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Background@#The rate and composition of bacterial co-infection in patients with coronavirus disease 2019 (COVID-19) were evaluated when microbiological testing was conducted on the majority of patients. We also evaluated whether the use of empirical antibacterials was associated with mortality. @*Methods@#In this retrospective study, all of the adult patients with COVID-19 hospitalized in a single tertiary hospital in South Korea between February 2020 and December 2021 were included. Bacterial co-infection was assessed by sputum cultures, blood cultures, and molecular testing, including polymerase chain reaction sputum testing and urinary antigen tests. Mortality was compared between patients who received empirical antibacterials and those who did not. @*Results@#Of the 367 adult patients admitted during the study period, 300 (81.7%) had sputum culture results and were included in the analysis. Of these 300 patients, 127 (42.3%) had a history of antibiotic exposure. The co-infection rate within 48 hours was 8.3% (25/300):6.4% (11/173) of patients without prior antibiotic exposure and 11% (14/127) of patients with prior antibacterial exposure. The co-infected bacteria were different according to antibacterial exposure before admission, and multi-drug resistant pathogens were detected exclusively in the antibacterial exposed group. Among the patients without positive results for the microbiological tests, empirical antibacterials were used in 33.3% of cases (100/300). Empirical antibacterial therapy was not significantly related to the 30-day mortality or inhospital mortality rates in the study cohort before or after the propensity score-matching. @*Conclusion@#In this study including only patients underwent microbiological testing, bacterial co-infection was not frequent, and the co-infected organisms varied depending on previous antibacterial exposures. Given the rarity of co-infection and the lack of potential benefits, empiric antibacterial use in COVID-19 should be an important target of antibiotic stewardship.
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Background@#Whether varicella zoster virus (VZV) antibody titer could discriminate patients with herpes zoster (HZ) from healthy controls (HCs) is unclear. We evaluated the diagnostic usefulness of VZV-specific immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies in patients with confirmed HZ. @*Methods@#Study subjects comprised patients with confirmed HZ by salivary VZV DNA positivity and control age- and sex-matched HCs. Saliva was collected and concurrent blood samples were obtained on the first visit day (acute phase) and after 4 weeks (convalescent phase) from 44 HZ patients. All 44 healthy volunteers provided blood and saliva samples once. @*Results@#The median VZV IgA titers in acute-phase (5.2 mIU/mL, P < 0.001) and convalescentphase (15.8 mIU/mL, P < 0.001) serum samples from HZ patients were significantly higher than those in HCs (1.35 mIU/mL). VZV IgA positivity was detected in about 20% of acute phase serum and convalescent-phase serum of HZ patients. The median VZV IgG antibody titers of HZ patients during acute (1,471.0 mIU/mL, P < 0.001) and convalescent (4,934.7 mIU/mL, P < 0.001) phases were significantly higher than the median titer reported for HCs (591.6 mIU/mL). A four-fold or higher increase in VZV IgG antibody titer was observed in 36.4% of HZ patients. @*Conclusion@#VZV IgA positivity or four-fold or higher increase in VZV IgG antibody titers were not detected in a satisfactory proportion of HZ-infected patients. However, the titer of VZV IgA or IgG antibody particularly in convalescent-phase sera may discriminate HZ patients from HCs.
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Background@#Ralstonia mannitolilytica is a causative organism of nosocomial infections, particularly associated with contaminated water, and resistant to various antibiotics, including carbapenems. Several clusters of R. mannitolilytica infections appeared in children at our institute from August 2018 to November 2019. @*Methods@#From March 2009 to March 2023, all patients admitted to Asan Medical Center Children’s Hospital in Seoul, Korea, with culture-confirmed R. mannitolilytica and corresponding clinical signs of infection were identified. Epidemiological and environmental investigations were conducted. Polymerase chain reaction (PCR) was performed for the genes of OXA-443 and OXA-444 on R. mannitolilytica isolates. @*Results@#A total of 18 patients with R. mannitolilytica infection were included in this study, with 94.4% (17/18) and 5.6% (1/18) being diagnosed with pneumonia and central line-associated bloodstream infection, respectively. All-cause 30-day mortality rate was 61.1% (11/18), and seven of the fatal cases were caused by R. mannitolilytica infection itself. The resistance rates to meropenem and imipenem werew 94.4% (17/18) and 5.6% (1/18), respectively. Although four out of nine meropenem-resistant R.mannitolilytica isolates had positive PCR results for OXA-443 and OXA-444 genes, there were no significant differences in antimicrobial susceptibility patterns. Environmental sampling identified R. mannitolylica at two sites: a cold-water tap of a water purifier and an exhalation circuit of a patient mechanical ventilator.After implementing and improving adherence to infection control policies, no additional R. mannitolilyticainfection cases have been reported since December 2019. @*Conclusion@#R. mannitolilytica can cause life-threatening infections with high mortality in fragile pediatric populations. To prevent outbreaks, healthcare workers should be aware of R. mannitolilytica infections and strive to comply with infection control policies.
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Background@#Preventive measures are needed to reduce the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among healthcare workers (HCWs). Notably, hospital staff are usually exposed when they are unmasked. There are limited data on the risk of transmission during mealtimes at hospital staff cafeterias. We aimed to evaluate the risk of transmission in cafeterias. @*Methods@#From January 2020 through September 2021, we analyzed the risk of SARS-CoV-2 transmission through closed-circuit television and radio-frequency identification tracking and follow-up testing when 33 HCWs, who were eventually diagnosed as coronavirus disease 2019 (COVID-19), ate in staff cafeterias during the infectious period. The seats were arranged so the HCWs would sit on either side without facing each other. There were no plastic barriers installed, and HCWs were encouraged not to talk during meals. @*Results@#Three of the 119 individuals who ate at seats next (about 30 cm) to index during the period of transmission and underwent follow-up SARS-CoV-2 polymerase chain reaction tests were diagnosed with COVID-19 (2.5%; 95% confidence interval, 0.5–7.4%). Among the 98 HCWs who were investigated about talking during meals, there was a higher attack rate among those who spoke with each other than among those who did not (12.5% [3/24] vs. 0% [0/74], P = 0.013). @*Conclusion@#The risk of transmission in a hospital’s employee cafeterias is not high with sideby-side seating, especially in the absence of conversation.
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Background/Aims@#Data comparing the antibody responses of different coronavirus disease 2019 (COVID-19) vaccine platforms according to dose with natural severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection-induced antibody responses are limited. @*Methods@#Blood samples from adult patients with mild and severe COVID-19 and healthcare workers who received ChAdOx1 nCoV-19 vaccine (2nd dose at 12-week intervals) and BNT162b2 vaccine (2nd dose at 3-week intervals) were collected and compared by immunoglobulin G immune responses to SARS-CoV-2 specific spike protein using an in-house-developed enzyme-linked immunosorbent assay. @*Results@#A total of 53 patients, including 12 and 41 with mild and severe COVID-19, respectively, were analyzed. In addition, a total of 73 healthcare workers, including 37 who received ChAdOx1 nCoV-19 and 36 who received BNT162b2, were enrolled. Antibody responses after the first and second doses of the ChAdOx1 nCoV-19 vaccine or the first dose of the BNT162b2 vaccine were similar to those in convalescent patients with mild COVID-19, but lower than those in convalescent patients with severe COVID-19, respectively. However, after the second dose of the BNT162b2 vaccine, the antibody response was comparable to that in convalescent patients with severe COVID-19. @*Conclusions@#Our data suggest that the second dose of mRNA vaccination may be more beneficial in terms of long-term immunity and prevention of SARS-CoV-2 variant infection than a single dose of COVID-19 vaccination or homologous second challenge ChAdOx1 nCoV-19.
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Poly (ADP-ribose) polymerase inhibitors (PARP inhibitor) is a new targeted drug for metastatic prostate cancer in which the patient has a mutation on homologous repair gene including BRCA1/2 gene. This drug was the first gene-based targeted agent in prostate cancer and there were more than 5 available drugs for PARP inhibitors. Only 4 were approved for clinical use for patients with cancer from the U.S. Food and Drug Administration. This review article deals with the overview of the PARP inhibitors and their use in future research and clinical fields.
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Purpose@#This study aimed to determine the prognostic roles of several immune-related laboratory parameters in patients with metastatic kidney and bladder cancer treated with immune checkpoint inhibitors (ICIs). @*Materials and Methods@#Overall, 36 patients with either metastatic bladder (N=18) or kidney cancer (N=18) were enrolled retrospectively. Progression-free survival (PFS) and overall survival according to the pretherapeutic serum De Ritis ratio (DRR), neutrophil-to-lymphocyte ratio (NLR), and albumin level after ICI treatment, were analyzed. Treatment duration was adjusted using Contal and O’Quigley’s method to explore the cutoff and maximize the log-rank test statistic. Cox proportional hazards model was used to analyze the laboratory parameters. @*Results@#A total of 9 patients received a combination therapy of multiple ICIs (N=9) and targeted agents (N=7). The median NLR, DRR, and albumin level at baseline were 1.7, 1.2, and 4.2 mg/dL, respectively. In the univariable analysis, combination of immunotherapies, total ICI cycles, baseline DRR, and albumin level were significant for PFS. Sex ratio, total ICI cycles, and baseline NLR and DRR were significant for cancer-specific survival (CSS). DRR and albumin levels, which were measured for up to 10 cycles, were significant in PFS and CSS. NLR was additionally significant in CSS. After adjusting total ICI cycles, DRR was significant in PFS and CSS, albumin level was significant only in PFS, and NLR was significant only in CSS in the multivariable analysis. @*Conclusions@#NLR, DRR, and albumin level are significant factors associated with the survival of patients with metastatic kidney and bladder cancer treated with ICI.
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Background@#Coronavirus disease 2019 (COVID-19) is often accompanied by secondary infections, such as invasive aspergillosis. In this study, risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA) and their clinical outcomes were evaluated. @*Methods@#This multicenter retrospective cohort study included critically ill COVID-19 patients from July 2020 through March 2021. Critically ill patients were defined as patients requiring high-flow respiratory support or mechanical ventilation. CAPA was defined based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Factors associated with CAPA were analyzed, and their clinical outcomes were adjusted by a propensity score-matched model. @*Results@#Among 187 eligible patients, 17 (9.1%) developed CAPA, which is equal to 33.10 per 10,000 patient-days. Sixteen patients received voriconazole-based antifungal treatment. In addition, 82.4% and 53.5% of patients with CAPA and without CAPA, respectively, received early high-dose corticosteroids (P = 0.022). In multivariable analysis, initial 10-day cumulative steroid dose > 60 mg of dexamethasone or dexamethasone equivalent dose) (adjusted odds ratio [OR], 3.77; 95% confidence interval [CI], 1.03–13.79) and chronic pulmonary disease (adjusted OR, 4.20; 95% CI, 1.26–14.02) were independently associated with CAPA. Tendencies of higher 90-day overall mortality (54.3% vs. 35.2%, P= 0.346) and lower respiratory support-free rate were observed in patients with CAPA (76.3% vs. 54.9%, P = 0.089). @*Conclusion@#Our study showed that the dose of corticosteroid use might be a risk factor for CAPA development and the possibility of CAPA contributing to adverse outcomes in critically ill COVID-19 patients.
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Background@#The potential for a nosocomial outbreak of coronavirus disease 2019 (COVID-19) from a fully vaccinated individual is largely unknown. @*Methods@#In October 2021, during the time when the delta variant was dominant, a nosocomial outbreak of COVID-19 occurred in two wards in a tertiary care hospital in Seoul, Korea. We performed airflow investigations and whole-genome sequencing (WGS) of the virus. @*Results@#The index patient developed symptoms 1 day after admission, and was diagnosed with COVID-19 on day 4 post-admission. He was fully vaccinated (ChAdOx1 nCoV-19) 2 months before the diagnosis. Three inpatients and a caregiver in the same room, two inpatients in an adjacent room, two inpatients in rooms remote from the index room, and one nurse on the ward tested positive. Also, two resident doctors who stayed in an on-call room located on the same ward tested positive (although they had no close contact), as well as a caregiver who stayed on an adjacent ward, and a healthcare worker who had casual contact with this caregiver. Samples from five individuals were available for WGS, and all showed ≤ 1 single-nucleotide polymorphism difference. CCTV footage showed that the index case walked frequently in the corridors of two wards. An airflow study showed that the air from the corridor flowed into the resident on-call room, driven by an air circulator that was always turned on. @*Conclusion@#Transmission of severe acute respiratory syndrome coronavirus 2 from a fully vaccinated index occurred rapidly via the wards and on-call room. Care must be taken to not use equipment that can change the airflow.
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We report a case of coronavirus disease 2019 (COVID-19)-associated radiologically suspected organizing pneumonia with repeated negative Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) results from nasopharyngeal swab and sputum samples, but positive result from bronchoalveolar lavage fluid. Performing SARS-CoV-2 RT-PCR in upper respiratory tract samples only could fail to detect COVID-19-associated pneumonia, and SARS-CoV-2 could be an etiology of radiologically suspected organizing pneumonia.
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Background@#This study aimed to evaluate whether fluvoxamine reduces clinical deterioration in adult patients with mild to moderate coronavirus disease 2019 (COVID-19), and to identify risk factors for clinical deterioration in patients admitted to a community treatment center (CTC). @*Materials and Methods@#A randomized, placebo-controlled trial was conducted in a CTC, in Seoul, Korea from January 15, 2021, to February 19, 2021. Symptomatic adult patients with positive results of severe acute respiratory syndrome coronavirus 2 real timepolymerase chain reaction within 3 days of randomization were assigned at random to receive 100 mg of fluvoxamine or placebo twice daily for 10 days. The primary outcome was clinical deterioration defined by any of the following criteria: oxygen requirement to keep oxygen saturation over 94.0%, aggravation of pneumonia with dyspnea, or World Health Organization clinical progression scale 4 or greater. @*Results@#Of 52 randomized participants [median (interquartile range) age, 53.5 (43.3 - 60.0) years; 31 (60.0%) men], 44 (85.0%) completed the trial. Clinical deterioration occurred in 2 of 26 patients in each group (P >0.99). There were no serious adverse events in either group. Clinical deterioration occurred in 15 (6.0%) of 271 patients admitted to the CTC, and all of them were transferred to a hospital. In multivariate analysis, age between 55 and 64, fever and pneumonia at admission were independent risk factors for clinical deterioration. @*Conclusion@#In this study of adult patients with symptomatic COVID-19 who were admitted to the CTC, there was no significant differences in clinical deterioration between patients treated with fluvoxamine and placebo (ClinicalTrials.gov Identifier: NCT04711863).
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A 64-year old woman who underwent lung transplantation and had T-cannula contracted classic scabies from her daughter. The patient was treated with 5% permethrin 10 times and had two consecutive negative follow-up microscopic examinations. However, the patient had recurrent symptoms and diagnosed with recurrent classic scabies 22 days after the last treatment. Unchanged tie string and unapplied topical agent around the T-cannula skin lesion may be reasons for recurrence. Thus, accurate application of topical treatment and changing the tie string of the t-cannula is needed to prevent a recurrence.
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Eosinophilic meningitis is defined as the presence of more than 10 eosinophils per μl in the cerebrospinal fluid (CSF), or eosinophils accounting for more than 10% of CSF leukocytes in patients with acute meningitis. Parasites are the most common cause of eosinophilic meningitis worldwide, but there is limited research on patients in Korea. Patients diagnosed with eosinophilic meningitis between January 2004 and June 2018 at a tertiary hospital in Seoul, Korea were retrospectively reviewed. The etiology and clinical characteristics of each patient were identified. Of the 22 patients included in the study, 11 (50%) had parasitic causes, of whom 8 (36%) were diagnosed as neurocysticercosis and 3 (14%) as Toxocara meningitis. Four (18%) patients were diagnosed with fungal meningitis, and underlying immunodeficiency was found in 2 of these patients. The etiology of another 4 (18%) patients was suspected to be tuberculosis, which is endemic in Korea. Viral and bacterial meningitis were relatively rare causes of eosinophilic meningitis, accounting for 2 (9%) and 1 (5%) patients, respectively. One patient with neurocysticercosis and 1 patient with fungal meningitis died, and 5 (23%) had neurologic sequelae. Parasite infections, especially neurocysticercosis and toxocariasis, were the most common cause of eosinophilic meningitis in Korean patients. Fungal meningitis, while relatively rare, is often aggressive and must be considered when searching for the cause of eosinophilic meningitis.
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Background/Aims@#Multi-drug resistant pathogens are increasing among healthcare-associated infections. It is well known that copper and copper alloys have antimicrobial activity. We evaluated the activity of copper against bacteria in a hospital setting in Korea. @*Methods@#This study was conducted in a laboratory and medical intensive care unit (ICU). Methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus faecium (VRE) were inoculated onto copper, copper alloy and stainless steel plates. After 24 hours of incubation, colony-forming units (CFU) were counted in the laboratory. Two similar rooms were chosen in the ICU; one room had copper-containing surface, and the other room contained items with a stainless steel surfaces. Items were sampled weekly for 8 weeks when the rooms were not crowded and when the rooms were busier with healthcare workers or visitors. @*Results@#In vitro time-kill curves showed copper or, a copper alloy yielded a significant reduction in MRSA and VRE CFUs over 15 minutes. Upon exposure to stainless steel plates, CFUs were slowly reduced for 24 hours. In vivo, MRSA CFUs were lower in rooms with copper-containing surfaces compared with controls, both after cleaning and after patients had received visitors (p < 0.05). Analysis of VRE revealed similar results, but VRE CFUs from copper-containing surfaces of drug carts in the ICU did not decrease significantly. @*Conclusions@#Copper has antimicrobial activity and appears to reduce the number of multi-drug resistant microorganisms in a hospital environment. This finding suggests the potential of the use of copper fittings, instruments and surfaces in hospital.
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Background/Aims@#The risk of herpes zoster (HZ) is increased in patients with autoimmune diseases (AID), probably due to immunosuppressive therapy. @*Methods@#This prospective cross-sectional study investigated varicella zoster virus (VZV)-specific immunity in relation to subclinical VZV reactivation in 48 AID patients and 48 healthy controls (HCs). We assessed humoral immunity (serum VZV immunoglobulin g [IgG], IgA, and IgM) and cell-mediated immunity (interferon-γ [IFNγ]-releasing assay) to VZV as well as salivary VZV DNA status. Subclinical VZV reactivation was confirmed by detecting VZV DNA in saliva or VZV IgM in serum in the absence of typical HZ symptoms. @*Results@#Median IgA levels were higher in the AID group than in the HC group, while VZV IgG and IgM levels were comparable between the groups. AID patients showed fewer IFNγ spot-forming cells (SFCs) upon VZV stimulation than HCs (58.2 vs. 122.0 SFCs/106 peripheral blood mononuclear cells [PBMCs], p < 0.0001). Subclinical VZV reactivation was more frequent in AID patients than in HCs (12.5% vs. 0%, p = 0.01). AID patients with VZV reactivation received prednisolone more frequently and at a higher dose than AID patients without reactivation. VZV-specific IFNγ SFCs were significantly lower in patients with VZV reactivation among AID patients (26.3 vs. 62.6 SFCs/106 PBMCs, p < 0.0001). @*Conclusions@#Results suggest that poor cellular response against VZV might cause clinical and subclinical reactivation of VZV in AID patients.
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Correlation between vaccine reactogenicity and immunogenicity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Thus, we investigated to determine whether the reactogenicity after coronavirus disease 2019 vaccination is associated with antibody (Ab) titers and T cell responses. This study was prospective cohort study done with 131 healthcare workers at tertiary center in Seoul, South Korea. The degrees of the local reactions after the 1st and 2nd doses of ChAdOx1 nCov-19 (ChAdOx1) vaccination were significantly associated with the S1-specific IgG Ab titers (p=0.003 and 0.01, respectively) and neutralizing Ab (p=0.04 and 0.10, respectively) in age- and sex-adjusted multivariate analysis, whereas those after the BNT162b2 vaccination did not show significant associations. T cell responses did not show significant associations with the degree of reactogenicity after the ChAdOx1 vaccination or the BNT162b2 vaccination. Thus, high degree of local reactogenicity after the ChAdOx1 vaccine may be used as an indicator of strong humoral immune responses against SARS-CoV-2.
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Recently, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (B.1.1.529) Omicron variant originated from South Africa in the middle of November 2021. SARS-CoV-2 is also called coronavirus disease 2019 (COVID-19) since SARS-CoV-2 is the causative agent of COVID-19. Several studies already suggested that the SARS-CoV-2 Omicron variant would be the fastest transmissible variant compared to the previous 10 SARS-CoV-2 variants of concern, interest, and alert. Few clinical studies reported the high transmissibility of the Omicron variant but there is insufficient time to perform actual experiments to prove it, since the spread is so fast. We analyzed the SARS-CoV-2 Omicron variant, which revealed a very high rate of mutation at amino acid residues that interact with angiostatin-converting enzyme 2. The mutation rate of COVID-19 is faster than what we prepared vaccine program, antibody therapy, lockdown, and quarantine against COVID-19 so far. Thus, it is necessary to find better strategies to overcome the current crisis of COVID-19 pandemic.
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There are limited data directly comparing humoral and T cell responses to the ChAdOx1 nCoV-19 and BNT162b2 vaccines. We compared Ab and T cell responses after first doses of ChAdOx1 nCoV-19 vs. BNT162b2 vaccines. We enrolled healthcare workers who received ChAdOx1 nCoV-19 or BNT162b2 vaccine in Seoul, Korea. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S1 protein-specific IgG Abs (S1-IgG), neutralizing Abs (NT Abs), and SARS-CoV-2-specific T cell response were evaluated before vaccination and at 1-wk intervals for 3 wks after vaccination. A total of 76 persons, comprising 40 injected with the ChAdOx1 vaccine and 36 injected with the BNT162b2 vaccine, participated in this study. At 3 wks after vaccination, the mean levels (±SD) of S1-IgG and NT Abs in the BNT162b2 participants were significantly higher than in the ChAdOx1 participants (S1-IgG, 14.03±7.20 vs. 6.28±8.87, p<0.0001; NT Ab, 183.1±155.6 vs. 116.6±116.2, p=0.035), respectively. However, the mean values of the T cell responses in the 2 groups were comparable after 2 wks. The humoral immune response after the 1st dose of BNT162b2 developed faster and was stronger than after the 1st dose of ChAdOx1. However, the T cell responses to BNT162b2 and ChAdOx1 were similar.
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Purpose@#This study aimed to analyze the overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with either combination or only secondary hormone therapy (2ndHTx) or docetaxel chemotherapy. @*Materials and Methods@#Between 2005 and 2018, 307 mCRPC patients’ medical records were retrospectively reviewed treated with either 2ndHTx (HTx [N=73, 23.8%] either abiraterone acetate or enzalutamide), docetaxel+2ndHTx (CTx-HTx [N=90, 29.3%]) or only docetaxel therapy (CTx-only [N=144, 46.9%]). The Cox proportional hazard model for risk factors of OS and Kaplan-Meier analysis with log-rank test for OS comparison among three therapeutic groups with a statistical significance of p＜0.05. @*Results@#During a median 49.6-month follow-up and a median 22 months of OS, the worst OS was observed in CTx-only (17.7 months) followed by the CTx-HTx (22.9 months), and only-HTx (42.6 months) groups (p＜0.001). The baseline comparison showed that age, body mass index, TN stagings, and prostate specific antigen level were significantly different between groups (p＜0.05). In the multivariable analysis for the risk factors of OS, age (hazard ratio [HR], 0.978), cT3–4 stage (HR, 1.606), and HTx (HR, 0.482) were significant factors. With the HTx agents, enzalutamide was the only left risk factor for OS regardless of underlying diseases (HR, 0.511; p＜0.001). The group analyses for the OS showed that only-CTx group (HR, 2.696) and CTx-HTx group (HR, 1.434) were unfavorable factors for OS with a reference of HTx group (p＜0.001). @*Conclusions@#2ndHTx was a significant prognostic factor for OS regardless of underlying diseases in patients with mCRPC and improved OS in comparison with docetaxel.
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Background@#Coronavirus disease 2019 (COVID-19) outbreaks emerged at two universityaffiliated hospitals in Seoul (hospital A) and Uijeongbu City (hospital S) in the metropolitan Seoul area in March 2020. The aim of this study was to investigate epidemiological links between the outbreaks using whole genome sequencing (WGS) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). @*Methods@#Fifteen patients were enrolled in the study, including four non-outbreak (A1–A4) and three outbreak cases (A5–A7) in hospital A and eight cases (S1–S8) in hospital S. Patients' hospital stays, COVID-19 symptoms, and transfer history were reviewed. RNA samples were submitted for WGS and genome-wide single nucleotide variants and phylogenetic relationships were analyzed. @*Results@#The index patient (A5) in hospital A was transferred from hospital S on 26 March.Patients A6 and A7 were the family caregiver and sister, respectively, of the patient who shared a room with A5 for 4 days. Prior to transfer, A5 was at the next bed to S8 in the emergency room on 25 March. Patient S6, a professional caregiver, took care of the patient in the room next to S8's room for 5 days until 22 March and then S5 for another 3 days.WGS revealed that SARS-CoV-2 in A2, A3, and A4 belong to clades V/B.2, S/A, and G/B.1, respectively, whereas that of A5–A7 and S1-S5 are of the V/B.2.1 clade and closely clustered. In particular, SARS-CoV-2 in patients A5 and S5 showed perfect identity. @*Conclusion@#WGS is a useful tool to understand epidemiology of SARS-CoV-2. It is the first study to elucidate the role of patient transfer and caregivers as links of nosocomial outbreaks of COVID-19 in multiple hospitals.