SARS-CoV-2 Infections in Children and Potential Fecal-oral Transmission
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 283
- 试验地点
- 4
- 主要终点
- Cytopathic effects and expression of subgenomic mRNA
研究概览
简要总结
The clinical courses of COVID-19 in children are reportedly mild, and may therefore readily escape diagnosis. Prolonged intestinal virus shedding has been reported in children, thus rendering the pediatric population a potentially important source of virus transmission. However, the infectious potential of SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) excreted in the stool has remained enigmatic.
The investigators hypothesize that stools carrying the virus can represent a source of infection, at least in a proportion of instances, and therefore intend to screen stools of children admitted to the hospital regardless of the indication in order to assess the frequency of intestinal virus excretion. The screening will be performed by validated RTQ-PCR (reverse transcription quantitative polymerase chain reaction) assays. In positive cases, stool extracts will be used to inoculate permissive cells (e.g. VeroE6) under BSL3 (Biosafety Level 3) conditions, and the infectious potential of the viruses will be determined. The readout will be based on the assessment of cell cytopathic effects and on the expression of subgenomic mRNA. it is expected to recruit ~100 patients for the study.
Additionally, the investigators will specifically examine children admitted to the hospital because of COVID-19, and will determine the temporal correlation between viral loads in the upper respiratory tract (URT) and serial stool specimens as well as swabs from the palms and from the oral cavity using RTQ-PCR. Longitudinal studies on the infectious potential of viruses from the URT and stool will be performed using the experimental approach outlined above. For this part of the study, is is intended to recruit ~100 children.
Furthermore, samples derived from >200 patients from our biorepository will be used.
The insights gained from the study will greatly expand the knowledge on the epidemiological and clinical significance of SARS-CoV-2 infections in children. If stools are identified as a potential source of infection, the data will have an important impact on safety measures in specific settings such as the kindergarten.
详细描述
Background:
Overt COVID-19 is reportedly far less frequent children. In a study from China, children <10 years of age represented only 0.9% and children between 10-19 years of age only 1.2% of the diagnostically confirmed cases1. Very similar data were published by the Italian registry, indicating 0.5% and 0.7%, respectively2. In the largest pediatric study published to date including >2000 children, 4% had asymptomatic courses, 90% had mild or moderate clinical courses, and severe manifestations were documented in 6% of cases, mostly involving infants below 1 year of age3. Some reports indicated asymptomatic courses in as many as 16-30% of affected children within individual age groups3,4. In addition to common symptoms such as fever and dry cough (40-100% of cases), diarrhea was a frequent observation in children with COVID-19 (10-30% of cases), in contrast to adults with overt disease (4% of cases) 5-11. Virus shedding into the stool was commonly observed in children for more than one month after resolution of acute infection7,10. However, the infectious potential of intestinal virus shedding, which has been demonstrated for the related viruses SARS-CoV and MERS-CoV (Middle East Respiratory syndrome coronavirus), is currently unclear for SARS-CoV-212,13. Due to the mild or even asymptomatic courses of COVID-19, children might represent an important source of disease transmission. With the increasing numbers of adults who are vaccinated and the appearance of new variants of the virus displaying different properties, the situation in children might certainly change and may need to be reevaluated. The proposed study in collaboration with different pediatric facilities in Austrian hospitals therefore offers an excellent opportunity to address different aspects of COVID-19 pertaining to the pediatric population.
Hypotheses:
- Shedding of SARS-CoV-2 into the stool is detectable in a proportion of asymptomatic children
- In patients with COVID-19, the frequency of intestinal virus excretion is higher and persists for prolonged time periods post infection
- Viruses excreted with the stool may display infectious potential
Study design:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Hospitalized pediatric patients: 0-18 years of age
- •Informed consent for collection and retention of biomaterial
排除标准
- •Absence of informed consent
结局指标
主要结局
Cytopathic effects and expression of subgenomic mRNA
时间窗: A single time point in each patient, upon admission to the hospital
Testing for infectious properties of SARS-CoV-2 pathogens detected in clinical specimens including particularly stool (and potentially swabs from the palms, nasopharyngeal swabs including swabs from the oral cavity) will be carried out by using permissive cell lines (VeroE6, CaCo2, or HCT116) under appropriate culture conditions. The readout will be based on the documentation of cell cytopathic effects and expression of subgenomic mRNA using established RTQ-PCR tests.
次要结局
未报告次要终点