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1.
Article in English | WPRIM (Western Pacific) | ID: wpr-1042036

ABSTRACT

A standardized protocol for the isolation of cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) is lacking. Therefore, we established a cfDNA isolation protocol optimized for clinical CSF specimens, integrating acceptable modifications and using artificial CSF generated from remnant CSF spiked with reference cell-free tumor DNA (ctDNA). We compared the isolation yields of in vitro diagnostic (IVD)-certified column-based (CB) and magnetic beadbased (MB) isolation. Furthermore, we modified both methods, including pre- and postelution steps. To confirm ctDNA integrity and quantify the variant allele frequency after isolation, we performed droplet digital PCR (ddPCR) targeting IDH1 R132C in the reference ctDNA. MB isolation had a higher yield than CB isolation (P < 0.0001), and post-isolation vacuum increased the final concentration in both methods, with little effect on cfDNA integrity. Our study provides a protocol to maximize CSF-ctDNA concentrations in IVD testing and future studies.

2.
Article in English | WPRIM (Western Pacific) | ID: wpr-1043307

ABSTRACT

Nasotracheal intubation (NTI) plays an important role in pediatric airway management, offering advantages in specific situations, such as oral and maxillofacial surgery and situations requiring stable tube positioning. However, compared to adults, NTI in children presents unique challenges owing to anatomical differences and limited space. This limited space, in combination with a large tongue and short mandible, along with large tonsils and adenoids, can complicate intubation. Owing to the short tracheal length in pediatric patients, it is crucial to place the tube at the correct depth to prevent it from being displaced due to neck movements, and causing injury to the glottis. The equipment used for NTI includes different tube types, direct laryngoscopy vs. video laryngoscopy, and fiberoptic bronchoscopy. Considering pediatric anatomy, the advantages of video laryngoscopy have been questioned. Studies comparing different techniques have provided insights into their efficacy. Determining the appropriate size and depth of nasotracheal tubes for pediatric patients remains a challenge. Various formulas based on age, weight, and height have been explored, including the recommendation of depth-mark-based NTI. This review provides a comprehensive overview of NTI in pediatric patients, including the relevant anatomy, equipment, clinical judgment, and possible complications.

3.
Article in English | WPRIM (Western Pacific) | ID: wpr-1043483

ABSTRACT

Background@#Since the emergence of hypervirulent strains of Clostridioides difficile, the incidence of C. difficile infections (CDI) has increased significantly. @*Methods@#To assess the incidence of CDI in Korea, we conducted a prospective multicentre observational study from October 2020 to October 2021. Additionally, we calculated the incidence of CDI from mass data obtained from the Health Insurance Review and Assessment Service (HIRA) from 2008 to 2020. @*Results@#In the prospective study with active surveillance, 30,212 patients had diarrhoea and 907 patients were diagnosed with CDI over 1,288,571 patient-days and 193,264 admissions in 18 participating hospitals during 3 months of study period; the CDI per 10,000 patientdays was 7.04 and the CDI per 1,000 admission was 4.69. The incidence of CDI was higher in general hospitals than in tertiary hospitals: 6.38 per 10,000 patient-days (range: 3.25–12.05) and 4.18 per 1,000 admissions (range: 1.92–8.59) in 11 tertiary hospitals, vs. 9.45 per 10,000 patient-days (range: 5.68–13.90) and 6.73 per 1,000 admissions (range: 3.18–15.85) in seven general hospitals. With regard to HIRA data, the incidence of CDI in all hospitals has been increasing over the 13-year-period: from 0.3 to 1.8 per 10,000 patient-days, 0.3 to 1.6 per 1,000 admissions, and 6.9 to 56.9 per 100,000 population, respectively. @*Conclusion@#The incidence of CDI in Korea has been gradually increasing, and its recent value is as high as that in the United State and Europe. CDI is underestimated, particularly in general hospitals in Korea.

4.
Article in English | WPRIM (Western Pacific) | ID: wpr-1045078

ABSTRACT

Objectives@#Between July 2, 2021, and September 20, 2022, a Mycobacterium bovis outbreak occurred among exhibition animals at a zoo in the Republic of Korea. This study was conducted to assess the likelihood of M. bovis transmission to human contacts through a contact investigation and to implement preventive treatment for latent tuberculosis infection (LTBI). @*Methods@#In this descriptive study, the Korea Disease Control and Prevention Agency conducted a contact investigation, which included interviews, interferon-gamma release assay (IGRA) tests, and chest X-rays. Contacts underwent IGRA testing on 2 occasions: initial testing of 29 contacts (15 in the first cluster of infection and 14 in the second cluster) and follow-up testing of the 15 contacts in the first cluster. @*Results@#The study included 29 participants, 18 of whom were male (62.1%) and 11 female (37.9%). The mean participant age was 37.3 years (standard deviation, 9.6 years). In the initial IGRA tests, 6 of the 29 participants tested positive, indicating a prevalence of 20.7%. Following prolonged exposure, 1 additional positive case was detected in follow-up testing, raising the prevalence of LTBI to 24.1%. None of the contacts had active tuberculosis. Among the 7 individuals with positive results, 2 (28.6%) underwent treatment for LTBI. @*Conclusion@#This study faced challenges in confirming the transmission of M. bovis infection from infected animals to humans in the Republic of Korea. Nevertheless, adopting a One Health approach necessitates the implementation of surveillance systems and infection control protocols, particularly for occupational groups at high risk of exposure.

5.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-991145

ABSTRACT

Sialylated N-glycan isomers with α2-3 or 42-6 linkage(s)have distinctive roles in glycoproteins,but are difficult to distinguish.Wild-type(WT)and glycoengineered(mutant)therapeutic glycoproteins,cyto-toxic T lymphocyte-associated antigen-4-immunoglobulin(CTLA4-Ig),were produced in Chinese ham-ster ovary cell lines:however,their linkage isomers have not been reported.In this study,N-glycans of CTLA4-Igs were released,labeled with procainamide,and analyzed by liquid chromatography-tandem mass spectrometry(MS/MS)to identify and quantify sialylated N-glycan linkage isomers.The linkage isomers were distinguished by comparison of 1)intensity of the N-acetylglucosamine ion to the sialic acid ion(Ln/Nn)using different fragmentation stability in MS/MS spectra and 2)retention time-shift for a selective m/z value in the extracted ion chromatogram.Each isomer was distinctively identified,and each quantity(>0.1%)was obtained relative to the total N-glycans(100%)for all observed ionization states.Twenty sialylated N-glycan isomers with only α2-3 linkage(s)in WT were identified,and each isomer's sum of quantities was 50.4%.Furthermore,39 sialylated N-glycan isomers(58.8%)in mono-(3 N-glycans;0.9%),bi-(18;48.3%),tri-(14;8.9%),and tetra-(4;0.7%)antennary structures of mutant were obtained,which comprised mono-(15 N-glycans;25.4%),di-(15;28.4%),tri-(8;4.8%),and tetra-(1;0.2%)sialy-lation,respectively,with only α2-3(10 N-glycans;4.8%),both α2-3 and α2-6(14;18.4%),and only α2-6(15;35.6%)linkage(s).These results are consistent with those for α2-3 neuraminidase-treated N-glycans.This study generated a novel plot of Ln/Nn versus retention time to distinguish sialylated N-glycan linkage isomers in glycoprotein.

6.
Article in English | WPRIM (Western Pacific) | ID: wpr-967488

ABSTRACT

Background@#Antimicrobial prescriptions for serious chronic or acute illness nearing its end stages raise concerns about the potential for futile use, adverse events, increased multidrugresistant organisms, and significant patient and social cost burdens. This study investigated the nationwide situation of how antibiotics are prescribed to patients during the last 14 days of life to guide future actions. @*Methods@#This nationwide multicenter retrospective cohort study was conducted at 13 hospitals in South Korea from November 1 to December 31, 2018. All decedents were included in the study. Antibiotic use during the last two weeks of their lives was investigated. @*Results@#A total of 1,201 (88.9%) patients received a median of two antimicrobial agents during the last two weeks of their lives. Carbapenems were prescribed to approximately half of the patients (44.4%) in the highest amount (301.2 days of therapy per 1,000 patient-days).Among the patients receiving antimicrobial agents, 63.6% were inappropriate and only 327 patients (27.2%) were referred by infectious disease specialists. The use of carbapenem (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.13–2.03; P = 0.006), underlying cancer (OR, 1.56; 95% CI, 1.20–2.01, P = 0.047), underlying cerebrovascular disease (OR, 1.88; 95% CI, 1.23–2.89, P = 0.004), and no microbiological testing (OR, 1.79; 95% CI, 1.15–2.73; P = 0.010) were independent predictors for inappropriate antibiotic prescribing. @*Conclusion@#A considerable number of antimicrobial agents are administered to patients with chronic or acute illnesses nearing their end-of-life, a high proportion of which are prescribed inappropriately. Consultation with an infectious disease specialist, in addition to an antimicrobial stewardship program, may be necessary to induce the optimal use of antibiotics.

7.
Article in English | WPRIM (Western Pacific) | ID: wpr-968443

ABSTRACT

Objectives@#The coronavirus disease 2019 (COVID-19) pandemic has continued since its first detection in the Republic of Korea on January 20, 2020. This study describes the early countermeasures used to minimize the risk of COVID-19 outbreaks during cohort quarantine and compares the epidemiological characteristics of 2 outbreaks in long-term care facilities (LTCFs) in Gwangju Metropolitan City in summer 2020. @*Methods@#An epidemiological investigation was conducted via direct visits. We investigated epidemiological characteristics, including incidence, morbidity, and mortality rates, for all residents and staff members. Demographic characteristics were analyzed using a statistical program. Additionally, the method of managing infection in LTCFs is described. @*Results@#Residents and caregivers had high incidence rates in LTCF-A and LTCF-B, respectively. LTCF-B had a longer quarantine period than LTCF-A. The attack rate was 20.02% in LTCF-A and 27.9% in LTCF- B. The mortality rate was 2.3% (1/43) in LTCF-B, the only facility in which a COVID-19 death occurred. @*Conclusion@#Extensive management requires contact minimization, which involves testing all contacts to mitigate further transmission in the early stages of LTCF outbreaks. The findings of this study can help inform and prepare public health authorities for COVID-19 outbreaks, particularly for early control in vulnerable facilities.

8.
Article in English | WPRIM (Western Pacific) | ID: wpr-1001246

ABSTRACT

Background@#Tuberculosis (TB) exposure in congregate settings related to neonates is a serious medical and social issue. TB exposure happens during the neonatal period, but contact investigations for exposed infants are usually conducted after the neonatal period.Generally, recommendations for screening and managing close contact are different for neonates and children. Thus, there are challenges in contact investigations. We aimed to report contact investigations with a single tuberculin skin test (TST) on infants exposed to infectious TB in a postpartum care center. @*Methods@#The index case was a healthcare worker with active pulmonary TB: sputum acidfast bacilli smear negative, culture positive, and no cavitary lesion. All exposed infants underwent medical examinations and chest X-ray. After TB disease was ruled out, contacts received window period prophylaxis with isoniazid (INH) until three months after the last exposure. TST was performed only once after completing the prophylaxis. @*Results@#A total of 288 infants were selected as high-priority contacts. At the initial contact investigation, the age of infants ranged from 8 to 114 days. None of these exposed infants had TB disease. The prevalence of latent TB infection (LTBI) was 25.3% (73/288; 95% confidence interval [CI], 20.7–30.7). There were no serious adverse events related to the window period prophylaxis or LTBI treatment with INH. During the 1-year follow-up period, no infants progressed to overt TB disease. The size of TST induration in infants vaccinated with percutaneous Bacillus Calmette-Guérin (BCG) vaccine was significantly larger than that of infants vaccinated with intradermal BCG vaccine (median, 8 mm vs. 5 mm; P = 0.002). In multiple logistic regression analysis, independent factors associated with TST positivity (≥ 10 mm induration) were male (adjusted odds ratio [aOR], 2.98; 95% CI, 1.6–5.64), percutaneous BCG vaccination (aOR, 3.30; 95% CI, 1.75–6.48), TST reading between 60 and 72 hours after injecting purified protein derivative (aOR, 2.87; 95% CI, 1.53–5.49), and INH prophylaxis more than four weeks (aOR, 0.49; 95% CI, 0.25–0.94). @*Conclusion@#A single TST at three months after the last TB exposure with INH prophylaxis could be used as a main protocol in contact investigations for infants exposed to infectious TB during the neonatal period in congregate settings in Korea.

9.
Article in English | WPRIM (Western Pacific) | ID: wpr-1001654

ABSTRACT

Sarcopenic dysphagia is a complication of coronavirus disease 2019 (COVID-19). This report describes the approach to rehabilitation in a 65-year-old man with sarcopenic dysphagia who contracted severe COVID-19 and underwent awake venovenous extracorporeal membrane oxygenation (vv-ECMO). He started active rehabilitation while receiving vv-ECMO and underwent a course of comprehensive inpatient rehabilitation lasting 115 days. The sarcopenic dysphagia improved, and he regained physical functional independence without any complications at hospital discharge.

10.
Immune Network ; : e31-2023.
Article in English | WPRIM (Western Pacific) | ID: wpr-1040773

ABSTRACT

Evidence suggests that the human respiratory tract, as with the gastrointestinal tract, has evolved to its current state in association with commensal microbes. However, little is known about how the airway microbiome affects the development of airway immune system. Here, we uncover a previously unidentified mode of interaction between host airway immunity and a unique strain (AIT01) of Staphylococcus epidermidis, a predominant species of the nasal microbiome. Intranasal administration of AIT01 increased the population of neutrophils and monocytes in mouse lungs. The recruitment of these immune cells resulted in the protection of the murine host against infection by Pseudomonas aeruginosa, a pathogenic bacterium.Interestingly, an AIT01-secreted protein identified as GAPDH, a well-known bacterial moonlighting protein, mediated this protective effect. Intranasal delivery of the purified GAPDH conferred significant resistance against other Gram-negative pathogens (Klebsiella pneumoniae and Acinetobacter baumannii) and influenza A virus. Our findings demonstrate the potential of a native nasal microbe and its secretory protein to enhance innate immune defense against airway infections. These results offer a promising preventive measure, particularly relevant in the context of global pandemics.

11.
Psychiatry Investigation ; : 1211-1220, 2023.
Article in English | WPRIM (Western Pacific) | ID: wpr-1041825

ABSTRACT

Objective@#Early trauma significantly affects the severity of panic disorder (PD) symptoms and suicidal ideation. However, few studies have explored the specific effects of different early trauma subtypes on PD. This study analyzed how childhood trauma subtypes, including general, physical, emotional, and sexual, influence panic and phobia levels and suicidal ideation in adults with PD and healthy controls (HCs). @*Methods@#In total, 455 adults with PD and 149 HCs participated in this study. The independent variables were sociodemographic and clinical variables such as coping strategies and early trauma subtypes from the Early Trauma Inventory Self Report-Short Form. The dependent variables were the Albany Panic and Phobia Questionnaire (APPQ), the Panic Disorder Severity Scale, and the Scale for Suicide Ideation (SSI). @*Results@#Early emotional trauma significantly influenced the APPQ scores, whereas early physical trauma significantly influenced the SSI scores in patients with PD. However, in HCs, only early emotional trauma was significantly associated with the APPQ and SSI scores. @*Conclusion@#These findings highlight the influence of early trauma subtypes on the phobic symptom severity of PD and suicidal ideation among patients with PD. Early emotional trauma is associated with the severity of phobic symptoms, whereas early physical trauma is associated with suicidal ideation, suggesting distinct clinical outcomes based on the type of trauma in patients with PD.

12.
Article in English | WPRIM (Western Pacific) | ID: wpr-916889

ABSTRACT

Contralateral axillary lymph node metastasis is a rare entity in breast cancer and is currently classified as a distant metastasis; however, recent studies have proposed aggressive curative treatment since this entity may manifest as a locoregional disease. Herein, we report a rare case of contralateral axillary lymph node metastasis that presented with imaging findings 22 months after the initial breast cancer diagnosis in a 67-year-old female. The patient underwent lymph node dissection of the axilla with adjuvant chemotherapy and radiotherapy. A follow-up examination 6 months after surgery showed no evidence of tumor recurrence or metastasis.

13.
Article in English | WPRIM (Western Pacific) | ID: wpr-925243

ABSTRACT

Background@#People with special needs tend to require diverse behavioral management in dentistry. They may feel anxious or uncomfortable or may not respond to any communication with the dentists. Patients with medical, physical, or psychological disorders may not cooperate and therefore require sedation (SED) or general anesthesia (GA) to receive dental treatment. Using the healthcare big data in Korea, this study aimed to analyze the trends of SED and GA in special needs patients undergoing dental treatment. It is believed that these data can be used as reference material for hospitals and for preparation of guidelines and related policy decisions of associations or governments for special needs patients in dentistry. @*Methods@#The study used selected health information data provided by the Korean National Health Insurance Service. Patients with a record of use of one of the eight selected drugs used in dental SED between January 2007 and September 2019, those with International Classification of Diseases-10 codes for attention deficit hyperactivity disorder (ADHD), phobia, brain disease, cerebral palsy, epilepsy, genetic disease, autism, mental disorder, mental retardation, and dementia were selected. The insurance claims data were analyzed for age, sex, sedative use, GA, year, and institution. @*Results@#The number of special needs patients who received dental treatment under SED or GA from January 2007 to September 2019 was 116,623. Number of SED cases was 136,018, performed on 69,265 patients, and the number of GA cases was 56,308, implemented on 47,257 patients. In 2007, 3100 special needs patients received dental treatment under SED while in 2018 the number of cases increased 6 times to 18,528 SED cases. In dentistry, ADHD was the most common disability for SED cases while phobia was the most common cause of disability for GA. The male-to-female ratio with respect to SED cases was higher for males (M : F = 64.36% : 35.64%). @*Conclusion@#The application of the SED method and GA for patients with special needs in dentistry is increasing rapidly; thus, preparing guidelines and reinforcing the education and system are necessary.

14.
Article in English | WPRIM (Western Pacific) | ID: wpr-925276

ABSTRACT

Purpose@#This study conducted a job analysis of visiting nurses in the process of change. @*Methods@#Participants were the visiting nurses working for the Seoul Metropolitan city. On the basis of the Public Health Intervention Wheel model, two times of the focus group interview (FGI) with seven visiting nurses and one time of the Developing a Curriculum (DACUM) with 34 visiting nurses were performed. A questionnaire survey of 380 visiting nurses was conducted to examine the frequency, importance and difficulty levels of the tasks created by using the FGI and DACUM. @*Results@#Visiting nurses’ job was derived as the theme of present versus transitional roles. The present role was categorized as ‘providing individual- and group-focused services’ and ‘conducting organization management’, while the transitional role was categorized as ‘providing district-focused services’ and ‘responding to new health issues’. The job generated 13 duties, 28 tasks, and 73task elements. The tasks showed the levels of frequency (3.65 scores), importance (4.27 scores), and difficulty (3.81 scores). All the tasks were determined as important, exceeding the average 4.00 scores. The group- and district-focused services of the tasks were recognized as more difficult but less frequent tasks. @*Conclusion@#The visiting nurses exert both present and transitional roles. The transitional roles identified in the present study should be recognized as an extended role of visiting nurses in accordance with the current changing healthcare needs in South Korea. Finally, the educational curriculum for visiting nurses that reflects the transitional roles from the present study is needed.

15.
Infection and Chemotherapy ; : 213-219, 2022.
Article in English | WPRIM (Western Pacific) | ID: wpr-937671

ABSTRACT

The emergence of hypervirulent Clostridioides difficile strains has decreased the efficacy of metronidazole in the treatment of C. difficile infection (CDI). Therefore, revised guidelines no longer recommend the use of metronidazole as a first-line regimen for CDI and restrict its use for non-severe CDI, only when vancomycin and fidaxomicin are unavailable. In Korea, an epidemic caused by a hypervirulent C. difficile strain or the emergence of metronidazole resistant C. difficile strains have not been reported. This review article aims to compare the treatment outcomes and adverse effects of vancomycin and metronidazole and discuss the validity of the guidelines of various agencies, which restrict the use of metronidazole, for Korean patients. There are no substantial adverse effects of metronidazole, and its clinical outcomes against non-severe CDI are similar to those of vancomycin. Based on these findings, we recommend that the use of metronidazole for the treatment of non-severe CDI is still an appropriate option in Korea.

16.
Infection and Chemotherapy ; : 812-853, 2022.
Article in English | WPRIM (Western Pacific) | ID: wpr-968907

ABSTRACT

The guidelines are intended to provide practical information for the correct use of antibiotics for intra-abdominal infections in Korea. With the aim of realizing evidence-based treatment, these guidelines for the use of antibiotics were written to help clinicians find answers to key clinical questions that arise in the course of patient care, using the latest research results based on systematic literature review. The guidelines were prepared in consideration of the data on the causative pathogens of intra-abdominal infections in Korea, the antibiotic susceptibility of the causative pathogens, and the antibiotics available in Korea.

17.
Anatomy & Cell Biology ; : 507-511, 2022.
Article in English | WPRIM (Western Pacific) | ID: wpr-966160

ABSTRACT

A three-dimensional (3D) segmentation and model reconstruction is a specialized tool to reveal spatial interrelationship between multiple internal organs by generating images without overlapping structures. This technique can also be applicable to mummy studies, but related reports have so far been very rare. In this study, we applied 3D segmentation and model reconstruction to computed tomography images of a Korean mummy with congenital diaphragmatic hernia. As originally revealed by the autopsy in 2013, the current 3D reconstruction reveals that the mummy’s heart is shifted to the left due to the liver pushing up to thoracic cavity thorough diaphragmatic hernial defect. We can generate 3D images by calling up the data exclusively from mummy’s target organs, thus minimizing the confusion of diagnosis that could be caused by overlapping organs.

18.
Article in English | WPRIM (Western Pacific) | ID: wpr-967291

ABSTRACT

Purpose@#This study aimed to evaluate the effects of a combined biofeedback and brief emotion regulation (C-BABER) program for sexually abused adolescents. @*Methods@#This study employed a non-equivalent control group pretest-posttest design. The participants included 26 sexually abused adolescents from eight Sunflower Centers of South Korea–with 13 in the experimental group and 13 in the control group. The experimental group received four sessions of the individual C-BABER program, each lasting 60 minutes. @*Results@#Compared with the control group, sexually abused adolescents in the experimental group exhibited significant score differences in traumatic symptoms, including depression (Z = - 2.24, p = .025), dissociation (Z = - 2.21, p = .027), anxiety (Z = - 2.02, p = .044), and posttraumatic stress (Z = - 2.01 p = .045); and impulsivity, including positive urgency (Z = - 3.35, p = .001) and negative urgency (Z = - 2.28, v = .023). Additionally, the experimental group exhibited significant score differences in meta-mood, including emotional attention (Z = - 2.45, p = .014), emotional clarity (Z = - 2.30, p = .021), and emotional repair (Z = - 2.28, p = .022); and emotional regulation modes, including emotional suppression (Z = - 2.65,p = .008) and cognitive reappraisal (Z = - 1.98, p = .047). Regarding bio-attention, significant changes were identified in the experimental group for the bio-attention rate and attention maintenance time in the posttest compared to the pretest (p = .001). @*Conclusion@#The C-BABER program for sexually abused adolescents is effective in decreasing traumatic symptoms and impulsivity, and in improving meta-mood, emotional regulation mode, and bio-attention. Therefore, we recommend providing sexually abused adolescents the C-BABER program to help them regulate their emotions and effectively adapt to their lives.

19.
Article in English | WPRIM (Western Pacific) | ID: wpr-967998

ABSTRACT

Background@#Measurement of ABO isoagglutinin titers is important for patients who have received an ABO-incompatible organ transplant. Specifically, IgG isoagglutinin is essential for predicting graft outcomes in kidney transplantation, but many laboratories measure only the total isoagglutinin taking into consideration time and labor efficiency. In this study, we propose a useful method for predicting IgG isoagglutinin by analyzing the mathematical relationship between total and IgG isoagglutinin titers. Furthermore, the effects of patients’ characteristics of isoagglutinin were also analyzed. @*Methods@#From January 2017 to April 2022, the results of 3,676 total/IgG isoagglutinin titers of 65 patients who underwent liver and kidney transplantation were analyzed. Isoagglutinin titration was performed using the column agglutination technique with serially diluted serum samples and dithiothreitol was added for measuring IgG isoagglutinin. A generalized estimation equation (GEE) and the Deming regression were used to analyze the relationship and agreement of total/IgG isoagglutinin titers. @*Results@#In A, B, and O types, total isoagglutinin titers were 1.6 (2

20.
Preprint in English | bioRxiv | ID: ppbiorxiv-453146

ABSTRACT

SARS-CoV-2 has made >190-million infections worldwide, thus it is pivotal to understand the viral impacts on host cells. Many viruses can significantly alter host chromatin1, but such roles of SARS-CoV-2 are largely unknown. Here, we characterized the three-dimensional (3D) genome architecture and epigenome landscapes in human cells after SARS-CoV-2 infection, revealing remarkable restructuring of host chromatin architecture. High-resolution Hi-C 3.0 uncovered widespread A compartmental weakening and A-B mixing, together with a global reduction of intra-TAD chromatin contacts. The cohesin complex, a central organizer of the 3D genome, was significantly depleted from intra-TAD regions, supporting that SARS-CoV-2 disrupts cohesin loop extrusion. Calibrated ChIP-Seq verified chromatin restructuring by SARS-CoV-2 that is particularly manifested by a pervasive reduction of euchromatin modifications. Built on the rewired 3D genome/epigenome maps, a modified activity-by-contact model2 highlights the transcriptional weakening of antiviral interferon response genes or virus sensors (e.g., DDX58) incurred by SARS-CoV-2. In contrast, pro-inflammatory genes (e.g. IL-6) high in severe infections were uniquely regulated by augmented H3K4me3 at their promoters. These findings illustrate how SARS-CoV-2 rewires host chromatin architecture to confer immunological gene deregulation, laying a foundation to characterize the long-term epigenomic impacts of this virus.

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