Workman, L. | Search bioRxiv

bioRxiv2025

Immune transcriptomic differences in paediatric patients with SARS-CoV-2 compared to other lower respiratory tract infections

The clinical severity of SARS-CoV-2 infection in children varies, with asymptomatic or mild illness predominating and a minority developing severe disease. Understanding the immunological responses that underlie severity of disease may guide future development of preventive or therapeutic interventions. This study compared whole blood transcriptomes of healthy children (N=127), children with mild/asymptomatic SARS-CoV-2 infection (N=71) and children hospitalised with severe SARS-COV-2 (N=41), lower respiratory tract illness (LRTI) or LRTI due to Respiratory Syncytial Virus (RSV-LRTI) (N=47) or Pulmonary Tuberculosis (PTB) (N=47). We identified >5000 differentially expressed genes including: OLFM4, IFI27, CBX7, IGF2BP3, OTOF for severe SARS-CoV-2; IFI27, OTOF, SIGLEC1, IFI44L and USP18 for RSV-LRTI, and MMP8, LTF, IGF2BP3, GPR84, CD177, C1QC and DEFA4 for PTB, at false discovery rate (FDR) <0.05. Pathway analysis identified enrichment for neutrophil degranulation, interferon gamma signalling, overexpression of ribosomal proteins and depletion of immune response in severe SARS-CoV-2 compared to healthy (SAR-COV-2 uninfected) children. Weighted Gene Co-expression Network Analysis (WGCNA) identified 10 correlated gene modules shared between LRTI showing similar underlying response mechanisms. Cellular decomposition analysis identified the depletion of 22 cell types in severe SARS-CoV-2, 16 for RSV-LRTI and 21 for PTB compared to healthy SARS-CoV-2 uninfected control children. We identified 82 genes important for discriminating asymptomatic/mild from severe SARS-CoV-2 including CBX7, TRAF1, ZNF324 and CASS4; 93 healthy from severe SARS-CoV-2 including RORC, CBX7, NR3C2, MID2 and ADAMTS2; 110 genes for RSV-LRTI and 95 for PTB children which can be used for future therapeutic targets. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=99 SRC="FIGDIR/small/687132v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@13db618org.highwire.dtl.DTLVardef@7df9e2org.highwire.dtl.DTLVardef@a0a448org.highwire.dtl.DTLVardef@818cef_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

Characterisation of Ornithobacterium hominis colonisation dynamics and interaction with the nasopharyngeal microbiome in a South African birth cohort.

Ornithobacterium hominis is a recently described Gram-negative bacterium that colonises the human nasopharynx and may be associated with poor upper respiratory tract health. Here, we describe the isolation of O. hominis from samples collected from a South African birth cohort, creating the first archive of cultured strains of the species from Africa. Sequenced genomes from this archive reveal that South African O. hominis is more similar to Australian strains than those from Southeast Asia, and that it may share genes with other members of the microbiome that are relevant for virulence, colonisation, and antibiotic resistance. Leveraging existing microbiome data from the cohort, O. hominis was found to be closely associated with bacterial co-colonisers that are rare in non-carrier individuals, including Suttonella, Helcococcus, Moraxella spp., and Gracilibacteria. Their collective acquisition has a significant impact on the diversity of nasopharyngeal communities that contain O. hominis. Individuals who have not yet acquired O. hominis have a higher abundance of Moraxella (particularly M. lincolnii) than individuals who never acquire O. hominis, suggesting that this could be a precursor state for successful colonisation. Finally, a novel co-coloniser species, Helcococcus ekapensis, was successfully isolated and sequenced. Data SummaryOrnithobacterium hominis data have been deposited under project accession ERP149886. This comprises genome sequences for isolates SA-OH-C1 (ERR13967269), SA-OH-C2 (ERR13967270), SA-OH-C3 (ERR13967271), SA-OH-C4 (ERR13967272, ERR13967275), SA-OH-C5 (ERR13967273), SA-OH-C6 (ERR13967274, ERR13967276). Previously published 16S rRNA gene data are deposited under project accessions PRJNA790843 and PRJNA548658. Helcococcus ekapensis genome data are deposited under project accession PRJEB85661. Software usedO_LIAMRFinderPlus v3.12.8: https://github.com/ncbi/amr C_LIO_LIAssembleBAC-ONT v1.1.1: https://github.com/avantonder/assembleBAC-ONT C_LIO_LIBAKTA v1.8.1: https://bakta.computational.bio/ C_LIO_LIBLAST v2.16.0: https://blast.ncbi.nlm.nih.gov/Blast.cgi C_LIO_LIComprehensive Antibiotic Resistance Database (CARD) Resistance Gene Identifier (RGI) tool v1.2.1: https://card.mcmaster.ca/analyze/rgi C_LIO_LIDecontam v1.12 (R package): https://github.com/benjjneb/decontam C_LIO_LIEggnog-mapper v2.0.1: http://eggnog-mapper.embl.de/ C_LIO_LIFastANI v1.1.0: https://github.com/ParBLiSS/FastANI C_LIO_LIFlye v2.9.2: https://github.com/fenderglass/Flye C_LIO_LIGuppy v6.5.7: https://community.nanoporetech.com/downloads/guppy/release_notes C_LIO_LIISEScan v1.7.2.3: https://usegalaxy.eu/root?tool_id=toolshed.g2.bx.psu.edu/repos/iuc/isescan/isescan/1.7.2.3+galaxy1 C_LIO_LIMedaka v1.9.1: https://github.com/nanoporetech/medaka C_LIO_LIMEGA11: https://www.megasoftware.net/ C_LIO_LIMMseqs2 v17: https://github.com/soedinglab/MMseqs2 C_LIO_LIMothur v1.44.3: https://github.com/mothur/mothur C_LIO_LINetCoMi v1.2.0 (R package): https://github.com/stefpeschel/NetCoMi C_LIO_LIPanaroo v1.4.3: https://github.com/gtonkinhill/panaroo C_LIO_LIPHASTEST: https://phastest.ca/submissions/new C_LIO_LIProwler (commit ID c3041ba): https://github.com/ProwlerForNanopore/ProwlerTrimmer C_LIO_LIR v4.4.3: https://www.r-project.org/ C_LI Databases usedO_LIComprehensive Antibiotic Resistance Database (CARD): https://card.mcmaster.ca/ C_LIO_LIEuropean Nucleotide Archive: https://www.ebi.ac.uk/ena/ C_LIO_LIGenome Taxonomy Database (GTDB) release 09-RS220: https://gtdb.ecogenomic.org/ C_LIO_LIRefSeq release 228: https://www.ncbi.nlm.nih.gov/refseq/about/prokaryotes/ C_LIO_LISILVA v132: https://www.arb-silva.de/ C_LI Impact statementFirst described in 2019, Ornithobacterium hominis is an understudied bacterium that may be associated with poor respiratory health in children. The study builds upon existing knowledge of O. hominis by describing the first African isolates of the species, its potential as a reservoir of virulence and antibiotic resistance genes in the upper respiratory tract, and the unique microbiome profile of O. hominis carriers.

microbiology↗