Di Pietro Giada Maria, Ronzoni Luisa, Meschia Lorenzo Maria, Tagliabue Claudia, Lombardi Angela, Pinzani Raffaella, Bosis Samantha, Marchisio Paola Giovanna, Valenti Luca
S.C. Pediatria-Pneumoinfettivologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Precision Medicine Lab, Transfusion Medicine and Hematology, Biological Resource Centre, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Front Pediatr. 2023 Feb 17;11:1082083. doi: 10.3389/fped.2023.1082083. eCollection 2023.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is characterized by a wide variety of expressions ranging from asymptomatic to, rarely, critical illness. The basis of this variability is not yet fully understood. The aim of this study was to identify clinical and genetic risk factors predisposing to disease susceptibility and progression in children.
We enrolled 181 consecutive children aged less than 18 years hospitalized with or for SARS-CoV-2 infection during a period of 24 months. Demographic, clinical, laboratory, and microbiological data were collected. The development of coronavirus disease 2019 (COVID-19)-related complications and their specific therapies were assessed. In a subset of 79 children, a genetic analysis was carried out to evaluate the role of common COVID-19 genetic risk factors (chromosome 3 cluster; -blood group system; , , , and loci).
The mean age of hospitalized children was 5.7 years, 30.9% of them being under 1 year of age. The majority of children (63%) were hospitalized for reasons different than COVID-19 and incidentally tested positive for SARS-CoV-2, while 37% were admitted for SARS-CoV-2 infection. Chronic underlying diseases were reported in 29.8% of children. The majority of children were asymptomatic or mildly symptomatic; only 12.7% developed a moderate to critical disease. A concomitant pathogen, mainly respiratory viruses, was isolated in 53.3%. Complications were reported in 7% of children admitted for other reasons and in 28.3% of those hospitalized for COVID-19. The respiratory system was most frequently involved, and the C-reactive protein was the laboratory test most related to the development of critical clinical complications. The main risk factors for complication development were prematurity [relative risk (RR) 3.8, 95% confidence interval (CI) 2.4-6.1], comorbidities (RR 4.5, 95% CI 3.3-5.6), and the presence of coinfections (RR 2.5, 95% CI 1.1-5.75). The risk variant was the main genetic risk factor for pneumonia development [Odds ratio (OR) 3.28, 95% CI 1-10.7; value 0.049].
Our study confirmed that COVID-19 is generally less severe in children, although complications can develop, especially in those with comorbidities (chronic diseases or prematurity) and coinfections. Variation at the genes cluster is the main genetic risk factor predisposing to COVID-19 pneumonia in children.
儿童感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的表现多种多样，从无症状感染到极少出现的危重症。这种变异性的基础尚未完全明确。本研究旨在确定儿童疾病易感性和病情进展的临床及遗传风险因素。
我们纳入了连续24个月内因SARS-CoV-2感染住院或就诊的181名18岁以下儿童。收集了人口统计学、临床、实验室和微生物学数据。评估了2019冠状病毒病（COVID-19）相关并发症的发生情况及其具体治疗方法。在79名儿童的亚组中进行了基因分析，以评估常见COVID-19遗传风险因素（3号染色体簇；血型系统； 、 、 及 基因座）的作用。
住院儿童的平均年龄为5.7岁，其中30.9%年龄小于1岁。大多数儿童（63%）因非COVID-19相关原因住院，SARS-CoV-2检测偶然呈阳性，而37%因SARS-CoV-2感染入院。29.8%的儿童有慢性基础疾病。大多数儿童无症状或症状轻微；只有12.7%发展为中重度疾病。53.3%的儿童分离出了合并病原体，主要是呼吸道病毒。因其他原因入院的儿童中有7%出现并发症，因COVID-19住院的儿童中有28.3%出现并发症。呼吸系统最常受累，C反应蛋白是与严重临床并发症发生最相关的实验室检查指标。并发症发生的主要风险因素是早产[相对危险度（RR）3.8，95%置信区间（CI）2.4 - 6.1]、合并症（RR 4.5，95% CI 3.3 - 5.6）和合并感染（RR 2.5，95% CI 1.1 - 5.75）。 风险变异是肺炎发生的主要遗传风险因素[比值比（OR）3.28，95% CI 1 – 10.7； 值0.049]。
我们的研究证实，COVID-19在儿童中通常病情较轻，尽管可能会出现并发症，尤其是在有合并症（慢性病或早产）和合并感染的儿童中。 基因簇的变异是儿童发生COVID-19肺炎的主要遗传风险因素。
