Publications by authors named "Pyoeng Gyun Choe"

117 Publications

Genetic regulation of nonsense-mediated decay underlies association with risk of severe COVID-19.

medRxiv 2021 Jul 13. Epub 2021 Jul 13.

Genomic regions have been associated with COVID-19 susceptibility and outcomes, including the chr12q24.13 locus encoding antiviral proteins OAS1-3. Here, we report genetic, functional, and clinical insights into genetic associations within this locus. In Europeans, the risk of hospitalized vs. non-hospitalized COVID-19 was associated with a single 19Kb-haplotype comprised of 76 variants included in a 95% credible set within a large genomic fragment introgressed from Neandertals. The risk haplotype was also associated with impaired spontaneous but not treatment-induced SARS-CoV-2 clearance in a clinical trial with pegIFN-λ1. We demonstrate that two exonic variants, rs10774671 and rs1131454, affect splicing and nonsense-mediated decay of . We suggest that genetically-regulated loss of expression contributes to impaired spontaneous clearance of SARS-CoV-2 and elevated risk of hospitalization for COVID-19. Our results provide the rationale for further clinical studies using interferons to compensate for impaired spontaneous SARS-CoV-2 clearance, particularly in carriers of the risk haplotypes.
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http://dx.doi.org/10.1101/2021.07.09.21260221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288155PMC
July 2021

Persistence of Neutralizing Antibody Response up to 1 Year After Asymptomatic or Symptomatic SARS-CoV-2 Infection.

J Infect Dis 2021 Sep;224(6):1097-1099

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

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http://dx.doi.org/10.1093/infdis/jiab339DOI Listing
September 2021

Antibody Responses One Year after Mild SARS-CoV-2 Infection.

J Korean Med Sci 2021 May 31;36(21):e157. Epub 2021 May 31.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Understanding the long-term kinetics of antibodies in coronavirus disease 2019 (COVID-19) is essential in interpreting serosurvey data. We investigated the antibody response one year after infection in 52 mildly symptomatic patients with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, using three commercial immunoassays and a surrogate virus neutralization test (sVNT) kit. Anti-N pan-immunoglobulin (Ig), anti-S IgG, and anti-S1 IgG were detected in 43 (82.7%), 44 (84.6%), and 30 (57.7%), respectively. In 49 (94.2%), the antibody could be detected by either anti-N pan-Ig or anti-S IgG assay. In the sVNT, 30 (57.7%) had positive neutralizing activity. Despite waning immunity, SARS-CoV-2 antibodies can be detected up to one year after infection, even in mild COVID-19 patients.
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http://dx.doi.org/10.3346/jkms.2021.36.e157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167408PMC
May 2021

Can reactogenicity predict immunogenicity after COVID-19 vaccination?

Korean J Intern Med 2021 May 28. Epub 2021 May 28.

Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.

Background/aims: This study aimed to assess the association between local and systemic reactogenicity and humoral immunogenicity after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination.

Methods: Adverse events were prospectively evaluated using an electronic diary in 135 healthy adults who received a SARS-CoV-2 vaccine (AZD1222, AstraZeneca/Oxford, n = 42; or BNT162b2, Pfizer/BioNTech, n = 93). We semi-quantitatively measured anti-S1 immunoglobulin G (IgG) using an enzyme-linked immunosorbent assay at baseline, 3 weeks after the first dose of AZD1222 or BNT162b2, and 2 weeks after the second dose of BNT162b2. We evaluated the association between the maximum grade of local or systemic adverse events and the anti-S1 IgG optical density using multivariate linear regression with adjustment for age, sex, and use of antipyretics.

Results: The median age of the 135 vaccinees was 30 years (36 years in the AZD1222 group and 29 years in the BNT162b2 group) and 25.9% were male (9.5% in the AZD1222 group and 33.3% in the BNT162b2 group). Local and systemic adverse events were generally comparable after the first dose of AZD1222 and the second dose of BNT162b2. The grades of local and systemic adverse events were not significantly associated with anti-S1 IgG levels in the AZD1222 or BNT162b2 group.

Conclusions: Local and systemic reactogenicity may not be associated with humoral immunogenicity after SARS-CoV-2 vaccination.
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http://dx.doi.org/10.3904/kjim.2021.210DOI Listing
May 2021

Clinical Application of the Standard Q COVID-19 Ag Test for the Detection of SARS-CoV-2 Infection.

J Korean Med Sci 2021 Apr 12;36(14):e101. Epub 2021 Apr 12.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

We evaluated the Standard Q COVID-19 Ag test for the diagnosis of coronavirus disease 2019 (COVID-19) compared to the reverse transcription-polymerase chain reaction (RT-PCR) test. We applied both tests to patients who were about to be hospitalized, had visited an emergency room, or had been admitted due to COVID-19 confirmed by RT-PCR. Two nasopharyngeal swabs were obtained; one was tested by RT-PCR and the other by the Standard Q COVID-19 Ag test. A total of 118 pairs of tests from 98 patients were performed between January 5 and 11, 2021. The overall sensitivity and specificity for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for the Standard Q COVID-19 Ag test compared to RT-PCR were 17.5% (95% confidence interval [CI], 8.8-32.0%) and 100% (95% CI, 95.3-100.0%). Analysis of the results using RT-PCR cycle thresholds of ≤ 30 or ≤ 25 increased the sensitivity to 26.9% (95% CI, 13.7-46.1%), and 41.1% (95% CI, 21.6-64.0%), respectively.
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http://dx.doi.org/10.3346/jkms.2021.36.e101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042480PMC
April 2021

Longitudinal Analysis of Human Memory T-Cell Response According to the Severity of Illness up to 8 Months After Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

J Infect Dis 2021 07;224(1):39-48

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: Understanding the memory T-cell response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for assessing the longevity of protective immunity after SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) vaccination. However, the longitudinal memory T-cell response up to 8 months post-symptom onset (PSO) according to the severity of illness is unknown.

Methods: We analyzed peripheral blood mononuclear cells (PBMCs) from healthy volunteers or patients with COVID-19 who experienced asymptomatic, mild, or severe illness at 2, 5, and 8 months PSO. SARS-CoV-2 spike, nucleocapsid, and membrane protein-stimulated PBMCs were subjected to flow cytometry analysis.

Results: A total of 24 patients (7 asymptomatic, 9 with mild disease, and 8 with severe disease) and 6 healthy volunteers were analyzed. SARS-CoV-2-specific OX40+CD137+CD4+ T cells and CD69+CD137+CD8+ T cells persisted at 8 months PSO. Also, antigen-specific cytokine-producing or polyfunctional CD4+ T cells were maintained for up to 8 months PSO. Memory CD4+ T-cell responses tended to be greater in patients who had severe illness than in those with mild or asymptomatic disease.

Conclusions: Memory response to SARS-CoV-2, based on the frequency and functionality, persists for 8 months PSO. Further investigations involving its longevity and protective effect from reinfection are warranted.
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http://dx.doi.org/10.1093/infdis/jiab159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083680PMC
July 2021

Clinical and Virologic Effectiveness of Remdesivir Treatment for Severe Coronavirus Disease 2019 (COVID-19) in Korea: a Nationwide Multicenter Retrospective Cohort Study.

J Korean Med Sci 2021 Mar 22;36(11):e83. Epub 2021 Mar 22.

Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Remdesivir is widely used for the treatment of coronavirus disease 2019 (COVID-19), but controversies regarding its efficacy still remain.

Methods: A retrospective cohort study was conducted to evaluate the effect of remdesivir on clinical and virologic outcomes of severe COVID-19 patients from June to July 2020. Primary clinical endpoints included clinical recovery, additional mechanical ventilator (MV) support, and duration of oxygen or MV support. Viral load reduction by hospital day (HD) 15 was evaluated by calculating changes in cycle threshold (Ct) values.

Results: A total of 86 severe COVID-19 patients were evaluated including 48 remdesivir-treated patients. Baseline characteristics were not significantly different between the two groups. Remdesivir was administered an average of 7.42 days from symptom onset. The proportions of clinical recovery of the remdesivir and supportive care group at HD 14 (56.3% and 39.5%) and HD 28 (87.5% and 78.9%) were not statistically different. The proportion of patients requiring MV support by HD 28 was significantly lower in the remdesivir group than in the supportive care group (22.9% vs. 44.7%, = 0.032), and MV duration was significantly shorter in the remdesivir group (average, 1.97 vs. 5.37 days; = 0.017). Analysis of upper respiratory tract specimens demonstrated that increases of Ct value from HD 1-5 to 11-15 were significantly greater in the remdesivir group than the supportive care group (average, 10.19 vs. 5.36; = 0.007), and the slope of the Ct value increase was also significantly steeper in the remdesivir group (average, 5.10 vs. 2.68; = 0.007).

Conclusion: The remdesivir group showed clinical and virologic benefit in terms of MV requirement and viral load reduction, supporting remdesivir treatment for severe COVID-19.
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http://dx.doi.org/10.3346/jkms.2021.36.e83DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985289PMC
March 2021

Comparison of Respiratory Specimens for the Detection of SARS-CoV-2.

Ann Clin Lab Sci 2021 Jan;51(1):140-144

Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea

We compared SARS-CoV-2 detection rate of different respiratory specimens (nasopharyngeal swab [NPS], n=92; oropharyngeal swab [OPS], n=18; sputum, n=11). We also compared cycle threshold (Ct) values of paired specimen types obtained from the same patient on the same day. Then we characterized viral load kinetics of NPS (n=142), OPS (n=126), and sputum (n=75), during disease course. Sputum samples showed higher detection rate than NPS, and OPS exhibited the lowest detection rate. The median Ct values in NPS were significantly lower than in paired OPS, and higher than in paired sputum, respectively (<0.05). During the disease course, viral load was the lowest in OPS and the highest in sputum samples.
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January 2021

Impact of a computerised clinical decision support system on vancomycin loading and the risk of nephrotoxicity.

Int J Med Inform 2021 05 4;149:104403. Epub 2021 Feb 4.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.

Background: A vancomycin loading dose is recommended for the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections. However, clinicians often do not adhere to these recommendations, mainly due to nephrotoxicity risk, unfamiliarity with the guideline, or complexity of calculating an individual dose. Therefore, we introduced a computerised clinical decision support system (CDSS) for vancomycin loading (hereafter Vancomycin CDSS) to promote the use of vancomycin loading dose.

Methods: We describe a quasi-experimental study spanning 6 months before and 18 months after the deployment of a Vancomycin CDSS. The Vancomycin CDSS was integrated into the hospital's electronic medical record system in the form of a vancomycin order set. Our primary endpoint was the incidence of nephrotoxicity; the secondary endpoint was mean initial vancomycin trough levels. We also conducted a survey to evaluate the reasons why clinicians opted not to utilise a vancomycin loading dose.

Results: After implementation of Vancomycin CDSS, 363 out of 746 patients (49 %) who were first administered vancomycin received a loading dose. We did not find significant differences in nephrotoxicity between the pre- and post-intervention groups, nor between the loading- and non-loading groups. In the pre-intervention group, the mean initial vancomycin trough level was 7.10 mg/L, which was significantly lower than that in the post-intervention group of 11.11 mg/L. In the vancomycin loading group, the mean initial trough level was 11.95 mg/L, compared to 7.55 mg/L in the non-loading group. The main reason stated for not prescribing a vancomycin loading dose was concern about nephrotoxicity.

Conclusion: Introduction of the Vancomycin CDSS did not increase nephrotoxicity and increased the mean initial dose and trough level of vancomycin.
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http://dx.doi.org/10.1016/j.ijmedinf.2021.104403DOI Listing
May 2021

Immunogenicity and safety of a live herpes zoster vaccine in hematopoietic stem cell transplant recipients.

BMC Infect Dis 2021 Jan 26;21(1):117. Epub 2021 Jan 26.

Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Background: Herpes zoster (HZ) infection of hematopoietic stem cell transplant (HSCT) patients is of clinical concern. Vaccination could help restore immunity to varicella zoster virus (VZV); however, temporal changes in immunogenicity and safety of live HZ vaccines after HSCT is still unclear. The aim of this study was to elucidate the temporal immunogenicity and safety of the HZ vaccine according to time since HSCT and to determine optimal timing of vaccination.

Methods: Live HZ vaccine was administered to patients 2-5 years or > 5 years post-HSCT. Control groups comprised patients with a hematologic malignancy who received cytotoxic chemotherapy and healthy volunteers. Humoral and cellular immunogenicity were measured using a glycoprotein enzyme-linked immunosorbent assay (gpELISA) and an interferon-γ (IFN-γ) enzyme-linked immunospot (ELISPOT) assay. Vaccine-related adverse events were also monitored.

Results: Fifty-six patients with hematologic malignancy (41 in the HSCT group and 15 in the chemotherapy group) along with 30 healthy volunteers were enrolled. The geometric mean fold rises (GMFRs) in humoral immune responses of the 2-5 year and > 5 year HSCT groups, and the healthy volunteer group, were comparable and significantly higher than that of the chemotherapy group (3.15, 95% CI [1.96-5.07] vs 5.05, 95% CI [2.50-10.20] vs 2.97, 95% CI [2.30-3.83] vs 1.42, 95% CI [1.08-1.86]). The GMFR of cellular immune responses was highest in the HSCT 2-5 year group and lowest in the chemotherapy group. No subject suffered clinically significant adverse events or reactivation of VZV within the follow-up period.

Conclusion: Our findings demonstrate that a live HZ vaccine is immunogenic and safe when administered 2 years post-HSCT.
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http://dx.doi.org/10.1186/s12879-021-05806-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836155PMC
January 2021

Stereotypic neutralizing V antibodies against SARS-CoV-2 spike protein receptor binding domain in patients with COVID-19 and healthy individuals.

Sci Transl Med 2021 01 4;13(578). Epub 2021 Jan 4.

Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.

Stereotypic antibody clonotypes exist in healthy individuals and may provide protective immunity against viral infections by neutralization. We observed that 13 of 17 patients with COVID-19 had stereotypic variable heavy chain (V) antibody clonotypes directed against the receptor binding domain (RBD) of SARS-CoV-2 spike protein. These antibody clonotypes were composed of immunoglobulin heavy variable 3-53 () or and immunoglobulin heavy joining 6 () genes. These clonotypes included IgM, IgG3, IgG1, IgA1, IgG2, and IgA2 subtypes and had minimal somatic mutations, which suggested swift class switching after SARS-CoV-2 infection. The different IGHV chains were paired with diverse light chains resulting in binding to the RBD of SARS-CoV-2 spike protein. Human antibodies specific for the RBD can neutralize SARS-CoV-2 by inhibiting entry into host cells. We observed that one of these stereotypic neutralizing antibodies could inhibit viral replication in vitro using a clinical isolate of SARS-CoV-2. We also found that these V clonotypes existed in 6 of 10 healthy individuals, with IgM isotypes predominating. These findings suggest that stereotypic clonotypes can develop de novo from naïve B cells and not from memory B cells established from prior exposure to similar viruses. The expeditious and stereotypic expansion of these clonotypes may have occurred in patients infected with SARS-CoV-2 because they were already present.
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http://dx.doi.org/10.1126/scitranslmed.abd6990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875332PMC
January 2021

Antibody Responses 8 Months after Asymptomatic or Mild SARS-CoV-2 Infection.

Emerg Infect Dis 2021 03 22;27(3):928-931. Epub 2020 Dec 22.

Waning humoral immunity in coronavirus disease patients has raised concern over usefulness of serologic testing. We investigated antibody responses of 58 persons 8 months after asymptomatic or mildly symptomatic infection with severe acute respiratory syndrome coronavirus 2. For 3 of 4 immunoassays used, seropositivity rates were high (69.0%-91.4%).
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http://dx.doi.org/10.3201/eid2703.204543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920668PMC
March 2021

Toll-like receptor 2 downregulation and cytokine dysregulation predict mortality in patients with Staphylococcus aureus bacteremia.

BMC Infect Dis 2020 Nov 30;20(1):901. Epub 2020 Nov 30.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 173 Gumi-ro, Bundang-gu, Seongnam, 463-707, Republic of Korea.

Background: Staphylococcus aureus bacteremia (SAB) presents heterogeneously, owing to the differences in underlying host conditions and immune responses. Although Toll-like receptor 2 (TLR2) is important in recognizing S. aureus, its function during S. aureus infection remains controversial. We aimed to examine the association of TLR2 expression and associated cytokine responses with clinical SAB outcomes.

Methods: Patients from a prospective SAB cohort at two tertiary-care medical centers were enrolled. Blood was sampled at several timepoints (≤5 d, 6-9 d, 10-13 d, 14-19 d, and ≥ 20 d) after SAB onset. TLR2 mRNA levels were determined via real-time PCR and serum tumor necrosis factor [TNF]-α, interleukin [IL]-6, and IL-10 levels were analyzed with multiplex-high-sensitivity electrochemiluminescent ELISA.

Results: TLR2 levels varied among 59 SAB patients. On days 2-5, TLR2 levels were significantly higher in SAB survivors than in healthy controls (p = 0.040) and slightly but not significantly higher than non-survivors (p = 0.120), and SAB patients dying within 7 d had lower TLR2 levels than survivors (P = 0.077) although statistically insignificant. IL-6 and IL-10 levels were significantly higher in non-survivors than in survivors on days 2-5 post-bacteremia (P = 0.010 and P = 0.021, respectively), and those dying within 7 d of SAB (n = 3) displayed significantly higher IL-10/TNF-α ratios than the survivors did (P = 0.007).

Conclusion: TLR2 downregulation and IL-6 and IL-10 concentrations suggestive of immune dysregulation during early bacteremia may be associated with mortality from SAB. TLR2 expression levels and associated cytokine reactions during early-phase SAB may be potential prognostic factors in SAB, although larger studies are warranted.
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http://dx.doi.org/10.1186/s12879-020-05641-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706030PMC
November 2020

Minimizing contamination in the use of personal protective equipment: Simulation results through tracking contamination and enhanced protocols.

Am J Infect Control 2021 06 5;49(6):713-720. Epub 2020 Nov 5.

Center for Infection Prevention and Control, Seoul National University Hospital, Seoul, Korea; Division of Infectious Diseases, Department of Internal Medicine, Seoul National University School of Medicine, Seoul, Korea.

Background: Due to variations and the inadequate use of personal protective equipment (PPE), this study aimed to evaluate our enhanced PPE protocols for minimizing doffing contamination.

Methods: Among 3 PPE kits (simple, Level D, and Level C), 30 participants conducted the first simulation in their adapted way and the second following enhanced protocols. After donning, participants performed a 1-minute simulation of direct care on a patient simulator covered with fluorescent powder. For tracking contamination routes between doffing processes, fluorescent powder contamination was examined with ultraviolet lamps in the darkened room.

Results: Participants were mostly registered nurses (N = 27, 90%), female (87%), and on average 31.7 years old with 8.5 years of clinical experience. Among 61 total simulations, 32 had at least 1 contamination (52.5%); "Noticeable" level (40%) at the "hands-fingers" and "shirt" body areas were most frequent. For first and second simulations with identical PPE kits, compared to the first with adapted practice, the second with enhanced protocols showed a significant reduction in doffing contamination rates (72.7% vs 22.7%, P = .0009 for both Level C and D; 77.8% vs 27.8%, P = .0027 for Level D).

Conclusions: Our enhanced protocols could significantly reduce contaminations. More studies are necessary to provide safer PPE protocol options.
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http://dx.doi.org/10.1016/j.ajic.2020.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832077PMC
June 2021

Waning Antibody Responses in Asymptomatic and Symptomatic SARS-CoV-2 Infection.

Emerg Infect Dis 2021 01 13;27(1). Epub 2020 Oct 13.

We investigated the kinetics of severe acute respiratory syndrome coronavirus 2 neutralizing antibodies in 7 asymptomatic persons and 11 patients with pneumonia. The geometric mean titer of neutralizing antibodies declined from 219.4 at 2 months to 143.7 at 5 months after infection, indicating a waning antibody response.
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http://dx.doi.org/10.3201/eid2701.203515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774548PMC
January 2021

Short course of voriconazole therapy as a risk factor for relapse of invasive pulmonary aspergillosis.

Sci Rep 2020 09 30;10(1):16078. Epub 2020 Sep 30.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

To investigate associations of the duration of voriconazole treatment and radiological response with relapse of invasive pulmonary aspergillosis (IPA) in immunocompromised patients, we explored the risk factors for IPA relapse after successful initial treatment. All patients with proven or probable IPA who had finished voriconazole treatment between 2005 and 2019 in a tertiary-care hospital were reviewed. IPA relapse was defined as re-diagnosis of proven or probable IPA at the same site within 1 year after treatment termination. Short course of voriconazole treatment was defined as a treatment less than 9 weeks, which is a median of the recommended minimum duration of therapy from the Infectious Disease Society of America. The radiological response was defined as a reduction in IPA burden by more than 50% on chest computed tomography. Of 87 patients who had completed voriconazole treatment, 14 (16.1%) experienced IPA relapse. Multivariable Cox regression identified that short voriconazole treatment duration (adjusted hazard ratio [aHR], 3.7; 95% confidence interval [CI], 1.1-12.3; P = 0.033) and radiological non-response (aHR, 4.6; 95% CI, 1.2-17.5; P = 0.026) were independently associated with relapse of IPA after adjusting for several clinical risk factors. Longer duration of therapy should be considered for those at higher risk of relapse.
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http://dx.doi.org/10.1038/s41598-020-73098-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527978PMC
September 2020

Impact of national policy on hand hygiene promotion activities in hospitals in Korea.

Antimicrob Resist Infect Control 2020 09 23;9(1):157. Epub 2020 Sep 23.

Department of Internal Medicine, Seoul National University College of Medicine, 103 Daehak-ro, Jongro-gu, Seoul,, 03080, Republic of Korea.

Background: After the Middle East respiratory syndrome coronavirus outbreak in Korea in 2015, the Government established a strategy for infection prevention to encourage infection control activities in hospitals. The new policy was announced in December 2015 and implemented in September 2016. The aim of this study is to evaluate how infection control activities improved within Korean hospitals after the change in government policy.

Methods: Three cross-sectional surveys using the WHO Hand Hygiene Self-Assessment Framework (HHSAF) were conducted in 2013, 2015, and 2017. Using a multivariable linear regression model, we analyzed the change in total HHSAF score according to survey year.

Results: A total of 32 hospitals participated in the survey in 2013, 52 in 2015, and 101 in 2017. The number of inpatient beds per infection control professionals decreased from 324 in 2013 to 303 in 2015 and 179 in 2017. Most hospitals were at intermediate or advanced levels of progress (90.6% in 2013, 86.6% in 2015, and 94.1% in 2017). In the multivariable linear regression model, total HHSAF score was significantly associated with hospital teaching status (β coefficient of major teaching hospital, 52.6; 95% confidence interval [CI], 8.9 to 96.4; P = 0.018), beds size (β coefficient of 100 beds increase, 5.1; 95% CI, 0.3 to 9.8; P = 0.038), and survey time (β coefficient of 2017 survey, 45.1; 95% CI, 19.3 to 70.9; P = 0.001).

Conclusions: After the new national policy was implemented, the number of infection control professionals increased, and hand hygiene promotion activities were strengthened across Korean hospitals.
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http://dx.doi.org/10.1186/s13756-020-00817-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509816PMC
September 2020

Predictive scoring models for persistent gram-negative bacteremia that reduce the need for follow-up blood cultures: a retrospective observational cohort study.

BMC Infect Dis 2020 Sep 17;20(1):680. Epub 2020 Sep 17.

Department of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea.

Background: Although the risk factors for positive follow-up blood cultures (FUBCs) in gram-negative bacteremia (GNB) have not been investigated extensively, FUBC has been routinely carried out in many acute care hospitals. We attempted to identify the risk factors and develop a predictive scoring model for positive FUBC in GNB cases.

Methods: All adults with GNB in a tertiary care hospital were retrospectively identified during a 2-year period, and GNB cases were assigned to eradicable and non-eradicable groups based on whether removal of the source of infection was possible. We performed multivariate logistic analyses to identify risk factors for positive FUBC and built predictive scoring models accordingly.

Results: Out of 1473 GNB cases, FUBCs were carried out in 1268 cases, and the results were positive in 122 cases. In case of eradicable source of infection, we assigned points according to the coefficients from the multivariate logistic regression analysis: Extended spectrum beta-lactamase-producing microorganism (+ 1 point), catheter-related bloodstream infection (+ 1), unfavorable treatment response (+ 1), quick sequential organ failure assessment score of 2 points or more (+ 1), administration of effective antibiotics (- 1), and adequate source control (- 2). In case of non-eradicable source of infection, the assigned points were end-stage renal disease on hemodialysis (+ 1), unfavorable treatment response (+ 1), and the administration of effective antibiotics (- 2). The areas under the curves were 0.861 (95% confidence interval [95CI] 0.806-0.916) and 0.792 (95CI, 0.724-0.861), respectively. When we applied a cut-off of 0, the specificities and negative predictive values (NPVs) in the eradicable and non-eradicable sources of infection groups were 95.6/92.6% and 95.5/95.0%, respectively.

Conclusions: FUBC is commonly carried out in GNB cases, but the rate of positive results is less than 10%. In our simple predictive scoring model, zero scores-which were easily achieved following the administration of effective antibiotics and/or adequate source control in both groups-had high NPVs. We expect that the model reported herein will reduce the necessity for FUBCs in GNB cases.
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http://dx.doi.org/10.1186/s12879-020-05395-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499917PMC
September 2020

Prolonged (6-Month) Shedding of Middle East Respiratory Syndrome Coronavirus RNA in the Sputum of a Lymphoma Patient.

Open Forum Infect Dis 2020 Aug 18;7(8):ofaa292. Epub 2020 Jul 18.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

During the 2015 Korea Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak, a lymphoma patient developed MERS pneumonia. His pneumonia improved by 45 days after illness onset, but the polymerase chain reaction tests remained (+) for 6 months. However, replication-competent virus was detected by 60 days after illness onset.
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http://dx.doi.org/10.1093/ofid/ofaa292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408226PMC
August 2020

Recovery of Tenofovir-induced Nephrotoxicity following Switch from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in Human Immunodeficiency Virus-Positive Patients.

Infect Chemother 2020 Sep 16;52(3):381-388. Epub 2020 Jul 16.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Background: Tenofovir disoproxil fumarate (TDF)-induced nephrotoxicity is related to high plasma tenofovir concentrations. Tenofovir alafenamide (TAF) is a tenofovir prodrug with 90% lower plasma tenofovir concentrations. The aim of this study was to evaluate changes in tenofovir-induced nephrotoxicity in Human Immunodeficiency Virus (HIV)-positive patients who switched from TDF to TAF.

Materials And Methods: We identified all HIV-positive patients who switched from elvitegravir/cobicistat/emtricitabine/TDF to elvitegravir/cobicistat/emtricitabine/TAF at a tertiary hospital. We assessed tubulopathy and renal dysfunction before TDF administration, at the time TAF was used following at least 3 months of TDF use, and 3 months after TAF administration. Tubulopathy was defined by the presence of at least three abnormalities in fractional excretion of phosphate, fractional excretion of uric acid, urinary β2-microglobulin, urinary N-acetyl-β-D-glucosaminidase, glucosuria or proteinuria. Renal dysfunction was defined as decreased by more than 25% in the estimated glomerular filtration rate (eGFR) relative to baseline.

Results: In 80 patients, the mean eGFR was 96.8 mL/min/1.73 m² before administration of TDF, 81.2 ( <0.001) at the time of change to TAF, 90.9 ( <0.001) after TAF administration. Renal dysfunction occurred in 19 patients (23.8%) after TDF use for a median 15 months, 11 (57.9%) of these patients recovered from renal dysfunction after TAF administration. Six patients (7.5%) had tubulopathy before TDF administration, 36 (45.0%) after TDF administration ( <0.001), 12 (15.0%) after TAF administration ( = 0.002).

Conclusion: Tenofovir-induced nephrotoxicity in HIV-positive patients receiving TDF was mostly reversible after changing to TAF. Thus, TAF-containing regimens can be administered safely to HIV-positive patients with tenofovir-induced nephrotoxicity.
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http://dx.doi.org/10.3947/ic.2020.52.3.381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533205PMC
September 2020

Antibody Responses to SARS-CoV-2 at 8 Weeks Postinfection in Asymptomatic Patients.

Emerg Infect Dis 2020 10 24;26(10):2484-2487. Epub 2020 Jun 24.

We compared levels of severe acute respiratory syndrome coronavirus 2 neutralizing antibodies in recovery plasma from 7 completely asymptomatic coronavirus disease patients with those in symptomatic patients in South Korea. We found that serologic diagnostic testing was positive for 71% (5/7) of completely asymptomatic patients, but neutralizing antibody response occurred in all 7 patients.
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http://dx.doi.org/10.3201/eid2610.202211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510710PMC
October 2020

A Case of Breakthrough COVID-19 during Hydroxychloroquine Maintenance.

J Korean Med Sci 2020 Jun 22;35(24):e231. Epub 2020 Jun 22.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

There have been controversies on the prophylactic effect of hydroxychloroquine against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We describe a patient, 60-year old Korean woman, with coronavirus disease 2019 (COVID-19) who had been taking hydroxychloroquine for 6 months. Her serum and saliva concentrations of hydroxychloroquine were 280 μg/L and 4,890 μg/L, respectively. The present case raises concerns on hydroxychloroquine's role as a prophylactic agent for COVID-19.
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http://dx.doi.org/10.3346/jkms.2020.35.e231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308141PMC
June 2020

Microbial Etiology of Pyogenic Vertebral Osteomyelitis According to Patient Characteristics.

Open Forum Infect Dis 2020 Jun 20;7(6):ofaa176. Epub 2020 May 20.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: It is difficult to select an appropriate empirical antibiotic treatment regimen for patients with culture-negative pyogenic vertebral osteomyelitis (PVO). Having knowledge of the distribution of microorganisms according to patient characteristics can help clinicians make informed choices regarding empirical antibiotics. The aim of this study was to determine the microbial distribution among individuals with PVO according to their demographic and clinical characteristics.

Methods: We reviewed the medical records of patients admitted to our hospital with culture-confirmed PVO between January 2005 and December 2017 and collected data on demographics, underlying diseases, and radiographic and microbiological results. Statistical analysis was performed to identify associations between specific bacteria and specific patient characteristics.

Results: A total of 586 patients were included in the study. The prevalence of infections was higher in young patients than in old patients, while gram-negative bacterial infections and were more prevalent in older patients. Gram-negative bacterial infections were more common in women than in men (32.1% vs 16.4%;  < .05), in patients with cirrhosis than in those without (32.7% vs 21.1%;  < .05), and in patients with a solid tumor than in those without (31.0% vs 20.7%;  < .05). Methicillin-resistant infections were more prevalent in patients with chronic renal disease than in those without (34.4% vs 14.7%;  < .05).

Conclusions: The microbial etiology of PVO varies according to patient characteristics. Patient characteristics should thus be considered when choosing empirical antibiotics in patients with culture-negative PVO.
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http://dx.doi.org/10.1093/ofid/ofaa176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270706PMC
June 2020

Risk factors for and clinical outcomes of carbapenem non-susceptible gram negative bacilli bacteremia in patients with acute myelogenous leukemia.

BMC Infect Dis 2020 Jun 9;20(1):404. Epub 2020 Jun 9.

Department of Internal Medicine, Seoul National University College of Medicine, Daehak-ro 101, Jongro-gu, Seoul, 03080, Republic of Korea.

Background: Carbapenem is frequently used when gram negative bacilli (GNB) bacteremia is detected especially in neutropenic patients. Consequently, appropriate treatment could be delayed in GNB bacteremia cases involving organisms which are not susceptible to carbapenem (carba-NS), resulting in a poor clinical outcomes. Here, we explored risk factors for carba-NS GNB bacteremia and its clinical outcomes in patients with acute myelogenous leukemia (AML) that underwent chemotherapy.

Methods: We reviewed all GNB bacteremia cases that occurred during induction or consolidation chemotherapy, over a 15-year period, in a tertiary-care hospital.

Results: Among 489 GNB bacteremia cases from 324 patients, 45 (9.2%) were carba-NS and 444 (90.8%) were carbapenem susceptible GNB. Independent risk factors for carba-NS GNB bacteremia were: carbapenem use at bacteremia onset (adjusted odds ratio [aOR]: 91.2; 95% confidence interval [95%CI]: 29.3-284.1; P < 0.001); isolation of carbapenem-resistant Acinetobacter baumannii (aOR: 19.4, 95%CI: 3.4-112.5; P = 0.001) in the prior year; and days from chemotherapy to GNB bacteremia (aOR: 1.1 per day, 95%CI: 1.1-1.2; P < 0.001). Carba-NS bacteremia was independently associated with in-hospital mortality (aOR: 6.6, 95%CI: 3.0-14.8; P < 0.001).

Conslusion: Carba-NS organisms should be considered for antibiotic selection in AML patients having these risk factors.
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http://dx.doi.org/10.1186/s12879-020-05131-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282079PMC
June 2020

A cluster of tertiary transmissions of 2019 novel coronavirus (SARS-CoV-2) in the community from infectors with common cold symptoms.

Korean J Intern Med 2020 07 11;35(4):758-764. Epub 2020 Jun 11.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Background/aims: As the global impact of the novel coronavirus disease 2019 (COVID-19) has been severe, many countries have intensified containment activities to eliminate virus transmission, through early detection and isolation strategies. To establish a proper quarantine strategy, it is essential to understand how easily the virus can spread in the communities.

Methods: In this study, we collected detailed information on the circumstances in which human-to-human transmission occurred in the tertiary transmission cases of COVID-19 in the community.

Results: On January 26, 2020, an imported case of COVID-19 was confirmed, and by February 10, 2020, one secondary transmission and three tertiary transmissions were identified. Secondary transmission occurred on the first day of illness of the infector, and his symptoms were suggestive of a common cold. The transmission occurred during a 90-minute long meal together in a restaurant. The people were sitting within one meter of each other, and had no direct contact. The tertiary transmission also occurred on the first-day illness of the other infector, and his only symptom was slight chills. The transmission occurred at a church during 2-hour-long worship, and two rows separated them.

Conclusion: Our findings suggest that mildly symptomatic patients with COVID-19 could transmit the virus from the first day of illness through daily activities in the community. Early detection and isolation of patients with COVID-19 may be challenging.
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http://dx.doi.org/10.3904/kjim.2020.122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373952PMC
July 2020

Aberrant hyperactivation of cytotoxic T-cell as a potential determinant of COVID-19 severity.

Int J Infect Dis 2020 Aug 31;97:313-321. Epub 2020 May 31.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea. Electronic address:

Objectives: We hypothesized that immune response may contribute to progression of coronavirus disease-19 (COVID-19) at the second week of illness. Therefore, we compared cell-mediated immune (CMI) responses between severe and mild COVID-19 cases.

Methods: We examined peripheral blood mononuclear cells of laboratory-confirmed COVID-19 patients from their first and third weeks of illness. Severe pneumonia was defined as an oxygen saturation ≤93% at room air. Expressions of molecules related to T-cell activation and functions were analyzed by flow cytometry.

Results: The population dynamics of T cells at the first week were not different between the two groups. However, total numbers of CD4 and CD8 T cells tended to be lower in the severe group at the third week of illness. Expressions of Ki-67, PD-1, perforin, and granzyme B in CD4 or CD8 T cells were significantly higher in the severe group than in the mild group at the third week. In contrast to the mild group, the levels of their expression did not decrease in the severe group.

Conclusions: Severe COVID-19 had a higher degree of proliferation, activation, and cytotoxicity of T-cells at the late phase of illness without cytotoxic T-cell contraction, which might contribute to the development of severe COVID-19.
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http://dx.doi.org/10.1016/j.ijid.2020.05.106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261468PMC
August 2020

Cell-Mediated Immunogenicity of Influenza Vaccination in Patients With Cancer Receiving Immune Checkpoint Inhibitors.

J Infect Dis 2020 11;222(11):1902-1909

Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: We assessed cell-mediated immune (CMI) responses of influenza vaccination in patients with cancer receiving immune checkpoint inhibitors (ICIs), which remain elusive.

Methods: Vaccine-elicited CMI responses in patients receiving ICIs or cytotoxic agents were investigated by flow cytometry. Polyfunctional cells were defined as T cells that express 2 or more of interleukin 2 (IL-2), interleukin 4 (IL-4), interferon gamma (IFN-γ), and CD107a. An adequate CMI response was defined as an increase of polyfunctional T cells against both H1N1 and H3N2 strains.

Results: When comparing ICI (n = 11) and cytotoxic chemotherapy (n = 29) groups, H1N1-specific IL-4 or IFN-γ-expressing CD4+ T cells, IL-2, IL-4, IFN-γ, or CD107a-expressing CD8+ T cells, H3N2-specific IFN-γ-expressing CD4+ T cells, and CD107a-expressing CD8+ T cells were more frequent in the ICI group. Fold changes in polyfunctional H3N2-specific CD4+ (median, 156.0 vs 95.7; P = .005) and CD8+ (155.0 vs 103.4; P = .044) T cells were greater in the ICI group. ICI administration was strongly associated with an adequate CMI response for both CD4+ and CD8+ T cells (P = .003).

Conclusions: CMI responses following influenza vaccination were stronger in the ICI group than in the cytotoxic chemotherapy group. Influenza vaccination should be strongly recommended in patients with cancer receiving ICIs.
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http://dx.doi.org/10.1093/infdis/jiaa291DOI Listing
November 2020

In vitro activity of lopinavir/ritonavir and hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 at concentrations achievable by usual doses.

Korean J Intern Med 2020 07 29;35(4):782-787. Epub 2020 May 29.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Background/aims: As the coronavirus disease-2019 global pandemic progresses, screening of antiviral agents effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is urgently needed. In addition, considering the viral load kinetics of SARS-CoV-2, which peaks early in the illness, and the massive burden of the disease, which may increase in the near future, identifying well-tolerated oral antivirals becomes increasingly important. We examined the in vitro activity of lopinavir/ritonavir and hydroxychloroquine on SARS-CoV-2, at concentrations which can be used to treat coronavirus-19 patients with little concern of toxicity.

Methods: Lopinavir/ritonavir (7/1.75 μg/mL), hydroxychloroquine base (1 or 2 μg/mL), or a combination thereof were administered 1 hour after the inoculation of SARS-CoV-2 to Vero cells at a multiplicity of infection of 0.05. We examined cytopathic effects of virus 48 hours after administration of the respective treatments and measured viral loads at three time points (0, 24, and 48 hours post-treatment) by quantitative real-time reverse-transcription polymerase chain reaction, and compared the results obtained from the different antiviral regimens tested.

Results: The severity of cytopathic effects was lower in lopinavir/ritonavir-treated cells, and viral load was significantly reduced in this group compared with the control group (p < 0.001). However, hydroxychloroquine did not show significant inhibitory effects on anti-SARS-CoV-2-mediated cytotoxicity or on viral load at either concentration.

Conclusion: Lopinavir/ritonavir showed significant inhibitory effects on SARS-CoV-2 in vitro at its usual plasma concentration. However, the in vitro antiviral activity of hydroxychloroquine at concentrations commonly used in humans was minimal, whether used alone or in combination with lopinavir/ritonavir.
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http://dx.doi.org/10.3904/kjim.2020.157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373950PMC
July 2020

Selecting coronavirus disease 2019 patients with negligible risk of progression: early experience from non-hospital isolation facility in Korea.

Korean J Intern Med 2020 07 29;35(4):765-770. Epub 2020 May 29.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Background/aims: As the novel coronavirus (coronavirus disease 2019 [COVID-19]) outbreak progresses rapidly, staying home is recommended for suspected patients; however, the safety of this recommendation is uncertain. In Korea, non-hospital facilities called "living and treatment centers (LTCs)" have been established since 5 March 2020. The LTCs provided a unique opportunity to evaluate the safety of selection criteria for low-risk groups.

Methods: Between 5 March and 9 April 2020, patients with COVID-19 who met the following criteria were admitted to the LTC; alert, age below 65 years old, no underlying disease or well-controlled underlying disease, body temperature below 38.0°C, whether taking antipyretics or not, and no dyspnea. Patients were closely observed by doctors or nurses' interviews twice a day and transferred to hospitals when symptoms worsened.

Results: A total of 113 patients were admitted to the LTC; 52.2% were female, with a median age of 25 years (interquartile range, 21.5 to 39.5). Of 113 patients, 54 (47.8%) were asymptomatic at diagnosis, and 15 (13.3%) had no symptoms until they were released from isolation. During the follow-up period, two (1.8%) patients were transferred to a hospital but did not progress to severe status during hospitalization.

Conclusion: The risk of progression was negligible in COVID-19 patients who met the admission criteria for LTC at the time of diagnosis. LTCs could be a safe alternative considering shortage of hospital beds.
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http://dx.doi.org/10.3904/kjim.2020.159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373958PMC
July 2020
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