• Title/Summary/Keyword: Coronavirus 19 (COVID-19)

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Analysis of SARS-CoV-2 Mutations after Nirmatrelvir Treatment in a Lung Cancer Xenograft Mouse Model

  • Bo Min Kang;Dongbum Kim;Jinsoo Kim;Kyeongbin Baek;Sangkyu Park;Ha-Eun Shin;Myeong-Heon Lee;Minyoung Kim;Suyeon Kim;Younghee Lee;Hyung-Joo Kwon
    • Biomolecules & Therapeutics
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    • v.32 no.4
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    • pp.481-491
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    • 2024
  • Paxlovid is the first approved oral treatment for coronavirus disease 2019 and includes nirmatrelvir, a protease inhibitor targeting the main protease (Mpro) of SARS-CoV-2, as one of the key components. While some specific mutations emerged in Mpro were revealed to significantly reduce viral susceptibility to nirmatrelvir in vitro, there is no report regarding resistance to nirmatrelvir in patients and animal models for SARS-CoV-2 infection yet. We recently developed xenograft tumors derived from Calu-3 cells in immunodeficient mice and demonstrated extended replication of SARS-CoV-2 in the tumors. In this study, we investigated the effect of nirmatrelvir administration on SARS-CoV-2 replication. Treatment with nirmatrelvir after virus infection significantly reduced the replication of the parental SARS-CoV-2 and SARS-CoV-2 Omicron at 5 days post-infection (dpi). However, the virus titers were completely recovered at the time points of 15 and 30 dpi. The virus genomes in the tumors at 30 dpi were analyzed to investigate whether nirmatrelvir-resistant mutant viruses had emerged during the extended replication of SARS-CoV-2. Various mutations in several genes including ORF1ab, ORF3a, ORF7a, ORF7b, ORF8, and N occurred in the SARS-CoV-2 genome; however, no mutations were induced in the Mpro sequence by a single round of nirmatrelvir treatment, and none were observed even after two rounds of treatment. The parental SARS-CoV-2 and its sublineage isolates showed similar IC50 values of nirmatrelvir in Vero E6 cells. Therefore, it is probable that inducing viral resistance to nirmatrelvir in vivo is challenging differently from in vitro passage.

Retrospective Analysis of Clinical Patterns and Antibiotic Utilization in Pediatric Patients Hospitalized with Respiratory Syncytial Virus Pneumonia at a Recently Established General Hospital (신생 대학병원에서 호흡기세포융합바이러스 폐렴으로 입원한 건강한 소아청소년환자에서의 임상 양상 및 항생제 사용에 대한 후향적 분석)

  • Hyejin So;Kyung Min Kim;Eun Young Cho
    • Pediatric Infection and Vaccine
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    • v.31 no.1
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    • pp.75-82
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    • 2024
  • Purpose: As the coronavirus disease 2019 (COVID-19) pandemic ended, the number of patients with respiratory syncytial virus (RSV) pneumonia increased during the spring/summer of 2022. This study aimed to analyze the clinical features and antibiotic usage of children hospitalized for RSV pneumonia in a recently established general hospital in Sejong city. Methods: In this retrospective review, we included inpatients of the Pediatric Department of Chungnam National University Sejong Hospital diagnosed with RSV pneumonia between March 2022 and April 2023. Patients were divided into 2 groups: with and without antibiotic treatment. Demographic data, initial presentations, and clinical courses were reviewed. Results: A total of 116 patients with RSV pneumonia were hospitalized during this period, of which 102 were analyzed, excluding 14 with underlying diseases or who did not fall within the definition of pneumonia. The median age was 17 months. Diagnoses of bacterial infections (acute otitis media and sinusitis) were documented in 9.8% of cases. Intravenous (IV) antibiotics were administered in 46% of cases. The group receiving IV antibiotics showed higher inflammatory levels (C-reactive protein; CRP), more infiltration on initial chest X-rays, and longer fever duration. There was no difference in the length of hospitalization between the groups with and without IV antibiotics. Conclusions: This study showed a tendency for the attending physician to prescribe IV antibiotics to patients with longer fever duration, pulmonary infiltrations on the initial chest X-ray, and higher CRP levels. However, given the high rate of IV antibiotic usage compared to previous studies, care should be taken in antibiotic use.

Analysis of the diet of obese elementary school students using various dietary intake survey methods (다양한 식사섭취 조사방법을 활용한 비만 초등학생의 식생활 실태 분석)

  • Hye Bin Yoon;Jin Seon Song;Youngshin Han;Kyung A Lee
    • Journal of Nutrition and Health
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    • v.56 no.1
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    • pp.97-111
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    • 2023
  • Purpose: Childhood obesity has become a social problem due to the social distancing necessitated by the coronavirus disease 2019 pandemic. This study aimed to identify the dietary problems of obese children through various dietary assessment methods and to confirm the usefulness of each method. Methods: The subjects were 88 students in the 4th to 6th grade of elementary school who participated in the nutrition camp organised by the Busan Metropolitan Office of Education, 2020. To evaluate dietary problems and assess diet quality, 24-hour meal records, monthly food intake frequency, and Dietary Screening Test (DST) data were analyzed. Results: Of the subjects, 15.7%, 30.3%, and 53.9% were normal weight, overweight, and obese, respectively. The average age was 11.77 ± 0.77 years and the average body mass index was 23.96 ± 3.01 kg/m2. It was observed from the 24-hour meal record method that the overweight and obese subject groups consumed fewer green vegetables (p < 0.001) and white vegetables (p < 0.01) than the normal weight group. In the monthly food intake frequency method, the consumption of ramen (p < 0.01), snacks (p < 0.05), and sausages (p < 0.05) were high in the obese group, and that of anchovies, broccoli, and sweet pumpkin was high in the normal group (p < 0.05). The comparative data from the DST revealed that the overweight and obese groups had less vegetable intake than the normal weight group (p < 0.01) and had higher intakes of dairy products, fast food, and sweet snacks (p < 0.05). Conclusion: The usefulness of each method in the dietary evaluation of obese children was confirmed. To address the problem of obesity, it is necessary to evaluate the dietary problem and approach it with a customized solution tailor-made for the individual subject.