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Burden of noninfluenza respiratory viral infections in adults admitted to hospital: analysis of a multiyear Canadian surveillance cohort from 2 centres
Authors:Nelson Lee  Stephanie Smith  Nathan Zelyas  Scott Klarenbach  Lori Zapernick  Christian Bekking  Helen So  Lily Yip  Graham Tipples  Geoff Taylor  Samira Mubareka
Affiliation:Division of Infectious Disease (Lee, Smith, Zapernick, Taylor), Department of Medicine, and Department of Laboratory Medicine and Pathology (Zelyas, Tipples), and Division of Nephrology (Klarenbach, So), Department of Medicine, University of Alberta, Edmonton, Alta.; Sunnybrook Research Institute (Bekking, Yip, Mubareka); Department of Laboratory Medicine and Pathobiology (Mubareka), University of Toronto, Toronto, Ont.
Abstract:BACKGROUND:Data on the outcomes of noninfluenza respiratory virus (NIRV) infections among hospitalized adults are lacking. We aimed to study the burden, severity and outcomes of NIRV infections in this population.METHODS:We analyzed pooled patient data from 2 hospital-based respiratory virus surveillance cohorts in 2 regions of Canada during 3 consecutive seasons (2015/16, 2016/17, 2017/18; n = 2119). We included patients aged ≥ 18 years who developed influenza-like illness or pneumonia and were hospitalized for management. We included patients confirmed positive for ≥ 1 virus by multiplex polymerase chain reaction assays (respiratory syncytial virus [RSV], human rhinovirus/enterovirus (hRV), human coronavirus (hCoV), metapneumovirus, parainfluenza virus, adenovirus, influenza viruses). We compared patient characteristics, clinical severity conventional outcomes (e.g., hospital length-of stay, 30-day mortality) and ordinal outcomes (5 levels: discharged, receiving convalescent care, acute ward or intensive care unit [ICU] care and death) for patients with NIRV infections and those with influenza.RESULTS:Among 2119 adults who were admitted to hospital, 1156 patients (54.6%) had NIRV infections (hRV 14.9%, RSV 12.9%, hCoV 8.2%) and 963 patients (45.4%) had influenza (n = 963). Patients with NIRVs were younger (mean 66.4 [standard deviation 20.4] yr), and more commonly had immunocompromising conditions (30.3%) and delay in diagnosis (median 4.0 [interquartile range (IQR) 2.0–7.0] days). Overall, 14.6% (12.4%–19.5%) of NIRV infections were acquired in hospital. Admission to ICU (18.2%, median 6.0 [IQR 3.0–13.0] d), hospital length-of-stay (median 5.0 [IQR 2.0–10.0] d) and 30-day mortality (8.4%; RSV 9.5%, hRV 6.6%, hCoV 9.2%) and the ordinal outcomes were similar for patients with NIRV infection and those with influenza. Age > 60 years, immunocompromised state and hospital-acquired viral infection were associated with worse outcomes. The estimated median cost per acute care admission was $6000 (IQR $2000–$16 000).INTERPRETATION:The burden of NIRV infection is substantial in adults admitted to hospital and associated outcomes may be as severe as for influenza, suggesting a need to prioritize therapeutics and vaccines for at-risk people.

The global burden of lower respiratory tract infections is substantial, leading to many hospital admissions and deaths, especially among young children and older adults.1 Respiratory viruses are responsible for almost half of such infections in adults that require in-hospital management; previous studies estimate that 28%–62% are caused by noninfluenza respiratory viruses (NIRVs).24 With some geographical and seasonal variations, respiratory syncytial virus (RSV), human rhinovirus (hRV) and human coronavirus (hCoV) are among the most frequently identified NIRV infections.17 Most infected adults develop mild, self-limiting illnesses, but increasing evidence suggest that NIRVs, either alone or with coinfecting bacteria, can result in severe pneumonia and death.8,9 For instance, RSV has been shown to cause severe respiratory failure, with fatality rates comparable to or exceeding those observed among adults admitted to hospital with influenza.1012 Data on hRV, hCoV and other NIRVs are more limited, owing to the lack of accurate diagnostics and systematic case-finding approaches.79 However, with the increasing availability of multiplex polymerase chain reaction (PCR) assays that can simultaneously detect influenza and NIRVs, these infections are now readily diagnosed as part of a syndromic approach in patients who present with acute respiratory illnesses.25,13,14 The burden, clinical significance and impacts of NIRVs on the health care system remain inadequately characterized.To address this gap, we analyzed the relative frequencies, patient characteristics, location of acquisition (community or hospital), severity and clinical outcomes of patients with NIRV and influenza infections diagnosed by multiplex PCR in a cohort of adults admitted to hospital in 2 large Canadian health care centres during a 3-year surveillance period. The associated health care resource use was also estimated.
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