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 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 () and Andrew J. Pollard
Additional contact information
Gu-Lung Lin: University of Oxford
Simon B. Drysdale: University of Oxford
Matthew D. Snape: University of Oxford
Daniel O’Connor: University of Oxford
Anthony Brown: University of Oxford
George MacIntyre-Cockett: University of Oxford
Esther Mellado-Gomez: University of Oxford
Mariateresa Cesare: University of Oxford
M. Azim Ansari: University of Oxford
David Bonsall: University of Oxford
James E. Bray: University of Oxford
Keith A. Jolley: University of Oxford
Rory Bowden: University of Oxford
Jeroen Aerssens: Janssen Pharmaceutica NV
Louis Bont: University Medical Center Utrecht
Peter J. M. Openshaw: Imperial College London
Federico Martinon-Torres: Hospital Clínico Universitario de Santiago de Compostela
Harish Nair: University of Edinburgh
Tanya Golubchik: University of Oxford
Andrew J. Pollard: University of Oxford

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: 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 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.

Date: 2024
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DOI: 10.1038/s41467-024-46648-3

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