Targeted metagenomics reveals association between severity and pathogen co-detection in infants with respiratory syncytial virus

Gu-Lung Lin, Simon B Drysdale, Matthew D Snape, Daniel O'Connor, Anthony Brown, George MacIntyre-Cockett, Esther Mellado-Gomez, Mariateresa de Cesare, M Azim Ansari, David Bonsall, James E Bray, Keith A Jolley, Rory Bowden, Jeroen Aerssens, Louis Bont, Peter J M Openshaw, Federico Martinon-Torres, Harish Nair, Tanya Golubchik, Andrew J Pollard

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Abstract

Respiratory syncytial virus (RSV) is the leading cause of hospitalisation for respiratory infection in young children. RSV disease severity is known to be age-dependent and highest in young infants, but other correlates of severity, particularly the presence of additional respiratory pathogens, are less well understood. In this study, nasopharyngeal swabs were collected from two cohorts of RSV-positive infants <12 months in Spain, the UK, and the Netherlands during 2017-20. We show, using targeted metagenomic sequencing of >100 pathogens, including all common respiratory viruses and bacteria, from samples collected from 433 infants, that burden of additional viruses is common (111/433, 26%) but only modestly correlates with RSV disease severity. In contrast, there is strong evidence in both cohorts and across age groups that presence of Haemophilus bacteria (194/433, 45%) is associated with higher severity, including much higher rates of hospitalisation (odds ratio 4.25, 95% CI 2.03-9.31). There is no evidence for association between higher severity and other detected bacteria, and no difference in severity between RSV genotypes. Our findings reveal the genomic diversity of additional pathogens during RSV infection in infants, and provide an evidence base for future causal investigations of the impact of co-infection on RSV disease severity.

Original languageEnglish
Article number2379
JournalNature Communications
Volume15
Issue number1
DOIs
Publication statusPublished - 16 Mar 2024

Keywords

  • Child
  • Child, Preschool
  • Coinfection
  • Hospitalization
  • Humans
  • Infant
  • Respiratory Syncytial Virus Infections/diagnosis
  • Respiratory Syncytial Virus, Human/genetics
  • Respiratory Tract Infections

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