The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide, igniting an unprecedented effort from the scientific community to understand the biological underpinning of COVID19 pathophysiology. In this Review, we summarize the current state of knowledge of innate and adaptive immune responses elicited by SARS-CoV-2 infection and the immunological pathways that likely contribute to disease severity and death. We also discuss the rationale and clinical outcome of current therapeutic strategies as well as prospective clinical trials to prevent or treat SARS-CoV-2 infection.

Background: Studies summarizing the clinical picture of COVID-19 in children are lacking. This review characterizes clinical symptoms, laboratory, and imaging findings, as well as therapies provided to confirmed pediatric cases of COVID-19. Methods: Adhering to PRISMA guidelines, we searched four medical databases (PubMed, LitCovid, Scopus, WHO COVID-19 database) between December 1, 2019 to May 14, 2020 using the keywords "novel coronavirus", "COVID-19" or "SARS-CoV-2". We included published or in press peer-reviewed cross-sectional, case series, and case reports providing clinical signs, imaging findings, and/or laboratory results of pediatric patients who were positive for COVID-19. Risk of bias was appraised through the quality assessment tool published by the National Institutes of Health. PROSPERO registration # CRD42020182261. Findings: We identified 131 studies across 26 countries comprising 7780 pediatric patients. Although fever (59¢1%) and cough (55¢9%) were the most frequent symptoms 19¢3% of children were asymptomatic. Patchy lesions (21¢0%) and ground-glass opacities (32¢9%) depicted lung radiograph and computed tomography findings, respectively. Immunocompromised children or those with respiratory/cardiac disease comprised the largest subset of COVID-19 children with underlying medical conditions (152 of 233 individuals). Coinfections were observed in 5.6% of children and abnormal laboratory markers included serum D-dimer, procalcitonin, creatine kinase, and interleukin-6. Seven deaths were reported (0¢09%) and 11 children (0¢14%) met inclusion for multisystem inflammatory syndrome in children. Interpretation: This review provides evidence that children diagnosed with COVID-19 have an overall excellent prognosis. Future longitudinal studies are needed to confirm our findings and better understand which patients are at increased risk for developing severe inflammation and multiorgan failure. Funding: Parker B. Francis and pilot grant from 2R25-HL126140. Funding agencies had no involvement in the study.

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Eosinophilia is a prognostic marker in patients with metastatic melanoma.