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.

Development of an Ordinal Scale Treatment Endpoint for Adults Hospitalized With Influenza.

BACKGROUND: An obstacle in influenza therapeutics development is the lack of clinical endpoints, especially in hospitalized patients. A single time-point binary outcome measure is limited by patients' diverse clinical trajectories and low event rates. METHODS: A 6-point ordinal scale with ascending clinical status severity (scoring: discharged; subacute care; acute care without/with respiratory failure; intensive care unit [ICU]; death) was proposed to study outcomes of adults hospitalized with influenza. Individual patient data from 2 active surveillance cohorts' datasets (2015/2016-2017/2018; Edmonton, Hong Kong) was used for evaluation. The impact of neuraminidase inhibitor (NAI) treatment on longitudinal ordinal outcome changes over 30 days was analyzed using mixed-effects ordinal logistic regression and group-based trajectory models. RESULTS: Patient (n = 1226) baseline characteristics included age (mean 68.0 years), virus-type (A 78.1%, B 21.9%), respiratory failure (57.2%), ICU admittance (14.4%), and NAI treatment within 5 days of illness (69.2%). Outcomes at 30 days included discharged (75.2%), subacute care (13.7%), acute care (4.5%), and death (6.6%). Two main clinical trajectories were identified, predictive by baseline scoring (mean ±â€…SD, 4.3 ±â€…0.6 vs 3.5 ±â€…0.6, P < .001). Improved outcomes with NAI treatment within 5 days were indicated by significantly lower clinical status scores over time (unadjusted odds ratio [OR], 0.53; 95% confidence interval [CI], .41-.69; P < .001; adjusted OR, 0.62; 95% CI, .50-.77; P < .001, for baseline score, age, and within-patient correlations). In subanalysis, influenza vaccination was also associated with lower scores (adjusted OR, 0.67; 95% CI, .50-.90; P = .007). Analyses of binary endpoints showed insignificant results. CONCLUSIONS: The ordinal outcome scale is a potentially useful clinical endpoint for influenza therapeutic trials, which could account for the diverse clinical trajectories of hospitalized patients, warranting further development.

Outcomes among critically ill adults with influenza infection.

Background: Influenza infection is a major cause of mortality in critical care units. Methods: ata on critically ill adult patients with influenza infection from 2014 to 2019 were retrospectively collected, including mortality and critical care resource utilization. Independent predictors of mortality were identified using Cox regression. Results: ne hundred thirty patients with confirmed influenza infection had a mean age of 56 (SD 16) years; 72 (55%) were male. Mean Acute Physiology and Chronic Health Evaluation (APACHE II) score was 22 (SD 9). One hundred eight (83%) patients had influenza A (46% H1N1pdm09, 33% H3N2); 21 (16%) had influenza B. Fifty-five (42%) patients had bacterial co-infection. Only 5 (4%) had fungal co-infection. One hundred eight (83%) patients required mechanical ventilation; 94 (72%), vasopressor support; 26 (20%), continuous renal replacement therapy (CRRT); and 11 (9%), extracorporeal membrane oxygenation. One hundred twenty one (93%) patients received antiviral therapy (median 5 d). Thirty-day mortality was 23%. Patients who received antiviral treatment were more likely to survive with an adjusted hazard ratio (aHR) of 0.15 (95% CI 0.04 to 0.51, p = 0.003). Other independent predictors of mortality were the need for CRRT (aHR 2.48, 95% CI 1.14 to 5.43, p = 0.023), higher APACHE II score (aHR 1.08, 95% CI 1.02 to 1.14, p = 0.011), and influenza A (aHR 7.10, 95% CI 1.37 to 36.8, p = 0.020) compared with influenza B infection. Conclusions: mong critically ill influenza patients, antiviral therapy was independently associated with survival. CRRT, higher severity of illness, and influenza A infection were associated with mortality.

Historique: L'infection par l'influenza est une cause majeure de décès en soins intensifs. Méthodologie: Les chercheurs ont procédé à la collecte rétrospective des données sur des patients adultes gravement malades à cause d'une infection par l'influenza entre 2014 et 2019, y compris la mortalité et l'utilisation des ressources en soins intensifs. Ils ont établi les prédicteurs indépendants de mortalité au moyen de la régression de Cox. Résultats: Les 130 patients atteints d'une infection confirmée par l'influenza avaient un âge moyen de 56 ans (±16), et 72 (55 %) étaient de sexe masculin. Le score APACHE II (acronyme anglais d'évaluation de la physiologie aiguë et de la santé chronique) s'élevait à 22 (±9). Au total, 108 patients (83 %) étaient atteints de la grippe de type A (46 % H1N1pdm09, 33 % H3N2) et 21 (16 %), de la grippe de type B. De plus, 55 patients (42 %) étaient atteints d'une co-infection bactérienne, et seulement cinq (4 %), d'une co-infection fongique. Par ailleurs, 108 patients (83 %) ont eu besoin de ventilation mécanique, 94 (72 %), d'un soutien vasopresseur; 26 (20 %), d'une thérapie continue de remplacement rénal (TCRR) et 11 (9 %), d'une oxygénation extracorporelle. Au total, 121 patients (93 %) ont reçu une antivirothérapie (pendant une période médiane de cinq jours). La mortalité au bout de 30 jours s'élevait à 23 %. Les patients qui avaient reçu une antivirothérapie étaient plus susceptibles de survivre, selon un risque relatif ajusté (RRa) de 0,15 (IC à 95 % : 0,04 à 0,51, p = 0,003). Il y avait d'autres prédicteurs indépendants de mortalité : la nécessité de recourir à une TCRR (RRa 2,48, IC à 95 % : 1,14 à 5,43, p = 0,023), un score APACHE II élevé (RRa 1,08, IC à 95 % : 1,02 à 1,14, p = 0,011) et l'infection par l'influenza de type A (RRa 7,10, IC à 95 % : 1,37 à 36,8, p = 0,020) plutôt que par l'influenza de type B. Conclusions: Chez les patients gravement malades atteints de l'influenza, l'antivirothérapie était associée de manière indépendante à la survie. La TCRR, la plus grande gravité de la maladie et l'infection par l'influenza de type A étaient liées à la mortalité.

High Rates of Influenza-Associated Invasive Pulmonary Aspergillosis May Not Be Universal: A Retrospective Cohort Study from Alberta, Canada.

From 2014-2019, invasive pulmonary aspergillosis complicated 7.2% (0-23.1% in different influenza seasons) of cases of influenza-associated respiratory failure in Edmonton, Alberta. Disease outcomes ranged from survival without therapy to death despite antifungals. Clinician vigilance, longitudinal local surveillance, and refined criteria to identify patients requiring therapy are needed.