Respiratory Season Research Articles

COVID-19 vaccine effectiveness and hybrid immunity in the respiratory season of 2022-23 in Hungary

Abstract Background There has been an increase in COVID-19 vaccine hesitancy among the general population, accompanied by a decline in confidence that vaccines provide adequate protection. We estimated the effectiveness of the COVID-19 vaccines (CVE) and hybrid immunity against medically attended COVID-19 during the 2022-2023 respiratory season in Hungary. Methods We conducted a test-negative design study involving 68 GPs. Patients aged ≥18 years presenting with acute respiratory infection were swabbed. Cases and controls were patients testing positive and negative for SARS-CoV-2 by RT-PCR, respectively. Exposure was defined as having received at least one COVID-19 booster dose, taking into account the time since the last vaccination. CVE was estimated using logistic regression, adjusted for symptom onset date, age, chronic condition and sex. Results We included 247 cases and 1073 controls in the analysis. 196 samples were sequenced, and Omicron BA.5, BQ.1 and XBB.1 were the most frequent sub-variants. The CVE was 52.9% (95% CI: 15.2-73.9%), and 72.3% (95% CI: 32.0-88.7%) in the 18-59, and 60+-year-old population who received the final dose within the past year, respectively. Self-reported COVID-19 in the previous 60-365 days did not confer protection against reinfection, however, when combined with booster vaccination, it reduced the risk of COVID-19 by 63.0% (95% CI: −28.0-89.3%) and 87.6% (95% CI: 26.4-97.9%) among the 18-59 and 60+ age groups, respectively. Conclusions Booster vaccination within one year after the last dose confers significant protection against symptomatic infection, particularly among the elderly. Those who have previously been infected with SARS-CoV-2 may also benefit from booster vaccinations. Key messages • COVID-19 booster campaigns must be intensified, focusing mainly on the elderly. • Providing clear guidance on the timing and target groups of vaccination and emphasising the benefits of vaccination can help to achieve higher coverage.

Comparing statistical forecasting methods for modelling respiratory virus healthcare demand

Abstract Background Emergency departments in the United Kingdom are under sustained pressure with rising demand for healthcare, gradually decreasing the functionality of the NHS. Forecasts can aid management in the allocation of appropriate healthcare supplies and staffing needs in advance of an expected surge, as well as allow stakeholders to assess most likely outcomes and potential worst-case scenarios. This is especially valuable during the seasonal waves of respiratory infections. Respiratory viruses are usually concentrated in a 6-8 week seasonal surge during the winter period, creating large pressure on the health system. Current forecast models’ performance depreciates significantly after 1 week. This analysis will forecast 6 weeks of respiratory health admissions, comparing traditional and newly emerging forecasting methods. Methods Using 20 years of English hospital admissions data, we evaluated both within season training models (2-20 weeks) and longer term seasonal models (1-10 years), to forecast 6 weeks of hospital admissions. Respiratory admissions were defined according to ARI/ILI ICD10 codes assigned in hospital, stratified by age and region. Models were iteratively constructed, trained and probabilistic forecasts were evaluated across the respiratory season of September to April using Weighted Interval Score. Averages of each model across iterations were generated for comparison. Results For non-seasonal models, shorter model training lengths created better forecast models for 6 weeks. For seasonal models, optimal training length varied across model complexity. Simple models performed best at forecasting 1 week, however performance deteriorated the most as the forecast window increased. Overall, the Prophet model performed best on average at forecasting 6 weeks across all scenarios. Conclusions Applying our framework for optimal model selection in forecasting analysis will help to inform better practice for future health demand modelling. Key messages • This analysis will inform better practice for future health demand forecasting 6 weeks in advance, allowing for preparation of resources for seasonal surges in healthcare demand. • This analysis suggests using models with modest levels of increased complexity over simpler models could significantly improve forecast performance in the short-medium term.

The impact of viral respiratory infection on surgical outcome of cavopulmonary shunt.

Undetected respiratory infections may adversely affect the intrapulmonary resistance after Stage 2 or Stage 3 Fontan palliation. A few studies describe a higher risk for viral pneumonia during respiratory virus season, but none of them have focused on the effect of symptomatic viral pneumonia on in-hospital clinical course after bidirectional Glenn shunt. We analysed 77 patients who underwent bidirectional Glenn shunt surgery. Six patients were detected with pneumonia and proof of viral ribonucleic acid in tracheal mucus in the very early postoperative time. We compared them retrospectively to the remaining 71 patients regarding preoperative inflammatory signs, mortality, paediatric ICU length of stay, and ventilation time. The infection rate was not seasonal dependent. Ventilation time was significantly elongated in the pneumonia group (558 h ± 634 vs. 8.7 h ± 1.9; p < 0.0001) and so was the paediatric ICU length of stay (29 days ± 26 vs. 3 days±1; p = 0.007). Significantly more patients in the pneumonia group required extracorporeal cardiac life support postoperatively. The mortality was significantly increased in patients with pneumonia. Even subclinical viral pneumonia may cause ventilation-to-perfusion mismatch by raising intrapulmonary resistance. Recorded parameters of postoperative paediatric ICU therapy showed a significant impact of a viral pneumonia on patients after bidirectional Glenn shunt. The respiratory syncytial virus vaccination does not protect these patients from infection with other respiratory viruses. The focus should be put on preoperative diagnosis of pulmonary infections in the vulnerable group of patients with univentricular hearts.

Respiratory syncytial virus (RSV) vaccine effectiveness against RSV-associated hospitalisations and emergency department encounters among adults aged 60 years and older in the USA, October, 2023, to March, 2024: a test-negative design analysis

Respiratory syncytial virus vaccines first recommended for use during 2023 were efficacious against lower respiratory tract disease in clinical trials. Limited real-world data regarding respiratory syncytial virus vaccine effectiveness are available. To inform vaccine policy and address gaps in evidence from the clinical trials, we aimed to assess the effectiveness against respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years. We conducted a test-negative design analysis in an electronic health records-based network in eight states in the USA, including hospitalisations and emergency department encounters with respiratory syncytial virus-like illness among adults aged at least 60 years who underwent respiratory syncytial virus testing from Oct 1, 2023, to March 31, 2024. Respiratory syncytial virus vaccination status at the time of the encounter was derived from electronic health record documentation, state and city immunisation registries, and, for some sites, medical claims. Vaccine effectiveness was estimated by immunocompromise status, comparing the odds of vaccination among respiratory syncytial virus-positive case patients and respiratory syncytial virus-negative control patients, and adjusting for age, race and ethnicity, sex, calendar day, social vulnerability index, number of underlying non-respiratory medical conditions, presence of respiratory underlying medical conditions, and geographical region. Among 28 271 hospitalisations for respiratory syncytial virus-like illness among adults aged at least 60 years without immunocompromising conditions, vaccine effectiveness was 80% (95% CI 71-85) against respiratory syncytial virus-associated hospitalisations, and vaccine effectiveness was 81% (52-92) against respiratory syncytial virus-associated critical illness (ICU admission or death, or both). Among 8435 hospitalisations for respiratory syncytial virus-like illness among adults with immunocompromising conditions, vaccine effectiveness was 73% (48-85) against associated hospitalisation. Among 36 521 emergency department encounters for respiratory syncytial virus-like illness among adults aged at least 60 years without an immunocompromising condition, vaccine effectiveness was 77% (70-83) against respiratory syncytial virus-associated emergency department encounters. Vaccine effectiveness estimates were similar by age group and product type. Respiratory syncytial virus vaccination was effective in preventing respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years in the USA during the 2023-24 respiratory syncytial virus season, which was the first season after respiratory syncytial virus vaccine was approved. The Centers for Disease Control and Prevention.

Changes in use of multiplex respiratory panel testing during the COVID-19 pandemic.

COVID-19 changed the epidemiology of community-acquired respiratory viruses. We explored patterns of respiratory viral testing to understand which tests are most clinically useful in the postpandemic era. We conducted a retrospective observational study of discharge data from PINC-AI (formerly Premier), a large administrative database. Use of multiplex nucleic acid amplification respiratory panels in acute care, including small (2-5 targets), medium (6-11), and large panels (>11), were compared between the early pandemic (03/2020-10/2020), late pandemic (11/2020-4/2021), and prepandemic respiratory season (11/2019 - 02/2020) using ANOVA. A median of 160.5 facilities contributed testing data per quarter (IQR 155.5-169.5). Prepandemic, facilities averaged 103 respiratory panels monthly (sd 138), including 79 large (sd 126), 7 medium (sd 31), and 16 small panels (sd 73). Relative to prepandemic, utilization decreased during the early pandemic (62 panels monthly/facility; sd 112) but returned to the prepandemic baseline by the late pandemic (107 panels monthly/facility; sd 211). Relative to prepandemic, late pandemic testing involved more small panel use (58 monthly/facility, sd 156) and less large panel use (47 monthly/facility, sd 116). Comparisons among periods demonstrated significant differences in overall testing (P < 0.0001), large panel use (P < 0.0001), and small panel use (P < 0.0001). Postpandemic, clinical use of respiratory panel testing shifted from predominantly large panels to predominantly small panels. Factors driving this change may include resource availability, costs, and the clinical utility of targeting important pathogenic viruses instead of testing "for everything."

Real-World Effectiveness of Nirsevimab Against Respiratory Syncytial Virus: A Test-Negative Case-Control Study.

Nirsevimab, a long-acting monoclonal antibody, has demonstrated efficacy against RSV-related lower respiratory tract infections (LRTIs) in clinical trials. Post-licensure monitoring is essential to confirm these benefits in real-world settings. To evaluate the real-world effectiveness of nirsevimab against medically attended RSV infections in infants and to assess how effectiveness varies by disease severity, dosage, and time since immunization. This test-negative case-control study used inpatient, outpatient, and emergency room data from the Yale New Haven Health System. Nirsevimab-eligible infants who were tested for RSV using polymerase chain reaction between October 1, 2023 and May 9, 2024 were included. Cases were infants with confirmed RSV infections; controls were those who tested negative. Nirsevimab immunization, verified through state immunization registries. Effectiveness was estimated using multivariable logistic regression, adjusting for age, calendar month, and individual risk factors. Separate models examined effectiveness by clinical setting, disease severity, dose, and time since immunization. Broader outcomes, including all-cause LRTI and LRTI-related hospitalization, were also analyzed, with stratification by early and late respiratory seasons. The analytic sample included 3,090 infants (median age 6.7 months, IQR 3.6-9.7), with 680 (22.0%) RSV-positive and 2,410 (78.0%) RSV-negative. 21 (3.1%) RSV-positive and 309 (12.8%) RSV-negative infants received nirsevimab. Effectiveness against RSV infection was 68.4% (95% CI, 50.3%-80.8%). Effectiveness was 61.6% (95% CI, 35.6%-78.6%) for outpatient visits and 80.5% (95% CI, 52.0%-93.5%) for hospitalizations. The highest effectiveness, 84.6% (95% CI, 58.7%-95.6%), was observed against severe RSV outcomes requiring ICU admission or high-flow oxygen. Although effectiveness against RSV infections declined over time, it remained significant at 55% (95% credible interval, 16%-75%) at 14 weeks post-immunization. Protective effectiveness was also observed against all-cause LRTI and LRTI-related hospitalizations during peak RSV season (49.4% [95% CI, 10.7%-72.9%] and 79.1% [95% CI, 27.6%-94.9%], respectively). However, from February to May, when RSV positivity was low, effectiveness against these broader outcomes was negligible. Nirsevimab provided substantial protection against RSV-related outcomes for at least three months. These findings support the continued use of nirsevimab and provide evidence that may help build public confidence in the immunization program. Question: What is the effectiveness of nirsevimab against medically attended respiratory syncytial virus (RSV) infections in infants?Findings: 680 RSV test-positive cases and 2,410 RSV test-negative controls were included in this test-negative case-control study. Nirsevimab's effectiveness was 69% against RSV infections, 81% against RSV-associated hospitalization, and 85% against severe RSV disease. Effectiveness against RSV infection declined from 79% at 2 weeks post-immunization to 55% at 14 weeks post-immunization.Meaning: Nirsevimab provides strong protection against a wide range of RSV outcomes, but its effectiveness diminishes over time. These data can be utilized to optimize nirsevimab's implementation and sustain its uptake.

Modelling the potential clinical and economic impact of universal immunisation with nirsevimab versus standard of practice for protecting all neonates and infants in their first respiratory syncytial virus season in Spain

BackgroundRespiratory syncytial virus (RSV) is associated with substantial morbidity among infants. This study modelled the potential public health and economic impact of nirsevimab, a long-acting monoclonal antibody, as an immunoprophylactic strategy for all infants in Spain in their first RSV season.MethodsA static decision-analytic model of the Spanish birth cohort during its first RSV season was developed to estimate the impact of nirsevimab on RSV-related health events and costs versus the standard of practice (SoP). Spain-specific costs and epidemiological data were used as model inputs. Modelled outcomes included RSV-related outpatient visits, emerging room (ER) visits, hospitalisations – including pediatric intensive care unit (PICU) admission, mechanical ventilation, and inpatient mortality.ResultsUnder the current SoP, RSV caused 151,741 primary care visits, 38,798 ER visits, 12,889 hospitalisations, 1,412 PICU admissions, and 16 deaths over a single season, representing a cost of €71.8 million from a healthcare payer perspective. Universal immunisation of all infants with nirsevimab was expected to prevent 97,157 primary care visits (64.0% reduction), 24,789 ER visits (63.9%), 8,185 hospitalisations (63.5%), 869 PICU admissions (61.5%), and 9 inpatient deaths (52.6%), saving €47.8 million (62.4%) in healthcare costs.ConclusionsThese results suggest that immunisation with nirsevimab of all infants experiencing their first RSV season in Spain is likely to prevent thousands of RSV-related health events and save considerable costs versus the current SoP.

Paid Family Leave and Prevention of Acute Respiratory Infections in Young Infants

Acute respiratory tract infections are the leading cause of emergency department visits and hospitalizations in US children, with highest risks in the first 2 months after birth. Out-of-home childcare settings increase the spread of respiratory tract infections. The study team hypothesized that access to state-paid family leave could reduce acute care encounters (hospital admissions or emergency department visits) for respiratory tract infections in young infants by reducing out-of-home childcare transmissions. To determine if the 2018 introduction of paid family leave in New York state reduced acute care encounters for respiratory tract infections in infants 8 weeks or younger. This population-based study of acute care encounters took place in New York state and New England control states (Maine, Massachusetts, New Hampshire, Vermont) from October 2015 through February 2020. Participants included infants aged 8 weeks or younger. Controlled time series analysis using Poisson regression was used to estimate the impact of paid family leave on acute care encounters for respiratory tract infections, comparing observed counts during respiratory virus season (October through March) with those predicted in the absence of the policy. Acute care encounters for respiratory tract infections in 1-year-olds (who would not be expected to benefit as directly from the policy) were modeled as a placebo test. New York State Paid Family Leave policy, introduced on January 1, 2018, providing 8 weeks of paid leave for eligible parents. Emergency department visits or hospitalizations with International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD) codes for upper or lower respiratory tract infections or associated symptoms (ie, fever, cough), excluding newborn hospitalizations. The secondary outcome was acute care encounters for respiratory syncytial virus (RSV) bronchiolitis. There were 52 943 acute care encounters for respiratory infection among infants 8 weeks or younger. There were 15 932 encounters that were hospitalizations (30%) and 33 304 of the encounters were paid for by Medicaid (63%). Encounters were 18% lower than predicted (relative percentage change = -17.9; 95% CI, -20.3 to -15.7) after the introduction of paid family leave. RSV encounters were 27.0% lower (95% CI, -30.9 to -23.5) than predicted. Similar reductions were not observed in 1-year-olds (relative percentage change = -1.5; 95% CI, -2.5 to -0.6). New York state's paid family leave policy was associated with reduced acute care encounters for respiratory tract infections in young infants. These findings may be useful for informing implementation of paid family leave federally and in the states that have not enacted paid family leave policies.

Respiratory virus disease and outcomes at a large academic medical center in the United States: a retrospective observational study of the early 2023/2024 respiratory viral season.

Respiratory disease, attributed to influenza, respiratory syncytial virus (RSV), and SARS-CoV-2, was reported nationally during the 2023/2024 respiratory viral season. The emergence of novel SARS-CoV-2 variants was considered a significant factor contributing to the rise in COVID-19 cases. Data from the Johns Hopkins Hospital System (JHHS) showed that enterovirus/rhinovirus had also been circulating at high rates. Analyzing clinical outcomes of the most prevalent respiratory viruses is crucial for understanding the role of circulating viral genotypes. A retrospective cohort of patients who tested positive for SARS-CoV-2, influenza, RSV, or enterovirus/rhinovirus between 1 June and 31 December 2023 was included in the study. Remnant clinical samples were utilized for targeted viral whole-genome sequencing and genotyping. Patients' metadata and outcomes following infection were studied, stratified by viral variants and genotypes. The increase of SARS-CoV-2 positivity in December was associated with the predominance of JN.1. Admissions for patients under 18 years old were primarily associated with enterovirus/rhinovirus and RSV, while older age groups were mainly linked to SARS-CoV-2 and influenza infections. SARS-CoV-2-related admissions increased with the predominance of the JN.1 variant in December. No significant difference in admissions for influenza subtypes, rhinovirus species, or SARS-CoV-2 variants was observed. RSV A was associated with slightly higher odds of admission compared with RSV B. Our data highlight the importance of systematically analyzing respiratory viral infections to inform public health strategies and clinical management, especially as SARS-CoV-2 becomes endemic. The findings highlight the value of expanded genomic surveillance in elucidating the clinical significance of viral evolution.IMPORTANCEThe analysis of the epidemiology and clinical outcomes of multiple co-circulating respiratory viruses in the early 2023/2024 respiratory virus season highlights the emergence of the SARS-CoV-2 JN.1 variant as well as underscores the importance of enterovirus/rhinovirus in respiratory infections. Understanding these dynamics is essential for refining public health strategies and clinical management, especially as SARS-CoV-2 transitions to an endemic status. This work emphasizes the need for ongoing surveillance, robust diagnostic algorithms, and detailed genomic analyses to anticipate and mitigate the burden of respiratory viral infections, ultimately contributing to more informed decision-making in healthcare settings and better patient outcomes.

Therapeutic relevance of eosinophilic inflammation and airway viral interactions in severe asthma.

The role of eosinophils in airway inflammation and asthma pathogenesis is well established, with raised eosinophil counts in blood and sputum associated with increased disease severity and risk of asthma exacerbation. Conversely, there is also preliminary evidence suggesting antiviral properties of eosinophils in the airways. These dual roles for eosinophils are particularly pertinent as respiratory virus infections contribute to asthma exacerbations. Biologic therapies targeting key molecules implicated in eosinophil-associated pathologies have been approved in patients with severe asthma and, therefore, the effects of depleting eosinophils in a clinical setting are of considerable interest. This review discusses the pathological and antiviral roles of eosinophils in asthma and exacerbations. We also highlight the significant reduction in asthma exacerbations seen with biologic therapies, even at the height of the respiratory virus season. Furthermore, we discuss the implications of these findings in relation to the role of eosinophils in inflammation and antiviral responses to respiratory virus infection in asthma.

Confronting the challenge: a regional perspective by the Latin American pediatric infectious diseases society (SLIPE) expert group on respiratory syncytial virus-tackling the burden of disease and implementing preventive solutions.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections in children around the world. The post-pandemic era has resulted in a notable increase in reported cases of RSV infections, co-circulation of other respiratory viruses, shifts in epidemiology, altered respiratory season timing, and increased healthcare demand. Low- and middle-income countries are responsible for the highest burden of RSV disease, contributing significantly to health expenses during respiratory seasons and RSV-associated mortality in children. Until recently, supportive measures were the only intervention to treat or prevent RSV-infection, since preventive strategies like palivizumab are limited for high-risk populations. Advances in new available strategies, such as long-acting monoclonal antibodies during the neonatal period and vaccination of pregnant women, are now a reality. As the Regional Expert Group of the Latin American Pediatric Infectious Diseases Society (SLIPE), we sought to evaluate the burden of RSV infection in Latin America and the Caribbean (LAC) region, analyze current strategies to prevent RSV infection in children, and provide recommendations for implementing new strategies for preventing RSV infection in children in LAC region.

Evidence base for yearly respiratory virus vaccines: Current status and proposed improved strategies.

Annual vaccination is widely recommended for influenza and SARS-CoV-2. In this essay, we analyse and question the prevailing policymaking approach to these respiratory virus vaccines, especially in the United States. Every year, licensed influenza vaccines are reformulated to include specific strains expected to dominate in the season ahead. Updated vaccines are rapidly manufactured and approved without further regulatory requirement of clinical data. Novel vaccines (i.e. new products) typically undergo clinical trials, though generally powered for clinically unimportant outcomes (e.g. lab-confirmed infections, regardless of symptomatology or antibody levels). Eventually, the current and future efficacy of influenza and COVID-19 vaccines against hospitalization or death carries considerable uncertainty. The emergence of highly transmissible SARS-CoV-2 variants and waning vaccine-induced immunity led to plummeting vaccine effectiveness, at least against symptomatic infection, and booster doses have since been widely recommended. No further randomized trials were performed for clinically important outcomes for licensed updated boosters. In both cases, annual vaccine effectiveness estimates are generated by observational research, but observational studies are particularly susceptible to confounding and bias. Well-conducted experimental studies, particularly randomized trials, are necessary to address persistent uncertainties about influenza and COVID-19 vaccines. We propose a new research framework which would render results relevant to the current or future respiratory viral seasons. We demonstrate that experimental studies are feasible by adopting a more pragmatic approach and provide strategies on how to do so. When it comes to implementing policies that seriously impact people's lives, require substantial public resources and/or rely on widespread public acceptance, high evidence standards are desirable.

Integrating discrete-event simulation and artificial intelligence for shortening bed waiting times in hospitalization departments during respiratory disease seasons

Seasonal Respiratory Diseases (SRDs) usually produce a heightened number of Emergency Department (ED) attendances due to their rapid dissemination within the community and the ineffective prevention measures. Such a context requires effective management of the emergency care processes to provide in-time diagnosis and treatment to infected patients. Nonetheless, EDs have evidenced severe operational deficiencies during these periods, thereby provoking extended bed waiting times in Hospitalization Departments (HDs). Therefore, this paper presents a hybrid approach merging Artificial Intelligence (AI) and Discrete-Event Simulation (DES) to shorten the bed waiting times in HDs considering patient records collated in the first emergency care stages. First, we implemented Random Forest (RF) to estimate the probability of respiratory worsening based on sociodemographic and clinical patient data. Second, we inserted these probabilities into a DES model mimicking the emergency care from the admission to the HD. We then pretested different HD configurations and strategies seeking to reduce the HD bed waiting time. A case study of a European hospital group was used to validate the suggested framework. The AI-DES model enabled decision-makers to identify an improvement proposal with hospitalization bed waiting time lessening, oscillating between 7.93 and 7.98 h.

Relative Contribution of Diagnostic Testing to the Diagnosis of Respiratory Syncytial Virus in Hospitalized Adults in the United States.

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illness (ARI) in older adults. Optimizing diagnosis could improve understanding of RSV burden. We enrolled adults ≥50 years of age hospitalized with ARI and adults of any age hospitalized with congestive heart failure or chronic obstructive pulmonary disease exacerbations at two hospitals during two respiratory seasons (2018-2020). We collected nasopharyngeal (NP) and oropharyngeal (OP) swabs (n=1558), acute and convalescent sera (n=568), and expectorated sputum (n=153) from participants, and recorded standard-of-care (SOC) NP results (n=805). We measured RSV antibodies by two immunoassays and performed BioFire testing on respiratory specimens. Of 1,558 eligible participants, 92 (5.9%) tested positive for RSV by any diagnostic method. Combined NP/OP PCR yielded 58 positives, while separate NP and OP testing identified 11 additional positives (18.9% increase). Compared to Study NP/OP PCR alone, the addition of paired serology increased RSV detection by 42.9% (28 vs 40) among those with both specimen types, while the addition of SOC swab RT-PCR results increased RSV detection by 25.9% (47 vs 59). The addition of paired serology testing, SOC swab results, and separate testing of NP and OP swabs improved RSV diagnostic yield in hospitalized adults.

Pneumococcal Colonization in Children With Persistent Asthma: A Retrospective Cohort.

Asthma is the most common chronic medical condition among children ≥5 years of age with invasive pneumococcal disease. How asthma or its management affects pneumococcal colonization is not fully understood. Our objective was to compare pneumococcal colonization rates between children with persistent asthma and children without asthma, and to characterize the pneumococcal serotype distribution. We used nasal mid-turbinate samples obtained per routine care from 5- to 18-year-old children with upper respiratory symptoms from November to April (respiratory seasons) of 2017 to 2018 and 2018 to 2019 in Kansas City, United States. Pneumococcal immunization status, prior antibiotic use and other clinical data were collected. Samples were tested for pneumococcal colonization by real-time polymerase chain reaction targeting lytA gene. Positive samples underwent multiplex serotype-specific polymerase chain reaction assays to determine the serotype. Of 363 children (120 with persistent asthma and 243 without asthma), 87.6% were 5 to 10 years old, 50.1% were female and 74.1% received ≥3 doses of a pneumococcal conjugate vaccine. The pneumococcal colonization rate was lower in children with persistent asthma than in children without asthma (10% versus 18.9%, P = 0.03). The odds of colonization were lower in children with persistent asthma [OR 0.4 (95% confidence interval: 0.2-0.9)] after adjusting for demographic and clinical data. Pneumococcal serotype was confirmed in 77.6% of positive samples; 35.6% of those samples corresponded to PCV13 serotypes and 64.4% to non-PCV13 serotypes. The most common serotypes were 19F (15%), 3 (13%) and 6C/6D (11%). Children with persistent asthma had lower rates of pneumococcal colonization than children without asthma when seeking care for respiratory symptoms.

Children's Hospital Resource Utilization During the 2022 Viral Respiratory Surge.

Multiple viral respiratory epidemics occurred concurrently in 2022 but their true extent is unclear. To aid future surge planning efforts, we compared epidemiology and resource utilization with prepandemic viral respiratory seasons in 38 US children's hospitals. We performed a serial cross-sectional study from October 2017 to March 2023. We counted daily emergency department (ED), inpatient, and ICU volumes; daily surgeries; viral tests performed; the proportion of ED visits resulting in revisit within 3 days; and proportion of hospitalizations with a 30-day readmission. We evaluated seasonal resource utilization peaks using hierarchical Poisson models. Peak volumes in the 2022 season were 4% lower (95% confidence interval [CI] -6 to -2) in the ED, not significantly different in the inpatient unit (-1%, 95% CI -4 to 2), and 8% lower in the ICU (95% CI -14 to -3) compared with each hospital's previous peak season. However, for 18 of 38 hospitals, their highest ED and inpatient volumes occurred in 2022. The 2022 season was longer in duration than previous seasons (P < .02). Peak daily surgeries decreased by 15% (95% CI -20 to -9) in 2022 compared with previous peaks. Viral tests increased 75% (95% CI 69-82) in 2022 from previous peaks. Revisits and readmissions were lowest in 2022. Peak ED, inpatient, and ICU volumes were not significantly different in the 2022 viral respiratory season compared with earlier seasons, but half of hospitals reached their highest volumes. Research on how surges impact boarding, transfer refusals, and patient outcomes is needed as regionalization reduces pediatric capacity.

Respiratory Syncytial Virus in Adult Patients at a Tertiary Care Hospital in Germany: Clinical Features and Molecular Epidemiology of the Fusion Protein in the Severe Respiratory Season of 2022/2023.

Following an interseasonal rise in mainly pediatric respiratory syncytial virus (RSV) cases in Germany in 2021, an exceptionally high number of adult cases was observed in the subsequent respiratory season of 2022/2023. The aim of this study was to compare the clinical presentation of RSV infections in the pre- and post-SARS-CoV-2 pandemic periods. Additionally, the local epidemiology of the RSV fusion protein was analyzed at a molecular genetic and amino acid level. RSV detections in adults peaked in calendar week 1 of 2023, 8 weeks earlier than the earliest peak observed in the three pre-pandemic seasons. Although the median age of the adult patients was not different (66.5 vs. 65 years), subtle differences between both periods regarding comorbidities and the clinical presentation of RSV cases were noted. High rates of comorbidities prevailed; however, significantly lower numbers of patients with a history of lung transplantation (p = 0.009), chronic kidney disease (p = 0.013), and immunosuppression (p = 0.038) were observed in the 2022/2023 season. In contrast, significantly more lower respiratory tract infections (p < 0.001), in particular in the form of pneumonia (p = 0.015) and exacerbations of obstructive lung diseases (p = 0.008), were detected. An ICU admission was noted for 23.7% of all patients throughout the study period. Sequence analysis of the fusion protein gene revealed a close phylogenetic relatedness, regardless of the season of origin. However, especially for RSV-B, an accumulation of amino acid point substitutions was noted, including in antigenic site Ø. The SARS-CoV-2 pandemic had a tremendous impact on the seasonality of RSV, and the introduction of new vaccination and immunization strategies against RSV warrants further epidemiologic studies of this important pathogen.

Influenza A, Influenza B, human respiratory syncytial virus and SARSCoV-2 molecular diagnostics and epidemiology in the post COVID-19 era

BackgroundThe concurrent circulation of SARS-CoV-2 with other respiratory viruses is unstoppable and represents a new diagnostic reality for clinicians and clinical microbiology laboratories. Multiplexed molecular testing on automated platforms that focus on the simultaneous detection of multiple respiratory viruses in a single tube is a useful approach for current and future diagnosis of respiratory infections in the clinical setting.MethodsTwo time periods were included in the study: from February to April 2022, an early 2022 period, during the gradual lifting of COVID-19 prevention measures in the country, and from October 2022 to April 2023, the 2022/23 respiratory infections season. We analysed a total of 1,918 samples in the first period and 18,131 respiratory samples in the second period using a multiplex molecular assay for the simultaneous detection of Influenza A (Flu-A), Influenza B (Flu-B), Human Respiratory Syncytial Virus (HRSV) and SARS-CoV-2.ResultsThe results from early 2022 showed a strong dominance of SARS-CoV-2 infections with 1,267/1,918 (66.1%) cases. Flu-A was detected in 30/1,918 (1.6%) samples, HRSV in 14/1,918 (0.7%) samples, and Flu-B in 2/1,918 (0.1%) samples. Flu-A/SARS-CoV-2 co-detections were observed in 11/1,267 (0.9%) samples, and HRSV/SARS-CoV-2 co-detection in 5/1,267 (0.4%) samples. During the 2022/23 winter respiratory season, SARS-CoV-2 was detected in 1,738/18,131 (9.6%), Flu-A in 628/18,131 (3.5%), Flu-B in 106/18,131 (0.6%), and HRSV in 505/18,131 (2.8%) samples. Interestingly, co-detections were present to a similar extent as in early 2022.ConclusionThe results show that the multiplex molecular approach is a valuable tool for the simultaneous laboratory diagnosis of SARS-CoV-2, Flu-A/B, and HRSV in hospitalized and outpatients. Infections with Flu-A/B, and HRSV occurred shortly after the COVID-19 control measures were lifted, so a strong reoccurrence of various respiratory infections and co-detections in the post COVID-19 period was to be expected.

Changes in seasonal respiratory viral infections among pediatric population around the COVID-19 pandemic; 2019-2023.

This study aims to describe the prevalence and the fluctuations of respiratory viral infections among the pediatric population in a tertiary care center during 2019-2023, parallel with the COVID-19 pandemic, and the specific preventative measures applied in the region during this time. In this observational study, we extracted all respiratory virus PCR tests collected from pediatric patients (< 15 years old) between January 2019 and March 2023. Data on the positivity rate and prevalence of 18 respiratory viruses were presented over the study period. The lowest rate for the studied respiratory viruses was observed in 2020/2021 (during the COVID-19 pandemic), followed by a gradual increase in positive cases in the 2021/2022 season. Timing (seasonality) was altered during 2022/2023 with an early circulation of respiratory viruses in May-June followed by an early start of the usual respiratory viruses' season in September, leading to prolonged respiratory virus activity. Most respiratory viruses were circulating at unprecedented levels during the 2022/2023 season, with rhinovirus/enterovirus being the most commonly detected virus in all seasons. Other viruses that had atypical activity after the COVID-19 pandemic were influenza A(H3) virus, adenovirus, and parainfluenza 3 virus. Our study demonstrates the extended influence of the COVID-19 pandemic and its associated community restriction measures on the timing and distribution of other respiratory viruses. Continuous monitoring of changes in the circulation of respiratory viruses is crucial for the success of related public health measures such as vaccination distributions and epidemic preparedness.

Retrospective Genotyping of Enteroviruses Using a Diagnostic Nanopore Sequencing Workflow.

Enteroviruses are among the most common viruses pathogenic to humans. They are associated with various forms of disease, ranging from mild respiratory illness to severe neurological diseases. In recent years, an increasing number of isolated cases of children developing meningitis or encephalitis as a result of enterovirus infection have been reported, as well as discrete enterovirus D68 outbreaks in North America in 2014 and 2016. We developed an assay to rapidly genotype enteroviruses by sequencing a region within the VP1 gene using nanopore Flongles. We retrospectively analyzed enterovirus-/rhinovirus-positive clinical samples from the Zurich, Switzerland area mainly collected during two seasons in 2019/2020 and 2021/2022. Respiratory, cerebrospinal fluid, and stool samples were analyzed. Whole-genome sequencing was performed on samples with ambiguous genotyping results and enterovirus D68-positive samples. Out of 255 isolates, a total of 95 different genotypes were found. A difference in the prevalence of enterovirus and rhinovirus infections was observed for both sample type and age group. In particular, children aged 0-4 years showed a higher frequency of enterovirus infections. Comparing the respiratory seasons, a higher prevalence was found, especially for enterovirus A and rhinovirus A after the SARS-CoV-2 pandemic. The enterovirus genotyping workflow provides a rapid diagnostic tool for individual analysis and continuous enterovirus surveillance.