Pediatric Infection and Vaccine

  • 제30권2호
  • /
  • Pages.73-83
  • /
  • 2023
  • /
  • 2384-1079(pISSN)
  • /
  • 2384-1087(eISSN)
대한소아감염학회 (The Korean Society of Pediatric Infectious Diseases)
권호 표지
DOI QR코드

DOI QR Code

Viral Load Dynamics After Symptomatic COVID-19 in Children With Underlying Malignancies During the Omicron Wave

  • Ye Ji Kim (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Hyun Mi Kang (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • In Young Yoo (Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Jae Won Yoo (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Seong Koo Kim (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Jae Wook Lee (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Dong Gun Lee (Infection Control Office, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Nack-Gyun Chung (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Yeon-Joon Park (Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Dae Chul Jeong (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Bin Cho (Department of Pediatrics, College of Medicine, The Catholic University of Korea)
  • 투고 : 2023.06.14
  • 심사 : 2023.07.27
  • 발행 : 2023.08.25
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

목적: 본 연구의 목적은 혈액종양 기저질환으로 치료 중 유증상 코로나바이러스감염증-19(COVID-19)으로 확진 된 소아청소년에서 바이러스 부하(viral load)의 변화를 확인하고자 하였다. 방법: 후향적 종단 코호트연구(retrospective longitudinal cohort study)로, 19세 미만 소아청소년 중 악성 빈혈, 혈액암, 또는 고형암으로 치료 중인 상태에서 2022년 3월 1일부터 8월 30일 사이에 SARS-CoV-2 PCR 양성으로 유증상 코로나바이러스감염증-19가 확진 된 환자를 대상으로 하였다. 환자들의 의무 기록과 전화 문진으로 임상 증상과 전파경로, 그리고 증상의 경과에 대한 자료를 얻었고, 서울성모병원에서 시행했던 SARS-CoV-2 PCR titer 값을 분석하였다. 확진 이후 E gene RT-PCR Ct value ≥25을 전파가능성이 낮은 상태로 정의하였다. 결과: 6개월의 연구 기간 동안 총 43명의 환자에서 44번의 COVID-19 확진 사례가 포함되었다. 환자의 평균 연령은 8세(interquartile range, 4.9-10.5)였으며, 가장 흔한 기저 질환은 급성 림프구성 백혈병(n=30, 68.2%)이었고, 다음으로 조혈모세포이식 후(n=8, 18.2%) 상태인 환자들이었다. 대부분 경증 COVID-19 (n=32, 72.7%)에 해당이 되었고, 3명의 환자(7.0%)는 중증/위중증 COVID-19에 해당되어 산소 치료를 받았다. 2.3% (n=1)는 COVID-19 관련 급성 호흡곤란 증후군으로 사망하였다. 확진 이후 E gene RT-PCR Ct값이 ≥25을 도달한 시점이 15-21일인 환자는 총 39.4%(n=13)이었고, 22-28일에 도달한 환자는 30.3% (n=10)이었다. 15.2% (n=5)의 환자에서는 확진 후 28일이 지난 시점에서도 Ct값 <25를 유지하였다. E gene Ct값이 <25 장기간 지속되는 위험인자로 난치성 악성 종양 상태(β, 67.0; 95% CI, 7.0-17.0; P=0.030)가 유의한 관련이 있었다. 한 환자는 확진 후 Ct 값이 <25으로 유지되던 중, 확진 후 86일 째 보호자로 상주하던 어머니에게 바이러스를 전파하였다. 결론: 난치성 악성 종양 상태에서 유증상 COVID-19에 확진 되는 경우 바이러스를 장기간 배출 할 수 있기 때문에, 이런 환자군에서는 PCR 기반 바이러스 전파 예방 조치가 도움이 될 수 있다.

Purpose: This study aimed to investigate the viral load dynamics in children with underlying malignancies diagnosed with symptomatic coronavirus disease 2019 (COVID-19). Methods: This was a retrospective longitudinal cohort study of patients <19 years old with underlying hemato-oncologic malignancies that were diagnosed with their first symptomatic severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (PCR)-confirmed COVID-19 infection during March 1 to August 30, 2022. Review of electronic medical records and telephone surveys were undertaken to assess the clinical presentations and transmission route of the patients. Thresholds of negligible likelihood of infectious virus was defined as E gene reverse transcription (RT)-PCR cycle threshold (Ct) value ≥25. Results: During the 6-month study period, a total of 43 children with 44 episodes of COVID-19 were included. Of the 44 episodes, the median age of the patients included was 8 years old (interquartile range [IQR], 4.9-10.5), and the most common underlying disease was acute lymphoid leukemia (n=30, 68.2%), followed by patients post-hematopoietic stem cell transplantation (n=8, 18.2%). Majority of the patients had mild COVID-19 (n=32, 72.7%), and three patients (7.0%) had severe/critical COVID-19. Furthermore, 2.3% (n=1) died of COVID-19 associated acute respiratory distress syndrome. The largest percentage of the patients showed E gene RT-PCR Ct value ≥25 between 15-21 days (n=13, 39.4%), followed by 22-28 days (n=10, 30.3%). In 15.2% (n=5), E gene RT-PCR Ct value remained <25 beyond 28 days after initial positive PCR. Refractory malignancy status (β, 67.0; 95% confidence interval, 7.0-17.0; P=0.030) was significantly associated with prolonged duration of E gene RT-PCR <25. A patient with prolonged duration of E gene RT-PCR Ct value <25 was suspected to have infectivity shown by the transmission of the virus to his mother at day 86 after his initial positive test. Conclusions: Children that acquire symptomatic COVID-19 during refractory malignancy state are at a high risk for prolonged shedding warranting PCR-based transmission precautions in this cohort of patients.

키워드

참고문헌

  1. van der Vries E, Stittelaar KJ, van Amerongen G, Veldhuis Kroeze EJ, de Waal L, Fraaij PL, et al. Prolonged influenza virus shedding and emergence of antiviral resistance in immunocompromised patients and ferrets. PLoS Pathog 2013;9:e1003343.
  2. Haessler S, Granowitz EV. Norovirus gastroenteritis in immunocompromised patients. N Engl J Med 2013;368:971.
  3. Niyonkuru M, Pedersen RM, Assing K, Andersen TE, Skov MN, Johansen IS, et al. Prolonged viral shedding of SARS-CoV-2 in two immunocompromised patients, a case report. BMC Infect Dis 2021;21:743.
  4. Altamirano-Molina M, Pacheco-Modesto I, Amado-Tineo J. Prolonged viral shedding of SARS-CoV-2 in patients with acute leukemia. Hematol Transfus Cell Ther 2022;44:299-300. https://doi.org/10.1016/j.htct.2021.11.017
  5. Shoji K, Suzuki A, Okamoto M, Tsinda EK, Sugawara N, Sasaki M, et al. Prolonged shedding of infectious viruses with haplotype switches of SARS-CoV-2 in an immunocompromised patient. J Infect Chemother 2022;28:1001-4. https://doi.org/10.1016/j.jiac.2022.04.004
  6. Epstein RL, Sperring H, Hofman M, Lodi S, White LF, Barocas JA, et al. Time to SARS-CoV-2 PCR clearance in immunocompromising conditions: is test-based removal from isolation necessary in severely immunocompromised individuals? Open Forum Infect Dis 2021;8:ofab164.
  7. Puhach O, Meyer B, Eckerle I. SARS-CoV-2 viral load and shedding kinetics. Nat Rev Microbiol 2023;21:147-61. https://doi.org/10.1038/s41579-022-00822-w
  8. Bullard J, Dust K, Funk D, Strong JE, Alexander D, Garnett L, et al. Predicting infectious severe acute respiratory syndrome coronavirus 2 from diagnostic samples. Clin Infect Dis 2020;71:2663-6. https://doi.org/10.1093/cid/ciaa638
  9. Jeong HW, Kim SM, Kim HS, Kim YI, Kim JH, Cho JY, et al. Viable SARS-CoV-2 in various specimens from COVID-19 patients. Clin Microbiol Infect 2020;26:1520-4. https://doi.org/10.1016/j.cmi.2020.07.020
  10. Singanayagam A, Patel M, Charlett A, Lopez Bernal J, Saliba V, Ellis J, et al. Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19, England, January to May 2020. Euro Surveill 2020;25:2001483.
  11. Zapor M. Persistent detection and infectious potential of SARS-CoV-2 virus in clinical specimens from COVID-19 patients. Viruses 2020;12:v12121384.
  12. Reich P, Elward A. Infection prevention during the coronavirus disease 2019 pandemic. Infect Dis Clin North Am 2022;36:15-37. https://doi.org/10.1016/j.idc.2021.12.002
  13. Weclawek-Tompol J, Zakrzewska Z, Gryniewicz-Kwiatkowska O, Pierlejewski F, Bien E, Zaucha-Prazmo A, et al. COVID-19 in pediatric cancer patients is associated with treatment interruptions but not with short-term mortality: a Polish national study. J Hematol Oncol 2021;14:163.
  14. COVID-19 Treatment Guidelines Panel. Coronavirus disease 2019 (COVID-19) treatment guidelines [Internet]. Bethesda: National Institutes of Health; c2023 [cited 2022 Nov 6]. Available from: https://www.covid19treatmentguidelines.nih.gov/.
  15. Cevik M, Tate M, Lloyd O, Maraolo AE, Schafers J, Ho A. SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis. Lancet Microbe 2021;2:e13-22. https://doi.org/10.1016/S2666-5247(20)30172-5
  16. Meiring S, Tempia S, Bhiman JN, Buys A, Kleynhans J, Makhasi M, et al. Prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at high viral loads among hospitalized immunocompromised persons living with human immunodeficiency virus (HIV), South Africa. Clin Infect Dis 2022;75:e144-56. https://doi.org/10.1016/j.ijid.2021.12.060
  17. Tabatabai M, Juarez PD, Matthews-Juarez P, Wilus DM, Ramesh A, Alcendor DJ, et al. An analysis of COVID-19 mortality during the dominancy of Alpha, Delta, and Omicron in the USA. J Prim Care Community Health 2023;14:21501319231170164.
  18. Jones TC, Biele G, Muhlemann B, Veith T, Schneider J, Beheim-Schwarzbach J, et al. Estimating infectiousness throughout SARS-CoV-2 infection course. Science 2021;373:eabi5273.
  19. Marks M, Millat-Martinez P, Ouchi D, Roberts CH, Alemany A, Corbacho-Monne M, et al. Transmission of COVID-19 in 282 clusters in Catalonia, Spain: a cohort study. Lancet Infect Dis 2021;21:629-36. https://doi.org/10.1016/S1473-3099(20)30985-3
  20. Johnston C, Hughes H, Lingard S, Hailey S, Healy B. Immunity and infectivity in Covid-19. BMJ 2022;378:e061402.