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      Unexpectedly Higher Morbidity and Mortality of Hospitalized Elderly Patients Associated with Rhinovirus Compared with Influenza Virus Respiratory Tract Infection

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          Abstract

          Rhinovirus is a common cause of upper and lower respiratory tract infections in adults, especially among the elderly and immunocompromised. Nevertheless, its clinical characteristics and mortality risks have not been well described. A retrospective analysis on a prospective cohort was conducted in a single teaching hospital center over a one-year period. We compared adult patients hospitalized for pneumonia caused by rhinovirus infection with those hospitalized for influenza infection during the same period. All recruited patients were followed up for at least 3 months up to 15 months. Independent risk factors associated with mortality for rhinovirus infection were identified. Between 1 March 2014 and 28 February 2015, a total of 1946 patients were consecutively included for analysis. Of these, 728 patients were hospitalized for rhinovirus infection and 1218 patients were hospitalized for influenza infection. Significantly more rhinovirus patients were elderly home residents and had chronic lung diseases ( p < 0.001), whereas more influenza patients had previous stroke ( p = 0.02); otherwise, there were no differences in the Charlson comorbidity indexes between the two groups. More patients in the rhinovirus group developed pneumonia complications ( p = 0.03), required oxygen therapy, and had a longer hospitalization period ( p < 0.001), whereas more patients in the influenza virus group presented with fever ( p < 0.001) and upper respiratory tract symptoms of cough and sore throat ( p < 0.001), and developed cardiovascular complications ( p < 0.001). The 30-day ( p < 0.05), 90-day ( p < 0.01), and 1-year ( p < 0.01) mortality rate was significantly higher in the rhinovirus group than the influenza virus group. Intensive care unit admission (odds ratio (OR): 9.56; 95% confidence interval (C.I.) 2.17–42.18), elderly home residents (OR: 2.60; 95% C.I. 1.56–4.33), requirement of oxygen therapy during hospitalization (OR: 2.62; 95% C.I. 1.62–4.24), and hemoglobin level <13.3 g/dL upon admission (OR: 2.43; 95% C.I. 1.16–5.12) were independent risk factors associated with 1-year mortality in patients hospitalized for rhinovirus infection. Rhinovirus infection in the adults was associated with significantly higher mortality and longer hospitalization when compared with influenza virus infection. Institutionalized older adults were particularly at risk. More stringent infection control among health care workers in elderly homes could lower the infection rate before an effective vaccine and antiviral become available.

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          Most cited references 30

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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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            Rhinovirus transmission within families with children: incidence of symptomatic and asymptomatic infections.

            Rhinoviruses are the most common cause of respiratory tract infections, but the transmission in families has not been studied using sensitive and specific molecular detection methods. Children hospitalized for any infection were screened for rhinoviruses. Eight families with a rhinovirus-positive index child and 16 families with a rhinovirus-negative index child were monitored for 3 weeks for disease symptoms, and the presence and quantity of rhinoviruses in nasal swab samples were determined by quantitative reverse transcription-polymerase chain reaction. Rhinoviruses were further identified by melting temperature and partial sequence analysis. The rates of rhinovirus infection were 1.00 cases per person among the 17 siblings and 0.50 cases per person among the 14 parents of rhinovirus-positive index patients; the rates were 0.54 cases per person among the 24 siblings and 0.23 cases per person among the 30 parents of rhinovirus-negative index patients. Symptomatic infections were associated with an age of <7 years but not with a high copy number of rhinovirus genomes. Virus typing revealed the transmission routes of the viruses and showed that several virus types could circulate in the families simultaneously. Rhinoviruses are frequently transmitted from children to other family members. Most rhinovirus infections in young children are symptomatic, but secondary infections in adults are often asymptomatic. Multiple virus types circulate simultaneously in families.
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              Toll-like receptor 3 is induced by and mediates antiviral activity against rhinovirus infection of human bronchial epithelial cells.

              Rhinoviruses (RV) are the major cause of the common cold and acute exacerbations of asthma and chronic obstructive pulmonary disease. Toll-like receptors (TLRs) are a conserved family of receptors that recognize and respond to a variety of pathogen-associated molecular patterns. TLR3 recognizes double-stranded RNA, an important intermediate of many viral life cycles (including RV). The importance of TLR3 in host responses to virus infection is not known. Using BEAS-2B (a human bronchial epithelial cell-line), we demonstrated that RV replication increased the expression of TLR3 mRNA and TLR3 protein on the cell surface. We observed that blocking TLR3 led to a decrease in interleukin-6, CXCL8, and CCL5 in response to poly(IC) but an increase following RV infection. Finally, we demonstrated that TLR3 mediated the antiviral response. This study demonstrates an important functional requirement for TLR3 in the host response against live virus infection and indicates that poly(IC) is not always a good model for studying the biology of live virus infection.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                26 January 2017
                February 2017
                : 18
                : 2
                Affiliations
                [1 ]State Key Laboratory for Emerging Infectious Diseases, Carol Yu’s Centre for Infection and Division of Infectious Diseases, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China; zhangajx@ 123456hku.hk (A.J.Z.); kelvinto@ 123456hku.hk (K.K.W.T.); jaspchan@ 123456gmail.com (J.F.W.C.); houshunzhu@ 123456gmail.com (S.H.S.Z.); rickychang87@ 123456gmail.com (R.Z.); chankh2@ 123456hku.hk (K.-H.C.); kyyuen@ 123456hku.hk (K.-Y.Y.)
                [2 ]Department of Medicine, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Pokfulam, Hong Kong SAR, China; tuenching@ 123456yahoo.com.hk
                Author notes
                [* ]Correspondence: ivanhung@ 123456hku.hk or ivanfn@ 123456gmail.com ; Tel.: +852-2255-4049; Fax: +852-2818-6474
                Article
                ijms-18-00259
                10.3390/ijms18020259
                5343795
                28134768
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                Categories
                Article

                Molecular biology

                tract, respiratory, mortality, elderly, hospitalized, influenza, rhinovirus

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