Nicastro Emanuele, Verdoni Lucio, Bettini Laura Rachele, Zuin Giovanna, Balduzzi Adriana, Montini Giovanni, Biondi Andrea, D'Antiga Lorenzo
Pediatric Hepatology, Gastroenterology and Transplantation Unit, Hospital Papa Giovanni XXIII, Bergamo, Italy.
Pediatric Unit, Hospital Papa Giovanni XXIII, Bergamo, Italy.
Front Pediatr. 2021 Apr 29;9:629240. doi: 10.3389/fped.2021.629240. eCollection 2021.
Following the spread of the SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) to a global pandemic, concerns have arisen for the disease impact in at-risk populations, especially in immunocompromised hosts. On the other hand, clinical studies have clarified that the COVID-19 clinical burden is mostly due to over-inflammation and immune-mediated multiorgan injury. This has led to downsizing the role of immunosuppression as a determinant of outcome, and early reports confirm the hypothesis that patients undergoing immunosuppressive treatments do not have an increased risk of severe COVID-19 with respect to the general population. Intriguingly, SARS-CoV-2 natural reservoirs, such as bats and mice, have evolved mechanisms of tolerance involving selection of genes optimizing viral clearance through interferon type I and III responses and also dampening inflammasome response and cytokine expression. Children exhibit resistance to COVID-19 severe manifestations, and age-related features in innate and adaptive response possibly explaining this difference are discussed. A competent recognition by the innate immune system and controlled pro-inflammatory signaling seem to be the pillars of an effective response and the premise for pathogen clearance in SARS-CoV-2 infection. Immunosuppression-if not associated with other elements of fragility-do not represent an obstacle to this competent/tolerant phenotype in children. Several reports confirm that children receiving immunosuppressive medications have similar clinical involvement and outcomes as the pediatric general population, indicating that maintenance treatments should not be interrupted in suspect or confirmed SARS-CoV-2 infection.
随着严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）感染和2019冠状病毒病（COVID-19）蔓延至全球大流行，人们开始关注该疾病对高危人群的影响，尤其是免疫功能低下的宿主。另一方面，临床研究已阐明，COVID-19的临床负担主要归因于过度炎症和免疫介导的多器官损伤。这导致免疫抑制作为预后决定因素的作用被弱化，早期报告证实了这一假设，即接受免疫抑制治疗的患者与普通人群相比，发生重症COVID-19的风险并未增加。有趣的是，SARS-CoV-2的天然宿主，如蝙蝠和小鼠，已经进化出耐受机制，包括通过I型和III型干扰素反应选择优化病毒清除的基因，以及抑制炎性小体反应和细胞因子表达。儿童对COVID-19的严重表现具有抵抗力，本文将讨论先天和适应性反应中与年龄相关的特征，这些特征可能解释了这种差异。先天免疫系统的有效识别和受控的促炎信号似乎是有效反应的支柱，也是SARS-CoV-2感染中病原体清除的前提。免疫抑制——如果不与其他脆弱因素相关——并不代表儿童出现这种有效/耐受表型的障碍。几份报告证实，接受免疫抑制药物治疗的儿童与儿科普通人群的临床受累情况和预后相似，这表明在疑似或确诊SARS-CoV-2感染时，维持治疗不应中断。
