Slide Session : OS-IFD-07 ; Infectious Disease : In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus

( Myung Jin Lee ),( Kye Hyung Kim ),( Jong Youn Yi ),( Su Jin Choi ),( Chung Jong Kim ),( Nak Hyun Kim ),( Kyoung Ho Song ),( Pyoeng Gyun Choi ),( Ji Hwan Bang ),( Wan Beom Park ),( Eu Suk Kim ),( San 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus Myung Jin LEE1, Kye-Hyung KIM1, Jongyoun YI2, SuJin CHOI1, Chung-Jong KIM1, Nak- Hyun KIM1, Kyoung-Ho SONG1, Pyoeng Gyun CHOI1, Ji-Hwan BANG1, Wan Beom PARK1, Eu Suk KIM1, Sang-Won PARK1, Hong Bin KIM1, Nam Joong KIM1, Myoung- Don OH1 Seoul National University College of Medicine, Korea1, Pusan National University School of Medicine, Korea2 Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel Bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV). No effective antiviral therapy is proven yet, but clinical use of ribavirin (RBV) has been tried. We investigated the antiviral effect of RBV against SFTSV in vitro. Methods: To test for cytotoxicity of RBV, Vero cells were treated with different concentrations of RBV (3.90 to 500 μg/mL, two-fold dilution) and analyzed by cell viability MTS assay 48h post-infection. To determine antiviral activity of RBV against SFTSV, Vero cells were infected with SFTSV strain Gangwon/Korea/2012 at 100 TCID50 (50% tissue culture infective dose) per well in a 96-well plate, and RBV was added at the concentrations showing no or minimal cytotoxicity. Viral RNAs were extracted from the culture supernatants and quantifi ed using one-step real-time reverse transcription- PCR to amplify the partial large segment of SFTSV. Statistical analysis was done by one-way ANOVA with Tukey`s post hoc test. Results: Cytotoxicity due to RBV was not observed at RBV concentration =31.3 μg/ mL. Viral RNAs at 24h post-RBV treatment were reduced with increasing RBV concentrations (1-32 μg/mL), compared with those of mock-treated cells (P <0.01, Figure). Half maximal inhibitory concentration (IC50) of RBV was 3.69 μg/mL at 24h post-RBV treatment. Conclusions: Our study shows that RBV has antiviral effect against SFTSV in a dose-dependent manner. Further studies are required to evaluate the effi cacy of RBV in SFTS.

Diagnostic Performance, Stability, and Usability of Self-Collected Combo Swabs and Saliva for Coronavirus Disease 2019 Diagnosis: A Case-Control Study

Choi Seong Jin,Jung Jongtak,Kim Eu Suk,Kim Hong Bin,Park Jeong Su,Park Kyoung Un,Lee Hyunju,Lee Eunyoung,Choe Pyoeng Gyun,Kim Ji-Yeon,Lee Eun Joo,Song Kyoung-Ho 대한감염학회 2022 Infection and Chemotherapy Vol.54 No.3

Background Self-sampling procedures to detect severe acute respiratory syndrome coronavirus 2 is important for patients who have difficulty visiting the hospital and may decrease the burden for health care workers (HCWs). The objective of this study was to evaluate the diagnostic performance, stability and usability of self-collected nasal and oral combo swabs and saliva specimens. Materials and Methods We conducted a case-control study with 50 patients with coronavirus disease 2019 (COVID-19) and 50 healthy volunteers from March, 2021 to June, 2021. We performed real-time reverse-transcription polymerase chain reaction to compare the diagnostic performance of self-collected specimens using positive percent agreements (PPAs). Results The PPAs between self-collected and HCW-collected specimens were 77.3 - 81.0% and 80.5 -86.7% for the combo swabs and saliva specimens, respectively. The PPAs increased to 88.9 - 89.2% and 81.2 - 82.1% with a cycle threshold value ≤30. Conclusion The diagnostic performance of self sampling was comparable to that of HCW sampling in patients with high viral loads and may thus assist in the early diagnosis of COVID-19. Background Self-sampling procedures to detect severe acute respiratory syndrome coronavirus 2 is important for patients who have difficulty visiting the hospital and may decrease the burden for health care workers (HCWs). The objective of this study was to evaluate the diagnostic performance, stability and usability of self-collected nasal and oral combo swabs and saliva specimens. Materials and Methods We conducted a case-control study with 50 patients with coronavirus disease 2019 (COVID-19) and 50 healthy volunteers from March, 2021 to June, 2021. We performed real-time reverse-transcription polymerase chain reaction to compare the diagnostic performance of self-collected specimens using positive percent agreements (PPAs). Results The PPAs between self-collected and HCW-collected specimens were 77.3 - 81.0% and 80.5 -86.7% for the combo swabs and saliva specimens, respectively. The PPAs increased to 88.9 - 89.2% and 81.2 - 82.1% with a cycle threshold value ≤30. Conclusion The diagnostic performance of self sampling was comparable to that of HCW sampling in patients with high viral loads and may thus assist in the early diagnosis of COVID-19.

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

Pyoeng Gyun Choe,Eun Kyo Kang,Sun Young Lee,Boram Oh,Dahae Im,Hyo Yeon Lee,Hyemin Jung,Chang Kyung Kang,Min Sun Kim,Wan Beom Park,Eun Hwa Choi,Be Long Cho,Myoung-don Oh,Nam Joong Kim 대한내과학회 2020 The Korean Journal of Internal Medicine Vol.35 No.4

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. Conclusions: 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.

S-513 : A case of Lemierre syndrome caused by Klebsiella pneumoniae in patient with diabetes mellitus

( Hong Mi Choi ),( Jun Won Park ),( Nak Hyun Kim ),( Wan Beom Park ),( Nam Joong Kim ),( Myoung Don Oh ),( Eui Chong Kim ),( Pyoeng Gyun Choe ) 대한내과학회 2013 대한내과학회 추계학술대회 Vol.2013 No.1

Lemierre`s syndrome is an uncommon complication of acute pharyngitis in adolescents and young adults characterized by septic thrombophlebitis of the internal jugular vein and metastatic lesions (septic emboli) of distant site. The organisms most frequently involved are anaerobic streptococci, Bacteroides species and Fusobacterium necrophorum. The prompt diagnosis and early treatment, sometimes including surgical intervention, are crucial because delayed treatment may be associated with high mortality rate. A 40-year-old man was admitted to our hospital with 6-day history of pain and swelling of neck which started one day after the dental procedure. Contrast-enhanced computed tomography showed soft tissue necrosis in mandibular area and focal thrombosis in the left internal jugular vein (Fig. 1A). Chest X-ray revealed multiple patchy pulmonary infiltration which suggests metastatic infection of lung (Fig. 1B). Cultures of the lesion and specimens of blood grew Klebsiella pneumoniae and were negative for anaerobic bacteria. He was treated with piperacillin/tazobactam and undergone surgical exploration and debridement of necrotic tissue. However, he expired on 6 days after admission. We report a fetal case of Lemierre`s syndrome by Klebsiella pneumoniae.

Hematological manifestations of human immunodeficiency virus infection and the effect of highly active anti-retroviral therapy on cytopenia

Se Youn Choi,Inho Kim,김남중,Seung-Ah Lee,Youn-Ak Choi,Ji-Yeon Bae,Ji Hyun Kwon,Pyoeng Gyun Choe,박완범,Sung-Soo Yoon,Seonyang Park,Byoung Kook Kim,Myoung-Don Oh 대한혈액학회 2011 Blood Research Vol.46 No.4

Background :The aim of this study is to investigate the hematological manifestations of human immunodeficiency virus (HIV) infection, the risk factors for cytopenia, and the effect of highly active anti-retroviral therapy (HAART) on cytopenia. Methods :Medical records of patients treated for HIV at the Seoul National University Hospital from January 2005 to March 2010 were retrospectively reviewed. To determine the impact of HIV itself, we excluded HIV patients who had other conditions that could have resulted in hematological manifestations. Multiple logistic regression analyses were performed to identify risk factors for cytopenia. Results :A total of 621 cases were investigated, and after exclusion, data of 472 patients were analyzed. The frequency of cytopenia was anemia, 3.0% (14/472); neutropenia, 10.0% (47/472); thrombocytopenia, 2.4% (12/472); lymphopenia, 25.7% (121/470); isolated cytopenia, 11.2% (53/472); and bicytopenia, 2.1% (10/472). The leading risk factor for cytopenia identified by multivariate logistic regression methods was AIDS status at initial presentation. After HAART, cytopenia was reversed in the majority of patients (thrombocytopenia, 100%; neutropenia, 91.1%; and anemia, 84.6%). Conclusion :This study isolated the impact of HIV infection alone on hematologic manifestations and confirmed that these changes were reversible by HAART. Control of the HIV infection will have the main role in the management of hematological manifestations of the virus.

국내 다기관에서 조사한 지역사회획득 메티실린내성 황색포도알균의 빈도와 임상적 특성

송진수,최평균,송경호,조재현,김성한,방지환,이창섭,박경화,박경운,신수,최희정,김의석,김동민,이미숙,박완범,김남중,오명돈,김의종,김홍빈,최강원 대한감염학회 2006 감염과 화학요법 Vol.38 No.6

목적 : 최근 전세계적으로 지역사회획득 메티실린내성 황색포도알균(community-associated methicillin-resistant Staphylococcus aureus, CA-MRSA)의 보고가 증가하고 있다. 하지만, 우리나라에서는 CA-MRSA 감염증에 대한 증례보고만 있을 뿐 아직까지 체계적인 연구결과가 없는 실정이다. 저자들은 국내에서 CA-MRSA의 빈도, 감염증의 임상적 양상, 분리된 균주의 항균제내성 양상을 조사하였다. 재료 및 방법 : 2005년 1월부터 2005년 6월까지 7개 병원에서 MRSA가 분리된 환자의 명단을 파악한 후 의무기록지와 건강보험심사평가원의 자료를 검토하였다. 외래나 응급실에서 혹은 입원 후 72시간 이내에 균주가 분리되고 MRSA 획득과 관련된 위험인자가 없는 경우 CA-MRSA로 정의하였으며, 분리된 균주의 임상적 의미에 따라 원인병원체(pathogen), 집락화(colonizer), 미결정(undetermined)으로 분류하였다. Penicillin과 oxacillin을 제외하고 3개 이상의 다른 계열 항균제에 내성이면 다제내성으로 정의하였다. 결과 : 연구기간동안 총 3,251주의 황색포도알균이 분리되었으며, 이 중 MRSA는 1,900주(58.4%)였다. MRSA 가운데 CA-MRSA는 114주(6.0%) 였으며, 이들이 분리된 부위는 귀(62주), 비뇨기계(14주), 피부 및 연부조직(11주), 호흡기계(10주), 혈액(3주) 등이었다. CA-MRSA 균주 가운데 집락균은 22주, 원인병원체는 22주였으며, 나머지 균주에 대해서는 그 임상적 의미를 결정할 수 없었다. 항균제 감수성 검사를 시행한 73균주 중 47주(64.4%)는 다제내성이었다. CA-MRSA 감염증 22예 중 피부 및 연부조직 감염(9예)과 중이염/외이도염(9예)이 가장 흔하였다. 침습적 감염증(invasive infection)은 4명(원발성 균혈증 3예, 감염성 관절염 1예)에서 확인되었지만, CA-MRSA 감염증으로 사망한 환자는 없었다. 결론 : 병원내 감염증에서는 MRSA가 심각한 문제이지만, 아직까지 지역사회 감염증에서 CA-MRSA는 흔하지 않았다. Background : Methicillin-resistant Staphylococcus aureus (MRSA) infection has emerged in patients who do not have the established risk factors. In Korea, little is known about the epidemiology and clinical features of community-associated MRSA (CA-MRSA). Material and Methods : Clinical microbiology laboratory databases of 7 hospitals were reviewed to identify the patients from whom MRSA was isolated during the period of January to July 2005. Only one isolate per patient was enrolled. In order to identify the risk factors of MRSA acquisition, the medical records and the Health Insurance Review Agency databases were reviewed. CA-MRSA was defined as MRSA isolated from patient without established risk factors. We analyzed patient demographics, underlying medical conditions, characteristics of infection, and antimicrobial susceptibility profiles. Results : Of total 3,251 S. aureus isolates, 1900 (58.4%) were MRSAs. Of the MRSA isolates, 114 (6.0%) were CA-MRSA. Of 114 CA-MRSA isolates, 22 (19.3%) were colonizers, 22 (19.3%) were pathogens, and the clinical significance of remaining 70 (61.4%) could not be determined. Median age of the 22 patients with CA-MRSA disease was 47 years. Nine patients had skin and soft tissue infections, 9 ear infections, 3 bacteremia, 1 septic arthritis. Seven patients had underlying medical disease. None died of the CA-MRSA infections. Of the 73 isolates of CA-MRSA, 47 (64.4%) were resistant to more than 3 classes of antibiotics besides β-lactams. Conclusion : Although MRSA is highly prevalent among hospital-associated S. aureus infection, CA-MRSA infections are not common.

¹⁸F-FDG PET and histopathologic findings in a patient with severe fever with thrombocytopenia syndrome

Kang, Chang Kyung,Choi, Su Jin,Koh, Jiwon,Jeon, Yoon Kyung,Kim, Ki Hyun,Chung, Junho,Choe, Pyoeng Gyun,Kim, Nam-Joong,Park, Wan Beom,Oh, Myoung-don Elsevier 2018 Ticks and tick-borne diseases Vol.9 No.4

<P><B>Abstract</B></P> <P>We report on a patient with severe fever with thrombocytopenia syndrome who fully recovered. Imaging with 2-deoxy-2-fluoro-glucose positron emission tomography showed hypermetabolism in regional lymph nodes and the spleen. Histopathological findings of affected lymph nodes showed subacute necrotizing lymphadenitis and the presence of virus-infected cells.</P>

Virus Isolation from the First Patient with SARS-CoV-2 in Korea

Wan Beom Park,권낙중,Su Jin Choi,강창경,Pyoeng Gyun Choe,Jin Yong Kim,Jiyoung Yun,Gir-Won Lee,성문우,Nam Joong Kim,서정선,Myoung-don Oh 대한의학회 2020 Journal of Korean medical science Vol.35 No.7

Novel coronavirus (SARS-CoV-2) is found to cause a large outbreak started from Wuhan since December 2019 in China and SARS-CoV-2 infections have been reported with epidemiological linkage to China in 25 countries until now. We isolated SARS-CoV-2 from the oropharyngeal sample obtained from the patient with the first laboratory-confirmed SARS- CoV-2 infection in Korea. Cytopathic effects of SARS-CoV-2 in the Vero cell cultures were confluent 3 days after the first blind passage of the sample. Coronavirus was confirmed with spherical particle having a fringe reminiscent of crown on transmission electron microscopy. Phylogenetic analyses of whole genome sequences showed that it clustered with other SARS- CoV-2 reported from Wuhan.

Replicative virus shedding in the respiratory tract of patients with Middle East respiratory syndrome coronavirus infection

Park, Wan Beom,Poon, Leo L.M.,Choi, Su-Jin,Choe, Pyoeng Gyun,Song, Kyoung-Ho,Bang, Ji Hwan,Kim, Eu Suk,Kim, Hong Bin,Park, Sang Won,Kim, Nam Joong,Peiris, Malik,Oh, Myoung-don Elsevier 2018 INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES Vol.72 No.-

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Information on the duration of replicative Middle East respiratory syndrome coronavirus (MERS-CoV) shedding is important for infection control. The detection of MERS-CoV sub-genomic mRNAs indicates that the virus is replicative. This study examined the duration for detecting MERS-CoV sub-genomic mRNA compared with genomic RNA in diverse respiratory specimens.</P> <P><B>Methods</B></P> <P>Upper and lower respiratory samples were obtained from 17 MERS-CoV-infected patients. MERS-CoV sub-genomic mRNA was detected by reverse transcription PCR (RT-PCR) and MERS-CoV genomic RNA by real-time RT-PCR.</P> <P><B>Results</B></P> <P>In sputum and transtracheal aspirate, sub-genomic mRNA was detected for up to 4 weeks after symptoms developed, which correlated with the detection of genomic RNA. In oropharyngeal and nasopharyngeal swab specimens, the detection of sub-genomic mRNA and genomic RNA did not correlate.</P> <P><B>Conclusions</B></P> <P>These findings suggest that MERS-CoV does not replicate well in the upper respiratory tract.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Middle East respiratory syndrome coronavirus (MERS-CoV) sub-genomic mRNAs indicates that the virus is replicative. </LI> <LI> Sub-genomic mRNA was detected in lower respiratory tract specimens for up to 4 weeks after symptoms developed. </LI> <LI> In upper respiratory tract specimens, the detection of sub-genomic mRNA and genomic RNA did not correlate. </LI> </UL> </P>

Isolation of Middle East Respiratory Syndrome Coronavirus from a Patient of the 2015 Korean Outbreak

Park, Wan Beom,Kwon, Nak-Jung,Choe, Pyoeng Gyun,Choi, Su-Jin,Oh, Hong Sang,Lee, Sang Min,Chong, Hyonyong,Kim, Jong-Il,Song, Kyoung-Ho,Bang, Ji Hwan,Kim, Eu Suk,Kim, Hong-Bin,Park, Sang Won,Kim, Nam Jo The Korean Academy of Medical Sciences 2016 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.31 No.2

<P>During the 2015 outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Korea, 186 persons were infected, resulting in 38 fatalities. We isolated MERS-CoV from the oropharyngeal sample obtained from a patient of the outbreak. Cytopathic effects showing detachment and rounding of cells were observed in Vero cell cultures 3 days after inoculation of the sample. Spherical virus particles were observed by transmission electron microscopy. Full-length genome sequence of the virus isolate was obtained and phylogenetic analyses showed that it clustered with clade B of MERS-CoV.</P>