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2.
J Prev Med Hyg ; 65(1): E11-E16, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38706768

ABSTRACT

Introduction: The 2021/2022 influenza season was not characterised by a well-defined incidence peak. As reported by the Italian National Institute of Health, a high value of incidence of influenza cases was recorded in week 13, but it was still lower than in other influenza seasons. This abnormal circulation was probably due to relaxation of the COVID-19 pandemic restriction measures, such as social distancing, smart-working, home leaning and the use of masks, which greatly reduced the circulation of respiratory-transmitted viruses, including human respiratory syncytial virus (HRSV). The symptoms of SARS-CoV-2 and influenza are quite similar, sharing the human-to-human transmission route via respiratory droplets. Methods: The aim of this study was to estimate the rate of coinfection with influenza viruses and/or HRSV in SARS-CoV-2-positive subjects (N = 940) in a population of central Italy during the 2021/2022 season. Results: A total of 54 cases of coinfection were detected during the study period, 51 cases (5.4%) of SARS-CoV-2 and influenza virus and three cases (0.3%) of SARS-CoV-2 and HRSV coinfection. Conclusions: These results highlight the importance of continuous monitoring of the circulation of influenza virus and other respiratory viruses in the context of the COVID-19 pandemic.


Subject(s)
COVID-19 , Coinfection , Influenza, Human , SARS-CoV-2 , Humans , Italy/epidemiology , COVID-19/epidemiology , Influenza, Human/epidemiology , Coinfection/epidemiology , Female , Adult , Male , Child , Middle Aged , Child, Preschool , Adolescent , Aged , Seasons , Infant , Young Adult , Incidence , Respiratory Syncytial Virus Infections/epidemiology
3.
Bol Med Hosp Infant Mex ; 81(2): 90-96, 2024.
Article in English | MEDLINE | ID: mdl-38768514

ABSTRACT

BACKGROUND: After the SARS-CoV-2 pandemic, there has been an increase in hospitalization for lower respiratory infection secondary to respiratory syncytial virus (RSV), with greater complications. Associated extrapulmonary alterations, biventricular dysfunction, acute kidney injury, among others, have been found. The objective of this study was to analize the evolution and complications in hospitalized children with lower respiratory infection secondary to RSV after COVID-19 pandemic. METHODS: All pediatric patients under 2 years of age admitted to the emergency department with RSV infection were included. Clinical characteristics, need for supplemental oxygen, use of amines, renal angina index, and requirement for renal replacement therapy were analyzed. Lung ultrasound was performed upon admission. Statistical analysis was carried out for the quantitative variables by means of mean and standard deviation, and qualitative variables by frequency and percentage. Differences in the distribution were evaluated with Fisher's exact distribution. RESULTS: 45 patients with RSV infection were identified, 26.7% required invasive mechanical ventilation and 11.1% requiered peritoneal dialysis. Fatality was observed in four cases, three of these younger than 12 months with a LUS score > 7; contrasts with 90.2% of survivors with a score < 7 (p = 0.0004). CONCLUSIONS: An increase in the incidence of bronchiolitis after pandemic was observed, with more than half having moderate to severe symptoms and requiring supplemental oxygen support in all patients upon admission. Acute kidney injury is the most common extrapulmonary manifestation.


INTRODUCCIÓN: Posterior a la pandemia por SARS-CoV-2 se ha observado un incremento en la hospitalización por virus respiratorio sincitial (VRS), con mayores complicaciones. Se han encontrado alteraciones extrapulmonares asociadas, disfunción biventricular y lesión renal aguda, entre otras. El objetivo de este estudio fue analizar la evolución y las complicaciones en niños hospitalizados con enfermedad respiratoria de vías bajas secundaria a infección por VRS tras la pandemia de COVID-19. MÉTODOS: Se incluyeron todos los menores de 2 años que ingresaron al servicio de urgencias con infección por VRS. Se analizaron las características clínicas, la necesidad de oxígeno suplementario, el uso de aminas, el índice de angina renal y el requerimiento de terapia de sustitución renal. Se realizó ecografía pulmonar al ingreso. En el análisis estadístico, para las variables cuantitativas se determinaron la media y la desviación estándar, y para las variables cualitativas la frecuencia y el porcentaje. Se evaluaron las diferencias de la distribución con la prueba exacta de Fisher. RESULTADOS: Hubo 45 pacientes con infección por VRS. El 26.7% requirieron ventilación mecánica invasiva y el 11.1% diálisis peritoneal. La letalidad fue de cuatro casos, tres de ellos menores de 12 meses con puntuación de LUS > 7; esto contrasta con el 90.2% de los sobrevivientes con puntaje < 7 (p = 0.0004). CONCLUSIONES: Se observó un aumento en la incidencia de bronquiolitis tras la pandemia, en más de la mitad de los casos con cuadros de moderados a graves, y todos requirieron oxígeno suplementario al ingreso. La lesión renal aguda fue la manifestación extrapulmonar más frecuente.


Subject(s)
COVID-19 , Hospitalization , Respiration, Artificial , Respiratory Syncytial Virus Infections , Severity of Illness Index , Humans , Respiratory Syncytial Virus Infections/epidemiology , COVID-19/epidemiology , COVID-19/complications , Infant , Male , Female , Hospitalization/statistics & numerical data , Infant, Newborn , Peritoneal Dialysis , Emergency Service, Hospital , Retrospective Studies
4.
Influenza Other Respir Viruses ; 18(5): e13310, 2024 May.
Article in English | MEDLINE | ID: mdl-38725276

ABSTRACT

BACKGROUND: A variety of viruses can cause acute respiratory infections (ARIs), resulting in a high disease burden worldwide. To explore the dominant viruses and their prevalence characteristics in children with ARIs, comprehensive surveillance was carried out in the Pudong New Area of Shanghai. METHODS: Between January 2013 and December 2022, the basic and clinical information, and respiratory tract specimens of 0-14 years old children with ARIs were collected in five sentinel hospitals in Shanghai Pudong. Each specimen was tested for eight respiratory viruses, and the positive rates of different age groups, case types (inpatient or outpatient) were analyzed. RESULTS: In our study, 30.67% (1294/4219) children with ARIs were positive for at least one virus. Influenza virus (IFV) was the most commonly detected respiratory virus (349/4219, 8.27%), followed by respiratory syncytial virus (RSV) (217/4219, 5.14%), para-influenza virus (PIV) (215/4219, 5.10%), and human coronavirus (HCoV, including 229E, OC43, NL63, and HKU1) (184/4219, 4.36%). IFV was the leading respiratory virus in outpatients aged 5-14 years (201/1673, 12.01%); RSV was the most prevalent respiratory virus in both inpatients (61/238, 25.63%) and outpatients (4/50, 8.00%) for ARI patients aged <6 months old. For PIV, HMPV, HCoV, and HRV, the risk of infection usually was higher among young children. Co-infection with more than two viruses was seen in 3.25% (137/4219). CONCLUSIONS: IFV and RSV played important roles in ARIs among children, but the risk populations were different. There are needs for targeted diagnosis and treatment and necessary immunization and non-pharmaceutical interventions.


Subject(s)
Respiratory Tract Infections , Humans , China/epidemiology , Child, Preschool , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Child , Infant , Male , Adolescent , Female , Prevalence , Infant, Newborn , Viruses/isolation & purification , Viruses/classification , Virus Diseases/epidemiology , Virus Diseases/virology , Coinfection/epidemiology , Coinfection/virology , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Virus Infections/virology , Acute Disease/epidemiology
5.
Hum Vaccin Immunother ; 20(1): 2348135, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-38738683

ABSTRACT

Nirsevimab has been recently licensed for universal RSV prophylaxis in infants. NIRSE-GAL is a three-year population-based study initiated in Galicia in September 2023. It aims to evaluate nirsevimab effectiveness against RSV-related hospitalizations lower respiratory tract infections (LRTI), severe RSV, all-cause LRTI, and all-cause hospitalization. NIRSE-GAL also aims to estimate nirsevimab impact on primary healthcare use in the short and mid-term, children's wheezing and asthma, and medical prescriptions for RSV. The immunization campaigns will be scheduled based on the expected start week for the RSV season and will last the whole season. Immunization will be offered to: i) infants born during the campaign (seasonal), ii) infants < 6 months at the start of the campaign (catch-up), and iii) infants with high-risk factors, aged 6-24 months at the start of the campaign (high-risk). The follow-up period will start: i) the immunization date for all immunized infants, ii) the start of the campaign, for the non-immunized catch-up or high-risk groups, or iii) the birthdate for the non-immunized seasonal group. Infants will be followed up until outcome occurrence, death, or end of study. Nirsevimab effectiveness will be estimated using Poisson and Cox regression models. Sensitivity and stratified analyses will be undertaken. The number of averted cases and the number needed to immunize will be estimated. Immunization failure and nirsevimab safety will be monitored. NIRSE-GAL was approved by the ethics committee of Galicia (CEIC 2023-377) and registered in ClinicalTrials.gov (ID: NCT06180993). Findings will be mainly shared via peer-reviewed publications and scientific conferences.


Subject(s)
Antiviral Agents , Hospitalization , Respiratory Syncytial Virus Infections , Humans , Respiratory Syncytial Virus Infections/prevention & control , Infant , Hospitalization/statistics & numerical data , Antiviral Agents/therapeutic use , Antiviral Agents/administration & dosage , Respiratory Syncytial Virus, Human/immunology , Female , Male , Respiratory Tract Infections/prevention & control , Immunization Programs , Infant, Newborn , Child, Preschool , Palivizumab/therapeutic use , Palivizumab/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage
6.
BMC Pediatr ; 24(1): 328, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38741033

ABSTRACT

BACKGROUND: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), influenza A, and respiratory syncytial virus (RSV) infections have similar modes of transmission and clinical symptoms. There is a need to identify simple diagnostic indicators to distinguish these three infections, particularly for community hospitals and low- and middle-income countries that lack nucleic acid detection kits. This study used clinical data to assess the diagnostic value of routine blood tests in differentiating between SARS-CoV-2, influenza A, and RSV infections in children. METHODS: A total of 1420 children treated at the Hangzhou Children's Hospital between December 2022 and June 2023 were enrolled in this study, of whom 351 had SARS-CoV-2, 671 had influenza, and 398 had RSV. In addition, 243 healthy children were also collected. The blood test results of SARS-CoV-2 patients were compared to those of patients with influenza A and RSV and the healthy controls. The area under the receiver operating characteristic curve (AUC-ROC) was employed to evaluate each blood parameter's diagnostic value. RESULTS: Children with SARS-CoV-2 exhibited notably elevated levels of white blood cell (WBC) count, platelet (PLT) count, neutrophil count, and neutrophil-to-lymphocyte ratio (NLR) compared to influenza A patients (P < 0.05). In contrast, SARS-CoV-2 patients exhibited a decrease in the mean platelet volume to platelet count ratio (MPV/PLT) and the lymphocyte-to-monocyte ratio (LMR) when compared to other individuals (P < 0.05). These parameters had an AUC between 0.5 and 0.7. Compared to patients with RSV, SARS-CoV-2 patients had significantly higher MPV/PLT and significantly lower WBC, lymphocyte, PLT, LMR, and lymphocyte multiplied by platelet (LYM*PLT) values (P < 0.05). However, only LYM*PLT had an acceptable diagnostic value above 0.7 for all age groups. Compared to healthy children, children with COVID-19 exhibited elevated NLR and MPV/PLT levels, alongside decreased lymphocyte, PLT, LMR, and LYM*PLT values. (P < 0.05). The AUC of the LMR, LYM*PLT, and PLT were above 0.7 in all age groups, indicating promising diagnostic values. CONCLUSIONS: The routine blood parameters among patients with COVID-19, influenza A, and RSV differ significantly early in the disease and could be used by clinicians to discriminate between the 3 types of infection.


Subject(s)
COVID-19 , Influenza, Human , Respiratory Syncytial Virus Infections , Humans , COVID-19/diagnosis , COVID-19/blood , Retrospective Studies , Influenza, Human/diagnosis , Influenza, Human/blood , Male , Female , Child , Child, Preschool , Respiratory Syncytial Virus Infections/diagnosis , Respiratory Syncytial Virus Infections/blood , Diagnosis, Differential , Infant , ROC Curve , Adolescent , Hematologic Tests/methods , Child, Hospitalized , SARS-CoV-2 , China
7.
Influenza Other Respir Viruses ; 18(5): e13294, 2024 May.
Article in English | MEDLINE | ID: mdl-38716791

ABSTRACT

BACKGROUND: Data from the sentinel surveillance system of severe acute respiratory infections in Spain were used to estimate the impact of administration of nirsevimab to children born from 1 April 2023 onwards. METHODS: Estimated RSV hospitalisations in < 1-year-olds during weeks 40, 2023, to 8, 2024, were compared to the number that would be expected after accounting for the background change in RSV circulation in the 2023/24 season, compared to 2022/23. RESULTS: We estimated 9364-9875 RSV hospitalisations less than expected, corresponding to a 74%-75% reduction.


Subject(s)
Antiviral Agents , Hospitalization , Respiratory Syncytial Virus Infections , Humans , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Virus Infections/drug therapy , Spain/epidemiology , Infant , Hospitalization/statistics & numerical data , Incidence , Antiviral Agents/therapeutic use , Female , Male , Respiratory Syncytial Virus, Human , Sentinel Surveillance , Infant, Newborn , Antibodies, Monoclonal, Humanized/therapeutic use
8.
Biol Pharm Bull ; 47(5): 924-929, 2024.
Article in English | MEDLINE | ID: mdl-38692870

ABSTRACT

The region-to-region spread of human infectious diseases is considered to be dependent on the human mobility flow (HMF). However, it has been hard to obtain the evidence for this. Since the onset of the coronavirus disease 2019 (COVID-19) pandemic in Japan 2020, the government has enforced countermeasures against COVID-19 nationwide, namely the restriction of personal travelling, universal masking, and hand hygiene. As a result, the spread of acute respiratory infections had been effectively controlled. However, COVID-19 as well as pediatric respiratory syncytial virus (RSV) infections were not well-controlled. The region-to-region spread of pediatric RSV infections in 2020-2021 was recognizable unlike those in 2018 and 2019. In this study, we investigated the correlation between the trend of regional reports of the pediatric RSV infections and the HMF based on cellular phone signal data. Upon closer examination of both epidemiological trend and HMF data, the spread of pediatric RSV infection from one region to another was logically explained by HMF, which would serve as the evidence of the dependence of regional transmission on HMF. This is the first solid evidence where this correlation has been clearly observed for the common respiratory infections. While social implementation of infection control measures has successfully suppressed the droplet-mediated respiratory infections, such as influenza, but not the airborne infections, it was suggested that the aerosol transmission and adult asymptomatic carrier were involved in the transmission of RSV akin to COVID-19.


Subject(s)
COVID-19 , Respiratory Syncytial Virus Infections , Humans , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Virus Infections/prevention & control , Infant , Japan/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/transmission , Respiratory Syncytial Virus, Human , SARS-CoV-2
9.
Influenza Other Respir Viruses ; 18(5): e13299, 2024 May.
Article in English | MEDLINE | ID: mdl-38700006

ABSTRACT

INTRODUCTION: Traditional surveillance systems may underestimate the burden caused by respiratory syncytial virus (RSV). Capture-recapture methods provide alternatives for estimating the number of RSV-related hospitalizations in a population. METHODS: Capture-recapture methods were used to estimate the number of RSV-related hospitalizations in adults in Middle Tennessee from two independent hospitalization surveillance systems during consecutive respiratory seasons from 2016-2017 to 2019-2020. Data from the Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) and the Emerging Infections Program (EIP) were used. Annual RSV hospitalization rates were calculated using the capture-recapture estimates weighted by hospitals' market share divided by the corresponding census population. RESULTS: Using capture-recapture methods, the estimated overall adult hospitalization rates varied from 8.3 (95% CI: 5.9-15.4) RSV-related hospitalizations per 10,000 persons during the 2016-2017 season to 28.4 (95% CI: 18.2-59.0) hospitalizations per 10,000 persons in the 2019-2020 season. The proportion of hospitalizations that HAIVEN determined ranged from 8.7% to 36.7% of the total capture-recapture estimated hospitalization, whereas EIP detected 23.5% to 52.7% of the total capture-recapture estimated hospitalizations. CONCLUSION: Capture-recapture estimates showed that individual traditional surveillance systems underestimated the hospitalization burden in adults. Using capture-recapture allows for a more comprehensive estimate of RSV hospitalizations.


Subject(s)
Hospitalization , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human , Humans , Respiratory Syncytial Virus Infections/epidemiology , Hospitalization/statistics & numerical data , Adult , Respiratory Syncytial Virus, Human/isolation & purification , Middle Aged , Tennessee/epidemiology , Young Adult , Aged , Male , Female , Adolescent , Seasons , Cost of Illness
10.
Influenza Other Respir Viruses ; 18(5): e13275, 2024 May.
Article in English | MEDLINE | ID: mdl-38692663

ABSTRACT

BACKGROUND: Influenza, respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) are common respiratory viruses causing similar symptoms. Optimal tools to assess illness severity for these viruses have not been defined. Using the Hospitalized Acute Respiratory Tract Infection (HARTI) study data, we report symptom severity by clinician-rated clinical severity scores (CSS) in adults with influenza, RSV, or hMPV and correlations between CSS and patient-reported outcomes (PROs). METHODS: HARTI was a global epidemiologic study in adults hospitalized with acute respiratory tract infections. Patients were assessed at enrollment within 24 h of admission with CSS and twice during hospitalization with CSS, Respiratory Infection Intensity and Impact Questionnaire™ (RiiQ™), and EQ-5D-5L. Data were summarized descriptively, stratified by pathogen and baseline and hospitalization characteristics. Domain (general, upper respiratory, and lower respiratory) and sign/symptom subscores are presented for CSS; sign/symptom subscores are presented for RiiQ™ results. RESULTS: Data from 635 patients with influenza, 248 with RSV, and 107 with hMPV were included. At enrollment, total CSS and general and lower respiratory signs/symptoms (LRS) scores were higher for RSV and hMPV than influenza. Between-pathogen differences were greatest for LRS scores. Dyspnea, rales/rhonchi, wheezing, and shortness of breath scores trended higher for RSV and hMPV than influenza. RiiQ™ scores for cough, fatigue, and short of breath were strongly correlated with corresponding clinician-rated symptoms. CONCLUSIONS: These findings support the use of PROs (e.g., the RiiQ™) correlating with clinician assessments to gauge patient well-being and aid patient management by accurately assessing respiratory illness severity due to RSV, hMPV, or influenza.


Subject(s)
Hospitalization , Influenza, Human , Metapneumovirus , Paramyxoviridae Infections , Respiratory Syncytial Virus Infections , Respiratory Tract Infections , Severity of Illness Index , Humans , Metapneumovirus/isolation & purification , Male , Female , Respiratory Tract Infections/virology , Respiratory Tract Infections/epidemiology , Middle Aged , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Virus Infections/complications , Respiratory Syncytial Virus Infections/epidemiology , Influenza, Human/virology , Influenza, Human/complications , Influenza, Human/epidemiology , Adult , Paramyxoviridae Infections/virology , Paramyxoviridae Infections/epidemiology , Paramyxoviridae Infections/complications , Aged , Young Adult , Respiratory Syncytial Virus, Human/isolation & purification , Aged, 80 and over , Adolescent
11.
New Microbiol ; 47(1): 60-67, 2024 May.
Article in English | MEDLINE | ID: mdl-38700885

ABSTRACT

Acute respiratory tract infection (ARTI) is common in all age groups, especially in children and the elderly. About 85% of children who present with bronchiolitis are infected with respiratory syncytial virus (RSV); however, nearly one-third are coinfected with another respiratory virus, such as human rhinovirus (HRV). Therefore, it is necessary to explore the immune response to coinfection to better understand the molecular and cellular pathways involving virus-virus interactions that might be modulated by innate immunity and additional host cell response mechanisms. This study aims to investigate the host innate immune response against RSV-HRV coinfection compared with monoinfection. Human primary bronchial/tracheal epithelial cells (HPECs) were infected with RSV, HRV, or coinfected with both viruses, and the infected cells were collected at 48 and 72 hours. Gene expression profiles of IL-6, CCL5, TNF-α, IFN-ß, IFN-λ1, CXCL10, IL-10, IL-13, IRF3, and IRF7 were investigated using real-time quantitative PCR, which revealed that RSV-infected cells exhibited increased expression of IL-10, whereas HRV infection increased the expression of CXCL10, IL-10, and CCL5. IFN-λ1 and CXCL10 expression was significantly different between the coinfection and monoinfection groups. In conclusion, our study revealed that two important cytokines, IFN-λ1 and CXCL10, exhibited increased expression during coinfection.


Subject(s)
Bronchi , Chemokine CXCL10 , Coinfection , Epithelial Cells , Interferon Lambda , Interferons , Interleukins , Picornaviridae Infections , Respiratory Syncytial Virus Infections , Rhinovirus , Humans , Rhinovirus/physiology , Coinfection/virology , Chemokine CXCL10/genetics , Chemokine CXCL10/metabolism , Epithelial Cells/virology , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Virus Infections/virology , Bronchi/virology , Bronchi/cytology , Picornaviridae Infections/virology , Picornaviridae Infections/immunology , Interferons/genetics , Interferons/metabolism , Respiratory Syncytial Virus, Human/physiology , Respiratory Syncytial Virus, Human/genetics , Cells, Cultured , Respiratory Syncytial Viruses/physiology
13.
Viruses ; 16(5)2024 05 14.
Article in English | MEDLINE | ID: mdl-38793659

ABSTRACT

Respiratory syncytial virus (RSV) is the most prevalent cause of acute lower respiratory infection in young children. Currently, the first RSV vaccines are approved by the FDA. Recently, N6-methyladenosine (m6A) RNA methylation has been implicated in the regulation of the viral life cycle and replication of many viruses, including RSV. m6A methylation of RSV RNA has been demonstrated to promote replication and prevent anti-viral immune responses by the host. Whether m6A is also involved in viral entry and whether m6A can also affect RSV infection via different mechanisms than methylation of viral RNA is poorly understood. Here, we identify m6A reader YTH domain-containing protein 1 (YTHDC1) as a novel negative regulator of RSV infection. We demonstrate that YTHDC1 abrogates RSV infection by reducing the expression of RSV entry receptor CX3C motif chemokine receptor 1 (CX3CR1) on the cell surface of lung epithelial cells. Altogether, these data reveal a novel role for m6A methylation and YTHDC1 in the viral entry of RSV. These findings may contribute to the development of novel treatment options to control RSV infection.


Subject(s)
Adenosine , CX3C Chemokine Receptor 1 , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human , Virus Internalization , Humans , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Virus Infections/metabolism , Respiratory Syncytial Virus, Human/genetics , Respiratory Syncytial Virus, Human/physiology , Adenosine/analogs & derivatives , Adenosine/metabolism , CX3C Chemokine Receptor 1/metabolism , CX3C Chemokine Receptor 1/genetics , Virus Replication , Methylation , Down-Regulation , RNA Splicing Factors/metabolism , RNA Splicing Factors/genetics , Epithelial Cells/virology , Epithelial Cells/metabolism , Cell Line , A549 Cells , RNA, Viral/genetics , RNA, Viral/metabolism , Host-Pathogen Interactions , Nerve Tissue Proteins
14.
PLoS Pathog ; 20(5): e1012198, 2024 May.
Article in English | MEDLINE | ID: mdl-38739647

ABSTRACT

Respiratory syncytial virus (RSV) is the most important viral agent of severe pediatric respiratory illness worldwide, but there is no approved pediatric vaccine. Here, we describe the development of the live-attenuated RSV vaccine candidate Min AL as well as engineered derivatives. Min AL was attenuated by codon-pair deoptimization (CPD) of seven of the 11 RSV open reading frames (ORFs) (NS1, NS2, N, P, M, SH and L; 2,073 silent nucleotide substitutions in total). Min AL replicated efficiently in vitro at the permissive temperature of 32°C but was highly temperature sensitive (shut-off temperature of 36°C). When serially passaged at increasing temperatures, Min AL retained greater temperature sensitivity compared to previous candidates with fewer CPD ORFs. However, whole-genome deep-sequencing of passaged Min AL revealed mutations throughout its genome, most commonly missense mutations in the polymerase cofactor P and anti-termination transcription factor M2-1 (the latter was not CPD). Reintroduction of selected mutations into Min AL partially rescued its replication in vitro at temperatures up to 40°C, confirming their compensatory effect. These mutations restored the accumulation of positive-sense RNAs to wild-type (wt) RSV levels, suggesting increased activity by the viral transcriptase, whereas viral protein expression, RNA replication, and virus production were only partly rescued. In hamsters, Min AL and derivatives remained highly restricted in replication in the upper and lower airways, but induced serum IgG and IgA responses to the prefusion form of F (pre F) that were comparable to those induced by wt RSV, as well as robust mucosal and systemic IgG and IgA responses against RSV G. Min AL and derivatives were fully protective against challenge virus replication. The derivatives had increased genetic stability compared to Min AL. Thus, Min AL and derivatives with selected mutations are stable, attenuated, yet highly-immunogenic RSV vaccine candidates that are available for further evaluation.


Subject(s)
Open Reading Frames , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus Vaccines , Vaccines, Attenuated , Virus Replication , Animals , Respiratory Syncytial Virus Vaccines/immunology , Respiratory Syncytial Virus Vaccines/genetics , Vaccines, Attenuated/immunology , Vaccines, Attenuated/genetics , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Virus Infections/virology , Cricetinae , Administration, Intranasal , Codon , Immunity, Mucosal , Antibodies, Viral/immunology , Antibodies, Viral/blood , Humans , Respiratory Syncytial Virus, Human/immunology , Respiratory Syncytial Virus, Human/genetics , Mesocricetus , Respiratory Syncytial Viruses/immunology , Respiratory Syncytial Viruses/genetics
15.
Sci Rep ; 14(1): 11823, 2024 05 23.
Article in English | MEDLINE | ID: mdl-38783052

ABSTRACT

Our previous findings indicated that many respiratory syncytial virus (RSV) isolates are unstable at 4 °C compared to 20 °C. Some of the strains completely lose infectivity after 24 h at 4 °C. This study analyzed the inactivation process at 4 °C using a representative strain, RSV/Sendai/851/13. After 24 h of storage at 4 °C, the virus was completely inactivated but retained its ability to attach to and to be taken into host cells. It suggested a reduced fusion ability between the viral and cellular membranes. During storage at 4 °C, the RSV fusion (F) protein underwent a conformational change and was no longer recognized by pre-fusion form-specific antibodies. When the RSV/Sendai/851/13 strain was passaged at 4 °C, a variant with an amino acid substitution, I148T, in the F protein fusion peptide was selected. Also, an amino acid change in G protein demonstrating stability at low temperatures was obtained. These results show that the inactivation of RSV at 4 °C is due to the loss of membrane fusion activity in the F protein, which cannot maintain its pre-fusion state at 4 °C.


Subject(s)
Cold Temperature , Respiratory Syncytial Virus, Human , Viral Fusion Proteins , Virus Inactivation , Viral Fusion Proteins/metabolism , Viral Fusion Proteins/genetics , Viral Fusion Proteins/chemistry , Humans , Respiratory Syncytial Virus, Human/physiology , Animals , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Viruses
16.
Front Immunol ; 15: 1377374, 2024.
Article in English | MEDLINE | ID: mdl-38745662

ABSTRACT

Respiratory syncytial virus (RSV) is the primary cause of bronchiolitis-related hospitalizations among children under 5 years of age, with reinfection being common throughout life. Maternal vaccination has emerged as a promising strategy, delivering elevated antibody levels to newborns for immediate protection. However, limited research has explored the protective efficacy of maternal antibodies (matAbs) against secondary RSV infections in offspring. To address this gap, we employed a mouse model of maternal RSV vaccination and secondary infection of offspring to evaluate lung pathology following RSV reinfection in mice with varying levels of maternal antibody (matAb). Additionally, we aimed to investigate the potential causes of exacerbated lung inflammation in offspring with high matAb levels following secondary RSV exposure. Our findings revealed that offspring with elevated levels of maternal pre-F antibody demonstrated effective protection against lung pathology following the initial RSV infection. However, this protection was compromised upon reinfection, manifesting as heightened weight loss, exacerbated lung pathology, increased expression of RSV-A N genes, eosinophilia, enhanced IL-5, IL-13, MUC5AC, and eosinophils Major Basic Protein (MBP) production in lung tissue compared to offspring lacking matAbs. Importantly, these unexpected outcomes were not attributed to antibody-dependent enhancement (ADE) resulting from declining matAb levels over time. Notably, our findings showed a decline in secretory IgA (sIgA), mucosal IgA, and mucosal IgG levels in offspring with high matAb levels post-primary RSV challenge. We propose that this decline may be a critical factor contributing to the ineffective protection observed during secondary RSV exposure. Overall, these findings offer valuable insights into maternal vaccination against RSV, contributing to a comprehensive understanding and mitigation of potential risks associated with maternal RSV vaccination.


Subject(s)
Antibodies, Viral , Pneumonia , Respiratory Syncytial Virus Infections , Animals , Respiratory Syncytial Virus Infections/immunology , Mice , Female , Antibodies, Viral/blood , Antibodies, Viral/immunology , Pneumonia/immunology , Immunity, Maternally-Acquired , Lung/immunology , Lung/virology , Lung/pathology , Pregnancy , Respiratory Syncytial Virus Vaccines/immunology , Respiratory Syncytial Virus Vaccines/adverse effects , Respiratory Syncytial Virus Vaccines/administration & dosage , Disease Models, Animal , Respiratory Syncytial Viruses/immunology , Mice, Inbred BALB C
17.
BMC Infect Dis ; 24(1): 510, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773455

ABSTRACT

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infections in children worldwide. The highest incidence of severe disease is in the first 6 months of life, with infants born preterm at greatest risk for severe RSV infections. The licensure of new RSV therapeutics (a long-acting monoclonal antibody and a maternal vaccine) in Europe, USA, UK and most recently in Australia, has driven the need for strategic decision making on the implementation of RSV immunisation programs. Data driven approaches, considering the local RSV epidemiology, are critical to advise on the optimal use of these therapeutics for effective RSV control. METHODS: We developed a dynamic compartmental model of RSV transmission fitted to individually-linked population-based laboratory, perinatal and hospitalisation data for 2000-2012 from metropolitan Western Australia (WA), stratified by age and prior exposure. We account for the differential risk of RSV-hospitalisation in full-term and preterm infants (defined as < 37 weeks gestation). We formulated a function relating age, RSV exposure history, and preterm status to the risk of RSV-hospitalisation given infection. RESULTS: The age-to-risk function shows that risk of hospitalisation, given RSV infection, declines quickly in the first 12 months of life for all infants and is 2.6 times higher in preterm compared with term infants. The hospitalisation risk, given infection, declines to < 10% of the risk at birth by age 7 months for term infants and by 9 months for preterm infants. CONCLUSIONS: The dynamic model, using the age-to-risk function, characterises RSV epidemiology for metropolitan WA and can now be extended to predict the impact of prevention measures. The stratification of the model by preterm status will enable the comparative assessment of potential strategies in the extended model that target this RSV risk group relative to all-population approaches. Furthermore, the age-to-risk function developed in this work has wider relevance to the epidemiological characterisation of RSV.


Subject(s)
Hospitalization , Infant, Premature , Respiratory Syncytial Virus Infections , Humans , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Virus Infections/prevention & control , Hospitalization/statistics & numerical data , Infant , Infant, Newborn , Western Australia/epidemiology , Female , Respiratory Syncytial Virus, Human , Age Factors , Male , Risk Assessment , Risk Factors
20.
Nurs Womens Health ; 28(3): 242-246, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38702040

ABSTRACT

Respiratory syncytial virus (RSV) is a prevalent cause of acute lower respiratory tract illness that disproportionately affects older adults, young children, and infants, which can lead to hospitalizations and death. The health impact on the elderly and infants accentuates the need for effective preventive strategies. Arexvy is the first approved vaccine to prevent lower respiratory tract illness caused by RSV in older adults ages 60 and older. It contains recombinant respiratory syncytial virus glycoprotein F stabilized in the prefusion conformation. Arexvy offers approximately 83% protection in adults and appears to maintain effectiveness for up to two RSV seasons. The vaccine was generally well tolerated in clinical trials, with the most frequently observed and reported adverse events being mild to moderate injection site pain, fatigue, myalgia, headache, and arthralgia. This article includes a description of Arexvy, the target population, contraindications, side effects, and clinical implications when considering the use of this vaccine.


Subject(s)
Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus Vaccines , Humans , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Virus Vaccines/therapeutic use , Middle Aged , Aged , Female , Male , Aged, 80 and over , Respiratory Syncytial Virus, Human/immunology , Adjuvants, Immunologic
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