Exploring nasopharyngeal microbiota profile in children affected by SARS-CoV-2 infection

Author:

Romani L.1,Del Chierico F.2ORCID,Pane S.3,Ristori M. V.2,Pirona I.4,Guarrasi V.4,Cotugno N.56,Bernardi S.1,Lancella L.1,Perno C. F.7ORCID,Rossi P.68,Villani A.9,Campana A.10,Palma P.56,Putignani L.11ORCID, ,Carducci Francesca Calò,Cancrini Caterina,Chiurchiù Sara,degli Atti Marta Ciofi,Cursi Laura,Cutrera Renato,D’Amore Carmen,D’Argenio Patrizia,De Ioris Maria A.,De Luca Maia,Finocchi Andrea,Manno Emma Concetta,Morrocchi Elena,Pansa Paola,Sessa Libera,Zangari Paola

Affiliation:

1. Infectious Disease Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy

2. Research Unit of Human Microbiome, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy

3. Unit of Microbiomics, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy

4. GenomeUp SRL, Viale Pasteur, Rome, Italy

5. Research Unit of Congenital and Perinatal Infections, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy

6. Department of Systems Medicine, University of Rome ‘‘Tor Vergata’’, Rome, Italy

7. Unit of Microbiology and Diagnostic Immunology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy

8. Academic Department of Pediatrics, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy

9. Pediatric Emergency Department and General Pediatrics, Bambino Gesù Children's Hospital Bambino Gesù, IRCCS, Rome, Italy

10. Department of Pediatrics, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy

11. Unit of Microbiomics and Research Unit of Human Microbiome, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy

Abstract

ABSTRACT The relationship between COVID-19 and nasopharyngeal (NP) microbiota has been investigated mainly in the adult population. We explored the NP profile of children affected by COVID-19, compared to healthy controls (CTRLs). NP swabs of children with COVID-19, collected between March and September 2020, were investigated at the admission ( T 0 ), 72 h to 7 days ( T 1 ), and at the discharge ( T 2 ) of the patients. NP microbiota was analyzed by 16S rRNA targeted-metagenomics. Data from sequencing were investigated by QIIME 2.0 and PICRUSt 2. Multiple machine learning (ML) models were exploited to classify patients compared to CTRLs. The NP microbiota of COVID-19 patients ( N = 71) was characterized by reduction of α-diversity compared to CTRLs ( N = 59). The NP microbiota of COVID-19 cohort appeared significantly enriched in Streptococcus , Haemophilus , Staphylococcus , Veillonella , Enterococcus , Neisseria , Moraxella , Enterobacteriaceae, Gemella , Bacillus , and reduced in Faecalibacterium , Akkermansia , Blautia , Bifidobacterium , Ruminococcus , and Bacteroides, compared to CTRLs (FDR < 0.001). Exploiting ML models, Enterococcus, Pseudomonas, Streptococcus, Capnocytopagha, Tepidiphilus, Porphyromonas, Staphylococcus , and Veillonella resulted as NP microbiota biomarkers, in COVID-19 patients. No statistically significant differences were found comparing the NP microbiota profile of COVID-19 patients during the time-points or grouping patients on the basis of high, medium, and low viral load (VL). This evidence provides specific pathobiont signatures of the NP microbiota in pediatric COVID-19 patients, and the reduction of anaerobic protective commensals. Our data suggest that the NP microbiota may have a specific disease-related signature since infection onset without changes during disease progression, regardless of the SARS-CoV-2 VL. IMPORTANCE Since the beginning of pandemic, we know that children are less susceptible to severe COVID-19 disease. A potential role of the nasopharyngeal (NP) microbiota has been hypothesized but to date, most of the studies have been focused on adults. We studied the NP microbiota modifications in children affected by SARS-CoV-2 infection showing a specific NP microbiome profile, mainly composed by pathobionts and almost missing protective anaerobic commensals. Moreover, in our study, specific microbial signatures appear since the first days of infection independently from SARS-CoV-2 viral load.

Funder

Ministero della Salute

The BioArte Limited

Italian Ministry of Health

Publisher

American Society for Microbiology

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