This is the first study on gut microbiota (GM) in children affected by coronavirus disease 2019 (COVID-19). Stool samples from 88 patients with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and 95 healthy subjects were collected (admission: 3-7 days, discharge) to study GM profile by 16S rRNA gene sequencing and relationship to disease severity. The study group was divided in COVID-19 (68), Non-COVID-19 (16), and MIS-C (multisystem inflammatory syndrome in children) (4). Correlations among GM ecology, predicted functions, multiple machine learning (ML) models, and inflammatory response were provided for COVID-19 and Non-COVID-19 cohorts. The GM of COVID-19 cohort resulted as dysbiotic, with the lowest α-diversity compared with Non-COVID-19 and CTRLs and by a specific β-diversity. Its profile appeared enriched in Faecalibacterium , Fusobacterium , and Neisseria and reduced in Bifidobacterium , Blautia , Ruminococcus , Collinsella , Coprococcus , Eggerthella , and Akkermansia , compared with CTRLs ( p < 0.05). All GM paired-comparisons disclosed comparable results through all time points. The comparison between COVID-19 and Non-COVID-19 cohorts highlighted a reduction of Abiotrophia in the COVID-19 cohort ( p < 0.05). The GM of MIS-C cohort was characterized by an increase of Veillonella , Clostridium , Dialister , Ruminococcus , and Streptococcus and a decrease of Bifidobacterium , Blautia , Granulicatella , and Prevotella , compared with CTRLs. Stratifying for disease severity, the GM associated to “moderate” COVID-19 was characterized by lower α-diversity compared with “mild” and “asymptomatic” and by a GM profile deprived in Neisseria , Lachnospira , Streptococcus , and Prevotella and enriched in Dialister , Acidaminococcus , Oscillospora , Ruminococcus , Clostridium , Alistipes , and Bacteroides. The ML models identified Staphylococcus , Anaerostipes , Faecalibacterium , Dorea , Dialister , Streptococcus , Roseburia , Haemophilus , Granulicatella , Gemmiger , Lachnospira , Corynebacterium , Prevotella , Bilophila , Phascolarctobacterium , Oscillospira , and Veillonella as microbial markers of COVID-19. The KEGG ortholog (KO)-based prediction of GM functional profile highlighted 28 and 39 KO-associated pathways to COVID-19 and CTRLs, respectively. Finally, Bacteroides and Sutterella correlated with proinflammatory cytokines regardless disease severity. Unlike adult GM profiles, Faecalibacterium was a specific marker of pediatric COVID-19 GM. The durable modification of patients’ GM profile suggested a prompt GM quenching response to SARS-CoV-2 infection since the first symptoms. Faecalibacterium and reduced fatty acid and amino acid degradation were proposed as specific COVID-19 disease traits, possibly associated to restrained severity of SARS-CoV-2-infected children. Altogether, this evidence provides a characterization of the pediatric COVID-19-related GM.
【저자키워드】 COVID-19, immunology, SARS-CoV-2, gut microbiota, Dysbiosis, diversity index,