IRIS: Infection with RespIratory Syncytial Virus in infants-a prospective observational cohort study

Martin Wetzke, Dominik Funken, Mathias Lange, Levente Bejo, Sibylle Haid, Joao G Tereno Monteiro, Katharina Schütz, Christine Happle, Thomas F Schulz, Jürgen Seidenberg, Thomas Pietschmann, Gesine Hansen, Martin Wetzke, Dominik Funken, Mathias Lange, Levente Bejo, Sibylle Haid, Joao G Tereno Monteiro, Katharina Schütz, Christine Happle, Thomas F Schulz, Jürgen Seidenberg, Thomas Pietschmann, Gesine Hansen

Abstract

Background: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory tract infection in infants. Globally, RSV is responsible for approximately 3.2 million hospital admissions and about 60,000 in-hospital deaths per year.

Methods: Infection with RespIratory Syncytial Virus (IRIS) is an observational, multi-centre study enrolling infants with severe RSV infection and healthy controls. Inclusion criteria are age between 0 and 36 months and hospitalisation due to RSV infection at three German sites. Exclusion criteria are premature birth, congenital or acquired bronchopulmonary or cardiac diseases, and immunodeficiency. Healthy control probands are enrolled via recruitment of patients undergoing routine surgical procedures. Blood and respiratory specimens are collected upon admission, and RSV and other pathogens are analysed by multiplex polymerase chain reaction. Different biomaterials, including plasma, nasal lining fluid, blood cells, DNA, and RNA specimens, are sampled in a dedicated biobank. Detailed information on demographic characteristics and medical history is recorded, and comprehensive clinical data, including vital signs, medication, and interventions.

Discussion: The IRIS study aims to discover host and viral factors controlling RSV disease courses in infants. The approach including multi-omics characterisation in clinically well-characterized children with RSV bronchiolitis seeks to improve our understanding of the immune response against this virus. It may disclose novel diagnostic and treatment approaches for respiratory infections in infants.

Trial registration: ClinicalTrials.gov, NCT04925310. Registered 01 October 2021-Retrospectively registered. https://ichgcp.net/clinical-trials-registry/NCT04925310?cond=NCT04925310&draw=2&rank=1.

Keywords: Bronchiolitis; Cohort study; Genetic susceptibility; Infants; Infection; Respiratory syncytial virus (RSV); Toddlers.

Conflict of interest statement

The authors declare no competing interests.

© 2022. The Author(s).

References

    1. Liu L, Oza S, Hogan D, Chu Y, Perin J, Zhu J, et al. Global, regional, and national causes of under-5 mortality in 2000–15: an updated systematic analysis with implications for the Sustainable Development Goals. Lancet. 2016;388(10063):3027–3035. doi: 10.1016/S0140-6736(16)31593-8.
    1. Shi T, McAllister DA, O'Brien KL, Simoes EAF, Madhi SA, Gessner BD, et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet. 2017;390(10098):946–958. doi: 10.1016/S0140-6736(17)30938-8.
    1. Chatterjee A, Mavunda K, Krilov LR. Current state of respiratory syncytial virus disease and management. Infect Dis Ther. 2021;10(Suppl 1):5–16. doi: 10.1007/s40121-020-00387-2.
    1. Hall CB, Weinberg GA, Iwane MK, Blumkin AK, Edwards KM, Staat MA, et al. The burden of respiratory syncytial virus infection in young children. N Engl J Med. 2009;360(6):588–598. doi: 10.1056/NEJMoa0804877.
    1. Griffiths C, Drews SJ, Marchant DJ. Respiratory syncytial virus: infection, detection, and new options for prevention and treatment. Clin Microbiol Rev. 2017;30(1):277–319. doi: 10.1128/CMR.00010-16.
    1. Choi EH, Lee HJ, Chanock SJ. Human genetics and respiratory syncytial virus disease: current findings and future approaches. Curr Top Microbiol Immunol. 2013;372:121–137.
    1. Bockova J, O'Brien KL, Oski J, Croll J, Reid R, Weatherholtz RC, et al. Respiratory syncytial virus infection in Navajo and White Mountain Apache children. Pediatrics. 2002;110(2 Pt 1):e20. doi: 10.1542/peds.110.2.e20.
    1. Thomsen SF, van der Sluis S, Stensballe LG, Posthuma D, Skytthe A, Kyvik KO, et al. Exploring the association between severe respiratory syncytial virus infection and asthma: a registry-based twin study. Am J Respir Crit Care Med. 2009;179(12):1091–1097. doi: 10.1164/rccm.200809-1471OC.
    1. Thomsen SF, Stensballe LG, Skytthe A, Kyvik KO, Backer V, Bisgaard H. Increased concordance of severe respiratory syncytial virus infection in identical twins. Pediatrics. 2008;121(3):493–496. doi: 10.1542/peds.2007-1889.
    1. Janssen R, Bont L, Siezen CL, Hodemaekers HM, Ermers MJ, Doornbos G, et al. Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes. J Infect Dis. 2007;196(6):826–834. doi: 10.1086/520886.
    1. Kenney AD, Dowdle JA, Bozzacco L, McMichael TM, St Gelais C, Panfil AR, et al. Human genetic determinants of viral diseases. Annu Rev Genet. 2017;51:241–263. doi: 10.1146/annurev-genet-120116-023425.
    1. Thwaites RS, Coates M, Ito K, Ghazaly M, Feather C, Abdulla F, et al. Reduced nasal viral load and IFN responses in infants with respiratory syncytial virus bronchiolitis and respiratory failure. Am J Respir Crit Care Med. 2018;198(8):1074–1084. doi: 10.1164/rccm.201712-2567OC.
    1. Rodriguez-Fernandez R, Tapia LI, Yang CF, Torres JP, Chavez-Bueno S, Garcia C, et al. Respiratory syncytial virus genotypes, host immune profiles, and disease severity in young children hospitalized with bronchiolitis. J Infect Dis. 2017;217(1):24–34. doi: 10.1093/infdis/jix543.
    1. Chi H, Hsiao KL, Weng LC, Liu CP, Liu HF. Persistence and continuous evolution of the human respiratory syncytial virus in northern Taiwan for two decades. Sci Rep. 2019;9(1):4704. doi: 10.1038/s41598-019-41332-9.
    1. Habibi MS, Thwaites RS, Chang M, Jozwik A, Paras A, Kirsebom F, et al. Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection. Science. 2020;370(6513):eaba9301. doi: 10.1126/science.aba9301.
    1. Jozwik A, Habibi MS, Paras A, Zhu J, Guvenel A, Dhariwal J, et al. RSV-specific airway resident memory CD8+ T cells and differential disease severity after experimental human infection. Nat Commun. 2015;6:10224. doi: 10.1038/ncomms10224.
    1. Zhivaki D, Lemoine S, Lim A, Morva A, Vidalain PO, Schandene L, et al. Respiratory syncytial virus infects regulatory B cells in human neonates via chemokine receptor CX3CR1 and promotes lung disease severity. Immunity. 2017;46(2):301–314. doi: 10.1016/j.immuni.2017.01.010.
    1. Reed JL, Welliver TP, Sims GP, McKinney L, Velozo L, Avendano L, et al. Innate immune signals modulate antiviral and polyreactive antibody responses during severe respiratory syncytial virus infection. J Infect Dis. 2009;199(8):1128–1138. doi: 10.1086/597386.
    1. Moreno-Solis G, Torres-Borrego J, de la Torre-Aguilar MJ, Fernandez-Gutierrez F, Llorente-Cantarero FJ, Perez-Navero JL. Analysis of the local and systemic inflammatory response in hospitalized infants with respiratory syncytial virus bronchiolitis. Allergol Immunopathol (Madr) 2015;43(3):264–271. doi: 10.1016/j.aller.2014.02.002.
    1. Palivizumab A. Humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics. 1998;102(3):531–537. doi: 10.1542/peds.102.3.531.
    1. Haynes LM. Progress and challenges in RSV prophylaxis and vaccine development. J Infect Dis. 2013;208(Suppl 3):S177–S183. doi: 10.1093/infdis/jit512.
    1. Duncan CJA, Randall RE, Hambleton S. Genetic lesions of type I interferon signalling in human antiviral immunity. Trends Genet. 2021;37(1):46–58. doi: 10.1016/j.tig.2020.08.017.
    1. Carvajal JJ, Avellaneda AM, Salazar-Ardiles C, Maya JE, Kalergis AM, Lay MK. Host components contributing to respiratory syncytial virus pathogenesis. Front Immunol. 2019;10:2152. doi: 10.3389/fimmu.2019.02152.
    1. McNamara PS, Fonceca AM, Howarth D, Correia JB, Slupsky JR, Trinick RE, et al. Respiratory syncytial virus infection of airway epithelial cells, in vivo and in vitro, supports pulmonary antibody responses by inducing expression of the B cell differentiation factor BAFF. Thorax. 2013;68(1):76–81. doi: 10.1136/thoraxjnl-2012-202288.
    1. Moreno-Solis G, Dela Torre-Aguilar MJ, Torres-Borrego J, Llorente-Cantarero FJ, Fernandez-Gutierrez F, Gil-Campos M, et al. Oxidative stress and inflamatory plasma biomarkers in respiratory syncytial virus bronchiolitis. Clin Respir J. 2017;11(6):839–846. doi: 10.1111/crj.12425.
    1. Harada Y, Kinoshita F, Yoshida LM, le Minh N, Suzuki M, Morimoto K, et al. Does respiratory virus coinfection increases the clinical severity of acute respiratory infection among children infected with respiratory syncytial virus? Pediatr Infect Dis J. 2013;32(5):441–445. doi: 10.1097/INF.0b013e31828ba08c.
    1. Haid S, Grethe C, Bankwitz D, Grunwald T, Pietschmann T. Identification of a human respiratory syncytial virus cell entry inhibitor by using a novel lentiviral pseudotype system. J Virol. 2015;90(6):3065–3073. doi: 10.1128/JVI.03074-15.
    1. Blockus S, Sake SM, Wetzke M, Grethe C, Graalmann T, Pils M, et al. Labyrinthopeptins as virolytic inhibitors of respiratory syncytial virus cell entry. Antiviral Res. 2020;177:104774. doi: 10.1016/j.antiviral.2020.104774.

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