 real-time RT-PCR: Severe acute respiratory syndrome-coronavirus-2 real-time reverse transcriptase polymerase chain reaction, COVID-19: Coronavirus disease 2019

Contact history with confirmed COVID-19 patients

After the first case was reported, epidemiologists from KCDC and the infection control unit of our hospital reviewed electronic medical charts, CCTV, and personal movements to identify individuals with potential contact with confirmed COVID-19 patients. An additional three confirmed cases were identified, and the contact list was updated. The number of people who underwent SARS-CoV-2 testing with real-time RT-PCR and had contact with COVID-19 confirmed patients is shown in Table 2. The overall proportion of people who came into contact with confirmed COVID-19 patients was 9.9%. Most of these individuals were inpatients (28.2%) who had stayed on the same ward with confirmed COVID-19 patients. Contact with confirmed COVID-19 cases was also frequent among medical support personnel (12.9%), including staff from the radiologic department, rehabilitation unit, and phlebotomists. Three confirmed COVID-19 patients (2nd, 3rd, 4th patients) stayed on 9GW. Four caregivers, 40 healthcare workers, and 12 inpatients came into contact with confirmed COVID-19 patients on 9GW. The most common area of contact with confirmed COVID-19 patients was the 9GW and medical support area, such as the clinical or imaging examination room (Table 3).
Table 2

Occupation and number of individuals who had contact with four confirmed COVID-19 patients.

Groups1st patient (Hospital staff)2nd patient (Inpatient, 9GW)3rd patient (Caregiver, 9GW)4th patient (Inpatient, 9GW)1st– 4th patient
Doctors1108420* (9.4%)
Nurses031363772* (8.0%)
Medical support personnel22281435* (12.9%)
Employee21011719* (2.0%)
Inpatients47344117138* (28.2%)
Caregivers04206 (6.8%)
Volunteer00000 (0%)
Total5211110679290* (9.9%)

COVID-19: Coronavirus disease 2019, SARS-CoV-2 real-time RT-PCR: Severe acute respiratory syndrome-coronavirus-2 real-time reverse transcriptase polymerase chain reaction, GW: general ward

*Multiply contacted person was counted as one.

† Percentage = 100 × number of people who had contact with confirmed patients/ total number of people in each group

Table 3

Place of contact and number of individuals who came into contact with four confirmed COVID-19 patients.

Places1st patient (Hospital staff)2nd patient (Inpatient, 9GW)3rd patient (Caregiver, 9GW)4th patient (Inpatient, 9GW)1st– 4th patient
Out-patient clinic343513*
Emergency room0100010
Medical support area7634133131*
Intensive care unit20002
7GW50005
8GW0251825
9GW833372260*
10GW2121123*
Others2501026
Total52111*106*79290*

COVID-19: Coronavirus disease 2019, SARS-CoV-2 real-time RT-PCR: Severe acute respiratory syndrome-coronavirus-2 real-time reverse transcriptase polymerase chain reaction, GW: general ward

*Multiply contacted person was counted as one.

COVID-19: Coronavirus disease 2019, SARS-CoV-2 real-time RT-PCR: Severe acute respiratory syndrome-coronavirus-2 real-time reverse transcriptase polymerase chain reaction, GW: general ward *Multiply contacted person was counted as one. † Percentage = 100 × number of people who had contact with confirmed patients/ total number of people in each group COVID-19: Coronavirus disease 2019, SARS-CoV-2 real-time RT-PCR: Severe acute respiratory syndrome-coronavirus-2 real-time reverse transcriptase polymerase chain reaction, GW: general ward *Multiply contacted person was counted as one.

Surveillance of people with contact history with confirmed COVID-19 patients

Discharged patients, caregivers, and healthcare workers who had left before the hospital closed were grouped according to the possibility of COVID-19 exposure, based on electronic medical charts, CCTV, and personal movements. Four hundred and seventy-nine people were determined as high-risk, including 58 caregivers, 11 healthcare workers, and 410 discharged patients, all of whom were notified by phone. They were also examined for respiratory symptoms and advised to stay home and avoid contact with other people even if they had no respiratory symptoms. Two discharged patients, one caregiver and one visitor were later diagnosed with COVID-19 at a different hospital or community health center (Fig 3). As additional patients were confirmed, the number of exposed people increased to 1,215; these individuals received advice as per the KCDC COVID-19 guidelines. Finally, the total number of hospital-associated infections was 14, consisting of four diagnosed at our hospital and ten diagnosed outside the hospital.

Discussion

Since the report of the first COVID-19 cases in Wuhan, China, 1,812,734 confirmed cases and 113,675 deaths have been reported worldwide until April 14, 2020 [9]. Severe symptoms develop in approximately 14% of COVID-19 patients, and the overall mortality is around 2% of confirmed COVID-19 cases [10]. Advanced age, development of severe symptoms, and comorbidities are the primary risk factors associated with COVID-19 mortality [11, 12]. As there are no effective treatments for COVID-19, prevention of further virus spread is the only way to control the COVID-19 pandemic [13]. Prevention measures are particularly important in hospitals, where numerous elderly patients and individuals with comorbidities are found. In 2015, nosocomial MERS outbreaks were reported in Korea, caused by contacts with infected outpatients and inpatients [14]. Although strict precaution and prevention measures were followed according to the KCDC guidelines, 14 healthcare-associated COVID-19 cases were reported in our hospital, including 4 people diagnosed in-hospital and 10 people diagnosed outside of the hospital. Compared to small hospitals or care units, the impact of healthcare-associated infections can be detrimental in large university hospitals with numerous visitors and severely ill patients. The first confirmed COVID-19 patient in our hospital was a hospital personnel responsible for transporting patients. However, the only person who came into contact with him and was later confirmed with COVID-19 was his father. The second confirmed COVID-19 patient (inpatient with pneumonia) showed high viral RNA load (CT values in RT-PCR: E gene, 17.19; RdRp gene, 17.64). Despite the high viral load, only two direct transmissions could be identified. Asymptomatic transmission of COVID-19 has also been reported [15, 16], and viral loads can be high as symptomatic carriers [17]. Therefore, to control the spread of the virus, we tested all people in the hospital to identify asymptomatic and undiagnosed individuals. Despite extensive exposure to four confirmed patients, only a few HAI were detected. Several reasons could explain the minimal spread of SARS-CoV-2 in our hospital. Importantly, Korea experienced an outbreak of MERS in 2015; hence, nearly all hospitals have implemented infection prevention guidelines [7]. Immediately after the outbreak of COVID-19 in China, the Korean government imposed prevention measures [18], and the infection control unit of our hospital restricted hospital visitors with respiratory symptoms or travel history. As per the KCDC recommendations [19], masks were recommended for all patients and medical staff, and the importance of hand-washing was emphasized. Furthermore, our hospital was newly built with good ventilation facilities. Distance between the beds in multi-bed rooms was over 2 m. We know from the SARS outbreak that distance between beds ≤ 1m was a significant risk factor associated with healthcare-associated SARS transmission [20]. Curtains were installed between the beds, most of which were kept closed for privacy. This could have greatly contributed to the containment of the virus spread [21]. Additionally, the maximum number of beds in a room was four, which is lower than other university hospitals in Seoul. Hospital closure, inpatient isolation in single rooms, self-isolation of individuals with contact history for two weeks, and complete enumeration survey of all inpatients, medical staff, and employees regardless of contact history or development of respiratory symptoms, further minimized the transmission of SARS-CoV-2 in the hospital and local communities. The robust control of the nosocomial COVID-19 outbreak reassured the remaining inpatients and local community that the risk of in-hospital transmission was low. However, the measures taken were time-consuming, laborious, and expensive. Complete enumeration could be achieved due to the rapid installation of new molecular equipment. Before the nosocomial outbreak, one ABI 7500 (Applied Biosystems) real-time PCR system and two QIAcube (Qiagen) preparation systems were available in the Department of Laboratory Medicine to test for SARS-CoV-2 and other pathogens. To increase SARS-CoV-2 RT-PCR testing capacities during the nosocomial outbreak, we installed new viral RNA preparation systems and one ABI 7500 system on February 24th. Comparison between Nextractor NX-48 systems and QIAcube systems, as well as between two ABI systems, were performed. The test capacity of SARS-CoV-2 RT-PCR testing increased to approximately 800 tests per day after the installation of the new equipment. Including the commercial laboratory tests, we could test approximately 1,000 samples in 24 hours. In addition to the introduction of new equipment, the working hours and shifts of laboratory medical technicians were adjusted to allow for 24-hour testing. The infection control unit and every department of our hospital continuously monitored inpatients and employees for fever and respiratory symptoms. Fifty-one individuals underwent SARS-CoV-2 RT-PCR testing more than twice to monitor the progress of respiratory symptoms. Moreover, for some individuals, several respiratory specimens were tested to account for the incubation period of SARS-CoV-2, which is estimated to be 5.1 days [22]. Moreover, SARS-CoV-2 RT-PCR testing was repeated prior to patient de-isolation; however, considering the cost, this may not be possible in all hospitals [23]. Our hospital was reopened on March 9th, 17 days after the closure and, until now, no additional COVID-19 cases have been confirmed. The duration of the hospital closure was based on the Seoul government guidelines established during the MERS outbreak [7]. According to “Management of medical center with COVID-19 confirmed patients” guidelines established by the Central Disaster and Safety Countermeasures Headquarters of Korea, hospitals should close when the risk of transmission is high [24]. On March 9th, the Korean Medical Association announced that 17 days of closure would be a laborious administrative process and suggested that the old guidelines based on the MERS outbreak should be revised. During the hospital closure, the existing patients could not receive treatments, and some were denied care elsewhere. Due to the complete hospital shutdown, patients with scheduled chemotherapy, radiation therapy, hemodialysis, emergency operation, or scheduled births faced health challenges. In conclusion, the robust control of the COVID-19 outbreak further minimized the transmission of SARS-CoV-2 in the hospital and local communities. However, there was also a debate over the appropriate period of hospital shutdown and testing of all hospital staff and patients. Future studies are required to refine and establish the in-hospital quarantine and de-isolation guidelines based on the epidemiological and clinical settings. 22 Jun 2020 PONE-D-20-13049 Containment of a healthcare-associated COVID-19 outbreak in a university hospital in Seoul, Korea: a single-center experience PLOS ONE Dear Dr. Lee, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Aug 06 2020 11:59PM. 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The PLOS ONE style templates can be found at http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Partly ********** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes ********** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes ********** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes ********** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: This paper illustrates actions taken by south Korea (hereafter Korea) in the case of the first COVID-19 confirmed cases in a university hospital. Korea is one of the countries managing COVID-19 under control without major shutdown. Therefore, their experience is unique and important for medical communities throughout the world. The hospital identified contact individual with the confirmed patients based on the following criteria: Stayed in the same room within 30 min. interval with confirmed patients including outpatient clinic or examination room. stayed within 2 m of confirmed patients. 2,924 inpatients and employees were tested for COVID-19. Everyone with contact history even without symptom was quarantined for 14 days including medical staff. Two discharged patients and one caregiver were tested positive. The same procedure for each newly confirmed case was taken. 1.1.This paper is not written clearly. The procedures taken is not easy to follow and confusing. For example, page 16 “14 healthcare-associated COVID-19 cases were reported in our hospital.” This number looks like including subsequent confirmed cases related to the hospital illustrated in Figure 2. Without clean explanation this sentence is confusing. 2.This paper conclude hospital shutdown for extended period was not necessary and testing of all hospital staff and inpatients without risk assessment are time-consuming. However, the paper does not provide enough scientific evidence how this conclusion is reached. Low confirmed probability ex-post is not the evidence you can use since the risk of outbreak is still exist. Just explaining the action taken by Korea is meaningful. ********** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: Beomsoo Kim [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. 14 Jul 2020 We really appreciate that the reviewer has provided valuable comments on how to improve our research. We fully understood the points from the reviewer and revised the manuscript. < Reviewer #1 > 1. This paper is not written clearly. The procedures taken is not easy to follow and confusing. For example, page 16 “14 healthcare-associated COVID-19 cases were reported in our hospital.” This number looks like including subsequent confirmed cases related to the hospital illustrated in Figure 2. Without clean explanation this sentence is confusing. : Thank you very much for the comment. Fourteen healthcare-associated COVID-19 cases consisted of four in-hospital diagnoses and ten out-of-hospital diagnoses. For clear explanation, we revised the figures and manuscript. 2. This paper conclude hospital shutdown for extended period was not necessary and testing of all hospital staff and inpatients without risk assessment are time-consuming. However, the paper does not provide enough scientific evidence how this conclusion is reached. Low confirmed probability ex-post is not the evidence you can use since the risk of outbreak is still exist. Just explaining the action taken by Korea is meaningful. : We fully agree with the comment and revised the manuscript. The revised conclusion is as follows. “In conclusion, the robust control of the COVID-19 outbreak further minimized the transmission of SARS-CoV-2 in the hospital and local communities. However, there was also a debate over the appropriate period of hospital shutdown and testing of all hospital staff and patients. Future studies are required to refine and establish the in-hospital quarantine and de-isolation guidelines based on the epidemiological and clinical settings.” Submitted filename: Response to Reviewers_20200711.docx Click here for additional data file. 3 Aug 2020 Containment of a healthcare-associated COVID-19 outbreak in a university hospital in Seoul, Korea: a single-center experience PONE-D-20-13049R1 Dear Dr. Lee, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Xia Jin, MD, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: 7 Aug 2020 PONE-D-20-13049R1 Containment of a healthcare-associated COVID-19 outbreak in a university hospital in Seoul, Korea: a single-center experience Dear Dr. Lee: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Xia Jin Academic Editor PLOS ONE
  19 in total

1.  Preliminary epidemiological assessment of MERS-CoV outbreak in South Korea, May to June 2015.

Authors:  B J Cowling; M Park; V J Fang; P Wu; G M Leung; J T Wu
Journal:  Euro Surveill       Date:  2015-06-25

Review 2.  Middle East Respiratory Syndrome Infection Control and Prevention Guideline for Healthcare Facilities.

Authors:  Jin Yong Kim; Joon Young Song; Young Kyung Yoon; Seong-Ho Choi; Young Goo Song; Sung-Ran Kim; Hee-Jung Son; Sun-Young Jeong; Jung-Hwa Choi; Kyung Mi Kim; Hee Jung Yoon; Jun Yong Choi; Tae Hyong Kim; Young Hwa Choi; Hong Bin Kim; Ji Hyun Yoon; Jacob Lee; Joong Sik Eom; Sang-Oh Lee; Won Sup Oh; Jung-Hyun Choi; Jin-Hong Yoo; Woo Joo Kim; Hee Jin Cheong
Journal:  Infect Chemother       Date:  2015-12-30

3.  Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.

Authors:  Chaolin Huang; Yeming Wang; Xingwang Li; Lili Ren; Jianping Zhao; Yi Hu; Li Zhang; Guohui Fan; Jiuyang Xu; Xiaoying Gu; Zhenshun Cheng; Ting Yu; Jiaan Xia; Yuan Wei; Wenjuan Wu; Xuelei Xie; Wen Yin; Hui Li; Min Liu; Yan Xiao; Hong Gao; Li Guo; Jungang Xie; Guangfa Wang; Rongmeng Jiang; Zhancheng Gao; Qi Jin; Jianwei Wang; Bin Cao
Journal:  Lancet       Date:  2020-01-24       Impact factor: 79.321

4.  Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany.

Authors:  Camilla Rothe; Mirjam Schunk; Peter Sothmann; Gisela Bretzel; Guenter Froeschl; Claudia Wallrauch; Thorbjörn Zimmer; Verena Thiel; Christian Janke; Wolfgang Guggemos; Michael Seilmaier; Christian Drosten; Patrick Vollmar; Katrin Zwirglmaier; Sabine Zange; Roman Wölfel; Michael Hoelscher
Journal:  N Engl J Med       Date:  2020-01-30       Impact factor: 91.245

5.  A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster.

Authors:  Jasper Fuk-Woo Chan; Shuofeng Yuan; Kin-Hang Kok; Kelvin Kai-Wang To; Hin Chu; Jin Yang; Fanfan Xing; Jieling Liu; Cyril Chik-Yan Yip; Rosana Wing-Shan Poon; Hoi-Wah Tsoi; Simon Kam-Fai Lo; Kwok-Hung Chan; Vincent Kwok-Man Poon; Wan-Mui Chan; Jonathan Daniel Ip; Jian-Piao Cai; Vincent Chi-Chung Cheng; Honglin Chen; Christopher Kim-Ming Hui; Kwok-Yung Yuen
Journal:  Lancet       Date:  2020-01-24       Impact factor: 79.321

6.  SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients.

Authors:  Lirong Zou; Feng Ruan; Mingxing Huang; Lijun Liang; Huitao Huang; Zhongsi Hong; Jianxiang Yu; Min Kang; Yingchao Song; Jinyu Xia; Qianfang Guo; Tie Song; Jianfeng He; Hui-Ling Yen; Malik Peiris; Jie Wu
Journal:  N Engl J Med       Date:  2020-02-19       Impact factor: 91.245

Review 7.  Relationship between hospital ward design and healthcare-associated infection rates: a systematic review and meta-analysis.

Authors:  Andrea Stiller; Florian Salm; Peter Bischoff; Petra Gastmeier
Journal:  Antimicrob Resist Infect Control       Date:  2016-11-29       Impact factor: 4.887

8.  Why did outbreaks of severe acute respiratory syndrome occur in some hospital wards but not in others?

Authors:  Ignatius T Yu; Zhan Hong Xie; Kelvin K Tsoi; Yuk Lan Chiu; Siu Wai Lok; Xiao Ping Tang; David S Hui; Nelson Lee; Yi Min Li; Zhi Tong Huang; Tao Liu; Tze Wai Wong; Nan Shan Zhong; Joseph J Sung
Journal:  Clin Infect Dis       Date:  2007-03-09       Impact factor: 9.079

9.  Early Epidemiological and Clinical Characteristics of 28 Cases of Coronavirus Disease in South Korea.

Authors: 
Journal:  Osong Public Health Res Perspect       Date:  2020-02

10.  Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts.

Authors:  Joel Hellewell; Sam Abbott; Amy Gimma; Nikos I Bosse; Christopher I Jarvis; Timothy W Russell; James D Munday; Adam J Kucharski; W John Edmunds; Sebastian Funk; Rosalind M Eggo
Journal:  Lancet Glob Health       Date:  2020-02-28       Impact factor: 26.763

View more
  8 in total

1.  Multi-site assessment of rapid, point-of-care antigen testing for the diagnosis of SARS-CoV-2 infection in a low-prevalence setting: A validation and implementation study.

Authors:  Stephen Muhi; Nick Tayler; Tuyet Hoang; Susan A Ballard; Maryza Graham; Amanda Rojek; Jason C Kwong; Jason A Trubiano; Olivia Smibert; George Drewett; Fiona James; Emma Gardiner; Socheata Chea; Nicole Isles; Michelle Sait; Shivani Pasricha; George Taiaroa; Julie McAuley; Eloise Williams; Katherine B Gibney; Timothy P Stinear; Katherine Bond; Sharon R Lewin; Mark Putland; Benjamin P Howden; Deborah A Williamson
Journal:  Lancet Reg Health West Pac       Date:  2021-03-02

2.  Impact of the first superspreading outbreak of COVID-19 related to a nightlife establishment in Andalusia, Spain.

Authors:  S Delgado-Sánchez; Á Serrano-Ortiz; R Ruiz-Montero; N Lorusso; J M Rumbao-Aguirre; I Salcedo-Leal
Journal:  J Healthc Qual Res       Date:  2021-12-29

3.  Factors Preventing Nosocomial Outbreak Following a Single case of COVID-19 Diagnosed During Hospitalization: A Retrospective Review.

Authors:  I-Nae Park
Journal:  Disaster Med Public Health Prep       Date:  2022-01-10       Impact factor: 1.385

Review 4.  Mitigating SARS-CoV-2 Transmission in Hospitals: A Systematic Literature Review.

Authors:  Chester Yan Hao Ng; Nicole-Ann Lim; Lena X Y Bao; Amy M L Quek; Raymond C S Seet
Journal:  Public Health Rev       Date:  2022-02-23

5.  Activity of daily life dependency predicts the risk of mortality in patients with COVID-19 undergoing hemodialysis: a retrospective analysis of a single center with nosocomial outbreak.

Authors:  Jun Ino; Fumika Iemura; Chihiro Nakajima; Mio Kodama; Saeko Kumon; Keitaro Sato; Hitoshi Eizumi; Nobuhiro Hijikata; Sadayuki Oshio; Shingo Tachibana; Kosaku Nitta; Junichi Hoshino
Journal:  Ren Replace Ther       Date:  2022-09-08

6.  Source Analysis and Effective Control of a COVID-19 Outbreak in a University Teaching Hospital during a Period of Increasing Community Prevalence of COVID-19.

Authors:  Unhee Lee; Seong Eun Kim; Seung Yeob Lee; Hang Nam Wi; Okja Choi; Ji Won Park; Dahee Kim; You Jung Kim; Hwa Young Shin; Mihee Kim; Eun Ji Kim; Seung Ji Kang; Sook In Jung; Kyung Hwa Park
Journal:  J Korean Med Sci       Date:  2021-06-21       Impact factor: 2.153

7.  Healthcare-associated COVID-19 in England: A national data linkage study.

Authors:  Alex Bhattacharya; Simon M Collin; James Stimson; Simon Thelwall; Olisaeloka Nsonwu; Sarah Gerver; Julie Robotham; Mark Wilcox; Susan Hopkins; Russell Hope
Journal:  J Infect       Date:  2021-08-30       Impact factor: 6.072

Review 8.  COVID-19 Prevention and Control Measures in Workplace Settings: A Rapid Review and Meta-Analysis.

Authors:  Carolyn Ingram; Vicky Downey; Mark Roe; Yanbing Chen; Mary Archibald; Kadri-Ann Kallas; Jaspal Kumar; Peter Naughton; Cyril Onwuelazu Uteh; Alejandro Rojas-Chaves; Shibu Shrestha; Shiraz Syed; Fionn Cléirigh Büttner; Conor Buggy; Carla Perrotta
Journal:  Int J Environ Res Public Health       Date:  2021-07-24       Impact factor: 4.614

  8 in total

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