The Challenges and Achievements in COVID-19 Treatment and Vaccines

( Pyoeng Gyun Choe ) 대한간학회 2021 Postgraduate Courses (PG) Vol.2021 No.1

In December 2019, a new strain of betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that cause coronavirus disease 2019 (COVID-19), emerged in Wuhan, China. Subsequently, the virus quickly spread worldwide, and the World Health Organization declared COVID-19 as a global pandemic on March 11, 2020. In response to the pandemic, many researchers are rushing to repurpose existing drugs to alter the course of severe COVID-19, as well as testing experimental treatments. Among antiviral agents, remdesivir, RNA-dependent RNA polymerase inhibitor, showed clinical benefit from randomized clinical trial. In October 2020, the FDA approved remdesivir for treating hospitalized patients with COVID-19, making it the first drug approved for COVID-19 treatment. The race to produce safe and effective vaccines is also moving at unprecedent speed. In December 2020, the FDA issued an emergency authorization use for the first vaccine for COVID-19.

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

Choe Pyoeng Gyun,Kim Kye-Hyung,Kang Chang Kyung,Suh Hyeon Jeong,Kang EunKyo,Lee Sun Young,Kim Nam Joong,Yi Jongyoun,Park Wan Beom,Oh Myoung-don 대한의학회 2021 Journal of Korean medical science Vol.36 No.21

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 syndromecoronavirus-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.

Clinical experience with COVID-19 patients

Pyoeng Gyun Choe(최평균) 한국실험동물학회 2022 한국실험동물학회 학술발표대회 논문집 Vol.2022 No.1

MERS-CoV Antibody Responses 1 Year after Symptom Onset, South Korea, 2015

Choe, Pyoeng Gyun,Perera, R.A.P.M.,Park, Wan Beom,Song, Kyoung-Ho,Bang, Ji Hwan,Kim, Eu Suk,Kim, Hong Bin,Ko, Long Wei Ronald,Park, Sang Won,Kim, Nam-Joong,Lau, Eric H.Y.,Poon, Leo L.M.,Peiris, Malik U.S. Department of Health and Human Services * Cen 2017 Emerging Infectious Diseases Vol.23 No.7

<P>We investigated the kinetics of the Middle East respiratory syndrome coronavirus (MERS-CoV) neutralizing and spike protein antibody titers over the course of 1 year in 11 patients who were confirmed by reverse transcription PCR to have been infected during the outbreak in South Korea in 2015. Robust antibody responses were detected in all survivors who had severe disease; responses remained detectable, albeit with some waning, for <U><</U>1 year. The duration of viral RNA detection (but not viral load) in sputum significantly correlated with the antibody response magnitude. The MERS S1 ELISA antibody titers correlated well with the neutralizing antibody response. Antibody titers in 4 of 6 patients who had mild illness were undetectable even though most had evidence of pneumonia. This finding implies that MERS-CoV seroepidemiologic studies markedly underestimate the extent of mild and asymptomatic infection. Obtaining convalescent-phase plasma with high antibody titers to treat MERS will be challenging.</P>

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.

Kinetics of Neutralizing Antibody Responses Against SARS-CoV-2 Delta Variant in Patients Infected at the Beginning of the Pandemic

Choe Pyoeng Gyun,Kim Yuri,Chang Euijin,Kang Chang Kyung,Kim Nam Joong,Cho Nam-Hyuk,Park Wan Beom,Oh Myoung-don 대한의학회 2022 Journal of Korean medical science Vol.37 No.8

We investigated the kinetics of the neutralizing antibody responses to the severe acute respiratory syndrome-coronavirus-2 delta variant over the course of 1 year in 16 patients infected at the beginning of the pandemic. In patients with severe disease, neutralizing responses to the delta variant were detectable, albeit at lower levels than responses to the wild type. Neutralizing responses to the delta variant were undetectable, however, in asymptomatic persons. This finding implies that the vaccination strategy for persons with past natural infection should depend on the severity of the previous infection.

노인 감염성 질환 ; 노인에서 사람면역결핍바이러스 감염증의 특성과 치료

최평균 ( Pyoeng Gyun Choe ),김남중 ( Nam Joong Kim ) 대한내과학회 2010 대한내과학회지 Vol.79 No.4

The proportion of human immunodeficiency virus (HIV) infected patients aged 50 and older has greatly increased since the beginning of the epidemic, particularly after the introduction of combination antiretroviral therapy. In Korea, 25% of those infected with HIV were older than 50 in 2009. Older untreated patients with HIV demonstrate faster rates of CD4 lymphocyte loss and more rapid progression to acquired immunodeficiency syndrome and death than younger individuals. Most studies have shown that compared with younger patients, patients over 50 generally have a slower immunologic response to antiretroviral therapy, despite better virological response. Management of HIV infection in older patients is particularly complex, mainly because they are more likely to have co-morbidities necessitating specific medications that may interact with antiretroviral drugs. Patients living longer with HIV are more likely to develop diseases associated with aging, and at an earlier age, than those without HIV. These include dementia, coronary artery disease, dyslipidemia, metabolic syndrome, diabetes, and osteoporosis. (Korean J Med 79:356-361, 2010)

코로나바이러스감염증-19 치료제와 백신 전망

최평균 ( Pyoeng Gyun Choe ) 대한내과학회 2020 대한내과학회지 Vol.95 No.6

In December 2019, a new strain of betacoronavirus, severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19), emerged in Wuhan, China. Subsequently, the virus quickly spread worldwide and the World Health Organization declared COVID-19 a global pandemic on March 11, 2020. In response to the pandemic, many researchers are working on repurposing existing drugs to alter the course of severe COVID-19, and are testing experimental treatments. Among antiviral agents, remdesivir, an RNA-dependent RNA polymerase inhibitor, showed clinical benefit in a randomized clinical trial. In October 2020, the Food and Drug Administration approved remdesivir for treating hospitalized patients with COVID-19, making it the first drug approved for the disease. The race to produce safe, effective vaccines is also progressing at unprecedented speed, with over 200 under development and 45 candidates already being tested in human clinical trials (as of October 2020). (Korean J Med 2020;95:364-369)

우리나라 사람면역결핍바이러스(Human Immunodeficiency Virus) 감염환자에서 발병한 악성종양

최평균,송진수,조재현,김성한,박경화,방지환,박완범,김홍빈,김동완,김태유,허대석,오명돈,김남중,최강원 대한감염학회 2006 감염과 화학요법 Vol.38 No.6

Background : Since highly active antiretroviral therapy has lengthened the life span of individuals infected with human immunodeficiency virus (HIV), the importance of malignancy associated with HIV has been increased. The relative frequencies of malignancies in HIV infected patients may vary in different race and region. The aim of this study is to determine the prevalence and characteristics of malignancies in patients with HIV infection in South Korea. Materials and Methods : To identify HIV patients with malignancy, we reviewed the electronic database of pathological reports for all HIV-infected patients seen from January 1986 to December 2005 at the Seoul National University Hospital. We retrospectively reviewed the medical records of them. Results : Among 850 patients infected with HIV, 33 episodes of malignant diseases were diagnosed in 32 patients (3.76%). Thirty were males, and median age was 46 years (range 29-70). At the time of the diagnosis of malignancy, median CD4^(+) lymphocytes count was 100/uL (range 5-620) and in 27 (82%) patients, CD4^(+) lymphocytes count were less than 200/uL. For 13 patients (40%), malignancy was initial presentation of HIV infection. Excluding patients initially diagnosed as malignancy, median follow-up duration from the first visit to diagnosis of malignancy was 36 months (range 3-96). Non-Hodgkin's lymphoma was the most frequent malignancy (13 patients), followed by Kaposi's sarcoma (7), Hodgkin‘s disease (3), acute myeloid leukemia (1), and other solid cancer (9) including one case of anal cancer associated with human papillomavirus. Among 13 patients with non- Hodgkin's lymphoma, 4(31%) achieved the complete remission after chemotherapy and/or radiation therapy, and had been followed without evidence of recurrence. Conclusion : Malignancy was diagnosed in 3.76% of patients infected with HIV. Non-Hodgkin‘s lymphoma is the most prevalent malignancy in HIV patients in South Korea. 목적 : 효과적인 항레트로바이러스 다제요법이 도입됨에 따라, HIV 감염환자들의 수명이 증가되었고, 이에 따라 HIV 감염환자에서 악성종양의 중요성 또한 증가하고 있다. 본 연구의 목적은 우리나라 HIV 감염환자에서 악성종양의 유병률과 호발하는 악성종양의 특성을 밝히는 것이다. 재료 및 방법 : 1986년부터 2005년까지 서울대학교병원에서 치료를 받은 HIV 감염환자의 의무기록을 후향적으로 분석하였고, 병리학적 검사 결과를 검토하여 악성종양이 진단된 환자들을 대상으로 연구를 시행하였다. 결과 : 총 850명의 환자 중, 32명(3.76%)에서 33예의 악성종양이 진단되어, 악성종양의 발병률은 1,000인년 당13.0명(95% 신뢰구간: 8.6∼17.4명)이었다. 그 중 남자는 30명이었고, 악성종양 진단 당시 연령의 중간값은 46 (29-70)세이었다. 악성종양 진단받을 당시, CD4 림프구 수의 중간값은 lOO/uL (5-620 uL) 이었고, CD4 림프구수가 200/ uL 미만인 환자가 27명(82%)이었다. 악성종양에 대한 검사 도중에 HIV 감염사실이 밝혀진 환자가 13명(40%)이었다. HIV를 진단 받은 후 악성종양이 발병한 환자들에서, HIV 진단 후 악성종양의 발병까지는 평균 36개월(3-96개월)이 걸렸다. 13명의 HIV 감염 환자에서 진단된 비호지킨림프종이 가장 흔한 악성종양이었고, 이외에 카포시육종이 7명, 호지킨병이 3명, HPV와 연관된 항문암이 1명의 HIV 환자에서 진단되었다. 그 밖에 급성백혈병, 방광암, 췌장장, 폐암, 진행성위암, 갑상선암, 간세포암, 후두암이 각각 1예씩 진단되었다. 비호지킨림프종이 진단된13명 환자 중, 4명(31%)은 항암치료 및 방사선치료를 받아 완전관해가 되었고, 현재 재발의 증거 없이 외래에서 경과 관찰 중이다. 결론 : 우리나라 HIV 감염환자에서 악성종양의 유병률은 3.76%이었고, 비호지킨림프종이 가장 흔한 악성종양이었다.

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.