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      Antiviral therapy for respiratory tract infections

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          Abstract:

          Viruses are important pathogens causing respiratory tract infections both in the community and health‐care facility settings. They are extremely common causes of morbidity in the competent hosts and some are associated with significant mortality in the compromised individuals. With wider application of molecular techniques, novel viruses are being described and old viruses are found to have new significance in different epidemiological and clinical settings. Some of these emerging pathogens may have the potential to cause pandemics or global spread of a severe disease, as exemplified by severe acute respiratory syndrome and avian influenza. Antiviral therapy of viral respiratory infections is often unnecessary in the competent hosts because most of them are self‐limiting and effective agents are not always available. In the immunocompromised individuals or for infections caused by highly pathogenic viruses, such as avian influenza viruses (AIV), antiviral treatment is highly desirable, despite the fact that many of the agents may not have undergone stringent clinical trials. In immunocompetent hosts, antiviral therapy can be stopped early because adaptive immune response can usually be mounted within 5–14 days. However, the duration of antiviral therapy in immunosuppressed hosts depends on clinical and radiological resolution, the degree and duration of immunosuppression, and therefore maintenance therapy is sometimes needed after the initial response. Immunotherapy and immunoprophylaxis appear to be promising directions for future research. Appropriate and targeted immunomodulation may play an important adjunctive role in some of these infections by limiting the extent of end‐organ damage and multi‐organ failure in some fulminant infections.

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          Most cited references287

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          Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats.

          Although the finding of severe acute respiratory syndrome coronavirus (SARS-CoV) in caged palm civets from live animal markets in China has provided evidence for interspecies transmission in the genesis of the SARS epidemic, subsequent studies suggested that the civet may have served only as an amplification host for SARS-CoV. In a surveillance study for CoV in noncaged animals from the wild areas of the Hong Kong Special Administration Region, we identified a CoV closely related to SARS-CoV (bat-SARS-CoV) from 23 (39%) of 59 anal swabs of wild Chinese horseshoe bats (Rhinolophus sinicus) by using RT-PCR. Sequencing and analysis of three bat-SARS-CoV genomes from samples collected at different dates showed that bat-SARS-CoV is closely related to SARS-CoV from humans and civets. Phylogenetic analysis showed that bat-SARS-CoV formed a distinct cluster with SARS-CoV as group 2b CoV, distantly related to known group 2 CoV. Most differences between the bat-SARS-CoV and SARS-CoV genomes were observed in the spike genes, ORF 3 and ORF 8, which are the regions where most variations also were observed between human and civet SARS-CoV genomes. In addition, the presence of a 29-bp insertion in ORF 8 of bat-SARS-CoV genome, not in most human SARS-CoV genomes, suggests that it has a common ancestor with civet SARS-CoV. Antibody against recombinant bat-SARS-CoV nucleocapsid protein was detected in 84% of Chinese horseshoe bats by using an enzyme immunoassay. Neutralizing antibody to human SARS-CoV also was detected in bats with lower viral loads. Precautions should be exercised in the handling of these animals.
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            A newly discovered human pneumovirus isolated from young children with respiratory tract disease

            From 28 young children in the Netherlands, we isolated a paramyxovirus that was identified as a tentative new member of the Metapneumovirus genus based on virological data, sequence homology and gene constellation. Previously, avian pneumovirus was the sole member of this recently assigned genus, hence the provisional name for the newly discovered virus: human metapneumovirus. The clinical symptoms of the children from whom the virus was isolated were similar to those caused by human respiratory syncytial virus infection, ranging from upper respiratory tract disease to severe bronchiolitis and pneumonia. Serological studies showed that by the age of five years, virtually all children in the Netherlands have been exposed to human metapneumovirus and that the virus has been circulating in humans for at least 50 years.
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              Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia.

              Despite extensive laboratory investigations in patients with respiratory tract infections, no microbiological cause can be identified in a significant proportion of patients. In the past 3 years, several novel respiratory viruses, including human metapneumovirus, severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), and human coronavirus NL63, were discovered. Here we report the discovery of another novel coronavirus, coronavirus HKU1 (CoV-HKU1), from a 71-year-old man with pneumonia who had just returned from Shenzhen, China. Quantitative reverse transcription-PCR showed that the amount of CoV-HKU1 RNA was 8.5 to 9.6 x 10(6) copies per ml in his nasopharyngeal aspirates (NPAs) during the first week of the illness and dropped progressively to undetectable levels in subsequent weeks. He developed increasing serum levels of specific antibodies against the recombinant nucleocapsid protein of CoV-HKU1, with immunoglobulin M (IgM) titers of 1:20, 1:40, and 1:80 and IgG titers of <1:1,000, 1:2,000, and 1:8,000 in the first, second and fourth weeks of the illness, respectively. Isolation of the virus by using various cell lines, mixed neuron-glia culture, and intracerebral inoculation of suckling mice was unsuccessful. The complete genome sequence of CoV-HKU1 is a 29,926-nucleotide, polyadenylated RNA, with G+C content of 32%, the lowest among all known coronaviruses with available genome sequence. Phylogenetic analysis reveals that CoV-HKU1 is a new group 2 coronavirus. Screening of 400 NPAs, negative for SARS-CoV, from patients with respiratory illness during the SARS period identified the presence of CoV-HKU1 RNA in an additional specimen, with a viral load of 1.13 x 10(6) copies per ml, from a 35-year-old woman with pneumonia. Our data support the existence of a novel group 2 coronavirus associated with pneumonia in humans.
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                Author and article information

                Journal
                Respirology
                Respirology
                10.1111/(ISSN)1440-1843
                RESP
                Respirology (Carlton, Vic.)
                Blackwell Publishing Asia (Melbourne, Australia )
                1323-7799
                1440-1843
                26 September 2008
                November 2008
                : 13
                : 7 ( doiID: 10.1111/res.2008.13.issue-7 )
                : 950-971
                Affiliations
                [ 1 ]Department of Microbiology, Research Centre of Infection and Immunology, The University of Hong Kong, Queen Mary Hospital, Hong Kong
                Author notes
                [*]Kwok‐Yung Yuen, Department of Microbiology, The University of Hong Kong, University Pathology Building, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong. Email: kyyuen@ 123456hkucc.hku.hk
                Article
                RESP1404
                10.1111/j.1440-1843.2008.01404.x
                7192202
                18922142
                543651c2-82e3-4b92-a13c-d8f2d58d6da4
                © 2008 The Authors. Journal compilation © 2008 Asian Pacific Society of Respirology

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                : 28 May 2008
                : 10 July 2008
                : 4 August 2008
                Page count
                links-crossref: 0, links-pubmed: 0, Figures: 0, Tables: 3, Equations: 0, References: 337, Pages: 22, Words: 21753
                Categories
                Invited Review Series: Infectious Diseases
                Custom metadata
                2.0
                November 2008
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.0 mode:remove_FC converted:15.04.2020

                Respiratory medicine
                antiviral,nosocomial,respiratory tract infection,virus
                Respiratory medicine
                antiviral, nosocomial, respiratory tract infection, virus

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