Impact of respiratory viral infections on mortality and critical illness among hospitalized patients with chronic obstructive pulmonary disease.

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. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT01517191.

Older Age and Frailty are Associated with Higher Mortality but Lower ICU Admission with COVID-19.

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.

Influenza surveillance case definitions miss a substantial proportion of older adults hospitalized with laboratory-confirmed influenza: A report from the Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) Network.

OBJECTIVE: Older adults often have atypical presentation of illness and are particularly vulnerable to influenza and its sequelae, making the validity of influenza case definitions particularly relevant. We sought to assess the performance of influenza-like illness (ILI) and severe acute respiratory illness (SARI) criteria in hospitalized older adults. DESIGN: Prospective cohort study. SETTING: The Serious Outcomes Surveillance Network of the Canadian Immunization Research Network undertakes active surveillance for influenza among hospitalized adults. METHODS: Data were pooled from 3 influenza seasons: 2011/12, 2012/13, and 2013/14. The ILI and SARI criteria were defined clinically, and influenza was laboratory confirmed. Frailty was measured using a validated frailty index. RESULTS: Of 11,379 adult inpatients (7,254 aged ≥65 years), 4,942 (2,948 aged ≥65 years) had laboratory-confirmed influenza. Their median age was 72 years (interquartile range [IQR], 58-82) and 52.6% were women. The sensitivity of ILI criteria was 51.1% (95% confidence interval [CI], 49.6-52.6) for younger adults versus 44.6% (95% CI, 43.6-45.8) for older adults. SARI criteria were met by 64.1% (95% CI, 62.7-65.6) of younger adults versus 57.1% (95% CI, 55.9-58.2) of older adults with laboratory-confirmed influenza. Patients with influenza who were prefrail or frail were less likely to meet ILI and SARI case definitions. CONCLUSIONS: A substantial proportion of older adults, particularly those who are frail, are missed by standard ILI and SARI case definitions. Surveillance using these case definitions is biased toward identifying younger cases, and does not capture the true burden of influenza. Because of the substantial fraction of cases missed, surveillance definitions should not be used to guide diagnosis and clinical management of influenza.

Canadian Association of Gastroenterology Clinical Practice Guideline for Immunizations in Patients With Inflammatory Bowel Disease (IBD)-Part 2: Inactivated Vaccines.

BACKGROUND AND AIMS: The effectiveness and safety of vaccinations can be altered by immunosuppressive therapies, and perhaps by inflammatory bowel disease (IBD) itself. These recommendations developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on immunizations in adult and pediatric patients with IBD. This publication focused on inactivated vaccines. METHODS: Systematic reviews evaluating the efficacy, effectiveness, and safety of vaccines in patients with IBD, other immune-mediated inflammatory diseases, and the general population were performed. Critical outcomes included mortality, vaccine-preventable diseases, and serious adverse events. Immunogenicity was considered a surrogate outcome for vaccine efficacy. Certainty of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Key questions were developed through an iterative online platform, and voted on by a multidisciplinary group. Recommendations were formulated using the Evidence-to-Decision framework. Strong recommendation means that most patients should receive the recommended course of action, whereas a conditional recommendation means that different choices will be appropriate for different patients. RESULTS: Consensus was reached on 15 of 20 questions. Recommendations address the following vaccines: Haemophilus influenzae type b, recombinant zoster, hepatitis B, influenza, pneumococcus, meningococcus, tetanus-diphtheria-pertussis, and human papillomavirus. Most of the recommendations for patients with IBD are congruent with the current Centers for Disease Control and Prevention and Canada's National Advisory Committee on Immunization recommendations for the general population, with the following exceptions. In patients with IBD, the panel suggested Haemophilus influenzae type b vaccine for patients older than 5 years of age, recombinant zoster vaccine for adults younger than 50 year of age, and hepatitis B vaccine for adults without a risk factor. Consensus was not reached, and recommendations were not made for 5 statements, due largely to lack of evidence, including double-dose hepatitis B vaccine, timing of influenza immunization in patients on biologics, pneumococcal and meningococcal vaccines in adult patients without risk factors, and human papillomavirus vaccine in patients aged 27-45 years. CONCLUSIONS: Patients with IBD may be at increased risk of some vaccine-preventable diseases. Therefore, maintaining appropriate vaccination status in these patients is critical to optimize patient outcomes. In general, IBD is not a contraindication to the use of inactivated vaccines, but immunosuppressive therapy may reduce vaccine responses.

Centenarians and extremely old people living with frailty can elicit durable SARS-CoV-2 spike specific IgG antibodies with virus neutralization functions following virus infection as determined by serological study.

BACKGROUND: The SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2) has led to more than 165 million COVID-19 cases and >3.4 million deaths worldwide. Epidemiological analysis has revealed that the risk of developing severe COVID-19 increases with age. Despite a disproportionate number of older individuals and long-term care facilities being affected by SARS-CoV-2 and COVID-19, very little is understood about the immune responses and development of humoral immunity in the extremely old person after SARS-CoV-2 infection. Here we conducted a serological study to investigate the development of humoral immunity in centenarians following a SARS-CoV-2 outbreak in a long-term care facility. METHODS: Extreme aged individuals and centenarians who were residents in a long-term care facility and infected with or exposed to SARS-CoV-2 were investigated between April and June 2020 for the development of antibodies to SARS-CoV-2. Blood samples were collected from positive and bystander individuals 30 and 60 days after original diagnosis of SARS-CoV-2 infection. Plasma was used to quantify IgG, IgA, and IgM isotypes and subsequent subclasses of antibodies specific for SARS-CoV-2 spike protein. The function of anti-spike was then assessed by virus neutralization assays against the native SARS-CoV-2 virus. FINDINGS: Fifteen long-term care residents were investigated for SARS-CoV-2 infection. All individuals had a Clinical Frailty scale score ≥5 and were of extreme older age or were centenarians. Six women with a median age of 98.8 years tested positive for SARS-CoV-2. Anti-spike IgG antibody titers were the highest titers observed in our cohort with all IgG positive individuals having virus neutralization ability. Additionally, 5 out of the 6 positive participants had a robust IgA anti-SARS-CoV-2 response. In all 5, antibodies were detected after 60 days from initial diagnosis.

COVID-19, frailty and long-term care: Implications for policy and practice.

Older adults have been disproportionately affected by the COVID-19 pandemic, with many outbreaks occurring in Long Term Care Facilities (LTCFs). We discuss this vulnerability among LTCF residents using an ecological framework, on levels spanning from the individual to families and caregivers, institutions, health services and systems, communities, and contextual government policies. Challenges abound for fully understanding the burden of COVID-19 in LTCF, including differences in nomenclature, data collection systems, cultural differences, varied social welfare models, and (often) under-resourcing of the LTC sector. Registration of cases and deaths may be limited by testing capacity and policy, record-keeping and reporting procedures. Hospitalization and death rates may be inaccurate depending on atypical presentations and whether or not residents' goals of care include escalation of care and transfer to hospital. Given the important contribution of frailty, use of the Clinical Frailty Scale (CFS) is discussed as a readily implementable measure, as are lessons learned from the study of frailty in relation to influenza. Biomarkers hold emerging promise in helping to predict disease severity and address the puzzle of why some frail LTCF residents are resilient to COVID-19, either remaining test-negative despite exposure or having asymptomatic infection, while others experience the full range of illness severity including critical illness and death. Strong and coordinated surveillance and research focused on LTCFs and their frail residents is required. These efforts should include widespread assessment of frailty using feasible and readily implementable tools such as the CFS, and rigorous reporting of morbidity and mortality in LTCFs.