Daily Respiratory Research Analysis
Three impactful studies advance respiratory science and practice: a prospective household cohort shows SARS-CoV-2 within-host evolution is dominated by drift and purifying selection with rare, spike-focused positive selection; a validated, 15-item CAP Risk Score stratifies 5‑year community-acquired pneumonia risk in adults; and modeling from German insurance data quantifies substantial RSV-attributable cardio‑respiratory hospitalizations in older adults.
Summary
Three impactful studies advance respiratory science and practice: a prospective household cohort shows SARS-CoV-2 within-host evolution is dominated by drift and purifying selection with rare, spike-focused positive selection; a validated, 15-item CAP Risk Score stratifies 5‑year community-acquired pneumonia risk in adults; and modeling from German insurance data quantifies substantial RSV-attributable cardio‑respiratory hospitalizations in older adults.
Research Themes
- Within-host viral evolution and immune selection in respiratory infections
- Risk prediction and prevention strategies for community-acquired pneumonia
- Population burden modeling of RSV-attributable cardio-respiratory hospitalizations
Selected Articles
1. In depth sequencing of a serially sampled household cohort reveals the within-host dynamics of Omicron SARS-CoV-2 and rare selection of novel spike variants.
Daily longitudinal sampling with replicate sequencing of 105 individuals (577 specimens) during early Omicron revealed very low within-host diversity and evolutionary rates, with dynamics dominated by drift and purifying selection. Positive selection events were rare but concentrated in spike (14 loci; 7 in spike, including S:448 and S:339), indicating narrow antibody-driven selection pressure during early Omicron.
Impact: This study rigorously quantifies within-host evolutionary dynamics of Omicron using high-frequency sampling and ABC modeling, clarifying when and where immune selection occurs during acute infection.
Clinical Implications: Findings inform surveillance and vaccine strategies by showing that meaningful within-host positive selection is rare and spike-focused, suggesting targeted monitoring of spike mutations and emphasizing population-level selection as the main driver.
Key Findings
- Sequenced 577 specimens from 105 individuals with daily longitudinal sampling during BA.1/BA.2.
- Within-host diversity and evolutionary rate were very low; dynamics dominated by drift and purifying selection.
- Wright–Fisher ABC modeling identified 14 positively selected loci (7 in spike, including S:448 and S:339).
Methodological Strengths
- Daily longitudinal sampling with replicate sequencing to reduce variant-calling threshold and errors
- Use of Wright–Fisher Approximate Bayesian Computation to infer selection within hosts
Limitations
- Study confined to early Omicron period; generalizability to other variants or later Omicron waves may differ
- Acute infections; limited inclusion of immunocompromised or chronically infected hosts where selection may differ
Future Directions: Extend high-frequency within-host sequencing to diverse host phenotypes (e.g., immunocompromised), variant contexts, and post-vaccination settings to map selection landscapes and transmission potential.
SARS-CoV-2 has undergone repeated and rapid evolution to circumvent host immunity. However, outside of prolonged infections in immunocompromised hosts, within-host positive selection has rarely been detected. Here we combine daily longitudinal sampling of individuals with replicate sequencing to increase the accuracy of and lower the threshold for variant calling. We sequenced 577 specimens from 105 individuals in a household cohort during the BA.1/BA.2 variant period. Individuals exhibited extremely low viral diversity, and we estimated a low within-host evolutionary rate. Within-host dynamics were dominated by genetic drift and purifying selection. Positive selection was rare but highly concentrated in spike. A Wright Fisher Approximate Bayesian Computational model identified positive selection at 14 loci with 7 in spike, including S:448 and S:339. This detectable immune-mediated selection is unusual in acute respiratory infections and may be caused by the relatively narrow antibody repertoire in individuals during the early Omicron phase of the SARS-CoV-2 pandemic.
2. Development and validation of a risk score to predict community-acquired pneumonia occurrence in the adult population.
A 15-item CAP Risk Score derived from population-based studies and validated in a five-year cohort of 47,836 adults (786 incident CAP cases) showed moderate discrimination (AUC 0.67) and stratified adults into graded annual risk tiers. Rising scores correlated with higher CAP incidence, supporting practical targeting of preventive strategies.
Impact: This work offers a validated, implementable risk tool for adult CAP that can guide vaccination, lifestyle counseling, and proactive monitoring at the primary care level.
Clinical Implications: Primary care can use CAP-RS to identify high-risk adults for vaccination (e.g., pneumococcal, influenza, RSV where appropriate), comorbidity optimization, and targeted prevention programs over a 5‑year horizon.
Key Findings
- Developed a 15-item CAP risk score using population-based case-control data with odds-ratio weighting.
- Validated in a 5-year retrospective cohort of 47,836 adults with 786 incident CAP cases; AUC-ROC 0.67.
- Established practical cut-offs (<1, <5, <10 points) that stratify annual CAP incidence into graded risk tiers.
Methodological Strengths
- Population-based development with external validation in a large cohort over 5 years
- Transparent weighting of predictors by odds ratios with prespecified cut-offs
Limitations
- Moderate discrimination (AUC ~0.67) limits individual-level precision
- Generalizability outside the studied region and healthcare context requires assessment
Future Directions: Calibrate and update CAP-RS across diverse populations, incorporate biomarker or imaging data, and test clinical impact in pragmatic trials.
BACKGROUND: Community-acquired pneumonia (CAP) preventive strategies can benefit from a quantification of individual CAP risk. This study develops and validates a CAP Risk Score (CAP-RS) for the adult population to predict CAP occurrence in the next five years. METHODS: The development phase was as follows: a population-based case-control study to identify potential CAP risk factors for inclusion in the CAP-RS after weighting according to odds ratios; development of a numerical scoring system for weighted risk factors; and establishment of cut-off points to discriminate between different risk levels. The validation phase consisted of a population-based case-control study and a retrospective cohort study (with 47 836 adults aged ≥18 years corresponding to three Maresme (Barcelona) primary care centres) followed up over a five-year period (2015-2019). RESULTS: 786 new CAP cases were identified. 15 factors were included in the CAP-RS. Risk was higher in subjects with CAP than without CAP (4.5 vs 1.9; p < 0.001), and the association (OR) between the CAP-RS and the occurrence of CAP increased as the CAP-RS value increased. AUC-ROC was 0.67 (p < 0.001). Cut-offs were established at <1, <5, and <10 points as best discriminating between risk groups. Annual CAP incidence was 1.9, 3.1, 6.2, and 12.4 new cases/10 CONCLUSIONS: The 15-item CAP-RS, which stratifies risk with good validity, can aid in the design and implementation of preventive CAP strategies for adult populations.
3. Estimated Incidence Rate of Specific Types of Cardiovascular and Respiratory Hospitalizations Attributable to Respiratory Syncytial Virus Among Adults in Germany Between 2015 and 2019.
Using statutory insurance data and quasi-Poisson models, the study estimated age-related RSV-attributable hospitalization rates for specific cardio-respiratory conditions in adults. In those ≥60 years, arrhythmia and ischemic heart disease (cardiovascular), and chronic lower respiratory disease and bronchitis/bronchiolitis (respiratory) showed the highest annual attributable incidences, underscoring prevention needs.
Impact: The work quantifies hidden RSV burden across cardio-respiratory endpoints using robust time-series modeling, informing vaccine and monoclonal antibody policy in older adults.
Clinical Implications: Supports prioritizing RSV immunization strategies (e.g., older adults) and integrating RSV into differential diagnosis and hospital preparedness for cardio-respiratory admissions during RSV seasons.
Key Findings
- Applied quasi-Poisson regression to insurance claims to estimate RSV-attributable hospitalizations by condition.
- In adults ≥60 years, RSV-attributable cardiovascular hospitalizations were highest for arrhythmia and ischemic heart disease (≈157–260 and 133–214 per 100,000 PY).
- Respiratory endpoints with highest RSV-attributable rates in ≥60 were chronic lower respiratory diseases and bronchitis/bronchiolitis (≈103–168 and 77–122 per 100,000 PY).
Methodological Strengths
- Large-scale administrative data with quasi-Poisson modeling adjusting for temporal trends and circulating viruses
- Condition-specific attribution across both cardiovascular and respiratory endpoints
Limitations
- Attribution relies on ecological time-series modeling, not individual-level RSV testing
- Potential misclassification and residual confounding inherent to claims data
Future Directions: Link individual testing to claims to refine attribution, evaluate cost-effectiveness of RSV immunization in older adults, and extend to multi-country comparisons.
BACKGROUND: RSV incidence in adults is frequently underestimated due to non-specific symptomatology, limited standard-of-care testing, and lower test sensitivity compared to infants. We conducted a retrospective observational study to estimate RSV-attributable incidence of specific types of cardiorespiratory hospitalizations among adults in Germany between 2015 and 2019. METHODS: Information on hospitalizations and the number of people at risk of hospitalization (denominator) was gathered from a Statutory Health Insurance database. A quasi-Poisson regression model accounting for periodic and aperiodic time trends and virus activity was fitted to estimate the RSV-attributable incidence rate (IR) of four specific cardiovascular hospitalizations (arrhythmia, ischemic heart diseases, chronic heart failure exacerbations, and cerebrovascular diseases) and four specific respiratory hospitalizations (influenza/pneumonia, bronchitis/bronchiolitis, chronic lower respiratory tract diseases, and upper respiratory tract diseases). RESULTS: The estimated RSV-attributable IRs of hospitalizations generally increased with age. Among estimated cardiovascular hospitalizations in adults aged ≥ 60 years, arrhythmia and ischemic heart diseases accounted for the highest incidence of RSV-attributable events, followed by chronic heart failure exacerbation, with annual IR ranges of 157-260, 133-214, and 105-169 per 100,000 person-years, respectively. The most frequent RSV-attributable respiratory hospitalizations in adults aged ≥ 60 years were estimated for chronic lower respiratory tract diseases and bronchitis/bronchiolitis, with annual IR ranges of 103-168 and 77-122 per 100,000 person-years, respectively. CONCLUSIONS: RSV causes a considerable burden of respiratory and cardiovascular hospitalizations in adults in Germany, similar to other respiratory viruses (e.g., influenza and SARS-CoV-2). This highlights the need to implement effective prevention strategies, especially for older adults.