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      Respiratory virus infection among hospitalized adult patients with or without clinically apparent respiratory infection: a prospective cohort study

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          Abstract

          Objectives

          To determine the viral epidemiology and clinical characteristics of patients with and without clinically apparent respiratory tract infection.

          Methods

          This prospective cohort study was conducted during the 2018 winter influenza season. Adult patients with fever/respiratory symptoms (fever/RS group) were age- and sex-matched with patients without fever/RS (non-fever/RS group) in a 1:1 ratio. Respiratory viruses were tested using NxTAG™ Respiratory Pathogen Panel IVD, a commercially-available multiplex PCR panel.

          Results

          A total of 214 acutely hospitalized patients were included in the final analysis, consisting of 107 with fever/RS (fever/RS group), and 107 age- and sex-matched patients without fever/RS (non-fever/RS group). Respiratory viruses were detected in 34.1% (73/214) of patients, and co-infection occurred in 7.9% (17/214) of patients. The incidence of respiratory virus was higher in the fever/RS group than in the non-fever/RS group (44.9% (48/107) versus 23.4% (25/107), p 0.001). Influenza B virus, enterovirus/rhinovirus and coronaviruses were detected more frequently in the fever/RS group, whereas parainfluenza virus 4B and adenovirus were detected more frequently in the non-fever/RS group. Among the non-fever/RS group, chest discomfort was more common among patients tested positive for respiratory viruses than those without respiratory virus detected (44% (11/25) versus 22% (18/82), p 0.04).

          Conclusions

          Respiratory viruses can be frequently detected among hospitalized patients without typical features of respiratory tract infection. These patients may be a source of nosocomial outbreaks.

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          Most cited references20

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          Delayed Clearance of Viral Load and Marked Cytokine Activation in Severe Cases of Pandemic H1N1 2009 Influenza Virus Infection

          Abstract Background. Infections caused by the pandemic H1N1 2009 influenza virus range from mild upper respiratory tract syndromes to fatal diseases. However, studies comparing virological and immunological profile of different clinical severity are lacking. Methods. We conducted a retrospective cohort study of 74 patients with pandemic H1N1 infection, including 23 patients who either developed acute respiratory distress syndrome (ARDS) or died (ARDS-death group), 14 patients with desaturation requiring oxygen supplementation and who survived without ARDS (survived-without-ARDS group), and 37 patients with mild disease without desaturation (mild-disease group). We compared their pattern of clinical disease, viral load, and immunological profile. Results. Patients with severe disease were older, more likely to be obese or having underlying diseases, and had lower respiratory tract symptoms, especially dyspnea at presentation. The ARDS-death group had a slower decline in nasopharyngeal viral loads, had higher plasma levels of proinflammatory cytokines and chemokines, and were more likely to have bacterial coinfections (30.4%), myocarditis (21.7%), or viremia (13.0%) than patients in the survived-without-ARDS or the mild-disease groups. Reactive hemophagocytosis, thrombotic phenomena, lymphoid atrophy, diffuse alveolar damage, and multiorgan dysfunction similar to fatal avian influenza A H5N1 infection were found at postmortem examinations. Conclusions. The slower control of viral load and immunodysregulation in severe cases mandate the search for more effective antiviral and immunomodulatory regimens to stop the excessive cytokine activation resulting in ARDS and death.
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            Respiratory Viral Detection in Children and Adults: Comparing Asymptomatic Controls and Patients With Community-Acquired Pneumonia

            Abstract Background.  The clinical significance of viruses detected in patients with community-acquired pneumonia (CAP) is often unclear. Methods.  We conducted a prospective study to identify the prevalence of 13 viruses in the upper respiratory tract of patients with CAP and concurrently enrolled asymptomatic controls with real-time reverse-transcriptase polymerase chain reaction. We compared age-stratified prevalence of each virus between patients with CAP and controls and used multivariable logistic regression to calculate attributable fractions (AFs). Results.  We enrolled 1024 patients with CAP and 759 controls. Detections of influenza, respiratory syncytial virus, and human metapneumovirus were substantially more common in patients with CAP of all ages than in controls (AFs near 1.0). Parainfluenza and coronaviruses were also more common among patients with CAP (AF, 0.5–0.75). Rhinovirus was associated with CAP among adults (AF, 0.93) but not children (AF, 0.02). Adenovirus was associated with CAP only among children <2 years old (AF, 0.77). Conclusions.  The probability that a virus detected with real-time reverse-transcriptase polymerase chain reaction in patients with CAP contributed to symptomatic disease varied by age group and specific virus. Detections of influenza, respiratory syncytial virus, and human metapneumovirus among patients with CAP of all ages probably indicate an etiologic role, whereas detections of parainfluenza, coronaviruses, rhinovirus, and adenovirus, especially in children, require further scrutiny.
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              MERS coronavirus induces apoptosis in kidney and lung by upregulating Smad7 and FGF2

              Middle East respiratory syndrome coronavirus (MERS-CoV) causes sporadic zoonotic disease and healthcare-associated outbreaks in human. MERS is often complicated by acute respiratory distress syndrome (ARDS) and multi-organ failure 1,2 . The high incidence of renal failure in MERS is a unique clinical feature not often found in other human coronavirus infections 3,4 . Whether MERS-CoV infects the kidney and how it triggers renal failure are not understood 5,6 . Here, we demonstrated renal infection and apoptotic induction by MERS-CoV in human ex vivo organ culture and a nonhuman primate model. High-throughput analysis revealed that the cellular genes most significantly perturbed by MERS-CoV have previously been implicated in renal diseases. Furthermore, MERS-CoV induced apoptosis through upregulation of Smad7 and fibroblast growth factor 2 (FGF2) expression in both kidney and lung cells. Conversely, knockdown of Smad7 effectively inhibited MERS-CoV replication and protected cells from virus-induced cytopathic effects. We further demonstrated that hyperexpression of Smad7 or FGF2 induced a strong apoptotic response in kidney cells. Common marmosets infected by MERS-CoV developed ARDS and disseminated infection in kidneys and other organs. Smad7 and FGF2 expression were elevated in the lungs and kidneys of the infected animals. Our results provide insights into the pathogenesis of MERS-CoV and host targets for treatment. Supplementary information The online version of this article (doi:10.1038/nmicrobiol.2016.4) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                Journal
                Clin Microbiol Infect
                Clin. Microbiol. Infect
                Clinical Microbiology and Infection
                European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd.
                1198-743X
                1469-0691
                18 April 2019
                December 2019
                18 April 2019
                : 25
                : 12
                : 1539-1545
                Affiliations
                [1) ]Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China
                [2) ]Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
                [3) ]Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region, China
                [4) ]State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
                [5) ]Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, China
                [6) ]Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China
                [7) ]Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China
                Author notes
                []Corresponding author. K.-Y. Yuen, Department of Microbiology, 19th Floor, Block T, Queen Mary Hospital, Pokfulam Road, Pokfulam, Hong Kong. . kyyuen@ 123456hku.hk
                [†]

                K.K.W. To and K.-H. Chan contributed equally.

                Article
                S1198-743X(19)30183-1
                10.1016/j.cmi.2019.04.012
                7129190
                31004768
                43f2df3a-2e6a-4e18-8d3c-1a29f37a069e
                © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. 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
                : 3 January 2019
                : 5 April 2019
                : 10 April 2019
                Categories
                Article

                Microbiology & Virology
                adenovirus,cardiac complications,influenza,parainfluenza virus,respiratory tract infection

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