Understanding the age spectrum of respiratory syncytial virus associated hospitalisation and mortality burden based on statistical modelling methods: a systematic analysis.

BACKGROUND: Statistical modelling studies based on excess morbidity and mortality are important for understanding RSV disease burden for age groups that are less frequently tested for RSV. We aimed to understand the full age spectrum of RSV morbidity and mortality burden based on statistical modelling studies, as well as the value of modelling studies in RSV disease burden estimation. METHODS: The databases Medline, Embase and Global Health were searched to identify studies published between January 1, 1995, and December 31, 2021, reporting RSV-associated excess hospitalisation or mortality rates of any case definitions using a modelling approach. All reported rates were summarised using median, IQR (Interquartile range) and range by age group, outcome and country income group; where applicable, a random-effects meta-analysis was conducted to combine the reported rates. We further estimated the proportion of RSV hospitalisations that could be captured in clinical databases. RESULTS: A total of 32 studies were included, with 26 studies from high-income countries. RSV-associated hospitalisation and mortality rates both showed a U-shape age pattern. Lowest and highest RSV acute respiratory infection (ARI) hospitalisation rates were found in 5-17 years (median: 1.6/100,000 population, IQR: 1.3-18.5) and < 1 year (2235.7/100,000 population, 1779.1-3552.5), respectively. Lowest and highest RSV mortality rates were found in 18-49 years (0.1/100,000 population, 0.06-0.2) and ≥ 75 years (80.0/100,000 population, 70.0-90.0) for high-income countries, respectively, and in 18-49 years (0.3/100,000 population, 0.1-2.4) and < 1 year (143.4/100,000 population, 143.4-143.4) for upper-middle income countries. More than 70% of RSV hospitalisations in children < 5 years could be captured in clinical databases whereas less than 10% of RSV hospitalisations could be captured in adults, especially for adults ≥ 50 years. Using pneumonia and influenza (P&I) mortality could potentially capture half of all RSV mortality in older adults but only 10-30% of RSV mortality in children. CONCLUSIONS: Our study provides insights into the age spectrum of RSV hospitalisation and mortality. RSV disease burden using laboratory records alone could be substantially severely underreported for age groups ≥ 5 years. Our findings confirm infants and older adults should be prioritised for RSV immunisation programmes. TRIAL REGISTRATION: PROSPERO CRD42020173430.

Risk factors for poor outcomes in hospitalised COVID-19 patients: A systematic review and meta-analysis.

BACKGROUND: Understanding the risk factors for poor outcomes among COVID-19 patients could help identify vulnerable populations who would need prioritisation in prevention and treatment for COVID-19. We aimed to critically appraise and synthesise published evidence on the risk factors for poor outcomes in hospitalised COVID-19 patients. METHODS: We searched PubMed, medRxiv and the WHO COVID-19 literature database for studies that reported characteristics of COVID-19 patients who required hospitalisation. We included studies published between January and May 2020 that reported adjusted effect size of any demographic and/or clinical factors for any of the three poor outcomes: mortality, intensive care unit (ICU) admission, and invasive mechanical ventilation. We appraised the quality of the included studies using Joanna Briggs Institute appraisal tools and quantitatively synthesised the evidence through a series of random-effect meta-analyses. To aid data interpretation, we further developed an interpretation framework that indicated strength of the evidence, informed by both quantity and quality of the evidence. RESULTS: We included a total of 40 studies in our review. Most of the included studies (29/40, 73%) were assessed as "good quality", with assessment scores of 80 or more. We found that male sex (pooled odds ratio (OR) = 1.32 (95% confidence interval (CI) = 1.18-1.48; 20 studies), older age (OR = 1.05, 95% CI = 1.04-1.07, per one year of age increase; 10 studies), obesity (OR = 1.59, 95% CI = 1.02-2.48; 4 studies), diabetes (OR = 1.25, 95% CI = 1.11-1.40; 11 studies) and chronic kidney diseases (6 studies; OR = 1.57, 95% CI = 1.27-1.93) were associated with increased risks for mortality with the greatest strength of evidence based on our interpretation framework. We did not find increased risk of mortality for several factors including chronic obstructive pulmonary diseases (5 studies), cancer (4 studies), or current smoker (5 studies); however, this does not indicate absence of risk due to limited data on each of these factors. CONCLUSION: Male sex, older age, obesity, diabetes and chronic kidney diseases are important risk factors of COVID-19 poor outcomes. Our review provides not only an appraisal and synthesis of evidence on the risk factors of COVID-19 poor outcomes, but also a data interpretation framework that could be adopted by relevant future research.

National burden estimates of hospitalisations for acute lower respiratory infections due to respiratory syncytial virus in young children in 2019 among 58 countries: a modelling study.

BACKGROUND: Respiratory syncytial virus (RSV) is the predominant viral pathogen associated with acute lower respiratory infection (ALRI) in children who are younger than 5 years. Little is reported on the national estimates of RSV-associated ALRI hospitalisations in these children on the basis of robust epidemiological data. We aimed to generate national level estimates for RSV-associated ALRI hospitalisations in children aged younger than 5 years. METHODS: We included data for RSV and ALRI hospitalisation in children who were younger than 5 years from systematic literature reviews (including unpublished data) and from inpatient databases, representing 58 countries. We used two different methods, the rate-based method and the proportion-based method, to estimate national RSV-associated ALRI hospitalisations in children younger than 5 years in 2019. The rate-based method synthesised data for laboratory-confirmed RSV-associated ALRI hospitalisation rates using a spatiotemporal Gaussian process meta-regression (ST-GPR). The proportion-based method applied data for RSV positive proportions among ALRI to all-cause ALRI hospitalisation envelopes (ie, total disease burden of ALRI hospitalisations of any cause) using a Bayesian regularised trimmed meta-regression (MR-BRT). Where applicable, we reported estimates by both methods to provide a plausible range for each country. FINDINGS: A total of 334 studies and 1985 data points (defined as an individual estimate for one age group and 1 year for each study) were included in our analysis, accounting for 398 million (59%) of the 677 million children aged younger than 5 years worldwide representing 58 countries. We reported the number of annual national RSV-associated ALRI hospitalisations for 29 countries using the rate-based method, and for 42 countries using the proportion-based method. The median number of RSV-associated ALRI hospitalisations in children younger than 5 years was 8·25 thousand (IQR 1·97-48·01), and the median rate of RSV-associated ALRI hospitalisations was 514 (339-866) hospitalisations per thousand children younger than 5 years. Despite large variation among countries, a high proportion of the RSV-associated ALRI hospitalisations were in infants aged younger than 1 year in all countries (median proportion 45%, IQR 32-56). In 272 (76%) of the 358 years included in the analysis, the RSV-associated ALRI hospitalisation rate fluctuated between 0·8 and 1·2 times the country's median yearly rate. General agreement was observed between estimates by the rate-based method and proportion-based method, with the exceptions of India, Kenya, Norway, and Philippines. INTERPRETATION: By incorporating data from various sources, our study provides robust estimates on national level burden of RSV-associated ALRI hospitalisation in children aged younger than 5 years. These estimates are important for informing policy for the introduction of RSV immunisations and also serve as baseline data for the RSV disease burden in young children. FUNDING: The Foundation for Influenza Epidemiology.