{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T12:26:28Z","timestamp":1762431988702,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,15]],"date-time":"2021-02-15T00:00:00Z","timestamp":1613347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The incidence of neutropenia and the association between neutropenia and severity of respiratory symptoms among infants with respiratory syncytial virus (RSV) infections remain to be elucidated. This single-center, retrospective study included immunocompetent infants (&lt;10 months old) with laboratory-confirmed RSV infection admitted to our center between January 2012 and December 2019. Incidence of neutropenia (&lt;1.0 \u00d7 109\/L) within 10 days of onset and risk factors associated with subsequent neutropenia were evaluated. Among the 292 infants with RSV infection, including 232 (79%) with mild infection, neutropenia was observed in 31 (11%), with severe neutropenia (&lt;0.5 \u00d7 109\/L) in 3 (1.0%). No neutropenic infants developed serious infection or hematological disorder. Infants without neutropenia showed age &lt;3 months at onset in 34%, C-reactive protein level &lt;1.0 mg\/L in 27%, and nasopharyngeal microbiota composition with any of Moraxella catarrhalis, Streptococcus pneumoniae, or Haemophilus influenzae in 63%. In comparison, infants with neutropenia showed age &lt;3 months at onset in 74% (relative risk [RR] 2.15; 95% confidence interval [CI] 1.65\u20132.81), C-reactive protein level &lt;1.0 mg\/L in 55% (RR 2.02; 95% CI 1.38\u20132.94), and microbiota including Moraxella catarrhalis, Streptococcus pneumoniae, or Haemophilus influenzae in 15% (RR 0.24; 95% CI 0.10\u20130.61). Multiple logistic regression analyses showed that younger age at onset and absence of that nasopharyngeal microbiota profile were associated with development of neutropenia. In conclusion, age and airway microbiota are considered as risk factors for the development of transient neutropenia among infants with RSV infection. However, the neutropenia seems not to develop serious infection or hematological disorder.<\/jats:p>","DOI":"10.3390\/v13020301","type":"journal-article","created":{"date-parts":[[2021,2,15]],"date-time":"2021-02-15T05:52:49Z","timestamp":1613368369000},"page":"301","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Transient Neutropenia in Immunocompetent Infants with Respiratory Syncytial Virus Infection"],"prefix":"10.3390","volume":"13","author":[{"given":"Tatsuya","family":"Korematsu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, National Hospital Organization Beppu Medical Center, 1473 Oaza-Uchikamado, Beppu, Oita 874-0011, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9583-9842","authenticated-orcid":false,"given":"Hiroshi","family":"Koga","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, National Hospital Organization Beppu Medical Center, 1473 Oaza-Uchikamado, Beppu, Oita 874-0011, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1128\/CMR.00010-16","article-title":"Respiratory Syncytial Virus: Infection, Detection, and New Options for Prevention and Treatment","volume":"30","author":"Griffiths","year":"2017","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1016\/S0140-6736(17)30938-8","article-title":"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","volume":"390","author":"Shi","year":"2017","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s00431-018-03310-7","article-title":"New therapies for acute RSV infections: Where are we?","volume":"178","author":"Xing","year":"2019","journal-title":"Eur. J. Pediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1056\/NEJMoa1413275","article-title":"Activity of Oral ALS-008176 in a Respiratory Syncytial Virus Challenge Study","volume":"373","author":"DeVincenzo","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_5","unstructured":"ClinicalTrials.gov (2020, July 07). A Study to Evaluate the Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of Orally Administered Lumicitabine (JNJ-64041575) Regimens in Hospitalized Infants and Children Aged 28 Days to 36 Months Infected with Respiratory Syncytial Virus, Available online: https:\/\/ClinicalTrials.gov\/show\/NCT03333317."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1007\/s00431-013-1965-z","article-title":"Transient neutropenia in children with febrile illness and associated infectious agents: 2 years\u2019 follow-up","volume":"172","author":"Alexandropoulou","year":"2013","journal-title":"Eur. J. Pediatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1007\/s10096-016-2708-7","article-title":"Outcomes and infectious etiologies of febrile neutropenia in non-immunocompromised children who present in an emergency department","volume":"35","author":"Pascual","year":"2016","journal-title":"Eur. J. Clin. Microbiol. Infect Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1542\/pir.29-1-12","article-title":"Neutropenia in pediatric practice","volume":"29","author":"Segel","year":"2008","journal-title":"Pediatr. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/S0140-6736(07)61602-X","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies","volume":"370","author":"Altman","year":"2007","journal-title":"Lancet"},{"key":"ref_10","first-page":"750","article-title":"Development of a Global Respiratory Severity Score for Respiratory Syncytial Virus Infection in Infants","volume":"215","author":"Caserta","year":"2017","journal-title":"J. Infect Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1164\/rccm.201903-0588OC","article-title":"Respiratory Syncytial Virus Disease Severity Is Associated with Distinct CD8(+) T-Cell Profiles","volume":"201","author":"Siefker","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_12","unstructured":"World Health Organization (2020, July 07). WHO Global Database on Child Growth and Malnutrition. The WHO Anthro Survey Analyser. Available online: https:\/\/www.who.int\/nutgrowthdb\/software\/en\/."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1097\/01.PCC.0000149131.72248.E6","article-title":"International pediatric sepsis consensus conference: Definitions for sepsis and organ dysfunction in pediatrics","volume":"6","author":"Goldstein","year":"2005","journal-title":"Pediatr. Crit. Care Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1093\/infdis\/jiy741","article-title":"Haemophilus-Dominant Nasopharyngeal Microbiota Is Associated with Delayed Clearance of Respiratory Syncytial Virus in Infants Hospitalized for Bronchiolitis","volume":"219","author":"Mansbach","year":"2019","journal-title":"J. Infect Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"486","DOI":"10.7326\/0003-4819-146-7-200704030-00004","article-title":"Prevalence of neutropenia in the U.S. population: Age, sex, smoking status, and ethnic differences","volume":"146","author":"Hsieh","year":"2007","journal-title":"Ann. Intern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.jpeds.2018.07.073","article-title":"Risk of Bacterial Coinfections in Febrile Infants 60 Days Old and Younger with Documented Viral Infections","volume":"203","author":"Mahajan","year":"2018","journal-title":"J. Pediatr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1542\/peds.113.6.1662","article-title":"Serious bacterial infections in febrile infants 1 to 90 days old with and without viral infections","volume":"113","author":"Byington","year":"2004","journal-title":"Pediatrics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e347","DOI":"10.1097\/MPH.0000000000000345","article-title":"The Risk of Serious Bacterial Infection in Neutropenic Immunocompetent Febrile Children","volume":"37","author":"Barg","year":"2015","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1542\/peds.112.2.282","article-title":"Prevalence of serious bacterial infections in febrile infants with respiratory syncytial virus infection","volume":"112","author":"Titus","year":"2003","journal-title":"Pediatrics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1542\/peds.113.6.1728","article-title":"Risk of serious bacterial infection in young febrile infants with respiratory syncytial virus infections","volume":"113","author":"Levine","year":"2004","journal-title":"Pediatrics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1111\/j.1651-2227.2006.tb02285.x","article-title":"Transient and chronic neutropenias detected in children with different viral and bacterial infections","volume":"95","author":"Karavanaki","year":"2006","journal-title":"Acta Paediatr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S407","DOI":"10.1093\/ofid\/ofy210.1167","article-title":"1335. Safety and Pharmacokinetic Profile of PC786, a Novel Inhibitor of Respiratory Syncytial Virus L-protein Polymerase, in a Single and Multiple-Ascending Dose Study in Healthy Volunteer and Mild Asthmatics","volume":"5","author":"Cass","year":"2018","journal-title":"Open Forum Infect Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S995","DOI":"10.1093\/ofid\/ofz415.2489","article-title":"LB6. EDP-938, a Novel RSV N-Inhibitor, Administered Once or Twice Daily Was Safe and Demonstrated Robust Antiviral and Clinical Efficacy in a Healthy Volunteer Challenge Study","volume":"6","author":"Coakley","year":"2019","journal-title":"Open Forum Infect Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1164\/rccm.201602-0220OC","article-title":"Nasopharyngeal Microbiota, Host Transcriptome, and Disease Severity in Children with Respiratory Syncytial Virus Infection","volume":"194","author":"Heinonen","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1183\/13993003.00152-2016","article-title":"Association of nasopharyngeal microbiota profiles with bronchiolitis severity in infants hospitalised for bronchiolitis","volume":"48","author":"Hasegawa","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1164\/rccm.201207-1297OC","article-title":"Pathogenic bacteria colonizing the airways in asymptomatic neonates stimulates topical inflammatory mediator release","volume":"187","author":"Folsgaard","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/pai.13183","article-title":"Airway microbiome, host immune response and recurrent wheezing in infants with severe respiratory syncytial virus bronchiolitis","volume":"31","author":"Zhang","year":"2020","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/S0022-3476(98)70234-3","article-title":"Respiratory syncytial virus RNA in cells from the peripheral blood during acute infection","volume":"133","author":"McGarvey","year":"1998","journal-title":"J. Pediatr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1165\/rcmb.2010-0121OC","article-title":"Respiratory syncytial virus infection in human bone marrow stromal cells","volume":"45","author":"Rezaee","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1086\/515575","article-title":"Immunopathogenesis of respiratory syncytial virus bronchiolitis","volume":"195","author":"Bennett","year":"2007","journal-title":"J. Infect Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1128\/CMR.00090-16","article-title":"The Human Immune Response to Respiratory Syncytial Virus Infection","volume":"30","author":"Russell","year":"2017","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/S0022-3476(05)82443-6","article-title":"Variation in severity of respiratory syncytial virus infections with subtype","volume":"117","author":"McConnochie","year":"1990","journal-title":"J. Pediatr."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/2\/301\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:24:22Z","timestamp":1760160262000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/2\/301"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,15]]},"references-count":32,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["v13020301"],"URL":"https:\/\/doi.org\/10.3390\/v13020301","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2021,2,15]]}}}