Burden of noninfluenza respiratory viral infections in adults admitted to hospital: analysis of a multiyear Canadian surveillance cohort from 2 centres.

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.

Evaluation of bioaerosol samplers for the detection and quantification of influenza virus from artificial aerosols and influenza virus-infected ferrets.

BACKGROUND: Bioaerosol sampling devices are necessary for the characterization of infectious bioaerosols emitted by naturally-infected hosts with acute respiratory virus infections. Assessment of these devices under multiple experimental conditions will provide insight for device use. OBJECTIVES: The primary objective of this study was to assess and compare bioaerosol sampling devices using a) an in vitro, environmentally-controlled artificial bioaerosol system at a range of different RH conditions and b) an in vivo bioaerosol system of influenza virus-infected ferrets under controlled environmental conditions. Secondarily, we also sought to examine the impact of NSAIDs on bioaerosol emission in influenza virus-infected ferrets to address its potential as a determinant of bioaerosol emission. METHODS: We examined the performance of low and moderate volume bioaerosol samplers for the collection of viral RNA and infectious influenza virus in vitroand in vivo using artificial bioaerosols and the ferret model of influenza virus infection. The following samplers were tested: the polytetrafluoroethylene filter (PTFE filter), the 2-stage National Institute of Occupational Safety and Health cyclone sampler (NIOSH cyclone sampler) and the 6-stage viable Andersen impactor (Andersen impactor). RESULTS: The PTFE filter and NIOSH cyclone sampler collected similar amounts of viral RNA and infectious virus from artificially-generated aerosols under a range of relative humidities (RH). Using the ferret model, the PTFE filter, NIOSH cyclone sampler and the Andersen impactor collected up to 3.66 log10 copies of RNA/L air, 3.84 log10 copies of RNA/L air and 6.09 log10 copies of RNA/L air respectively at peak recovery. Infectious virus was recovered from the PTFE filter and NIOSH cyclone samplers on the peak day of viral RNA recovery. CONCLUSION: The PTFE filter and NIOSH cyclone sampler are useful for influenza virus RNA and infectious virus collection and may be considered for clinical and environmental settings.

Loss of PTEN expression by mouse fibroblasts results in lung fibrosis through a CCN2-dependent mechanism.

Elevated adhesive signaling promotes fibrosis. Protein phosphatase and tensin homologue (PTEN) dephosphorylates focal adhesion kinase and suppresses the activation of Akt and hence suppresses adhesive signaling. Loss of PTEN expression is associated with lung fibrosis, but whether PTEN expression by type I collagen-expressing cells controls lung fibrosis is unclear. Here, we use mice expressing tamoxifen-dependent cre recombinase expressed under the control of a COL1A2 promoter/enhancer and mice harboring floxed-PTEN and/or floxed-CCN2 alleles to assess whether loss of PTEN expression by type I collagen producing cells results in lung fibrosis in a CCN2-dependent fashion. In vivo, loss of PTEN expression resulted in the overexpression of both collagen type I and the pro-adhesive matricellular protein connective tissue growth factor (CTGF/CCN2). However, α-smooth muscle actin expression was unaffected. Loss of CCN2 expression by lung fibroblasts rescues this phenotype; i.e.., mice deficient in both PTEN and CCN2 in collagen type I-expressing cells do not develop significant collagen deposition in the lung. PTEN expression by collagen type I-expressing cells controls collagen deposition; therapeutic strategies blocking CCN2 may be of benefit in blocking excessive collagen deposition in fibrosis.