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Rationale:Children usually develop less severe symptoms responding to Coronavirus Disease 2019 (COVID-19) than adults. However, little is known about the molecular alterations and pathogenesis of COVID-19 in children. Methods:We conducted plasma proteomic and metabolomic profilings of the blood samples of a cohort containing 18 COVID-19-children with mild symptoms and 12 healthy children, which were enrolled from hospital admissions and outpatients, respectively. Statistical analyses were performed to identify molecules specifically altered in COVID-19-children. We also developed a machine learning-based pipeline named inference of biomolecular combinations with minimal bias (iBM) to prioritize proteins and metabolites strongly altered in COVID-19-children, and experimentally validated the predictions. Results: By comparing to the multi-omic data in adults, we identified 44 proteins and 249 metabolites differentially altered in COVID-19-children against healthy children or COVID-19-adults. Further analyses demonstrated that both deteriorative immune response/inflammation processes and protective antioxidant or anti-inflammatory processes were markedly induced in COVID-19-children. Using iBM, we prioritized two combinations that contained 5 proteins and 5 metabolites, respectively, each exhibiting a total area under curve (AUC) value of 100% to accurately distinguish COVID-19-children from healthy children or COVID-19-adults. Further experiments validated that all the 5 proteins were up-regulated upon coronavirus infection. Interestingly, we found that the prioritized metabolites inhibited the expression of pro-inflammatory factors, and two of them, methylmalonic acid (MMA) and mannitol, also suppressed coronaviral replication, implying a protective role of these metabolites in COVID-19-children. Conclusion:The finding of a strong antagonism of deteriorative and protective effects provided new insights on the mechanism and pathogenesis of COVID-19 in children that mostly underwent mild symptoms. The identified metabolites strongly altered in COVID-19-children could serve as potential therapeutic agents of COVID-19.

In response to the current COVID-19 pandemic, it is crucial to understand the origin, transmission, and evolution of SARS-CoV-2, which relies on close surveillance of genomic diversity in clinical samples. Although the mutation at the population level had been extensively investigated, how the mutations evolve at the individual level is largely unknown. Eighteen time-series fecal samples were collected from nine COVID-19 patients during the convalescent phase. The nucleic acids of SARS-CoV-2 were enriched by the hybrid capture method. First, we demonstrated the outstanding performance of the hybrid capture method in detecting intra-host variants. We identified 229 intra-host variants at 182 sites in 18 fecal samples. Among them, nineteen variants presented frequency changes > 0.3 within 1-5 days, reflecting highly dynamic intra-host viral populations. Moreover, the evolving of the viral genome demonstrated that the virus was probably viable in the gastrointestinal tract during the convalescent period. Meanwhile, we also found that the same mutation showed distinct pattern of frequency changes in different individuals, indicating a strong random drift. In summary, dramatic changes of SARS-CoV-2 genome were detected in fecal samples during the convalescent period; whether the viral load in feces is sufficient to establish an infection warranted further investigation.

Importance The clinical characteristics of infectious mononucleosis (IM) in Chinese children have not been evaluated in multicenter studies, and the effectiveness of antiviral treatment are controversial. Objective To investigate the clinical characteristics of Chinese children with IM and current status of antiviral therapy for affected patients. Methods Hospitalized patients with IM were enrolled between 2018 and 2020 in five children’s hospitals in China. The clinical characteristics were compared among four age groups: <3 years, 3–<6 years, 6–<10 years, and ≥10 years. The clinical characteristics of IM and effectiveness of antiviral therapy were compared among patients receiving acyclovir (ACV), ganciclovir (GCV), and no antiviral therapy (i.e., non‐antiviral group). Results In total, 499 patients were analyzed; most patients were 3–<6 years of age. The most common symptoms and signs included fever (100%), lymphadenopathy (98.6%), pharyngitis (86.4%), eyelid edema (76.8%), and snoring (72.9%). There were significant differences in rash, hepatomegaly, and liver dysfunction among the four age groups. Patients aged < 3 years had a lower incidence of liver dysfunction and a higher incidence of rash. Among the 499 patients, 50.1% were treated with GCV, 26.3% were treated with ACV, and 23.6% received no antiviral therapy. Compared with the non‐antiviral group, patients in the ACV and GCV groups had longer durations of fever (P < 0.001). There were no significant differences in the incidences of complications among the three treatment groups. Interpretation The incidence of IM in Chinese children peaked at 3–<6 years of age. Clinical features of IM varied according to age. Patients receiving antiviral therapy exhibited more serious clinical manifestations than did patients without antiviral therapy. The effectiveness of antiviral therapy for IM requires further analysis.

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