Measuring waning protection from seasonal influenza vaccination during nine influenza seasons, Ontario, Canada, 2010/11 to 2018/19.

BackgroundWaning immunity from seasonal influenza vaccination can cause suboptimal protection during peak influenza activity. However, vaccine effectiveness studies assessing waning immunity using vaccinated and unvaccinated individuals are subject to biases.AimWe examined the association between time since vaccination and laboratory-confirmed influenza to assess the change in influenza vaccine protection over time.MethodsUsing linked laboratory and health administrative databases in Ontario, Canada, we identified community-dwelling individuals aged ≥ 6 months who received an influenza vaccine before being tested for influenza by RT-PCR during the 2010/11 to 2018/19 influenza seasons. We estimated the adjusted odds ratio (aOR) for laboratory-confirmed influenza by time since vaccination (categorised into intervals) and for every 28 days.ResultsThere were 53,065 individuals who were vaccinated before testing for influenza, with 10,264 (19%) influenza-positive cases. The odds of influenza increased from 1.05 (95% CI: 0.91-1.22) at 42-69 days after vaccination and peaked at 1.27 (95% CI: 1.04-1.55) at 126-153 days when compared with the reference interval (14-41 days). This corresponded to 1.09-times increased odds of influenza every 28 days (aOR = 1.09; 95% CI: 1.04-1.15). Individuals aged 18-64 years showed the greatest decline in protection against influenza A(H1N1) (aORper 28 days = 1.26; 95% CI: 0.97-1.64), whereas for individuals aged ≥ 65 years, it was against influenza A(H3N2) (aORper 28 days = 1.20; 95% CI: 1.08-1.33). We did not observe evidence of waning vaccine protection for individuals aged < 18 years.ConclusionsInfluenza vaccine protection wanes during an influenza season. Understanding the optimal timing of vaccination could ensure robust protection during seasonal influenza activity.

Effectiveness of maternal influenza vaccination during pregnancy against laboratory-confirmed seasonal influenza among infants under 6 months of age in Ontario, Canada.

BACKGROUND: Randomized trials conducted in low- and middle-income settings demonstrated efficacy of influenza vaccination during pregnancy against influenza infection among infants <6 months of age. However, vaccine effectiveness (VE) estimates from settings with different population characteristics and influenza seasonality remain limited. METHODS: We conducted a test-negative study in Ontario, Canada. All influenza virus tests among infants <6 months from 2010-2019 were identified and linked with health databases to ascertain information on maternal-infant dyads. VE was estimated from the odds ratio for influenza vaccination during pregnancy among cases versus controls, computed using logistic regression with adjustment for potential confounders. RESULTS: Among 23,806 infants tested for influenza, 1,783 (7.5%) were positive and 1,708 (7.2%) were born to mothers vaccinated against influenza during pregnancy. VE against laboratory-confirmed infant influenza infection was 64% (95% confidence interval [CI]: 50%-74%). VE was similar by trimester of vaccination (1st/2nd: 66%, 40%-80%; 3rd: 63%, 46%-74%), infant age at testing (0-<2 months: 63%, 46%-75%; 2-<6 months: 64%, 36%-79%), and gestational age at birth (≥37 weeks: 64%, 50%-75%; < 37 weeks: 61%, 4%-86%). VE against influenza hospitalization was 67% (95%CI: 50%-78%). CONCLUSIONS: Influenza vaccination during pregnancy offers effective protection to infants <6 months, for whom vaccines are not currently available.

The bad and the good of trends in model building and refinement for sparse-data regions: pernicious forms of overfitting versus good new tools and predictions.

Model building and refinement, and the validation of their correctness, are very effective and reliable at local resolutions better than about 2.5 Šfor both crystallography and cryo-EM. However, at local resolutions worse than 2.5 Šboth the procedures and their validation break down and do not ensure reliably correct models. This is because in the broad density at lower resolution, critical features such as protein backbone carbonyl O atoms are not just less accurate but are not seen at all, and so peptide orientations are frequently wrongly fitted by 90-180°. This puts both backbone and side chains into the wrong local energy minimum, and they are then worsened rather than improved by further refinement into a valid but incorrect rotamer or Ramachandran region. On the positive side, new tools are being developed to locate this type of pernicious error in PDB depositions, such as CaBLAM, EMRinger, Pperp diagnosis of ribose puckers, and peptide flips in PDB-REDO, while interactive modeling in Coot or ISOLDE can help to fix many of them. Another positive trend is that artificial intelligence predictions such as those made by AlphaFold2 contribute additional evidence from large multiple sequence alignments, and in high-confidence parts they provide quite good starting models for loops, termini or whole domains with otherwise ambiguous density.

Evaluating the Impact of Statin Use on Influenza Vaccine Effectiveness and Influenza Infection in Older Adults.

BACKGROUND: Older adults are recommended to receive influenza vaccination annually, and many use statins. Statins have immunomodulatory properties that might modify influenza vaccine effectiveness (VE) and alter influenza infection risk. METHODS: Using the test-negative design and linked laboratory and health administrative databases in Ontario, Canada, we estimated VE against laboratory-confirmed influenza among community-dwelling statin users and nonusers aged ≥66 years during the 2010-2011 to 2018-2019 influenza seasons. We also estimated the odds ratio for influenza infection comparing statin users and nonusers by vaccination status. RESULTS: Among persons tested for influenza across the 9 seasons, 54 243 had continuous statin exposure before testing and 48 469 were deemed unexposed. The VE against laboratory-confirmed influenza was similar between statin users and nonusers (17% [95% confidence interval, 13%-20%] and 17% [13%-21%] respectively; test for interaction, P = .87). In both vaccinated and unvaccinated persons, statin users had higher odds of laboratory-confirmed influenza than nonusers (odds ratios for vaccinated and unvaccinated persons 1.15 [95% confidence interval, 1.10-1.21] and 1.15 [1.10-1.20], respectively). These findings were consistent by mean daily dose and statin type. VE did not differ between users and nonusers of other cardiovascular drugs, except for ß-blockers. We did not observe that vaccinated and unvaccinated users of these drugs had increased odds of influenza, except for unvaccinated ß-blocker users. CONCLUSIONS: Influenza VE did not differ between statin users and nonusers. Statin use was associated with increased odds of laboratory-confirmed influenza in vaccinated and unvaccinated persons, but these associations might be affected by residual confounding.

Long-term ice phenology records spanning up to 578 years for 78 lakes around the Northern Hemisphere.

In recent decades, lakes have experienced unprecedented ice loss with widespread ramifications for winter ecological processes. The rapid loss of ice, resurgence of winter biology, and proliferation of remote sensing technologies, presents a unique opportunity to integrate disciplines to further understand the broad spatial and temporal patterns in ice loss and its consequences. Here, we summarize ice phenology records for 78 lakes in 12 countries across North America, Europe, and Asia to permit the inclusion and harmonization of in situ ice phenology observations in future interdisciplinary studies. These ice records represent some of the longest climate observations directly collected by people. We highlight the importance of applying the same definition of ice-on and ice-off within a lake across the time-series, regardless of how the ice is observed, to broaden our understanding of ice loss across vast spatial and temporal scales.

A functional definition to distinguish ponds from lakes and wetlands.

Ponds are often identified by their small size and shallow depths, but the lack of a universal evidence-based definition hampers science and weakens legal protection. Here, we compile existing pond definitions, compare ecosystem metrics (e.g., metabolism, nutrient concentrations, and gas fluxes) among ponds, wetlands, and lakes, and propose an evidence-based pond definition. Compiled definitions often mentioned surface area and depth, but were largely qualitative and variable. Government legislation rarely defined ponds, despite commonly using the term. Ponds, as defined in published studies, varied in origin and hydroperiod and were often distinct from lakes and wetlands in water chemistry. We also compared how ecosystem metrics related to three variables often seen in waterbody definitions: waterbody size, maximum depth, and emergent vegetation cover. Most ecosystem metrics (e.g., water chemistry, gas fluxes, and metabolism) exhibited nonlinear relationships with these variables, with average threshold changes at 3.7 ± 1.8 ha (median: 1.5 ha) in surface area, 5.8 ± 2.5 m (median: 5.2 m) in depth, and 13.4 ± 6.3% (median: 8.2%) emergent vegetation cover. We use this evidence and prior definitions to define ponds as waterbodies that are small (< 5 ha), shallow (< 5 m), with < 30% emergent vegetation and we highlight areas for further study near these boundaries. This definition will inform the science, policy, and management of globally abundant and ecologically significant pond ecosystems.

The importance of residue-level filtering and the Top2018 best-parts dataset of high-quality protein residues.

We have curated a high-quality, "best-parts" reference dataset of about 3 million protein residues in about 15,000 PDB-format coordinate files, each containing only residues with good electron density support for a physically acceptable model conformation. The resulting prefiltered data typically contain the entire core of each chain, in quite long continuous fragments. Each reference file is a single protein chain, and the total set of files were selected for low redundancy, high resolution, good MolProbity score, and other chain-level criteria. Then each residue was critically tested for adequate local map quality to firmly support its conformation, which must also be free of serious clashes or covalent-geometry outliers. The resulting Top2018 prefiltered datasets have been released on the Zenodo online web service and are freely available for all uses under a Creative Commons license. Currently, one dataset is residue filtered on main chain plus Cß atoms, and a second dataset is full-residue filtered; each is available at four different sequence-identity levels. Here, we illustrate both statistics and examples that show the beneficial consequences of residue-level filtering. That process is necessary because even the best of structures contain a few highly disordered local regions with poor density and low-confidence conformations that should not be included in reference data. Therefore, the open distribution of these very large, prefiltered reference datasets constitutes a notable advance for structural bioinformatics and the fields that depend upon it.

Seeing the PDB.

Ever since the first structures of proteins were determined in the 1960s, structural biologists have required methods to visualize biomolecular structures, both as an essential tool for their research and also to promote 3D comprehension of structural results by a wide audience of researchers, students, and the general public. In this review to celebrate the 50th anniversary of the Protein Data Bank, we present our own experiences in developing and applying methods of visualization and analysis to the ever-expanding archive of protein and nucleic acid structures in the worldwide Protein Data Bank. Across that timespan, Jane and David Richardson have concentrated on the organization inside and between the macromolecules, with ribbons to show the overall backbone "fold" and contact dots to show how the all-atom details fit together locally. David Goodsell has explored surface-based representations to present and explore biological subjects that range from molecules to cells. This review concludes with some ideas about the current challenges being addressed by the field of biomolecular visualization.

Improving SARS-CoV-2 structures: Peer review by early coordinate release.

This work builds upon the record-breaking speed and generous immediate release of new experimental three-dimensional structures of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins and complexes, which are crucial to downstream vaccine and drug development. We have surveyed those structures to catch the occasional errors that could be significant for those important uses and for which we were able to provide demonstrably higher-accuracy corrections. This process relied on new validation and correction methods such as CaBLAM and ISOLDE, which are not yet in routine use. We found such important and correctable problems in seven early SARS-CoV-2 structures. Two of the structures were soon superseded by new higher-resolution data, confirming our proposed changes. For the other five, we emailed the depositors a documented and illustrated report and encouraged them to make the model corrections themselves and use the new option at the worldwide Protein Data Bank for depositors to re-version their coordinates without changing the Protein Data Bank code. This quickly and easily makes the better-accuracy coordinates available to anyone who examines or downloads their structure, even before formal publication. The changes have involved sequence misalignments, incorrect RNA conformations near a bound inhibitor, incorrect metal ligands, and cis-trans or peptide flips that prevent good contact at interaction sites. These improvements have propagated into nearly all related structures done afterward. This process constitutes a new form of highly rigorous peer review, which is actually faster and more strict than standard publication review because it has access to coordinates and maps; journal peer review would also be strengthened by such access.

Influenza Vaccine Effectiveness Against All-Cause Mortality Following Laboratory-Confirmed Influenza in Older Adults, 2010-2011 to 2015-2016 Seasons in Ontario, Canada.

BACKGROUND: Older adults are at increased risk of mortality from influenza infections. We estimated influenza vaccine effectiveness (VE) against mortality following laboratory-confirmed influenza. METHODS: Using a test-negative design study and linked laboratory and health administrative databases in Ontario, Canada, we estimated VE against all-cause mortality following laboratory-confirmed influenza for community-dwelling adults aged >65 years during the 2010-2011 to 2015-2016 influenza seasons. RESULTS: Among 54 116 older adults tested for influenza across the 6 seasons, 6837 died within 30 days of specimen collection. Thirteen percent (925 individuals) tested positive for influenza, and 50.6% were considered vaccinated for that season. Only 23.2% of influenza test-positive cases had influenza recorded as their underlying cause of death. Before and after multivariable adjustment, we estimated VE against all-cause mortality following laboratory-confirmed influenza to be 20% (95% confidence interval [CI], 8%-30%) and 20% (95% CI, 7%-30%), respectively. This estimate increased to 34% after correcting for influenza vaccination exposure misclassification. We observed significant VE against deaths following influenza confirmation during 2014-2015 (VE = 26% [95% CI, 5%-42%]). We also observed significant VE against deaths following confirmation of influenza A/H1N1 and A/H3N2, and against deaths with COPD as the underlying cause. CONCLUSIONS: These results support the importance of influenza vaccination in older adults, who account for most influenza-associated deaths annually.

Deeper waters are changing less consistently than surface waters in a global analysis of 102 lakes.

Globally, lake surface water temperatures have warmed rapidly relative to air temperatures, but changes in deepwater temperatures and vertical thermal structure are still largely unknown. We have compiled the most comprehensive data set to date of long-term (1970-2009) summertime vertical temperature profiles in lakes across the world to examine trends and drivers of whole-lake vertical thermal structure. We found significant increases in surface water temperatures across lakes at an average rate of + 0.37 °C decade-1, comparable to changes reported previously for other lakes, and similarly consistent trends of increasing water column stability (+ 0.08 kg m-3 decade-1). In contrast, however, deepwater temperature trends showed little change on average (+ 0.06 °C decade-1), but had high variability across lakes, with trends in individual lakes ranging from - 0.68 °C decade-1 to + 0.65 °C decade-1. The variability in deepwater temperature trends was not explained by trends in either surface water temperatures or thermal stability within lakes, and only 8.4% was explained by lake thermal region or local lake characteristics in a random forest analysis. These findings suggest that external drivers beyond our tested lake characteristics are important in explaining long-term trends in thermal structure, such as local to regional climate patterns or additional external anthropogenic influences.

The impact of repeated vaccination using 10-year vaccination history on protection against influenza in older adults: a test-negative design study across the 2010/11 to 2015/16 influenza seasons in Ontario, Canada.

IntroductionAnnual influenza vaccination is recommended for older adults, but evidence regarding the impact of repeated vaccination has been inconclusive.AimWe investigated vaccine effectiveness (VE) against laboratory-confirmed influenza and the impact of repeated vaccination over 10 previous seasons on current season VE among older adults.MethodsWe conducted an observational test-negative study in community-dwelling adults aged > 65 years in Ontario, Canada for the 2010/11 to 2015/16 seasons by linking laboratory and health administrative data. We estimated VE using multivariable logistic regression. We assessed the impact of repeated vaccination by stratifying by previous vaccination history.ResultsWe included 58,304 testing episodes for respiratory viruses, with 11,496 (20%) testing positive for influenza and 31,004 (53%) vaccinated. Adjusted VE against laboratory-confirmed influenza for the six seasons combined was 21% (95% confidence interval (CI): 18 to 24%). Patients who were vaccinated in the current season, but had received no vaccinations in the previous 10 seasons, had higher current season VE (34%; 95%CI: 9 to 52%) than patients who had received 1-3 (26%; 95%CI: 13 to 37%), 4-6 (24%; 95%CI: 15 to 33%), 7-8 (13%; 95%CI: 2 to 22%), or 9-10 (7%; 95%CI: -4 to 16%) vaccinations (trend test p = 0.001). All estimates were higher after correcting for misclassification of current season vaccination status. For patients who were not vaccinated in the current season, residual protection rose significantly with increasing numbers of vaccinations received previously.ConclusionsAlthough VE appeared to decrease with increasing numbers of previous vaccinations, current season vaccination likely provides some protection against influenza regardless of the number of vaccinations received over the previous 10 influenza seasons.

Influenza Vaccine Effectiveness in Preventing Hospitalizations in Older Patients With Chronic Obstructive Pulmonary Disease.

BACKGROUND: Annual influenza immunization is recommended for people with chronic obstructive pulmonary disease (COPD) by all major COPD clinical practice guidelines. We sought to determine the seasonal influenza vaccine effectiveness (VE) against laboratory-confirmed influenza-associated hospitalizations among older adults with COPD. METHODS: We conducted a test-negative study of influenza VE in community-dwelling older adults with COPD in Ontario, Canada using health administrative data and respiratory specimens collected from patients tested for influenza during the 2010-11 to 2015-16 influenza seasons. Influenza vaccination was ascertained from physician and pharmacist billing claims. Multivariable logistic regression was used to estimate the adjusted odds ratio of influenza vaccination in people with, compared to those without, laboratory-confirmed influenza. RESULTS: Receipt of seasonal influenza vaccine was associated with an adjusted 22% (95% confidence interval [CI], 15%-27%) reduction in laboratory-confirmed influenza-associated hospitalization. Adjustment for potential misclassification of vaccination status increased this to 43% (95% CI, 35%-52%). Vaccine effectiveness was not found to vary by patient- or influenza-related variables. CONCLUSIONS: During the studied influenza seasons, influenza vaccination was at least modestly effective in reducing laboratory-confirmed influenza-associated hospitalizations in people with COPD. The imperfect effectiveness emphasizes the need for better influenza vaccines and other preventive strategies.

New tools in MolProbity validation: CaBLAM for CryoEM backbone, UnDowser to rethink "waters," and NGL Viewer to recapture online 3D graphics.

The MolProbity web service provides macromolecular model validation to help correct local errors, for the structural biology community worldwide. Here we highlight new validation features, and also describe how we are fighting back against outside developments which compromise that mission. Our new tool called UnDowser analyzes the properties and context of clashing HOH "waters" to diagnose what they might actually represent; a dozen distinct scenarios are illustrated and described. We now treat alternate conformations more thoroughly, and switching to the Neo4j database (graphical rather than relational) enables cleaner, more comprehensive, and much larger reference datasets. A problematic outside change is that refinement software now increasingly restrains traditional validation criteria (geometry, clashes, rotamers, and even Ramachandran) in order to supplement the sparser experimental data at 3-4 Å resolutions typical of modern cryoEM. But unfortunately the broad density allows model optimization without fixing underlying problems, which means these structures often score much better on validation than they really are. CaBLAM, our tool designed for evaluating peptide orientations at lower resolutions, was described in the previous Tools issue, and here we demonstrate its effectiveness in diagnosing local errors even when other validation outliers have been artificially removed. Sophisticated hacking of the MolProbity server has required continual monitoring and various security measures short of restricting user access. The deprecation of Java applets now prevents KiNG interactive online display of outliers on the 3D model during a MolProbity run, but that important functionality has now been recaptured with a modified version of the Javascript NGL Viewer.

Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix.

Diffraction (X-ray, neutron and electron) and electron cryo-microscopy are powerful methods to determine three-dimensional macromolecular structures, which are required to understand biological processes and to develop new therapeutics against diseases. The overall structure-solution workflow is similar for these techniques, but nuances exist because the properties of the reduced experimental data are different. Software tools for structure determination should therefore be tailored for each method. Phenix is a comprehensive software package for macromolecular structure determination that handles data from any of these techniques. Tasks performed with Phenix include data-quality assessment, map improvement, model building, the validation/rebuilding/refinement cycle and deposition. Each tool caters to the type of experimental data. The design of Phenix emphasizes the automation of procedures, where possible, to minimize repetitive and time-consuming manual tasks, while default parameters are chosen to encourage best practice. A graphical user interface provides access to many command-line features of Phenix and streamlines the transition between programs, project tracking and re-running of previous tasks.

Influenza Vaccine Effectiveness Among Patients With Cancer: A Population-Based Study Using Health Administrative and Laboratory Testing Data From Ontario, Canada.

PURPOSE: Seasonal influenza vaccination is recommended for patients with cancer despite concerns of disease or treatment-associated immunosuppression. The objective of this study was to evaluate vaccine effectiveness (VE) against laboratory-confirmed influenza for patients with cancer. PATIENTS AND METHODS: We conducted an observational test-negative design study of previously diagnosed patients with cancer 18 years of age and older who underwent influenza testing during the 2010-2011 to 2015-2016 influenza seasons in Ontario, Canada. We linked individual-level cancer registry, respiratory virus testing, and health administrative data to identify the study population and outcomes. Vaccination status was determined from physician and pharmacist billing claims. We used multivariable logistic regression to estimate VE, adjusting for age, sex, rurality, income quintile, cancer characteristics, chemotherapy exposure, comorbidities, previous health care use, influenza season, and calendar time. RESULTS: We identified 26,463 patients with cancer who underwent influenza testing, with 4,320 test-positive cases (16%) and 11,783 (45%) vaccinated. Mean age was 70 years, 52% were male, mean time since diagnosis was 6 years, 69% had solid tumor malignancies, and 23% received active chemotherapy. VE against laboratory-confirmed influenza was 21% (95% CI, 15% to 26%), and VE against laboratory-confirmed influenza hospitalization was 20% (95% CI, 13% to 26%). For patients with solid tumor malignancies, VE was 25% (95% CI, 18% to 31%), compared with 8% (95% CI, -5% to 19%) for patients with hematologic malignancies (P = .015). Active chemotherapy usage did not significantly affect VE, especially among patients with solid tumor cancer. CONCLUSION: Our results support recommendations for influenza vaccination for patients with cancer. VE was decreased for patients with hematologic malignancies, and there was no significant difference in VE among patients with solid tumor cancer receiving active chemotherapy. Strategies to optimize influenza prevention among patients with cancer are warranted.

Can routinely collected laboratory and health administrative data be used to assess influenza vaccine effectiveness? Assessing the validity of the Flu and Other Respiratory Viruses Research (FOREVER) Cohort.

BACKGROUND: Linking data on laboratory specimens collected during clinical practice with health administrative data permits highly powered vaccine effectiveness (VE) studies to be conducted at relatively low cost, but bias from using convenience samples is a concern. We evaluated the validity of using such data for estimating VE. METHODS: We created the Flu and Other Respiratory Viruses Research (FOREVER) Cohort by linking individual-level data on respiratory virus laboratory tests, hospitalizations, emergency department visits, and physician services. For community-dwelling adults aged > 65 years, we assessed the presence and magnitude of information and selection biases, generated VE estimates under various conditions, and compared our VE estimates with those from other studies. RESULTS: We included 65,648 unique testing episodes obtained from 54,434 individuals during the 2010-11 to 2015-16 influenza seasons. To examine information bias, we found the proportion testing positive for influenza for patients with unknown interval from illness onset to specimen collection was more similar to patients for whom illness onset date was ≤ 7 days before specimen collection than to patients for whom illness onset was > 7 days before specimen collection. To assess the presence of selection bias, we found the likelihood of influenza testing was comparable between vaccinated and unvaccinated individuals, although the adjusted odds ratios were significantly greater than 1 for some healthcare settings and during some influenza seasons. Over 6 seasons, VE estimates ranged between 36% (95%CI, 27-44%) in 2010-11 and 5% (95%CI, -2, 11%) in 2014-15. VE estimates were similar under a range of conditions, but were consistently higher when accounting for misclassification of vaccination status through a quantitative sensitivity analysis. VE estimates from the FOREVER Cohort were comparable to those from other studies. CONCLUSIONS: Routinely collected laboratory and health administrative data contained in the FOREVER Cohort can be used to estimate influenza VE in community-dwelling older adults.

Characteristics and Outcomes of Young Children Hospitalized With Laboratory-confirmed Influenza or Respiratory Syncytial Virus in Ontario, Canada, 2009-2014.

BACKGROUND: Respiratory illnesses are a major contributor to pediatric hospitalizations, with influenza and respiratory syncytial virus (RSV) causing substantial morbidity and cost each season. We compared the characteristics and outcomes of children 0-59 months of age who were hospitalized with laboratory-confirmed influenza or RSV between 2009 and 2014 in Ontario, Canada. METHODS: We included hospitalized children who were tested for influenza A, influenza B and RSV and were positive for a single virus. We characterized individuals by their demographics and healthcare utilization patterns and compared their hospital outcomes, in-hospital cost and postdischarge healthcare use by virus type and by presence of underlying comorbidities. RESULTS: We identified and analyzed 7659 hospitalizations during which a specimen tested positive for influenza or RSV. Children with RSV were the youngest whereas children with influenza B were the oldest [median ages 6 months (interquartile range: 2-17 months) and 25 months (interquartile range: 10-45 months), respectively]. Complex chronic conditions were more prevalent among children with all influenza (sub)types than RSV (31%-34% versus 20%). In-hospital outcomes were similar by virus type, but in children with comorbidities, postdischarge outcomes varied. We observed no differences in in-hospital cost between viruses or by presence of comorbidities [overall median cost: $4150 Canadian dollars (interquartile range: $3710-$4948)]. CONCLUSIONS: Influenza and RSV account for large numbers of pediatric hospitalizations. RSV and influenza were similar in terms of severity and cost in hospitalized children. Influenza vaccination should be promoted in pregnant women and young children, and a vaccine against RSV would mitigate the high burden of RSV.