Jinhu Wang

Abstract To provide a comprehensive and systematic analysis of demographic characteristics, clinical symptoms, laboratory findings, and imaging features of coronavirus disease 2019 (COVID‐19) in pediatric patients. A meta‐analysis was carried out to identify studies on COVID‐19 from 25 December 2019 to 30 April 2020. A total of 48 studies with 5829 pediatric patients were included. Children of all ages were at risk for COVID‐19. The main illness classification ranged as: 20% (95% confidence interval [CI]: 14%‐26%; I 2 = 91.4%) asymptomatic, 33% (95% CI: 23%‐43%; I 2 = 95.6%) mild and 51% (95% CI: 42%‐61%; I 2 = 93.4%) moderate. The typical clinical manifestations were fever 51% (95% CI: 45%‐57%; I 2 = 78.9%) and cough 41% (95% CI: 35%‐47%, I 2 = 81.0%). The common laboratory findings were normal white blood cell 69% (95% CI: 64%‐75%; I 2 = 58.5%), lymphopenia 16% (95% CI: 11%‐21%; I 2 = 76.9%) and elevated creatine‐kinase MB 37% (95% CI: 25%‐48%; I 2 = 59.0%). The frequent imaging features were normal images 41% (95% CI: 30%‐52%; I 2 = 93.4%) and ground‐glass opacity 36% (95% CI: 25%‐47%; I 2 = 92.9%). Among children under 1 year old, critical cases account for 14% (95% CI: 13%‐34%; I 2 = 37.3%) that should be of concern. In addition, vomiting occurred in 33% (95% CI: 18%‐67%; I 2 = 0.0%) cases that may also need attention. Pediatric patients with COVID‐19 may experience milder illness with atypical clinical manifestations and rare lymphopenia. High incidence of critical illness and vomiting symptoms reward attention in children under 1 year old.

Natural models of heart regeneration in lower vertebrates such as zebrafish are based on invasive surgeries causing mechanical injuries that are limited in size. Here, we created a genetic cell ablation model in zebrafish that facilitates inducible destruction of a high percentage of cardiomyocytes. Cell-specific depletion of over 60% of the ventricular myocardium triggered signs of cardiac failure that were not observed after partial ventricular resection, including reduced animal exercise tolerance and sudden death in the setting of stressors. Massive myocardial loss activated robust cellular and molecular responses by endocardial, immune, epicardial and vascular cells. Destroyed cardiomyocytes fully regenerated within several days, restoring cardiac anatomy, physiology and performance. Regenerated muscle originated from spared cardiomyocytes that acquired ultrastructural and electrophysiological characteristics of de-differentiation and underwent vigorous proliferation. Our study indicates that genetic depletion of cardiomyocytes, even at levels so extreme as to elicit signs of cardiac failure, can be reversed by natural regenerative capacity in lower vertebrates such as zebrafish.

Recent lineage-tracing studies have produced conflicting results about whether the epicardium is a source of cardiac muscle cells during heart development. Here, we examined the developmental potential of epicardial tissue in zebrafish during both embryonic development and injury-induced heart regeneration. We found that upstream sequences of the transcription factor gene tcf21 activated robust, epicardium-specific expression throughout development and regeneration. Cre recombinase-based, genetic fate-mapping of larval or adult tcf21(+) cells revealed contributions to perivascular cells, but not cardiomyocytes, during each form of cardiogenesis. Our findings indicate that natural epicardial fates are limited to non-myocardial cell types in zebrafish.