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BMC Pediatrics May 2024Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory tract infections, particularly in infants and young children during winter. We aimed to...
BACKGROUND
Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory tract infections, particularly in infants and young children during winter. We aimed to study the demographics and clinical characteristics of RSV infections and age-related patterns.
METHODS
This retrospective study evaluated pediatric respiratory syncytial virus (RSV) infections conducted in Jordan from September 2021 to March 2022. Patients under the age of five who had viral polymerase chain reaction results showing RSV infection from nasopharyngeal aspiration were included. In addition, demographic information, medical history, and clinical data were gathered. These included comorbidities, outcomes, length of stay, ICU hospitalization, use of antibiotics, and oxygen supplementation.
RESULTS
A total of 199 patients were included. Most patients were males (56.8%) and less than one year (43.7%). Children aged between 1 and 2 years presented with more shortness of breath (90.1%) than infants and children more than two years (66.7% and 87%, respectively) (p < 0.001). Older children (> 2 years) were significantly more likely to use antibiotics and have ICU admission than younger children ≤ 2 years (p = 0.045 and 0.018, respectively). There was no relationship between age groups, recurrent hospitalization, previous RSV infection, oxygen therapy, coinfection, and hospitalization duration. The respiratory rate was higher among patients with co-infection (p = 0.031).
CONCLUSION
The current study provides information on the demographics and clinical characteristics of RSV infections. These findings contribute to a nuanced understanding of RSV infections in the specified population, emphasizing age-specific variations and clinical implications for better management strategies.
Topics: Humans; Respiratory Syncytial Virus Infections; Male; Female; Retrospective Studies; Infant; Child, Preschool; Jordan; Tertiary Care Centers; Hospitalization; Age Factors; Length of Stay; Respiratory Syncytial Virus, Human; Anti-Bacterial Agents
PubMed: 38750503
DOI: 10.1186/s12887-024-04799-8 -
Frontiers in Immunology 2024Respiratory syncytial virus (RSV) is the primary cause of bronchiolitis-related hospitalizations among children under 5 years of age, with reinfection being common...
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.
Topics: Animals; Respiratory Syncytial Virus Infections; Mice; Female; Antibodies, Viral; Pneumonia; Immunity, Maternally-Acquired; Lung; Pregnancy; Respiratory Syncytial Virus Vaccines; Disease Models, Animal; Respiratory Syncytial Viruses; Mice, Inbred BALB C
PubMed: 38745662
DOI: 10.3389/fimmu.2024.1377374 -
Tropical Medicine & International... Jul 2024Respiratory syncytial virus (RSV) is undoubtedly the single most important cause of severe lower respiratory tract infection (LRTI) globally. While new prevention...
Risk factors for the development of severe or very severe respiratory syncytial virus-related lower respiratory tract infection in Indian infants: A cohort study in Melghat, India.
OBJECTIVES
Respiratory syncytial virus (RSV) is undoubtedly the single most important cause of severe lower respiratory tract infection (LRTI) globally. While new prevention measures in young infants have become available, their use in developing countries is likely many years away. While risk factors for severe or very severe RSV LRTI in impoverished rural areas likely differ to urban areas, there are very few studies, especially those conducted in India, the major country contributing to the global burden of disease.
METHODS
Active surveillance for acute LRTI in enrolled infants and children <2 years of age, was conducted through weekly home visits in 93 villages of Melghat, India, from August 2016 to December 2020. Local hospitals and primary health centres were surveyed for admissions of enrolled subjects. Nasopharyngeal swabs were collected from children with severe, or very severe LRTIs and all who died, with RSV testing using nucleic acid tests at ICMR, National Institute of Virology Pune. Risk factors for both RSV associated and non-RSV associated, severe and very severe LRTI were identified through univariate and multivariate logistic regression.
RESULTS
There were 483 severe or very severe RSV LRTI cases and 2807 non-RSV severe or very severe LRTI infections in a cohort of 13,318 children. Weight for age z-score ≤-2, the use of kerosene or wood for cooking, obtaining drinking water from a public tap and low gestational age significantly increased the risk of RSV LRTI. A higher wealth score index and water purification were protective. Comparison with non-RSV LRTI showed male sex as an additional risk factor. The analysis highlighted the risk of kerosene use [OR = 17.8 (3.0-104.4) (p ≤ 0.001)] and [OR = 3.4 (0.8-14.4) (p ≤ 0.05)] for RSV and non-RSV LRTIs, respectively.
CONCLUSIONS
Nutritional status and environmental air quality are predisposing factors for developing an RSV LRI in young children, factors which are amenable to environmental and behavioural interventions.
Topics: Humans; India; Infant; Respiratory Syncytial Virus Infections; Risk Factors; Female; Male; Respiratory Tract Infections; Cohort Studies; Severity of Illness Index; Respiratory Syncytial Virus, Human; Infant, Newborn
PubMed: 38741367
DOI: 10.1111/tmi.14003 -
Nature Communications May 2024Rapid and accurate detection of respiratory virus aerosols is highlighted for virus surveillance and infection control. Here, we report a wireless immunoassay technology...
Rapid and accurate detection of respiratory virus aerosols is highlighted for virus surveillance and infection control. Here, we report a wireless immunoassay technology for fast (within 10 min), on-site (wireless and battery-free), and sensitive (limit of detection down to fg/L) detection of virus antigens in aerosols. The wireless immunoassay leverages the immuno-responsive hydrogel-modulated radio frequency resonant sensor to capture and amplify the recognition of virus antigen, and flexible readout network to transduce the immuno bindings into electrical signals. The wireless immunoassay achieves simultaneous detection of respiratory viruses such as severe acute respiratory syndrome coronavirus 2, influenza A H1N1 virus, and respiratory syncytial virus for community infection surveillance. Direct detection of unpretreated clinical samples further demonstrates high accuracy for diagnosis of respiratory virus infection. This work provides a sensitive and accurate immunoassay technology for on-site virus detection and disease diagnosis compatible with wearable integration.
Topics: Immunoassay; Humans; Hydrogels; SARS-CoV-2; Wireless Technology; Influenza A Virus, H1N1 Subtype; Aerosols; COVID-19; Antigens, Viral; Respiratory Syncytial Viruses; Limit of Detection
PubMed: 38740742
DOI: 10.1038/s41467-024-48294-1 -
PLoS Pathogens May 2024Respiratory syncytial virus (RSV) is the most important viral agent of severe pediatric respiratory illness worldwide, but there is no approved pediatric vaccine. Here,...
Intranasal respiratory syncytial virus vaccine attenuated by codon-pair deoptimization of seven open reading frames is genetically stable and elicits mucosal and systemic immunity and protection against challenge virus replication in hamsters.
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.
Topics: Animals; Respiratory Syncytial Virus Vaccines; Vaccines, Attenuated; Virus Replication; Respiratory Syncytial Virus Infections; Open Reading Frames; Cricetinae; Administration, Intranasal; Codon; Immunity, Mucosal; Antibodies, Viral; Humans; Respiratory Syncytial Virus, Human; Mesocricetus; Respiratory Syncytial Viruses
PubMed: 38739647
DOI: 10.1371/journal.ppat.1012198 -
Human Vaccines & Immunotherapeutics Dec 2024Nirsevimab 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....
Assessment of effectiveness and impact of universal prophylaxis with nirsevimab for prevention of hospitalizations due to respiratory syncytial virus in infants. The NIRSE-GAL study protocol.
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.
Topics: Humans; Respiratory Syncytial Virus Infections; Infant; Hospitalization; Antiviral Agents; Respiratory Syncytial Virus, Human; Female; Male; Respiratory Tract Infections; Immunization Programs; Infant, Newborn; Child, Preschool; Palivizumab; Antibodies, Monoclonal, Humanized
PubMed: 38738683
DOI: 10.1080/21645515.2024.2348135 -
Journal of the Pediatric Infectious... Jun 2024Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality among US infants. A child's calendar birth month determines their age at first exposure(s)...
BACKGROUND
Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality among US infants. A child's calendar birth month determines their age at first exposure(s) to RSV. We estimated birth month-specific risk of medically attended (MA) RSV lower respiratory tract infection (LRTI) among infants during their first RSV season and first year of life (FYOL).
METHODS
We analyzed infants born in the USA between July 2016 and February 2020 using three insurance claims databases (two commercial, one Medicaid). We classified infants' first MA RSV LRTI episode by the highest level of care incurred (outpatient, emergency department, or inpatient), employing specific and sensitive diagnostic coding algorithms to define index RSV diagnoses. In our main analysis, we focused on infants' first RSV season. In our secondary analysis, we compared the risk of MA RSV LRTI during infants' first RSV season to that of their FYOL.
RESULTS
Infants born from May through September generally had the highest risk of first-season MA RSV LRTI-approximately 6-10% under the specific RSV index diagnosis definition and 16-26% under the sensitive. Infants born between October and December had the highest risk of RSV-related hospitalization during their first season. The proportion of MA RSV LRTI events classified as inpatient ranged from 9% to 54% (specific) and 5% to 33% (sensitive) across birth month and comorbidity group. Through the FYOL, the overall risk of MA RSV LRTI is comparable across birth months within each claims database (6-11% under the specific definition, 17-30% under the sensitive), with additional cases progressing to care at outpatient or ED settings.
CONCLUSIONS
Our data support recent national recommendations for the use of nirsevimab in the USA. For infants born at the tail end of an RSV season who do not receive nirsevimab, a dose administered prior to the onset of their second RSV season could reduce the incidence of outpatient- and ED-related events.
Topics: Humans; Respiratory Syncytial Virus Infections; United States; Infant; Seasons; Hospitalization; Infant, Newborn; Risk Assessment; Male; Female; Respiratory Syncytial Virus, Human; Databases, Factual
PubMed: 38738450
DOI: 10.1093/jpids/piae042 -
Pediatrics Jun 2024Human metapneumovirus (hMPV) and parainfluenza virus type 3 (PIV3) are common respiratory illnesses in children. The safety and immunogenicity of an investigational... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Human metapneumovirus (hMPV) and parainfluenza virus type 3 (PIV3) are common respiratory illnesses in children. The safety and immunogenicity of an investigational mRNA-based vaccine, mRNA-1653, encoding membrane-anchored fusion proteins of hMPV and PIV3, was evaluated in hMPV/PIV3-seropositive children.
METHODS
In this phase 1b randomized, observer-blind, placebo-controlled, dose-ranging study, hMPV/PIV3-seropositive children were enrolled sequentially into 2 dose levels of mRNA-1653 administered 2 months apart; children aged 12 to 36 months were randomized (1:1) to receive 10-μg of mRNA-1653 or placebo and children aged 12 to 59 months were randomized (3:1) to receive 30-μg of mRNA-1653 or placebo.
RESULTS
Overall, 27 participants aged 18 to 55 months were randomized; 15 participants received 10-μg of mRNA-1653 (n = 8) or placebo (n = 7), whereas 12 participants received 30-μg of mRNA-1653 (n = 9) or placebo (n = 3). mRNA-1653 was well-tolerated at both dose levels. The only reported solicited local adverse reaction was tenderness at injection site; solicited systemic adverse reactions included grade 1 or 2 chills, irritability, loss of appetite, and sleepiness. A single 10-μg or 30-μg mRNA-1653 injection increased hMPV and PIV3 neutralizing antibody titers (geometric mean fold-rise ratio over baseline: hMPV-A = 2.9-6.1; hMPV-B = 6.2-13.2; PIV3 = 2.8-3.0) and preF and postF binding antibody concentrations (geometric mean fold-rise ratio: hMPV preF = 5.3-6.1; postF = 4.6-6.5 and PIV3 preF = 13.9-14.2; postF = 11.0-12.1); a second injection did not further increase antibody levels in these seropositive children. Binding antibody responses were generally preF biased.
CONCLUSIONS
mRNA-1653 was well-tolerated and boosted hMPV and PIV3 antibody levels in seropositive children aged 12 to 59 months, supporting the continued development of mRNA-1653 or its components for the prevention of hMPV and PIV3.
Topics: Humans; Female; Male; Child, Preschool; Infant; Parainfluenza Virus 3, Human; Metapneumovirus; Single-Blind Method; Paramyxoviridae Infections; Antibodies, Viral; Parainfluenza Vaccines; Immunogenicity, Vaccine; RNA, Messenger
PubMed: 38738290
DOI: 10.1542/peds.2023-064748 -
Journal of Clinical Virology : the... Aug 2024Following the pandemic restrictions, the epidemiology of respiratory syncytial virus (RSV) has changed, leading to intense hospitalization peaks.
BACKGROUND
Following the pandemic restrictions, the epidemiology of respiratory syncytial virus (RSV) has changed, leading to intense hospitalization peaks.
OBJECTIVES
This study, conducted at multiple sites in Italy, aimed to describe the temporal dynamics of two post-COVID-19 RSV epidemics. Additionally, the circulating RSV-A and -B lineages were characterized and compared to those found in 2018 and 2019.
STUDY DESIGN
Respiratory specimens and data were collected from RSV-positive patients, both inpatients, and outpatients, of all ages at three sites in north-central Italy. To analyze these samples, roughly one-sixth were sequenced in the attachment glycoprotein G gene and subjected to phylogenetic and mutational analyses, including pre-pandemic sequences from north-central Italy.
RESULTS
The first post-pandemic surge of RSV cases was quite intense, occurring from October 2021 to early January 2022. The subsequent RSV epidemic (from November 2022 to early March 2023) also had a high impact, characterized by a rise in elderly patient cases. Post-pandemic cases of RSV-A were caused by various strains present in Italy prior to COVID-19. In contrast, a distinct RSV-B lineage, which was concurrently spreading in other countries, was identified as the main cause of the surge in 2022-2023 but remained undetected in Italy before the pandemic.
CONCLUSIONS
This study describes the temporal dynamics of post-pandemic RSV subgroups and uncovers a lineage of RSV-B with high genetic divergence that may have increased the impact of decreased population immunity.
Topics: Humans; Italy; Respiratory Syncytial Virus Infections; Phylogeny; Respiratory Syncytial Virus, Human; Infant; Child, Preschool; Child; Aged; Adolescent; Adult; Middle Aged; COVID-19; Female; Male; Young Adult; SARS-CoV-2; Infant, Newborn; Pandemics
PubMed: 38733664
DOI: 10.1016/j.jcv.2024.105681 -
Microbiology Spectrum Jun 2024The immune response induced by respiratory syncytial virus (RSV) infection is closely related to changes in the composition and function of gastrointestinal...
UNLABELLED
The immune response induced by respiratory syncytial virus (RSV) infection is closely related to changes in the composition and function of gastrointestinal microorganisms. However, the specific mechanism remains unknown and the pulmonary-intestinal axis deserves further study. In this study, the mRNA levels of ROR-γt and Foxp3 in the lung and intestine increased first and then decreased. IL-17 and IL-22 reached the maximum on the third day after infection in the lung, and on the second day after infection in the small intestine and colon, respectively. RegⅢγ in intestinal tissue reached the maximum on the third day after RSV infection. Moreover, the genus enriched in the RSV group was , and was reduced. RSV infection not only causes Th17/Treg cell imbalance in the lungs of mice but also leads to the release of excessive IL-22 from the lungs through blood circulation which binds to IL-22 receptors on the intestinal surface, inducing RegⅢγ overexpression, impaired intestinal Th17/Treg development, and altered gut microbiota composition. Our research reveals a significant link between the pulmonary and intestinal axis after RSV infection.
IMPORTANCE
RSV is the most common pathogen causing acute lower respiratory tract infections in infants and young children, but the complex interactions between the immune system and gut microbiota induced by RSV infection still requires further research. In this study, it was suggested that RSV infection in 7-day-old BALB/c suckling mice caused lung inflammation and disruption of Th17/Treg cells development, and altered the composition of gut microbiota through IL-22 induced overexpression of RegⅢγ, leading to intestinal immune injury and disruption of gut microbiota. This research reveals that IL-22 may be the link between the lung and gut. This study may provide a new insight into the intestinal symptoms caused by RSV and other respiratory viruses and the connection between the lung and gut axis, as well as new therapeutic ideas for the treatment of RSV-infected children.
Topics: Animals; Respiratory Syncytial Virus Infections; Gastrointestinal Microbiome; T-Lymphocytes, Regulatory; Mice; Mice, Inbred BALB C; Th17 Cells; Lung; Interleukin-22; Interleukins; Respiratory Syncytial Viruses; Nuclear Receptor Subfamily 1, Group F, Member 3; Interleukin-17; Female; Pancreatitis-Associated Proteins; Intestines; Forkhead Transcription Factors
PubMed: 38727214
DOI: 10.1128/spectrum.03283-23