The Finnish influenza surveillance system monitors the influenza prevalence, disease burden, vaccine uptake and effectiveness. Since the start of the COVID-19 pandemic the publication of the yearly surveillance report has been paused. Therefore, this paper summarizes the past five seasons based on surveillance data from 2019 to 2024 and describes the epidemiology of influenza during the COVID-19 pandemic in Finland. Clinical surveillance showed that the 2019/20 epidemic ended concomitantly with the introduction of COVID-19 containment measures in March 2020, in 2020/21 influenza was absent, and the 2021/22 epidemic peaked exceptionally late. Influenza activity has roughly returned to pre-pandemic levels since 2022/23, when there were 13,728 and 2,172 laboratory-confirmed influenza A and influenza B cases, 1,485 and 179 of which were hospitalized due to influenza. Virological surveillance confirmed that circulation of the influenza B/Yamagata lineage had ceased. One to two million influenza vaccinations were given each season. While the percentage of vaccinated children younger than seven years was constant (ranging from 31% to 37%), the percentage of vaccinated people aged 65 years and above increased from 48% in 2019/20 to 63% in 2021/22 and has remained moderately high. The vaccine effectiveness against hospitalization due to laboratory-confirmed influenza in young children and elderly people was 68% (95% confidence interval: 38%; 83%) and 42% (34%; 50%) in 2022/23 and slightly lower in 2023/24. The COVID-19 pandemic had two hopefully lasting effects on the epidemiology of influenza: elimination of the influenza B/Yamagata lineage and improved influenza vaccination coverage among the elderly population in Finland.

Prognosis factors of respiratory syncytial virus reinfection in hospitalized pediatric inpatients: A retrospective cohort study

Background The patterns of circulation and burden of influenza and respiratory syncytial virus (RSV) in Singapore are affected by the COVID-19 pandemic containment measures. These patterns in relation to SARS-CoV-2 in a post-pandemic era are unclear. Methods Using data from 2015 to 2023, we estimated excess influenza-, RSV- and SARS-CoV-2-associated hospitalisation in Singapore, adjusted for rhinovirus/enterovirus activity in generalised additive models. The data includes pneumonia and influenza (P&I) hospitalisation from a national inpatient database and a community-wide acute respiratory infection (ARI) sentinel surveillance programme, stratified by age groups. Results Across all age groups, the proportion of hospitalisation associated with influenza, SARS-CoV-2 and RSV was 15.7% (95% CI 6.4%–25.0%), 16.5% (95% CI 10.5%–22.6%) and 6.3% (95% CI 2.2%–12.5%) in 2023. From 2019 to 2023, all-age influenza-associated hospitalisation declined from 129.8 per 100,000 person-years (95% CI 110.9–148.4) to 95.7 per 100,000 person-years (95% CI 38.9–152.2). In contrast, all-age RSV-associated hospitalisation after the pandemic was 38.4 per 100,000 person-years (95% CI 13.1-75.9), similar to pre-pandemic observations. Peak seasonal influenza occurred 3-8 weeks later as compared to the time of pre-pandemic peak influenza activity. Conclusion The overall burden of influenza has declined after the COVID-19 pandemic and its burden is comparable with SARS-CoV-2. Furthermore, shifts in the timing of peak influenza activity suggest a potential need to review the timing of vaccine recommendations in Singapore.

Purpose Overuse of antibiotics for lower respiratory tract infections (LRTI) is common. It would therefore be useful to identify symptoms that predict a high likelihood of viral infection, so these patients could be triaged for home care to avoid antibiotics. Methods We recruited adults presenting to US primary or urgent care sites with a chief complaint of cough and symptoms consistent with LRTI. Data collected included demographics, comorbidities, symptoms, and 46 viral and bacterial respiratory pathogens by PCR. Chi-square tests were done to evaluate the association between individual symptoms and viral versus bacterial infections. Symptoms with a p < 0.10 for the association were retained for logistic regression. We created 4 regression models using stepwise backward elimination at p < 0.20, with viral infection, bacterial infection, and mixed infection as the dependent variables. A simple risk score was created assigning positive and negative points for viral and bacterial symptoms. Results We enrolled 718 adults with acute cough and obtained valid PCR specimens for 618. Four symptoms were significantly more likely with viral infections and less common in bacterial: coryza, confusion, fever, and chest congestion. Three symptoms were more likely with bacterial infections and less likely with viral infections: presence of sputum, sputum that is colored, and double-sickening (feeling better but then worsening). A simple risk score identified patients with a low (29%), moderate (56%) or high (79%) likelihood of having only viral pathogens detected. Conclusions Seven symptoms were identified that could help primary care clinicians distinguish between viral and bacterial LRTI. A simple risk score is proposed but requires prospective validation.

Background: This study aimed to establish a Severity Scale for influenza and other acute respiratory infections (ARI), requiring hospitalization, for surveillance and research purposes (the SevScale). Such a scale could aid the interpretation of data gathered from disparate settings. This could facilitate pooled analyses linking viral genetic sequencing data to clinical severity, bringing insights to inform influenza surveillance and the vaccine strain selection process. Methods: We used a subset of data from the Global Influenza Hospital Surveillance Network database, including data from different geographical areas and income levels. To quantify the underlying concept of severity, an item response model was developed using sixteen indicators of severity related to the hospital stay. Each patient in the dataset was assigned a Severity Score and a Severity Category (low, medium, or high severity). Finally, we compared the model scores across different subgroups. Results: Data from 9 countries were included, covering between 4 and 11 seasons from 2012 to 2022, with a total of 96,190 ARI hospitalizations. Not for all severity indicators data was available for all included seasons. Subgroups with a high percentage of patients in the High Severity Category included influenza A(H1N1)pdm09, age ≥50, lower-middle income countries, and admission since the start of the COVID-19 pandemic. Conclusions: The initial model successfully highlighted severity disparities across patient subgroups. Repeating this exercise with new, more complete data would allow recalibration and validation of the current model. The SevScale proved to be a promising method to define severity for influenza vaccine strain selection, surveillance and research.

We conducted a retrospective study to explore molecular insights into human respiratory syncytial virus (HRSV) group B strains among patients attending outpatient clinics at government medical facilities both before and during the influenza A/H1N1/2009 pandemic outbreak. We screened 2300 nasopharyngeal swabs using multiplex real time reverse transcriptase polymerase chain reaction. We amplified a segment of the first and second hypervariable regions, as well as the conserved portion of the third domain of the G-gene using HRSV-B specific primers, sequenced by Sanger di-deoxy chain termination method and thereafter analyzed the sequences. We characterized the circulating strains into 3 known genotypes: SAB4 (1.4%), BA7(1.4%) and multiple lineages of BA9 (97.2%). The majority of BA9 viruses were uniquely Kenyan with only 4% aligning with BA9 lineages found elsewhere. The mean evolutionary rate of the HRSV-B was estimated to be 3.08 × 10 -3 substitutions per site per year. Our findings indicate that the circulating HRSV-B viruses in Kenya underwent more rapid evolution during the overlapping period of 2007 to 2012. Additionally, our findings reveal the existence of unique lineages as well as new variants that have not been reported elsewhere to date.

Respiratory syncytial virus (RSV) is one of the leading causes of severe respiratory diseases in children, especially in infants. The immune responses induced by RSV infection are a fairly complex process that can contribute significantly to disease severity. Despite decades of research on RSV, many immune mechanisms remain to be explored. A full exploration of these immune response can contribute to the discovery of new therapeutic and prophylactic approaches. Despite substantial progress in vaccine development and the development of monoclonal antibodies over the years, there are still not enough effective preventive and therapeutic strategies. This review focuses on how the immune system reacts when children contract the respiratory syncytial virus. We described the biological characteristics of RSV, the pathological process of RSV infection, innate immunity（including Pattern Recognition Receptors and inflammatory cells）, adaptive immunity (including CD4+ and CD8+ T cells and Humoral Immune Response), and immune evasion. Understanding the complicated immune response to RSV infection is essential for developing effective interventions and vaccine developments. This review will enable an appreciation of how RSV affects the immune system and enhance the advancement of pragmatic therapeutic methodologies.

Background: Respiratory syncytial virus (RSV) is an important cause of bronchiolitis and pneumonia in children globally. This study aimed to incorporate new data to update estimates of RSV burden in children through 5 years of age in Western Pacific and Southeast Asia Regions. Methods: A systematic review and meta-analysis was conducted to examine the proportion of RSV among cases of respiratory tract infection (RTI) in children in Western Pacific and Southeast Asia Regions using random effects models. Studies were eligible if they met the following inclusion criteria: (1) observational studies such as cohort and cross-sectional studies; (2) studies on humans; (3) studies on patients with respiratory tract infection (RTI) or influenza-like illness (ILI); (4) studies reporting incidence or proportion of RSV infection among respiratory related illness; and (5) studies on children aged 5 years or less. Findings: A total of 4,403 studies were identified from an initial search. After screening titles, abstracts, and full-text review, a total of 173 studies that met predefined eligibility criteria were included in the analysis. The overall proportion of RSV infections among all ARTIs was 18.7% (95% CI: 16.0-21.5%), while the proportion of RSV infections among LRTIs was 28.7% (95% CI: 2.6-30.3) in children in Western Pacific and Southeast Asia Regions between 1970 and 2021. The proportion trend increased from 10.6% (95% CI: 2.90-22.2%) in the 1970s to 26.8% (95% CI: 22.0-31.9%) in the 1980s and 33.3% (95% CI :14.7-55.3%) in the 1990s. It then decreased to 25.0% (95% CI 22.8-27.3%) in the 2000s and 19.7% (95% CI 17.3-22.2%) in the 2010s. By country, Myanmar (50.0%; 95% CI, 47.5-52.4%) and New Zealand (45.3%; 95% CI, 37.2-56.4%) had the highest proportion during the overall time period, followed by Bhutan (45.2%; 95% CI, 36.4-54.3%), Lao PDR (41.0%; 95% CI, 36.2-46.0%), and Vietnam (36.0%; 95% CI, 19.3-53.6%). Interpretation: Substantial RSV-associated disease burden occurs in children in Western Pacific and Southeast Asia Regions. Our findings provide new and important evidence of the need for RSV prevention in Western Pacific and Southeast Asia countries. They could inform future preventive policy.

Four significant influenza outbreaks have occurred over the past 100 years, and the 1918 flu pandemic is the most severe. Since influenza viruses undergo antigenic evolution, they are the pathogens most likely to trigger a new pandemic shortly. Intranasal vaccination offers a promising strategy for preventing diseases triggered by respiratory viruses by eliciting an immunoglobulin A (IgA) response, limiting virus replication and transmission from the respiratory tract more efficiently than intramuscular vaccines. Combining intranasal administration and mRNA-lipid nanoparticles can be an ideal strategy for limiting the extent of the next flu pandemic. This study explored the immunogenicity of intranasally delivered mRNA encapsulated in mannose-histidine-conjugated chitosan lipid nanoparticles (MHCS-LNPs) as a vaccine against influenza A (H1N1) in BALB/c mice. Intranasal administration of mRNA-MHCS-LNPs resulted in the generation of influenza A (H1N1) hemagglutinin-specific neutralizing antibodies in vaccinated animals. The ELISA results indicated a notable increase in the quantity of IgG and IgA antibodies in serum and the Bronchoalveolar Lavage Fluid (BALF), respectively, and exhibited influenza A-specific IFN-γ secretion in vaccinated mice, as well as a noticeable alteration in IL-5 production. Overall, this study demonstrated an effective immunogenic response against respiratory viral infections through intranasal delivery of an mRNA-MHCS-LNP vaccine.

Influenza viruses continue to cause severe morbidity and remain a continuous pandemic threat. Virus challenge studies in animal models are performed during preclinical vaccine development. Improved methods are needed to improve data quality in animal models to reduce both animal stress and the animal numbers. By evaluating automated activity monitors as a tool for Influenza vaccine development, we demonstrate that activity in mice declines after viral challenge and that this reduction in activity can be prevented by vaccination. Notably, the decline in activity precedes weight loss and could thus provide an objective and early endpoint in Influenza virus challenge studies.

Background In 2021, the Norwegian Institute of Public Health established temporary registry-based surveillance of severe acute respiratory infections (SARI). We aimed to describe the surveillance system and evaluate selected attributes to inform the establishment of a permanent SARI surveillance system. Methods SARI cases were defined using ICD-10 discharge codes from national health and administrative registries, including codes for acute upper or lower respiratory infection (URI, LRI), COVID-19, acute respiratory distress syndrome, pertussis, or otitis media. Data from polymerase chain reaction (PCR) analyses were available for 10 respiratory pathogens including SARS-CoV-2, influenza virus, and respiratory syncytial virus (RSV). We included data from 28.9.2020–31.3.2024 and calculated the following parameters: the proportion of cases tested for SARS-CoV-2, influenza virus and/or RSV; time between admission and registration of a SARI-related ICD-10 code; and proportion of cases with URI, LRI and COVID-19. Results We identified 214,730 SARI cases, of whom 82%, 73% and 53% were tested for SARS-CoV-2, influenza virus and RSV. Case peaks were predominantly driven by one or a combination of these pathogens. Median time between admission and a registered SARI diagnostic code was 5 (lower-upper quartile 3-10) days. Nowcasting and alternative case definitions for SARI with COVID-19, -influenza, and RSV improved the timeliness. The ICD-10 codes for LRIs and COVID-19 captured only ~55% of the cases in the age group 0-29 years compared to the routine case definition, where URIs were included. Conclusions Registry-based SARI surveillance provides timely data for handling epidemics of respiratory infections in Norway. We recommend establishing a permanent SARI surveillance system.

In recent years, the world has witnessed in the emergence of several infectious diseases, with notable examples being coronavirus disease 2019 (COVID-19), avian influenza, and Mpox, which continue to present serious and persistent threats to global public health. The rapid spread and devastating impact of these diseases underscore the urgent need for effective combat strategies. One promising area of research in the field of antiviral drug development is the exploration of multi-specific antibodies. These have attracted significant attention owing to their diverse benefits compared to monoclonal antibodies. Multi-specific antibodies exhibit a more versatile function, possess a stronger binding affinity for viral targets, demonstrate enhanced antiviral activity, and show reduced susceptibility to viral escape mechanisms. These characteristics make them promising candidates for the development of novel antiviral therapies against a range of emerging infectious diseases. This review examines the current research progress surrounding multi-specific antibodies in the context of combating SARS-CoV-2, influenza virus, and other newly emerging infectious viruses. It offers insights into the potential applications and future prospects of multi-specific antibodies, with the aim to contribute to the ongoing efforts to address the global health challenges posed by infectious diseases.

Background Nirsevimab, a novel monoclonal antibody, provides passive immunity against RSV-infections in infants. In October/2023, Spain adopted immunization for children <6 months and those born during the epidemic season. Our main goal was to compare clinical, epidemiological and virological characteristics of respiratory infections in hospitalized infants before and after nirsevimab introduction. Methods. A prospective study was conducted in two Madrid hospitals during the 2022-23 and 2023-24 epidemic seasons. Infants <12 months admitted with lower respiratory tract infections were included. Clinical, epidemiological, and virological characteristics were compared based on admission before or after nirsevimab introduction and whether they received it. Results A total of 717 infants were included: 526 before October/2023 and 191 thereafter. Admissions from October-March 2023/24 decreased by 59% (95%CI:58.7-62.3%) compared to October-March 2022/23. ICU admissions dropped by 74% (95%CI:70.7-77.3%). Of those hospitalized after October/2023, 55(28.8%) received nirsevimab, with 11(20%) contracting RSV. The RSV-detection rate was lower after October/2023 (39% vs. 65%, P<0.001), as was the detection of other respiratory viruses, except rhinovirus and human bocavirus. Patients admitted after October/2023 were older (P=0.002), included fewer infants under 1 month (P=0.005), and had shorter hospital stays (P=0.001). For infants under 3 months, the likelihood of needing a stay > 5 days was 70% lower compared to those admitted before October/2023 (P<0.001;OR:0.39, 95%CI:0.22-0.66). Conclusions Nirsevimab has shown considerable effectiveness in shielding young infants from severe outcomes linked to RSV-infection. Furthermore, our study observed a notable decrease in hospitalizations for infections caused by other respiratory viruses after the introduction of nirsevimab.

Background: Respiratory Syncytial Virus (RSV) is a major health concern, particularly for infants. In France, Nirsevimab, a long-acting monoclonal antibody to prevent RSV-associated lower respiratory tract infections (LRTI) was available from September 2023. We described RSV-associated LRTI hospitalisations during the 2023-2024 season among infants younger than six months born at the Hospices Civils de Lyon (HCL), and evaluated the effectiveness of Nirsevimab against RSV-LRTI hospitalisation. Methods: This observational study included infants born and hospitalised at the HCL during the 2023-2024 season, along with pre-COVID-19 and 2022-2023 seasons. Information on Nirsevimab immunisation status, clinical and perinatal variables were collected through routine care. Infants’ characteristics and incidence risk of hospitalisation per 100 births during 2023-2024 were compared with the historical periods overall and by delay between birth and the onset of the RSV season. Nirsevimab effectiveness was computed by the screening method. Results: During the 2023-2024 season, 83 infants younger than six months were hospitalised with an RSV-associated LRTI. Compared with the historical periods these infants were older. Incidence risk for infants born during the period when immunisation was available were lower than the previous seasons; incidence risk ratios were 0.45 (95% confidence interval (CI): [0.33;0.62]) in 2023-2024 compared with pre-COVID-19 period and 0.53 (95%CI: [0.36;0.77]) compared with 2022-2023 season. Nirsevimab effectiveness was 78.3% (95%CI: [55.9 ;89.5]) with a coverage of 79.3% in the HCL maternities. Conclusions: This study revealed a change in the epidemiology of RSV-associated LRTI hospitalisations in 2023-2024. High coverage and effectiveness were estimated in real-world setting.

Background: Limited data are available regarding the infection status, clinical characteristics, treatments and outcomes of lung transplant recipients (LTRs) afflicted with coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 Omicron Variant in China. Methods: We conducted a study on LTRs with COVID-19 caused by the Omicron Variant from November 17, 2022, to May 1, 2023. Clinical information was gathered retrospectively through electronic medical records, questionnaires, or follow-up telephone calls. Results: 178 LTRs with COVID-19 were included, with 50% (89/178) requiring hospitalization for an average stay of 16 days (IQR: 9.5-25.5 days). The most common symptoms were fever (79.8%), dry cough (75.3%) and fatigue (61.8%). Ultimately, 17 recipients succumbed to COVID-19-related respiratory failure or secondary multiple organ dysfunction, resulting in an overall mortality rate of 9.6%. Of the 89 hospitalized patients, 41.6% (37/89) eventually progressed to severe or critical disease, forming the Severe/Critical Group (S/C group), while the remaining 58.4% (52/89) had mild to moderate disease (M/M group). In comparison to the M/M group, the S/C group had higher CRP (59.6 vs. 16.8 mg/L, P＜0.01), ESR (45.5 vs. 22.5mm/h, P＜0.01) and D-dimer (1.09 vs. 0.65 mg/L, P＜0.05), but lower CD3 + T lymphocytes (577 vs. 962 cells/ul, P＜0.01) and CD4 + T lymphocytes (217 vs. 427 cells/ul, P＜0.01). The S/C group had significantly higher rates of combined pulmonary bacterial infection (67.6% vs. 38.5%, P＜0.01) and pulmonary fungal infection (73.0% vs. 38.5%, P＜0.01) during the course of COVID-19, nearly double that of the M/M group. In a multivariate logistic analysis, elevated CRP (>41.8mg/L), combined pulmonary fungal infection, and interstitial lung disease(ILD) as primary disease emerged as high-risk factors for developing the severe disease phenotype following Omicron variant infection in LTRs, with respective OR values of 4.23 (95% CI: 1.68-11.23), 4.76 (95% CI: 1.59-15.64), and 5.13 (95% CI: 1.19-29.17). Conclusions: LTRs displayed an increased vulnerability to combined lung bacterial or fungal infections following Omicron infection. CRP> 41.8mg/L, ILD as primary disease, and combined pulmonary fungal infection are high-risk factors for developing severe disease.

Background Viral interference is the concept that different viruses have an effect on the incidence of other viruses– either positive or negative. While this has been demonstrated in vitro and in animal models, it is not well described in large observational studies. Methods We analysed all patients tested for positive respiratory viruses between January 2016– December 2019 just prior to the pandemic in the National University Hospital laboratory, Singapore. Nasal, throat, and/ or nasopharyngeal swabs were collected by treating clinicians and tested by either multiplex PCR or immunofluorescence. Survival plots were created to study the time for a second viral infection following the initial respiratory viral detection. Results RSV (HR: 0.63, 95%CI: 0.43–0.92; p<0.01) and influenza (HR: 0.41, 95%CI: 0.27-0.61; p<0.001) -positive cases showed a greater delay in subsequent respiratory infections compared to other pathogens, suggesting relative protection, while enterovirus/ rhinovirus (HR: 2.05, 95%CI: 1.52-2.77; p<0.001) and Parainfluenza (HR: 1.76, 95%CI: 1.18-2.63; p<0.001) showed heightened susceptibility. No significant associations were found for Adenovirus, seasonal coronaviruses, and other pathogens. Conclusion We found that it is possible that prior infections with Influenza virus or RSV conferred significant cross-protection against subsequent circulating respiratory viral infections for the next 4 years. Larger studies are needed to explore mechanisms behind this possible broad-spectrum antiviral response in human hosts as this may have implications for vaccination strategies.

Background: Global influenza-associated acute respiratory infections contribute to 3-5 million severe illnesses requiring hospitalization annually, with 90% of hospitalizations occurring among children <5 years in developing countries. In Bangladesh, limited availability of nationally representative, robust estimates of influenza-associated hospitalizations limit allocation of resources for prevention and control measures. Methods: This study used data from the Hospital Based Influenza Surveillance (HBIS) system in Bangladesh from 2010-2019 and Healthcare Utilization Surveys to determine hospital utilization patterns in the catchment area. We estimated annual influenza-associated hospitalization numbers and rates for all age groups in Bangladesh using methods outlined by the World Health Organization and adjusted for enrolment, laboratory testing practices, and healthcare seeking behavior. We then estimated national hospitalization rates by multiplying age-specific hospitalization rates with the corresponding annual national census population. Results: Annual influenza-associated hospitalization rates per 100,000 population for all ages ranged from 31 (95% CI: 27-36) in 2011 to 139 (95% CI: 130-149) in 2019. Children <5 years old had the highest rates of influenza-associated hospitalization, ranging from 114 (95% CI: 90-138) in 2011 to 529 (95% CI: 481-578) in 2019, followed by adults aged ≥65 years with rates ranging from 46 (95% CI: 34-57) in 2012 to 252 (95% CI: 213-292) in 2019. The national hospitalization estimates for all ages from 2010-2019 ranged from 47,891 to 236,380 per year. Conclusions: The impact of influenza-associated hospitalizations in Bangladesh may be considerable, particularly for young children and older adults. Targeted interventions, such as influenza vaccination for these age groups, should be prioritized and evaluated.

Using a common protocol across seven countries in the European Union/European Economic Area, we estimated XBB.1.5 monovalent vaccine effectiveness (VE) against COVID-19 hospitalisation and death in ≥65-year-olds, during October-November 2023. We linked electronic records to construct retrospective cohorts and used Cox models to estimate adjusted Hazard Ratios and derive VE. VE for COVID-10 hospitalisation and death was, respectively, 67% (95%CI: 60-72) and 68% (95%CI: 44-82) in 65–79-year-olds, and 64% (95%CI: 49-75) and 74% (95%CI: 56-85) in ≥80-year-olds. Results indicate that periodic vaccination of individuals ≥65 years has an ongoing benefit, and support the current vaccination strategies in the EU/EEA.