Background. Oseltamivir is recommended for the treatment of adults hospitalized with influenza, but adherence is often suboptimal. This may be due to doubts about the reliability of the evidence supporting its benefits, particularly when initiation is delayed. We aimed to assess the effectiveness of oseltamivir in reducing mortality in older adults hospitalized with influenza, with a focus on the timing of initiation. Methods. The CIRN-SOS Network gathered data on severe respiratory illnesses across 5 Canadian provinces during the influenza seasons 2012-2019. Individuals aged >= 65 years with confirmed influenza and available antiviral prescription data were included. We compared the 30-day survival rates of hospitalized patients based on oseltamivir prescription status. Kaplan-Meier estimated survival probability and inverse probability of treatment (IPT)-weighted Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. The analyses considered the time to antiviral initiation (>48 vs <= 48 hours). Results. Among the 8135 influenza patients studied, 2126 did not receive antiviral treatment, whereas 6009 were treated with oseltamivir. A total of 395 patients were hospitalized for >30 days. The overall mortality rate was 8.32 per 1000 person-days, with 53.9% of the deaths occurring within the first week. Oseltamivir recipients had a 18% lower risk of 30-day mortality (IPT-weighted HR, 0.82 [95% CI, .69-.98]). The benefit was significant for influenza A (IPT-weighted HR, 0.74 [95% CI, .61-.91]) but not for influenza B (IPT-weighted HR, 1.12 [95% CI, .81-1.56]). Oseltamivir remained effective even when initiated after 48 hours (IPT-weighted HR, 0.66 [95% CI, .49-.90]). Influenza vaccination did not mediate the effectiveness of oseltamivir in reducing mortality. Conclusions. Oseltamivir significantly reduces mortality risk in older adults hospitalized with influenza, even when administered after 48 hours, independent of vaccination status.

Background Influenza and RSV coinfections are not commonly seen but are concerning as they can lead to serious illness and adverse clinical outcomes among vulnerable populations. Here we describe the clinical features and outcomes of influenza and RSV coinfections in hospitalized adults. Methods A cohort study was performed with pooled active surveillance in hospitalized adults ≥ 50 years from the Serious Outcomes Surveillance Network of the Canadian Immunization Research Network (CIRN SOS) during the 2012/13, 2013/14, and 2014/15 influenza seasons. Descriptive statistics summarized the characteristics of influenza/RSV coinfections. Kaplan-Meier estimated the probability of survival over the first 30 days of hospitalization. Results Over three influenza seasons, we identified 33 cases of RSV and influenza coinfection, accounting for 2.39 cases per 1,000 hospitalizations of patients with acute respiratory illnesses. Adults aged 50 + years commonly reported cough (81.8%), shortness of breath (66.7%), sputum production (45.5%), weakness (33.3%), fever (27.3%), and nasal congestion (24.2%) as constitutional and lower respiratory tract infection symptoms. The mortality rate was substantial (12.1%), and age, comorbidity burden, and frailty were associated with a higher risk for adverse clinical outcomes. Conclusions Older adults are at higher risk for complications from influenza and RSV coinfections, especially those over 65 with a high comorbidity burden and frailty.

Abstract We developed and validated the Influenza Severity Scale (ISS), a standardized risk assessment for influenza, to estimate and predict the probability of major clinical events in patients with laboratory-confirmed infection. Data from the Canadian Immunization Research Network’s Serious Outcomes Surveillance Network (2011/2012–2018/2019 influenza seasons) enabled the selecting of all laboratory-confirmed influenza patients. A machine learning-based approach then identified variables, generated weighted scores, and evaluated model performance. This study included 12,954 patients with laboratory-confirmed influenza infections. The optimal scale encompassed ten variables: demographic (age and sex), health history (smoking status, chronic pulmonary disease, diabetes mellitus, and influenza vaccination status), clinical presentation (cough, sputum production, and shortness of breath), and function (need for regular support for activities of daily living). As a continuous variable, the scale had an AU-ROC of 0.73 (95% CI, 0.71–0.74). Aggregated scores classified participants into three risk categories: low (ISS < 30; 79.9% sensitivity, 51% specificity), moderate (ISS ≥ 30 but < 50; 54.5% sensitivity, 55.9% specificity), and high (ISS ≥ 50; 51.4% sensitivity, 80.5% specificity). ISS demonstrated a solid ability to identify patients with hospitalized laboratory-confirmed influenza at increased risk for Major Clinical Events, potentially impacting clinical practice and research.

Background: Influenza vaccines prevent influenza-related morbidity and mortality; however, suboptimal vaccine effectiveness (VE) of non-adjuvanted trivalent inactivated influenza vaccine (naTIV) or quadrivalent formulations in older adults prompted the use of enhanced products such as adjuvanted TIV (aTIV). Here, the VE of aTIV is compared to naTIV for preventing influenza-associated hospitalization among older adults. Methods: A test-negative design study was used with pooled data from the 2012 to 2015 influenza seasons. An inverse probability of treatment (IPT)-weighted logistic regression estimated the Odds Ratio (OR) for laboratory-confirmed influenza-associated hospitalization. VE was calculated as (1-OR)*100% with accompanying 95% confidence intervals (CI). Results: Of 7,101 adults aged > 65, 3,364 received naTIV and 526 received aTIV. The overall VE against influenza hospitalization was 45.9% (95% CI: 40.2%-51.1%) for naTIV and 53.5% (42.8%-62.3%) for aTIV. No statistically significant differences in VE were found between aTIV and naTIV by age group or influenza season, though a trend favoring aTIV over naTIV was noted. Frailty may have impacted VE in aTIV recipients compared to those receiving naTIV, according to an exploratory analysis; VE adjusted by frailty was 59.1% (49.6%-66.8%) for aTIV and 44.8% (39.1%-50.0%) for naTIV. The overall relative VE of aTIV to naTIV against laboratory-confirmed influenza hospital admission was 25% (OR 0.75; 0.61-0.92), demonstrating statistically significant benefit favoring aTIV. Conclusions: Adjusting for frailty, aTIV showed statistically significantly better protection than naTIV against influenza-associated hospitalizations in older adults. In future studies, it is important to consider frailty as a significant confounder of VE.

Infectious diseases continue to account for a significant portion of global deaths despite the use of vaccines for several centuries. Immunization programs around the world are a testament to the great success of multiple vaccines, yet there are still diseases without vaccines and others that require safer more effective ones. Addressing uncontrolled and emerging disease threats is restrained by the limitations and bottlenecks encountered with traditional vaccine development paradigms. Recent advances in modern molecular biology technologies have enhanced the interrogation of host pathogen interaction and deciphered complex pathways, thereby uncovering the myriad interplay of biological events that generate immune protection against foreign agents. Consequent to insights into the immune system, modern biology has been instrumental in the development and production of next generation 21st century vaccines. As these biological tools, commonly and collectively referred to as ‘omics, became readily available, there has been a renewed consideration of Controlled Human Infection Models (CHIMs). Successful and reproducible CHIMs can complement modern molecular biology for the study of infectious diseases and development of effective vaccines in a regulated process that mitigates risk, cost, and time, with capacity to discern immune correlates of protection.

Background:Respiratory syncytial virus (RSV) disease in older adults is undercharacterized. To help inform future immunization policies, this study aimed to describe the disease burden in Canadian adults aged ≥50 years hospitalized with RSV. Methods:Using administrative data and nasopharyngeal swabs collected from active surveillance among adults aged ≥50 years hospitalized with an acute respiratory illness (ARI) during the 2012-2013, 2013-2014, and 2014-2015 influenza seasons, RSV was identified using a respiratory virus multiplex polymerase chain reaction test to describe the associated disease burden, incidence, and healthcare costs. Results:Of 7797 patients tested, 371 (4.8%) were RSV positive (2.2% RSV-A and 2.6% RSV-B). RSV prevalence varied by season from 4.2% to 6.2%. Respiratory virus coinfection was observed in 11.6% (43/371) of RSV cases, with influenza A being the most common. RSV hospitalization rates varied between seasons and increased with age, from 8-12 per 100 000 population in adults aged 50-59 years to 174-487 per 100 000 in adults aged ≥80 years. The median age of RSV cases was 74.9 years, 63.7% were female, and 98.1% of cases had ≥1 comorbidity. Among RSV cases, the mean length of hospital stay was 10.6 days, 13.7% were admitted to the intensive care unit, 6.4% required mechanical ventilation, and 6.1% died. The mean cost per RSV case was $13 602 (Canadian dollars) but varied by age and Canadian province. Conclusions:This study adds to the growing literature on adult RSV burden by showing considerable morbidity, mortality, and healthcare costs in hospitalized adults aged ≥50 years with ARIs such as influenza.

Background We report characteristics and outcomes of adults admitted to Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) Network hospitals with COVID-19 in 2020. Methods Patients with laboratory-confirmed COVID-19 admitted to 11 sites in Ontario, Quebec, Alberta, and Nova Scotia up to December 31, 2020 were enrolled in this prospective observational cohort study. Measures included age, sex, demographics, housing, exposures, Clinical Frailty Scale, comorbidities; in addition, length of stay, intensive care unit (ICU) admission, mechanical ventilation, and survival were assessed. Descriptive analyses and multivariable logistic regressions were conducted. Results Among 2,011 patients, mean age was 71.0 (range 19–105) years. 29.7% were admitted from assisted living or long-term care facilities. The full spectrum of frailty was represented in both younger and older age groups. 81.8% had at least one underlying comorbidity and 27.2% had obesity. Mortality was 14.3% without ICU admission, and 24.6% for those admitted to ICU. Older age and frailty were independent predictors of lower ICU use and higher mortality; accounting for frailty, obesity was not an independent predictor of mortality, and associations of comorbidities with mortality were weakened. Conclusions Frailty is a critical clinical factor in predicting outcomes of COVID-19, which should be considered in research and clinical settings.

Background: Seasonal respiratory viral infections are associated with exacerbations and morbidity among patients with COPD. The real-world clinical outcomes associated with seasonal viral infections are less well established among hospitalized patients. Research Question: To estimate the association between seasonal respiratory viral infections, 30-day mortality, and intensive care unit (ICU) admission among hospitalized COPD patients. Study Design and Methods: We conducted an analysis of a national prospective multicenter cohort of COPD patients hospitalized with acute respiratory illness during winter seasons (2011-2015) in Canada. Nasopharyngeal swabs were performed on all patients at the onset of hospital admission for diagnosis of viral infection. Primary outcomes were 30-day mortality and ICU admissions. Secondary outcomes included invasive/non-invasive ventilation use. Results: Among 3931 hospitalized patients with COPD, 28.5% (1122/3931) were diagnosed with seasonal respiratory viral infection. Viral infection was associated with increased admission to ICU (OR 1.5, 95% CI 1.2-1.9) and need for mechanical ventilation (OR 1.9, 95% CI 1.4-2.5), but was not associated with mortality (OR 1.1, 95% CI 0.8-1.4). Patients with respiratory syncytial virus (RSV) were equally likely to require ICU admission (OR 1.09, 95% CI 0.67-1.78), and more likely to need non-invasive ventilation (OR 3.1; 95% CI 1.8-5.1) compared to patients with influenza. Interpretation: Our results suggest COPD patients requiring hospitalization for respiratory symptoms should routinely receive viral testing at admission, especially for RSV and influenza, to inform prognosis, clinical management, and infection control practices during winter seasons. Patients with COPD will be an important target population for newly developed RSV therapeutics.

OBJECTIVE(S):In the context of age- and risk-based pneumococcal vaccine recommendations in Canada, this study presents updated data from active surveillance of pneumococcal community acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD) in hospitalized adults from 2010 to 2017. METHODS:S. pneumoniae was detected using culture (blood and sputum), and urine antigen detection (UAD). Serotyping was performed with Quellung, PCR, or using the PCV13- and PPV23 (non-PCV13)-specific UADs. Laboratory results, demographic, and outcome data were categorized by age (16-49, 50-64, and 65 + ) and by disease [non-bacteremic pCAP, bacteremic pCAP, and IPD(non-CAP)]. RESULTS:11,129 CAP cases and 216 cases of IPD (non-CAP) were identified. Laboratory testing for S. pneumoniae was performed in 8912 CAP cases, identifying 1264 (14.2%) as pCAP. Of pCAP cases, 811 (64.1%) were non-bacteremic and 455 (35.9%) were bacteremic. Adults 65 + years represented 54.5% of non-bacteremic pCAP, 41.4% of bacteremic pCAP, and 48.6% of IPD cases. Adults 50-64 years contributed 30.3%, 33.1%, and 29.9%, respectively. In pCAP, PCV13 serotypes declined between 2010 and 2014 due to declines in serotypes 7F and 19A, then plateaued from 2015 to 2017 with persistence of serotype 3. In later study years, non-bacteremic pCAP was predominant, and PPV23 (non-PCV13) serotypes increased from 2015 to 2017, with serotypes 22F, 11A, and 9 N being most frequently identified. Compared to non-pCAP, pCAP cases were more likely to be admitted to intensive care units and require mechanical ventilation. These outcomes and mortality were more common in bacteremic pCAP and IPD, versus non-bacteremic pCAP. CONCLUSION(S):Along with IPD, pCAP surveillance (bacteremic and non-bacteremic) is important as their trends may differ over time. With insufficient herd protection from PCV13 childhood immunization, or use of PPV23 in adults, this study supports direct adult immunization with PCV13 or higher valency conjugate vaccines to reduce the residual burden of pCAP and IPD.

BACKGROUND:Serological assays designed to detect SARS-CoV-2 antibodies are being used in serological surveys and other specialized applications. As a result, and to ensure that the outcomes of serological testing meet high quality standards, evaluations are required to assess the performance of these assays and the proficiency of laboratories performing them.METHODS:A panel of 60 plasma/serum samples from blood donors who had reverse transcriptase-polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 infections and 21 SARS-CoV-2 negative samples were secured and distributed to interested laboratories within Canada (n = 30) and the United States (n = 1). Participating laboratories were asked to provide details on the diagnostic assays used, the platforms the assays were performed on, and the results obtained for each panel sample. Laboratories were blinded with respect to the expected outcomes.RESULTS:The performance of the different assays evaluated was excellent, with the high-throughput platforms of Roche, Ortho, and Siemens demonstrating 100% sensitivity. Most other high-throughput platforms had sensitivities of >93%, with the exception of the IgG assay using the Abbott ARCHITECT which had an average sensitivity of only 87%. The majority of the high-throughput platforms also demonstrated very good specificities (>97%).CONCLUSION:This proficiency study demonstrates that most of the SARS-CoV-2 serological assays utilized by provincial public health or hospital laboratories in Canada have acceptable sensitivity and excellent specificity.

Abstract Background Pneumococcal vaccine recommendations in Canada include both age- and risk-based guidance. This study aimed to describe the burden of vaccine-preventable pneumococcal community acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD) by age in hospitalized adults. Methods Active surveillance for all-cause CAP and IPD in hospitalized adults was performed from 2010 to 2017, including laboratory results, patient demographics, and outcomes. Streptococcus pneumoniae was detected using blood and sputum culture, or urine antigen detection (UAD). Serotype was assigned using Quellung reaction, PCR, or serotype-specific UADs spanning the 24 serotypes in PCV13 and PPV23 vaccines. Data were categorized by age (16-49, 50-64, 65+, and 50+ years) and over time. Results 11129 ACP cases and 216 cases of IPD (non-CAP) were identified. A laboratory test for S. pneumoniae was performed in 8912 of ACP cases, identifying 1264 (14.2%) as pCAP. Compared to non-pCAP, pCAP cases were more likely to be admitted to intensive care units and require mechanical ventilation. These serious outcomes, as well as mortality, were more prominent in bacteremic pCAP and IPD. Risk factors for death in pCAP included aged 75+ years, immune compromising conditions, and BMI < 18.5. When categorized by age, the proportion of individuals aged 65+ years for pCAP and IPD was 49.8% and 48.6%, and the 50-64 year age cohort represented 31.3% and 29.9%, respectively. The contributions of PCV13 and PPV23 serotypes remained relatively stable over time, and overall represented 57.6% and 90.9% for pCAP, and 35.0% and 72.0% for IPD, respectively. Conclusion Seven years following infant PCV13 immunization programs in Canada, PCV13 and PPV23 serotypes in pCAP and IPD remained predominant causes of pneumococcal disease. Serious outcomes were particularly evident in adults 50+, suggesting pneumococcal vaccines should be encouraged in this age group. Disclosures Jason J. LeBlanc, PhD, FCCM, D[ABMM], GSK (Research Grant or Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support) Todd F Hatchette, MD, GSK (Grant/Research Support)Pfizer (Grant/Research Support) Melissa K. Andrew, MD, PhD, GSK (Grant/Research Support)Pfizer (Grant/Research Support, Advisor or Review Panel member)Sanofi (Consultant, Grant/Research Support, Advisor or Review Panel member)Seqirus (Advisor or Review Panel member) Allison McGeer, MSc,MD,FRCPC,FSHEA, GlaxoSmithKline (Advisor or Review Panel member)Merck (Advisor or Review Panel member, Research Grant or Support)Pfizer (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member) Louis Valiquette, MD, M.Sc., Cubist (Consultant)GSK (Grant/Research Support)Merck (Consultant)Optimer (Consultant)Pfizer (Grant/Research Support) Shelly McNeil, FRCPC, MD, GSK (Grant/Research Support)Pfizer (Grant/Research Support)Sinofi Pasteur (Grant/Research Support)

Background: We report characteristics and outcomes of adults admitted to Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) Network hospitals with COVID-19 in 2020.  Methods: Adult patients with laboratory-confirmed COVID-19 admitted to eleven sites in Ontario, Quebec, Alberta and Nova Scotia up to December 31, 2020 were enrolled in this prospective observational cohort study. Age, sex, demographics, housing, exposure characteristics, Clinical Frailty Scale, comorbidities, and outcomes including length of stay, intensive care unit (ICU) admission, mechanical ventilation, and survival were conducted. Descriptive analyses and multivariable logistic regressions were conducted.  Findings: Among 2011 patients, mean age was 71·0 (range 19-105) years. 45·7% were women and 74·0% were white. 21·5% were admitted from Assisted Living facilities, 8·2% from long term care, and 2·1% from homeless shelters. The full spectrum of frailty was represented in both younger and older age groups. The majority (61·7% of adults =65) had at least one underlying comorbidity and 27·2% had obesity. Mortality was 14·3% among those not admitted to ICU, and 24·6% for those admitted to ICU. Older age and higher frailty were associated with reduced ICU admission but increased mortality. Obesity was independently associated with ICU admission but not with death. Associations between underlying comorbidities and adverse outcomes were attenuated but persisted when adjusting for frailty. Interpretation: Frailty and age were independent predictors of lower ICU use and higher mortality; when accounting for frailty, obesity was not an independent predictor of mortality, and associations of comorbidities with mortality were weakened. Funding Statement: Funding was provided by the Public Health Agency of Canada and the Canadian Institutes of Health Research. Declaration of Interests: MKA reports grant funding from the Public Health Association of Canada, CIHR, Canadian Frailty Network, Sanofi Pasteur and GSK group of companies, and payments from Pfizer, Sanofi Pasteur and Seqirus outside the submitted work. AM reports payments from GSK, Seqirus and Sanofi Pasteur, outside the submitted work. JEM reports payments from RestorBio, Sanofi, GSK, Merck and Medicago outside of the submitted work. TFH reports grants from Pfizer and GSK. ML reports payments from Sanofi, Medicago, Sequirus, and Pfizer outside the submitted work. SAM reports grants and payments from Pfizer, GSK, Merck, Novartis and Sanofi, outside the submitted work. JG, JJL, GB, LV, ME, DM-C, AA, KW, ST, SS, AMc and KK report no conflicts of interest. Ethics Approval Statement: The protocol for active COVID-19 surveillance has been approved by each local site’s Research Ethics Board.

Inactivated influenza vaccines efficacy is variable and often poor. We conducted a phase 1 trial (NCT02188810), to assess the safety and immunogenicity of a novel nanoparticle Toll-like receptor 7/8 agonist adjuvant (Papaya Mosaic Virus) at different dose levels combined with trivalent influenza vaccine in healthy persons 18–50 years of age. Hemagglutination-inhibition assays, antibody to Influenza A virus nucleoprotein and peripheral blood mononuclear cells for measurement of interferon-gamma ELISPOT response to influenza antigens, Granzyme B and IFNγ:IL-10 ratio were measured. The most common adverse events were transient mild to severe injection site pain and no safety signals were observed. A dose-related adjuvant effect was observed. Geometric mean hemagglutination-inhibition titers increased at day 28 in most groups and waned over time, but fold-antibody responses were poor in all groups. Cell mediated immunity results were consistent with humoral responses. The Papaya Mosaic Virus adjuvant in doses of 30 to 240 µg combined with reduced influenza antigen content was safe with no signals up to 3 years after vaccination. A dose-related adjuvant effect was observed and immunogenicity results suggest that efficacy study should be conducted in influenza antigen-naïve participants.

Jason LeBlanc, May ElSherif, Lingyun Ye, Donna MacKinnonCameron, Ardith Ambrose, Todd F Hatchette, Amanda LS Lang, Hayley D Gillis, Irene Martin, Walter H Demczuk, Craig LaFerriere, Melissa K Andrew, Guy Boivin, William Bowie, Karen Green, Jennie Johnstone, Mark Loeb, Anne McCarthy, Allison McGeer, Makeda Semret, Sylvie Trottier, Louis Valiquette, Duncan Webster, Shelly A McNeil Respiratory epidemiology

BackgroundIn Canada, 13-valent pneumococcal conjugate vaccine (PCV13) is recommended in childhood, in individuals at high risk of invasive pneumococcal disease (IPD) and in healthy adults aged ≥65 years for protection against vaccine-type IPD and pneumococcal community-acquired pneumonia (pCAP). Since vaccine recommendations in Canada include both age-based and risk-based guidance, this study aimed to describe the burden of vaccine-preventable pCAP in hospitalised adults by age.MethodsSurveillance for community-acquired pneumonia (CAP) in hospitalised adults was performed prospectively from 2010 to 2015. CAP was radiologically confirmed, and pCAP was identified using blood and sputum culture and urine antigen testing. Patient demographics and outcomes were stratified by age (16–49, 50–64, ≥65 and ≥50 years).ResultsOf 6666/8802 CAP cases tested, 830 (12.5%) had pCAP, and 418 (6.3%) were attributed to a PCV13 serotype. Of PCV13 pCAP, 41% and 74% were in adults aged ≥65 and ≥50 years, respectively. Compared with non-pCAP controls, pCAP cases aged ≥50 years were more likely to be admitted to intensive care units (ICUs) and to require mechanical ventilation. Older adults with pCAP were less likely to be admitted to ICU or required mechanical ventilation, given their higher mortality and goals of care. Of pCAP deaths, 67% and 90% were in the ≥65 and ≥50 age cohorts, respectively.ConclusionsAdults hospitalised with pCAP in the age cohort of 50–64 years contribute significantly to the burden of illness, suggesting that an age-based recommendation for adults aged ≥50 years should be considered in order to optimise the impact of pneumococcal vaccination programmes in Canada.

Background The effectiveness of influenza vaccination in reducing influenza-related hospitalizations among patients with COPD is not well described, and influenza vaccination uptake remains suboptimal. Methods Data were analyzed from a national, prospective, multicenter cohort study including patients with COPD, hospitalized with any acute respiratory illness or exacerbation between 2011 and 2015. All patients underwent nasopharyngeal swab screening with polymerase chain reaction (PCR) testing for influenza. The primary outcome was an influenza-related hospitalization. We identified influenza-positive cases and negative control subjects and used multivariable logistic regression with a standard test-negative design to estimate the vaccine effectiveness for preventing influenza-related hospitalizations. Results Among 4,755 hospitalized patients with COPD, 4,198 (88.3%) patients with known vaccination status were analyzed. The adjusted analysis showed a 38% reduction in influenza-related hospitalizations in vaccinated vs unvaccinated individuals. Influenza-positive patients (n = 1,833 [38.5%]) experienced higher crude mortality (9.7% vs 7.9%; P = .047) and critical illness (17.2% vs 12.1%; P < .001) compared with influenza-negative patients. Risk factors for mortality in influenza-positive patients included age > 75 years (OR, 3.7 [95% CI, 0.4-30.3]), cardiac comorbidity (OR, 2.0 [95% CI, 1.3-3.2]), residence in long-term care (OR, 2.6 [95% CI, 1.5-4.5]), and home oxygen use (OR, 2.9 [95% CI, 1.6-5.1]). Conclusions Influenza vaccination significantly reduced influenza-related hospitalization among patients with COPD. Initiatives to increase vaccination uptake and early use of antiviral agents among patients with COPD could reduce influenza-related hospitalization and critical illness and improve health-care costs in this vulnerable population. Trial Registry ClinicalTrials.govNo.:NCT01517191; URL www.clinicaltrials.gov

BACKGROUND:The 13-valent pneumococcal conjugate vaccine (PCV13) was recently shown to be effective against PCV13-type invasive pneumococcal disease (IPD) and pneumococcal community acquired pneumonia (CAPSpn) in healthy adults aged ≥65 years, prompting many countries to re-assess adult immunization. In Canada, the potential benefits of adult PCV13 immunization were unclear given anticipated herd immunity from PCV13 childhood immunization introduced since 2010. This study describes the serotype distribution and clinical outcomes of Canadian adults aged ≥16 years, who were hospitalized with CAPSpn and IPD from 2010 to 2015. METHODS:Active surveillance for CAP and IPD was performed in adult hospitals across five Canadian provinces. IPD was identified when Streptococcus pneumoniae was isolated from sterile sites. Bacteremic and non-bacteremic CAPSpn were identified using blood culture, and sputum culture or PCV13-specific urine antigen detection (UADPCV13), respectively. Serotype was assigned using Quellung reaction, PCR, or UADPCV13. RESULTS:Of 6687 CAP cases where a test was performed, S. pneumoniae positivity decreased from 15.9% in 2011 to 8.8% in 2014, but increased to 12.9% in 2015. CAPSpn attributed to PCV13 serotypes followed a similar trend, dropping from 8.3% in 2010 to 4.6% in 2014, but increasing to 6.3% in 2015. The decline was primarily attributed to serotypes 7F and 19A, and the proportional increase to serotype 3. Similar trends were noted for bacteremic and non-bacteremic CAPSpn. Serious outcomes such as 30-day mortality, intensive care unit admission, and requirement for mechanical ventilation were prominent in CAPSpn and IPD cases, but remained unchanged over the study years. CONCLUSION:Herd immunity afforded primarily by serotypes 7F and 19A appears to be partly masked by a concomitant proportional increase of serotype 3. Despite evidence of herd immunity, these PCV13 serotypes remain persistent in Canadian adults hospitalized with CAPSpn, and represent between 5 and 10% of all CAP in this patient population.

Abstract Background Inactivated influenza vaccines (IV) efficacy is variable and sometimes poor. In this phase 1 trial the safety and immunogenicity of a novel nanoparticle adjuvant (Papaya Mosaic Virus (PapMV or PAL) at different dose levels combined with inactivated trivalent IV (TIV; FLUVIRAL® 2013–2014, GSK, Kirkland PQ) was assessed. Nonpathogenic in mammals, PAL is recognized as a pathogen-associated molecular pattern (PAMP) which stimulates innate, cell-mediated immunity (CMI) and adaptive immunity in naïve mice through activation of toll like receptor 7 and 8. Methods Healthy persons 18–50 years of age were randomized to one of 6 study groups: 30 µg, 60 µg, 120 µg or 240 µg of PAL with 0.25 mL TIV, 240 µg of PAL with 0.125 mL TIV, or control (0.5 mL TIV). Solicited local and general adverse events (AE) were collected Day (D)0 to 6, unsolicited AE to D28, and serious AE to D1095. Hemagglutination-inhibition assays (HI), antibody to Influenza A virus nucleoprotein (NP), and peripheral blood mononuclear cells (PBMC) for measurement of interferon-gamma (IFNg) ELISPOT (response to PepMix influenza A H2N2 Ann Arbour NP, MP1, and an influenza peptide pool), granzyme B, and IFNg:IL:10 ratio were collected on D0, 7, 28, 120, and 180. Results The most common solicited AEs were transient mild-to-moderate local pain (62.5%–87.5% of participants/group), drowsiness (≤37.5% of participants/group) and generalized muscle aches (12.5–50% of participants/group). There was one unrelated SAE. All participants had HI and anti-NP titers at baseline. HI GMTs increased at D28 post vaccine in most groups (Figure 1) and waned over time. HI fold Ab (Far) responses to TIV strains were poor in all groups (≤37.5% of participants/group had 4-Far to any strain). CMI results were consistent with humoral responses. Conclusion The PAL adjuvant in doses of 30 to 240µg combined with reduced TIV dosages was safe with no signals up to 3 years after vaccine. Reduced doses of TIV co-presented with 240 µg PAL had similar HI GMTs as TIV. The CMI results suggest that the assessment of PAL efficacy on TIV immunization would have to be conducted in an influenza naïve population. Disclosures Scott Halperin, MD, GlaxoSmithKline: Ad hoc advisory boards, Other Financial or Material Support, Research Grant; Janssen Pharm: Research Grant; sanofi pasteur: Ad hoc advisory boards, Other Financial or Material Support, Research Grant.

Abstract Background In healthy adults aged ≥65 years, direct immunization with the 13-valent pneumococcal conjugate vaccine (PCV13) was shown effective at preventing vaccine-type pneumococcal community-acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD). Although PCV13 was licensed for use in Canadian adults aged >50 years, it was recommended for immunocompromised individuals who are at highest risk of IPD. In 2016, a recommendation was issued for use of PCV13 in immunocompetent adults aged ≥65 years, for the prevention of pCAP and IPD. This study aimed to compare pCAP cases attributed to PCV13 serotypes in adults aged 50–64 and ≥65 years. Methods Active surveillance for CAP and IPD was performed from 2010 to 2015 in adult hospitals across five Canadian provinces. To identify pCAP, blood culture, sputum culture, or a PCV13 serotype-specific urine antigen detection (ssUAD) were used. Serotype was assigned using Quellung reaction, PCR, or ssUAD. All pCAP cases were categorized by serotype and age groups. Patient demographics and outcome data were collected. Results Over years 2010–2015, 6687 CAP cases were tested. 835 pCAP cases were identified, of which 418 (50%) caused by a PCV13 serotype. The majority (74%) of PCV13-associated pCAP occurred in the adults aged ≥50 years, whereas only 41.4% (173/418) were in adults ≥65 years. PCV13 pCAP cases declined over the years, likely through herd immunity from childhood immunization. The yearly proportion of pCAP attributed to PCV13 serotypes for ages ≥50 remained high (67.5 to 80.6%), compared those occurring in the ≥65 age groups (35.1 to 49.4%). Compared with test-negative controls, pCAP cases in both age groups were more likely to be admitted to ICU, require mechanical ventilation, and had higher mortality. Of pCAP deaths, 61.4% and 82.3% were in the ≥65 and ≥50 age cohorts, respectively. Conclusion From year 2010 to 2015, adults hospitalized with PCV13 pCAP in the ≥65 age cohort accounted for less than half of the cases, whereas including the 50–64 age cohort increased the proportion to 74%. Similarly, the proportion of PCV13 pCAP deaths that occurred in adults aged ≥50 years was 82%, compared with 61% in the ≥65 age cohort. Expansion of PCV13 recommendations to include adults 50–64 years of age should be considered. Disclosures All authors: No reported disclosures.

Abstract Background Streptococcus pneumoniae can colonizes the human nasopharynx, and can cause life-threatening infections like community-acquired pneumonia (CAP) and invasive pneumococcal diseases (IPD). In Canada, the 13-valent conjugate vaccine (PCV13) was introduced in childhood immunization since 2010, with hopes that it would not only protect the vaccinated, but also confer indirect protection to adults through herd immunity. Given data on S. pneumoniae nasopharyngeal (NP) carriage in adults is scarce, this study reports on S. pneumoniae-positivity and serotype distribution in adult carriage from years 2010 to 2017. Methods Active surveillance was performed in adults hospitalized with for CAP or IPD from December 2010 to 2017. For assessment of S. pneumoniae carriage, NP swabs were tested using lytA and cpsA real-time PCR. S. pneumoniae-positive NPs were subjected to serotyping using conventional and real-time multiplex PCRs. Results Overall, 6472 NP swabs were tested, and Spn was identified in 366 (5.7%). Of the 366 S. pneumoniae-positive NP swabs, a serotype was assigned in 355 (97.0%). From years 2010 to 2017, the proportion of S. pneumoniae-positive NP swabs declined from 8.9% to 4.3%. This was also reflected in the proportion of serotypeable results attributed to PCV13 serotypes, which also declined from 76.9% to 42.2%. The decline was primarily attributed to PCV13 serotypes 7F and 19A. PCV13 serotype 3 remained predominant throughout the study, as did non-PCV13 serotypes like 22F, 33F, and 11A. On the other hand, a proportional rise over time was noted for non-vaccine serotypes (from 15.4% to 31.1%). This was primarily attributed to serotypes 23A, 15A, and 35B. Conclusion Monitoring serotype trends is important to assess the impact of pneumococcal vaccines. While herd immunity from PCV13 childhood immunization was anticipated, few studies have assessed its impact on adult carriage. This study described Spn serotype distribution in adults over years 2010 to 2017, demonstrating not only a reduction of PCV13 serotypes over time, but a proportional rise in non-vaccine serotypes. These emerging serotypes may represent the emergence of serotype replacement. Ongoing serotype surveillance will be needed to compare S. pneumoniae carriage to serotypes associated with pneumococcal CAP and IPD. Disclosures All authors: No reported disclosures.