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      Human rhinovirus C: Age, season, and lower respiratory illness over the past 3 decades

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          Abstract

          Background

          Human rhinoviruses (HRVs) cause common colds, and the recently discovered HRV-C is increasingly associated with lower respiratory illness among populations such as children and asthmatic patients.

          Objective

          To determine how HRV-C is associated with respiratory illness and to evaluate changes in prevalence and species over 2 decades.

          Methods

          A prospective study of children younger than 5 years was performed at the Vanderbilt Vaccine Clinic over a 21-year period. Nasal-wash specimens from children presenting with upper or lower respiratory illness at acute care visits were tested for HRV and HRV-positives genotyped. Demographic and clinical features were compared between children with or without HRV, and with different HRV species.

          Results

          HRV was detected in 190 of 527 (36%) specimens from a population of 2009 children from 1982 through 2003. Of these, 36% were HRV-C. Age ( P = .039) and month of illness ( P < .001) were associated with HRV infection and HRV species. HRV-C was significantly associated with lower respiratory illness, compared with HRV-A ( P = .014). HRV-A and HRV-C prevalence fluctuated throughout the 21-year period; HRV-C was more prevalent during winter ( P = .058).

          Conclusions

          HRV-C is not a new virus but has been significantly associated with childhood lower respiratory illness in this population for several decades. Temporal changes in virus prevalence occur, and season may predict virus species. Our findings have implications for diagnostic, preventive, and treatment strategies due to the variation in disease season and severity based on species of HRV infection.

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          Most cited references38

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          Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children.

          We sought to determine the role of human metapneumovirus in lower respiratory tract illness in previously healthy infants and children. We tested nasal-wash specimens, obtained over a 25-year period from otherwise healthy children presenting with acute respiratory tract illness, for human metapneumovirus. A viral cause other than human metapneumovirus was determined for 279 of 687 visits for acute lower respiratory tract illness (41 percent) by 463 children in a population of 2009 infants and children prospectively seen from 1976 to 2001. There were 408 visits for lower respiratory tract illness by 321 children for which no cause was identified. Of these 321 children, specimens from 248 were available. Forty-nine of these 248 specimens (20 percent) contained human metapneumovirus RNA or viable virus. Thus, 20 percent of all previously virus-negative lower respiratory tract illnesses were attributable to human metapneumovirus, which means that 12 percent of all lower respiratory tract illnesses in this cohort were most likely due to this virus. The mean age of human metapneumovirus-infected children was 11.6 months, the male:female ratio was 1.8:1, 78 percent of illnesses occurred between December and April, and the hospitalization rate was 2 percent. The virus was associated with bronchiolitis in 59 percent of cases, pneumonia in 8 percent, croup in 18 percent, and an exacerbation of asthma in 14 percent. We also detected human metapneumovirus in 15 percent of samples from 261 patients with upper respiratory tract infection but in only 1 of 86 samples from asymptomatic children. Human metapneumovirus infection is a leading cause of respiratory tract infection in the first years of life, with a spectrum of disease similar to that of respiratory syncytial virus. Copyright 2004 Massachusetts Medical Society
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            Rhinovirus illnesses during infancy predict subsequent childhood wheezing.

            The contribution of viral respiratory infections during infancy to the development of subsequent wheezing and/or allergic diseases in early childhood is not established. To evaluate these relationships prospectively from birth to 3 years of age in 285 children genetically at high risk for developing allergic respiratory diseases. By using nasal lavage, the relationship of timing, severity, and etiology of viral respiratory infections during infancy to wheezing in the 3rd year of life was evaluated. In addition, genetic and environmental factors that could modify risk of infections and wheezing prevalence were analyzed. Risk factors for 3rd year wheezing were passive smoke exposure (odds ratio [OR]=2.1), older siblings (OR=2.5), allergic sensitization to foods at age 1 year (OR=2.0), any moderate to severe respiratory illness without wheezing during infancy (OR=3.6), and at least 1 wheezing illness with respiratory syncytial virus (RSV; OR=3.0), rhinovirus (OR=10) and/or non-rhinovirus/RSV pathogens (OR=3.9) during infancy. When viral etiology was considered, 1st-year wheezing illnesses caused by rhinovirus infection were the strongest predictor of subsequent 3rd year wheezing (OR=6.6; P < .0001). Moreover, 63% of infants who wheezed during rhinovirus seasons continued to wheeze in the 3rd year of life, compared with only 20% of all other infants (OR=6.6; P < .0001). In this population of children at increased risk of developing allergies and asthma, the most significant risk factor for the development of preschool childhood wheezing is the occurrence of symptomatic rhinovirus illnesses during infancy that are clinically and prognostically informative based on their seasonal nature.
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              Clinical features and complete genome characterization of a distinct human rhinovirus (HRV) genetic cluster, probably representing a previously undetected HRV species, HRV-C, associated with acute respiratory illness in children.

              Although human rhinoviruses (HRVs) are common causes of respiratory illness, their molecular epidemiology has been poorly investigated. Despite the recent findings of new HRV genotypes, their clinical disease spectrum and phylogenetic positions were not fully understood. In this study, 203 prospectively collected nasopharyngeal aspirates (NPAs), negative for common respiratory viruses (83 were human bocavirus [HBoV] positive and 120 HBoV negative), from hospitalized children during a 1-year period were subjected to reverse transcription-PCR for HRV. HRV was detected in 14 NPAs positive and 12 NPAs negative for HBoV. Upon VP4 gene analysis, 5 of these 26 HRV strains were found to belong to HRV-A while 21 belonged to a genetic clade probably representing a previously undetected HRV species, HRV-C, that is phylogenetically distinct from the two known HRV species, HRV-A and HRV-B. The VP4 sequences of these HRV-C strains were closely related to the newly identified HRV strains from the United States and Australia. Febrile wheeze or asthma was the most common presentation (76%) of HRV-C infection, which peaked in fall and winter. Complete genome sequencing of three HRV-C strains revealed that HRV-C represents an additional HRV species, with features distinct from HRV-A and HRV-B. Analysis of VP1 of HRV-C revealed major deletions in regions important for neutralization in other HRVs, which may be signs of a distinct species, while within-clade amino acid variation in potentially antigenic regions may indicate the existence of different serotypes among HRV-C strains. A newly identified HRV species, HRV-C, is circulating worldwide and is an important cause of febrile wheeze and asthmatic exacerbations in children requiring hospitalization.
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                Author and article information

                Contributors
                Journal
                J Allergy Clin Immunol
                J. Allergy Clin. Immunol
                The Journal of Allergy and Clinical Immunology
                American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc.
                0091-6749
                1097-6825
                10 November 2012
                January 2013
                10 November 2012
                : 131
                : 1
                : 69-77.e6
                Affiliations
                [a ]Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tenn
                [b ]Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tenn
                [c ]Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tenn
                [d ]Division of Infectious Disease and International Health, Geisel School of Medicine at Dartmouth, Hanover, NH
                Author notes
                []Corresponding author: E. Kathryn Miller, MD, MPH, Department of Pediatrics, 1161 21st Ave South, D7201 Medical Center North, Vanderbilt University, Nashville, TN 37232. eva.k.miller@ 123456vanderbilt.edu
                [∗]

                These authors contributed equally to this work.

                Article
                S0091-6749(12)01611-9
                10.1016/j.jaci.2012.09.033
                3748586
                23146382
                b9f4d44a-f29e-4179-a016-db3e41879bb9
                Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 23 July 2012
                : 10 September 2012
                : 11 September 2012
                Categories
                Article

                Immunology
                rhinovirus,hrv-c,children,season,lower respiratory illness,hmpv, human metapneumovirus,hrv, human rhinovirus,lri, lower respiratory illness,piv, parainfluenza virus,rsv, respiratory syncytial virus,uri, upper respiratory illness,vvc, vanderbilt vaccine clinic

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