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Viruses May 2024When designing live-attenuated respiratory syncytial virus (RSV) vaccine candidates, attenuating mutations can be developed through biologic selection or reverse-genetic...
When designing live-attenuated respiratory syncytial virus (RSV) vaccine candidates, attenuating mutations can be developed through biologic selection or reverse-genetic manipulation and may include point mutations, codon and gene deletions, and genome rearrangements. Attenuation typically involves the reduction in virus replication, due to direct effects on viral structural and replicative machinery or viral factors that antagonize host defense or cause disease. However, attenuation must balance reduced replication and immunogenic antigen expression. In the present study, we explored a new approach in order to discover attenuating mutations. Specifically, we used protein structure modeling and computational methods to identify amino acid substitutions in the RSV nonstructural protein 1 (NS1) predicted to cause various levels of structural perturbation. Twelve different mutations predicted to alter the NS1 protein structure were introduced into infectious virus and analyzed in cell culture for effects on viral mRNA and protein expression, interferon and cytokine expression, and caspase activation. We found the use of structure-based machine learning to predict amino acid substitutions that reduce the thermodynamic stability of NS1 resulted in various levels of loss of NS1 function, exemplified by effects including reduced multi-cycle viral replication in cells competent for type I interferon, reduced expression of viral mRNAs and proteins, and increased interferon and apoptosis responses.
Topics: Humans; Machine Learning; Viral Nonstructural Proteins; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Virus Replication; Vaccines, Attenuated; Respiratory Syncytial Virus Infections; Amino Acid Substitution; Mutation; Cell Line
PubMed: 38932114
DOI: 10.3390/v16060821 -
Communicable Diseases Intelligence... Jun 2024Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in infants. Little is known about the epidemiology, burden, and seasonality of RSV...
Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in infants. Little is known about the epidemiology, burden, and seasonality of RSV in subtropical regions of Australia like Central Queensland. This information is important to plan prevention strategies, including therapeutics, future vaccines, and health system preparedness. We collected data on laboratory-confirmed RSV cases and admissions in Central Queensland for the period 1 July 2021 to 31 December 2022. From July 2021, RSV was listed as a nationally notifiable condition on laboratory-confirmed diagnosis. During the study period, 1,142 laboratory-confirmed cases of RSV (50.0% female sex) were reported, with 169 cases (14.8%) requiring hospital admission, 12 of which (7.1%) required intensive care unit/high dependency unit admissions; two deaths occurred. Of cases requiring hospital admission, RSV was listed as the primary diagnosis in 113/169 cases (66.9%); 63/169 admitted cases (37.3%) had a major comorbidity. Of all cases, 55.4% were in children < 5 years of age (20.9% hospitalised); 35.7% in children < 2 years of age (24.3% hospitalised), and 19.1% in children < 12 months of age (27.5% hospitalised). Children under five years of age made up 78.1% of admissions, a rate of 9.0 admissions per 1,000 children over the 18-month study period, with an average age of 15.8 months (standard deviation, SD: 13.1 months) in this cohort. Indigenous children aged < 5 years were over-represented in cases (rate ratio, RR: 1.6; 95% confidence interval [95% CI]: 1.3-1.9) and admissions (RR: 1.6; 95% CI: 1.0-2.4). Antibiotics were prescribed to 48.5% of admitted cases under two years of age, despite documented bacterial infection in only 26.3% of these cases; antibiotic prescription was significantly higher in those who received a chest X-ray (p < 0.001). Of all cases, 33.5% occurred in July 2022 alone, with greater than 75.0% of cases occurring during June-August 2022. RSV showed year-round activity with a distinctive winter peak in 2022; however, this season was likely affected by coronavirus disease 2019 (COVID-19) restrictions and behaviours. Ongoing surveillance is required to better understand the epidemiology and seasonality of RSV in Central Queensland.
Topics: Humans; Respiratory Syncytial Virus Infections; Queensland; Female; Male; Infant; Child, Preschool; Hospitalization; Respiratory Syncytial Virus, Human; Child; Seasons; Adolescent; Infant, Newborn; Adult; Middle Aged
PubMed: 38926651
DOI: 10.33321/cdi.2024.48.45 -
Influenza and Other Respiratory Viruses Jun 2024Respiratory syncytial virus (RSV) and influenza infections cause significant annual morbidity and mortality worldwide in at-risk populations. This study is aimed at... (Comparative Study)
Comparative Study
BACKGROUND
Respiratory syncytial virus (RSV) and influenza infections cause significant annual morbidity and mortality worldwide in at-risk populations. This study is aimed at assessing hospital burden and healthcare resource utilization (HRU) of RSV and influenza in adults in Spain.
METHODS
Data were obtained from the Projected Hospitalisation Database of inpatient episodes (ages: younger adults 18-50 and 51-64 years; older adults 65-74, 75-84, and ≥ 85 years) during 2015, 2017, and 2018 in Spanish public hospitals. Incidence, mean hospitalization, and HRU assessments, including length of stay (LOS), intensive care unit (ICU) usage, and age-standardized mortality rates, were collected and stratified by age group, with analyses focusing on the adult population (≥ 18 years old).
RESULTS
Mean hospitalization rate in the population across all years was lower in individuals with RSV versus influenza (7.2/100,000 vs. 49.7/100,000 individuals). ICU admissions and median LOS were similar by age group for both viruses. Age-standardized mortality was 6.3/100,000 individuals and 6.1/100,000 individuals in patients with RSV and influenza, respectively, and mortality rates were similar in older adults (≥ 65 years) for both viruses.
CONCLUSIONS
RSV and influenza infection were associated with considerable HRU. There is a substantial disease burden for RSV infection in older adults ≥ 65 years. While RSV hospitalization rates in adults reported here appeared lower than influenza, RSV is still underdiagnosed in the hospital setting and its incidence might be similar to, or higher than, influenza.
Topics: Humans; Influenza, Human; Respiratory Syncytial Virus Infections; Middle Aged; Spain; Aged; Adult; Hospitalization; Young Adult; Adolescent; Aged, 80 and over; Male; Female; Incidence; Length of Stay; Cost of Illness; Respiratory Syncytial Virus, Human; Intensive Care Units
PubMed: 38923767
DOI: 10.1111/irv.13341 -
BMC Infectious Diseases Jun 2024Annual epidemics of respiratory syncytial virus (RSV) had consistent timing and intensity between seasons prior to the SARS-CoV-2 pandemic (COVID-19). However, starting...
BACKGROUND
Annual epidemics of respiratory syncytial virus (RSV) had consistent timing and intensity between seasons prior to the SARS-CoV-2 pandemic (COVID-19). However, starting in April 2020, RSV seasonal activity declined due to COVID-19 non-pharmaceutical interventions (NPIs) before re-emerging after relaxation of NPIs. We described the unusual patterns of RSV epidemics that occurred in multiple subsequent waves following COVID-19 in different countries and explored factors associated with these patterns.
METHODS
Weekly cases of RSV from twenty-eight countries were obtained from the World Health Organisation and combined with data on country-level characteristics and the stringency of the COVID-19 response. Dynamic time warping and regression were used to cluster time series patterns and describe epidemic characteristics before and after COVID-19 pandemic, and identify related factors.
RESULTS
While the first wave of RSV epidemics following pandemic suppression exhibited unusual patterns, the second and third waves more closely resembled typical RSV patterns in many countries. Post-pandemic RSV patterns differed in their intensity and/or timing, with several broad patterns across the countries. The onset and peak timings of the first and second waves of RSV epidemics following COVID-19 suppression were earlier in the Southern than Northern Hemisphere. The second wave of RSV epidemics was also earlier with higher population density, and delayed if the intensity of the first wave was higher. More stringent NPIs were associated with lower RSV growth rate and intensity and a shorter gap between the first and second waves.
CONCLUSION
Patterns of RSV activity have largely returned to normal following successive waves in the post-pandemic era. Onset and peak timings of future epidemics following disruption of normal RSV dynamics need close monitoring to inform the delivery of preventive and control measures.
Topics: Humans; COVID-19; Respiratory Syncytial Virus Infections; SARS-CoV-2; Global Health; Seasons; Respiratory Syncytial Virus, Human; Pandemics
PubMed: 38918718
DOI: 10.1186/s12879-024-09509-4 -
Scientific Reports Jun 2024Nonpharmaceutical interventions (NPIs) implemented during the COVID-19 pandemic have disrupted the dynamics of respiratory syncytial virus (RSV) on a global scale;...
Nonpharmaceutical interventions (NPIs) implemented during the COVID-19 pandemic have disrupted the dynamics of respiratory syncytial virus (RSV) on a global scale; however, the cycling of RSV subtypes in the pre- and post-pandemic period remains poorly understood. Here, we used a two subtype RSV model supplemented with epidemiological data to study the impact of NPIs on the two circulating subtypes, RSV-A and RSV-B. The model is calibrated to historic RSV subtype data from the United Kingdom and Finland and predicts a tendency for RSV-A dominance over RSV-B immediately following the implementation of NPIs. Using a global genetic dataset, we confirm that RSV-A has prevailed over RSV-B in the post-pandemic period, consistent with a higher R for RSV-A. With new RSV infant monoclonals and maternal and elderly vaccines becoming widely available, these results may have important implications for understanding intervention effectiveness in the context of disrupted subtype dynamics.
Topics: Humans; COVID-19; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; United Kingdom; SARS-CoV-2; Finland; Infant; Pandemics
PubMed: 38914626
DOI: 10.1038/s41598-024-64624-1 -
BMC Infectious Diseases Jun 2024Although administrative claims data have a high degree of completeness, not all medically attended Respiratory Syncytial Virus-associated lower respiratory tract...
BACKGROUND
Although administrative claims data have a high degree of completeness, not all medically attended Respiratory Syncytial Virus-associated lower respiratory tract infections (RSV-LRTIs) are tested or coded for their causative agent. We sought to determine the attribution of RSV to LRTI in claims data via modeling of temporal changes in LRTI rates against surveillance data.
METHODS
We estimated the weekly incidence of LRTI (inpatient, outpatient, and total) for children 0-4 years using 2011-2019 commercial insurance claims, stratified by HHS region, matched to the corresponding weekly NREVSS RSV and influenza positivity data for each region, and modelled against RSV, influenza positivity rates, and harmonic functions of time assuming negative binomial distribution. LRTI events attributable to RSV were estimated as predicted events from the full model minus predicted events with RSV positivity rate set to 0.
RESULTS
Approximately 42% of predicted RSV cases were coded in claims data. Across all regions, the percentage of LRTI attributable to RSV were 15-43%, 10-31%, and 10-31% of inpatient, outpatient, and combined settings, respectively. However, when compared to coded inpatient RSV-LRTI, 9 of 10 regions had improbable corrected inpatient LRTI estimates (predicted RSV/coded RSV ratio < 1). Sensitivity analysis based on separate models for PCR and antigen-based positivity showed similar results.
CONCLUSIONS
Underestimation based on coding in claims data may be addressed by NREVSS-based adjustment of claims-based RSV incidence. However, where setting-specific positivity rates is unavailable, we recommend modeling across settings to mirror NREVSS's positivity rates which are similarly aggregated, to avoid inaccurate adjustments.
Topics: Humans; Respiratory Syncytial Virus Infections; Infant; Incidence; Child, Preschool; Infant, Newborn; United States; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Male; Female; Clinical Coding; Influenza, Human
PubMed: 38907351
DOI: 10.1186/s12879-024-09474-y -
The Pediatric Infectious Disease Journal Jul 2024To assess the burden of respiratory syncytial virus (RSV)-related bronchiolitis in primary care and at 15 days and 6 months after a primary care visit.
Assessing the Burden of Respiratory Syncytial Virus-related Bronchiolitis in Primary Care and at 15-Day and 6-Month Follow-up Before Prophylaxis in France: A Test-negative Study.
OBJECTIVE
To assess the burden of respiratory syncytial virus (RSV)-related bronchiolitis in primary care and at 15 days and 6 months after a primary care visit.
STUDY DESIGN
In this test-negative study, children <2 years old with a first episode of bronchiolitis were prospectively enrolled by 45 ambulatory pediatricians in France from February 2021 to April 2023. RSV was assessed with a rapid antigen detection test. The burden of the disease was assessed with a questionnaire, including quality of life (PedsQL 1.0 Infant Scales), at 15-day and 6-month follow-up. Children with a positive RSV test result (RSV+) were compared to those with a negative test result (RSV-).
RESULTS
Among the 1591 children enrolled, 750 (47.1%) were RSV+. At 15 days follow-up (data availability: 69%), as compared with RSV- children, RSV+ children more frequently had fever (20.5% vs. 13.7%, P = 0.004) and decreased food intake (27.0% vs. 17.4%, P < 0.001) during the last 3 days. They had higher rates of hospitalization (11.8% vs. 5.8%, P < 0.001), childcare absenteeism (83.5% vs. 66.1%, P < 0.001) and parents who had to stop working to care for them (59.1% vs. 41.0%, P < 0.001) as well as lower quality of life (median PedsQL score 76.2 vs. 78.4, P = 0.03). At 6 months (data availability: 48.5%), the 2 groups did not differ in proportion of medical attendance, hospitalization, antibiotic treatment or quality of life.
CONCLUSION
RSV+ children experienced much more severe disease and follow-up family and societal burden than RSV- children. These data may be used as baseline data as RSV prophylaxis is about to be implemented.
Topics: Humans; Respiratory Syncytial Virus Infections; France; Infant; Primary Health Care; Female; Male; Prospective Studies; Quality of Life; Follow-Up Studies; Cost of Illness; Respiratory Syncytial Virus, Human; Bronchiolitis; Infant, Newborn; Surveys and Questionnaires; Antiviral Agents
PubMed: 38900603
DOI: 10.1097/INF.0000000000004360 -
Pediatric Allergy and Immunology :... Jun 2024Several clinical trials have shown that nirsevimab, an antibody targeting the respiratory syncytial virus (RSV), reduces RSV bronchiolitis requiring admission. In...
BACKGROUND
Several clinical trials have shown that nirsevimab, an antibody targeting the respiratory syncytial virus (RSV), reduces RSV bronchiolitis requiring admission. In 2023-2024, Catalonia and Andorra adopted immunization strategies for children <6 months and those born during the epidemic season. This study evaluates the effectiveness of nirsevimab in preventing hospitalizations from RSV bronchiolitis.
METHODS
In the epidemic season of 2023-2024, a test-negative case-control study was conducted in three hospitals from Catalonia and Andorra. Patients <12 months old admitted with bronchiolitis and tested for RSV using molecular microbiology tests were included. The effectiveness in preventing RSV bronchiolitis hospitalization and severe disease was estimated using multivariate models. Comparisons between immunized, non-immunized, and non-eligible patients were made in prospectively collected epidemiological, clinical, and microbiological variables.
RESULTS
Two hundred thirty-four patients were included. RSV was detected in 141/234 (60.2%), being less common in the immunized group (37% vs 75%, p < .001). The rate of immunized patients among those eligible was 59.7%. The estimated effectiveness for RSV-associated lower respiratory tract infection was 81.0% (95% confidence interval: 60.9-90.7), and for preventing severe disease (the need for NIV/CMV), 85.6% (41.7-96.4%). No significant differences by immunization status were observed in patients with RSV concerning viral coinfections, the need for NIV/CMV or length of hospital stay.
CONCLUSIONS
This study provides real-world evidence of the effectiveness of nirsevimab in preventing RSV-lower respiratory tract infection hospitalization and severe disease in infants during their first RSV season following a systematic immunization program. Immunized patients did not exhibit a higher rate of viral coinfections nor differences in clinical severity once admitted.
Topics: Humans; Infant; Respiratory Syncytial Virus Infections; Case-Control Studies; Male; Female; Hospitalization; Spain; Immunization; Respiratory Syncytial Virus, Human; Bronchiolitis; Treatment Outcome; Infant, Newborn; Severity of Illness Index; Bronchiolitis, Viral
PubMed: 38899631
DOI: 10.1111/pai.14175 -
BMC Medical Genomics Jun 2024Respiratory Syncytial Virus (RSV) disease in young children ranges from mild cold symptoms to severe symptoms that require hospitalization and sometimes result in death....
BACKGROUND
Respiratory Syncytial Virus (RSV) disease in young children ranges from mild cold symptoms to severe symptoms that require hospitalization and sometimes result in death. Studies have shown a statistical association between RSV subtype or phylogenic lineage and RSV disease severity, although these results have been inconsistent. Associations between variation within RSV gene coding regions or residues and RSV disease severity has been largely unexplored.
METHODS
Nasal swabs from children (< 8 months-old) infected with RSV in Rochester, NY between 1977-1998 clinically presenting with either mild or severe disease during their first cold-season were used. Whole-genome RSV sequences were obtained using overlapping PCR and next-generation sequencing. Both whole-genome phylogenetic and non-phylogenetic statistical approaches were performed to associate RSV genotype with disease severity.
RESULTS
The RSVB subtype was statistically associated with disease severity. A significant association between phylogenetic clustering of mild/severe traits and disease severity was also found. GA1 clade sequences were associated with severe disease while GB1 was significantly associated with mild disease. Both G and M2-2 gene variation was significantly associated with disease severity. We identified 16 residues in the G gene and 3 in the M2-2 RSV gene associated with disease severity.
CONCLUSION
These results suggest that phylogenetic lineage and the genetic variability in G or M2-2 genes of RSV may contribute to disease severity in young children undergoing their first infection.
Topics: Humans; Respiratory Syncytial Virus Infections; Phylogeny; Genetic Variation; Severity of Illness Index; Infant; Respiratory Syncytial Virus, Human; Male; Genotype; Female; Genome, Viral
PubMed: 38898440
DOI: 10.1186/s12920-024-01930-7 -
BMJ Paediatrics Open Jun 2024During the COVID-19 pandemic, the introduction of non-pharmaceutical interventions (NPIs) resulted in an unprecedented reduction in the transmission of the respiratory... (Observational Study)
Observational Study
During the COVID-19 pandemic, the introduction of non-pharmaceutical interventions (NPIs) resulted in an unprecedented reduction in the transmission of the respiratory syncytial virus (RSV), the predominant cause of bronchiolitis. As NPIs were eased, it was speculated that RSV transmission would return with an increase in the severity of bronchiolitis. In a large tertiary hospital, a dramatic reduction in the incidence of bronchiolitis was seen during the COVID-19 pandemic. The easing of NPIs correlated with an increase in RSV transmission particularly in the community; however, there was no evidence of an increase in the severity of bronchiolitis.
Topics: Humans; Respiratory Syncytial Virus Infections; COVID-19; Infant; SARS-CoV-2; Female; Male; Bronchiolitis; Incidence; Infant, Newborn; Respiratory Syncytial Virus, Human
PubMed: 38897622
DOI: 10.1136/bmjpo-2024-002603