It is not fully understood why COVID-19 is typically milder in children^1–3. Here, to examine the differences between children and adults in their response to SARS-CoV-2 infection, we analysed paediatric and adult patients with COVID-19 as well as healthy control individuals (total n = 93) using single-cell multi-omic profiling of matched nasal, tracheal, bronchial and blood samples. In the airways of healthy paediatric individuals, we observed cells that were already in an interferon-activated state, which after SARS-CoV-2 infection was further induced especially in airway immune cells. We postulate that higher paediatric innate interferon responses restrict viral replication and disease progression. The systemic response in children was characterized by increases in naive lymphocytes and a depletion of natural killer cells, whereas, in adults, cytotoxic T cells and interferon-stimulated subpopulations were significantly increased. We provide evidence that dendritic cells initiate interferon signalling in early infection, and identify epithelial cell states associated with COVID-19 and age. Our matching nasal and blood data show a strong interferon response in the airways with the induction of systemic interferon-stimulated populations, which were substantially reduced in paediatric patients. Together, we provide several mechanisms that explain the milder clinical syndrome observed in children.

Three-dimensional hydrogel-based organ-like cultures can be applied to study development, regeneration, and disease in vitro. However, the control of engineered hydrogel composition, mechanical properties and geometrical constraints tends to be restricted to the initial time of fabrication. Modulation of hydrogel characteristics over time and according to culture evolution is often not possible. Here, we overcome these limitations by developing a hydrogel-in-hydrogel live bioprinting approach that enables the dynamic fabrication of instructive hydrogel elements within pre-existing hydrogel-based organ-like cultures. This can be achieved by crosslinking photosensitive hydrogels via two-photon absorption at any time during culture. We show that instructive hydrogels guide neural axon directionality in growing organotypic spinal cords, and that hydrogel geometry and mechanical properties control differential cell migration in developing cancer organoids. Finally, we show that hydrogel constraints promote cell polarity in liver organoids, guide small intestinal organoid morphogenesis and control lung tip bifurcation according to the hydrogel composition and shape.

Background: Pregnant women have been identified as a potentially at‐risk group concerning COVID‐19 infection, but little is known regarding the susceptibility of the fetus to infection. Co‐expression of ACE2 and TMPRSS2 has been identified as a prerequisite for infection, and expression across different tissues is known to vary between children and adults. However, the expression of these proteins in the fetus is unknown.Methods: We performed a retrospective analysis of a single cell data repository. The data were then validated at both gene and protein level by performing RT‐qPCR and two‐colour immunohistochemistry on a library of second‐trimester human fetal tissues.Findings: TMPRSS2 is present at both gene and protein level in the predominantly epithelial fetal tissues analysed. ACE2 is present at significant levels only in the fetal intestine and kidney, and is not expressed in the fetal lung. The placenta also does not co‐express the two proteins across the second trimester or at term.Interpretation: This dataset indicates that the lungs are unlikely to be a viable route of SARS‐CoV2 fetal infection. The fetal kidney, despite presenting both the proteins required for the infection, is anatomically protected from the exposure to the virus. However, the gastrointestinal tract is likely to be susceptible to infection due to its high co‐expression of both proteins, as well as its exposure to potentially infected amniotic fluid.Tweetable This work provides detailed mechanistic insight into the relative protection & vulnerabilities of the fetus & placenta to SARS‐CoV‐2 infection by scRNAseq & protein expression analysis for ACE2 & TMPRSS2. The findings help to explain the low rate of vertical transmission.

Laparoscopic percutaneous extraperitoneal closure (LPEC) has become a common procedure for repairing inguinal hernia. As a laparoscopic approach, pediatric surgical trainees require more training to learn LPEC than a traditional open approach. This study aimed to clarify the experience needed to acquire the skill to perform LPEC adequately. This descriptive single-center study used clinical data from patients who underwent LPEC between May 2009 and May 2016. The mean operative time for ten consecutive unilateral repairs was used as an index of proficiency with the procedure. The number of repairs performed before the mean operative time became less than 20 min was evaluated for each trainee. During the study period, six pediatric surgical trainees participated in the training independently. The number of the patients was 987. The total number of repairs was 1436, including 538 unilateral repairs and 449 concurrent bilateral repairs. Overall, the mean operative time was 21.8 ± 8.1 min for unilateral repair and 31.4 ± 9.7 min for concurrent bilateral repairs. The mean number of repairs performed before the acquisition of skill for dexterous LPEC was 125.1 ± 29.5. Although there were individual differences, all trainees acquired the skill to perform LPEC adequately within one year. With appropriate guidance, LPEC can become a standard technique for pediatric surgical trainees, along with traditional open surgery. These results provide valuable information for planning LPEC training.

Background: CDH UK is a registered charity governed by a volunteer committee and providing informal support to patients, families and healthcare workers affected directly or indirectly with congenital diaphragmatic hernia (CDH) internationally. This is the first patient-led survey undertaken by CDH UK aiming for highlighting the feeding problems and their impact on the daily life of CDH survivors. Methods: Answers from CDH survivors were collected through an online questionnaire (SurveyMonkey^®) undertaken by CDH UK. The questionnaire contained questions about their feeding problems and support they were receiving for it. Main results: Overall, 151 patients answered some parts of the survey and 102 patients completed the questionnaire. Overall, 116 (76.8%) responders reported suffering from any type of feeding issue. Gastric acid reflux (GER) and growth retardation were the commonest symptoms experienced by 97 (91.5%) and 72 (62.2%) responders, respectively. Only 18 (17.0%) responders have received any written information on feeding or details of patient/parent support. Eighty (75.5%) responders are satisfied with the level of support they are receiving, but 78 (76.4%) answered that the whole experience associated with the disease has been very or extremely stressful. Conclusions: CDH survivors frequently have various issues with feeding, which may not be adequately supported or discussed clinically. It is desirable to assist the patients to reliable resources of long-term support, including multidisciplinary team (MDT) approach.