Variability in the Timing of Respiratory Syncytial Virus Epidemics in Guatemala, 2008-2018.

BACKGROUND: The description of local seasonality patterns in respiratory syncytial virus (RSV) incidence is important to guide the timing of administration of RSV immunization products. METHODS: We characterized RSV seasonality in Guatemala using the moving epidemic method (MEM) with absolute counts of RSV-associated acute respiratory infections (ARI) from hospital surveillance in Santa Rosa and Quetzaltenango departments of Guatemala. RESULTS: From Week 17 of 2008 through Week 16 of 2018, 8487 ARI cases tested positive for RSV by rRT-PCR. Season onsets varied up to 5 months; early seasons starting in late May to early August and finishing in September to November were most common, but late seasons starting in October to November and finishing in March to April were also observed. Both epidemic patterns had similar durations ranging from 4 to 6 months. Epidemic thresholds (the levels of virus activity that signal the onset and end of a seasonal epidemic) calculated prospectively using previous seasons' data captured between 70% and 99% of annual RSV detections. Onset weeks differed by 2-10 weeks, and offset weeks differed by 2-16 weeks between the two surveillance sites. CONCLUSIONS: Variability in the timing of seasonal RSV epidemics in Guatemala demonstrates the difficulty in precisely predicting the timing of seasonal RSV epidemics based on onset weeks from past seasons and suggests that maximal reduction in RSV disease burden would be achieved through year-round vaccination and immunoprophylaxis administration to at-risk infants.

Comparison of the Burden and Temporal Pattern of Hospitalisations Associated With Respiratory Syncytial Virus (RSV) Before and After COVID-19 in New Zealand.

BACKGROUND: Changes in the epidemiology of illnesses caused by respiratory syncytial virus (RSV) infection following the COVID-19 pandemic are reported. The New Zealand (NZ) COVID-19 situation was unique; RSV community transmission was eliminated with the 2020 border closure, with a rapid and large increase in hospitalizations following the relaxation of social isolation measures and the opening of an exclusive border with Australia. METHODS: This active population-based surveillance compared the age-specific incidence and seasonality of RSV-associated hospitalizations in Auckland, NZ, for 2 years before and after the 2020 border closures. Hospitalisation rates between years were compared by age, ethnicity (European/other, Maori, Pacific and Asian) and socioeconomic group (1 = least, 5 = most deprived). RESULTS: There was no RSV transmission in 2020. In all other years, hospitalisation rates were highest for people of Pacific versus other ethnic groups and for people living in the most deprived quintile of households. RSV hospitalisation rates were higher in 2021 and 2022 than in 2018-19. The epidemic peak was higher in 2021, but not 2022, and the duration was shorter than in 2018-19. In 2021, the increase in RSV hospitalisation rates was significant across all age, sex, ethnic and socioeconomic groups. In 2022, the increase in hospitalisation rates was only significant in one age (1- < 3 years), one ethnic (Asian) and one socioeconomic group (quintile 2). CONCLUSIONS: COVID pandemic responses altered RSV-related hospitalisation seasonal patterns. Atypical features of RSV hospitalisation epidemiology were the increase in rates in older children and young adults, which lessened in 2022. Despite these variations, RSV hospitalisations in NZ continue to disproportionately affect individuals of Pacific ethnicity and those living in more socioeconomically deprived households. Whilst future public health strategies focused on RSV disease mitigation need to consider the potential shifts in epidemiological patterns when the transmission is disrupted, these variances must be considered in the context of longer-standing patterns of unequal disease distribution.

Direct-acting antivirals for RSV treatment, a review.

Respiratory syncytial virus (RSV) causes respiratory disease and complications in infants, the elderly and the immunocompromised. While three vaccines and two prophylactic monoclonal antibodies are now available, only one antiviral, ribavirin, is currently approved for treatment. This review aims to summarize the current state of treatments directly targeting RSV. Two major viral processes are attractive for RSV-specific antiviral drug discovery and development as they play essential roles in the viral cycle: the entry/fusion process carried out by the fusion protein and the replication/transcription process carried out by the polymerase complex constituted of the L, P, N and M2-1 proteins. For each viral target resistance mutations to small molecules of different chemotypes seem to delineate definite binding pockets in the fusion proteins and in the large proteins. Elucidating the mechanism of action of these inhibitors thus helps to understand how the fusion and polymerase complexes execute their functions. While many inhibitors have been studied, few are currently in clinical development for RSV treatment: one is in phase III, three in phase II and two in phase I. Progression was halted for many others because of strategic decisions, low enrollment, safety, but also lack of efficacy. Lessons can be learnt from the halted programs to increase the success rate of the treatments currently in development.

Phase 3 Study Assessing Lot-to-lot Consistency of RSVPreF3 Vaccine and its Immune Response, Safety, and Reactogenicity When Co-administered with FLU-D-QIV.

BACKGROUND: A single-dose investigational respiratory syncytial virus (RSV) vaccine, RSV prefusion protein F3 (RSVPreF3), was co-administered with a single-dose quadrivalent influenza vaccine (FLU-D-QIV) in a phase 3, randomized, controlled, multicenter study in healthy, non-pregnant women aged 18-49 years. METHODS: The study was observer-blind to evaluate the lot-to-lot consistency of RSVPreF3, and single-blind to evaluate the immune response, safety, and reactogenicity of RSVPreF3 co-administered with FLU-D-QIV. RESULTS: A total of 1415 participants were included in the per-protocol set. There was a robust immune response at day 31 across each of the 3 RSVPreF3 vaccine lots; adjusted geometric mean concentration ratios (95% confidence interval [CI]) were 1.01 (0.91, 1.12), 0.93 (0.84, 1.03), and 0.92 (0.83, 1.02) for RSV1/RSV2, RSV1/RSV3, and RSV2/RSV3, respectively. For FLU-D-QIV co-administered with RSVPreF3, versus FLU-D-QIV alone at day 31, noninferiority was satisfied for 3 of 4 strains assessed, with the lower limit of the 95% CI for geometric mean ratio >0.67. CONCLUSIONS: Immunogenic consistency was demonstrated for 3 separate lots of RSVPreF3. Immunogenic noninferiority was demonstrated when comparing FLU-D-QIV administered alone, versus co-administered with RSVPreF3, for 3 strains of FLU-D-QIV. Co-administration was well tolerated, and both vaccines had clinically acceptable safety and reactogenicity profiles. CLINICAL TRIALS REGISTRATION: NCT05045144; EudraCT, 2021-000357-26.

This was a phase 3 study that compared antibodies against respiratory syncytial virus (or RSV for short) between women who were given 3 different production batches of RSV prefusion protein F3 (known as RSVPreF3) vaccine. The study also compared the antibodies between women who received either an RSV vaccine together with a flu vaccine (known as FLU-D-QIV), or a flu vaccine alone. The flu vaccine contained 4 different strains of flu virus. The study involved 1415 healthy, non-pregnant women aged 18­49 years. The antibodies checked after 31 days showed strong immune responses for all 3 RSV vaccine production batches, and similar immune responses between each of the 3 RSV vaccine production batches. The immune response of 3 of the 4 flu strains was not less when the flu vaccine was given together with the RSV vaccine than the immune response when flu vaccine was given alone and both vaccines were well tolerated.

Differences Between RSV A and RSV B Subgroups and Implications for Pharmaceutical Preventive Measures.

INTRODUCTION: Understanding the differences between respiratory syncytial virus (RSV) subgroups A and B provides insights for the development of prevention strategies and public health interventions. We aimed to describe the structural differences of RSV subgroups, their epidemiology, and genomic diversity. The associated immune response and differences in clinical severity were also investigated. METHODS: A literature review from PubMed and Google Scholar (1985-2023) was performed and extended using snowballing from references in captured publications. RESULTS: RSV has two major antigenic subgroups, A and B, defined by the G glycoprotein. The RSV F fusion glycoprotein in the prefusion conformation is a major target of virus neutralizing antibodies and differs in surface exposed regions between RSV A and RSV B. The subgroups co-circulate annually, but there is considerable debate as to whether clinical severity is impacted by the subgroup of the infecting RSV strain. Large variations between the studies reporting RSV subgroup impact on clinical severity were observed. A tendency for higher disease severity may be attributed to RSV A but no consensus could be reached as to whether infection by one of the subgroup caused more severe outcomes. RSV genotype diversity decreased over the last two decades, and ON and BA have become the sole lineages detected for RSV A and RSV B, since 2014. No studies with data obtained after 2014 reported a difference in disease severity between the two subgroups. RSV F is relatively well conserved and highly similar between RSV A and B, but changes in the amino acid sequence have been observed. Some of these changes led to differences in F antigenic sites compared to reference F sequences (e.g., RSV/A Long strain), which are more pronounced in antigenic sites of the prefusion conformation of RSV B. Initial results from the second season after vaccination suggest specific RSV B efficacy wanes more rapidly than RSV A for RSV PreF-based monovalent vaccines. CONCLUSIONS: RSV A and RSV B both contribute substantially to the global RSV burden. Both RSV subgroups cause severe disease and none of the available evidence to date suggests any differences in clinical severity between the subgroups. Therefore, it is important to implement measures effective at preventing disease due to both RSV A and RSV B to ensure impactful public health interventions. Monitoring overtime will be needed to assess the impact of waning antibody levels on subgroup-specific efficacy.

Intranasal antivirals against respiratory syncytial virus: the current therapeutic development landscape.

INTRODUCTION: Respiratory syncytial virus (RSV) causes bronchiolitis and other respiratory issues in immunocompromised individuals, the elderly, and children. After six decades of research, we have only recently seen the approval of two RSV vaccines, Arexvy and Abrysvo. Direct-acting antivirals against RSV have been more difficult to develop with ribavirin and palivizumab giving very modest reductions in hospitalizations and no differences in mortality. Recently, nirsevimab was licensed and has proven to be much more effective when given prophylactically. These are delivered intravenously (IV) and intramuscularly (IM), but an intranasal (IN) antiviral has several advantages in terms of ease of use, lower resource need, and acting at the site of infection. AREAS COVERED: In this paper, we review the available literature on the current pre-clinical research landscape of anti-RSV therapeutics tested for IN delivery. EXPERT OPINION: As RSV is a respiratory virus that infects both the upper and lower respiratory tracts, efforts are focused on developing a therapeutic that can be delivered via the nasal route. The rationale is to directly target the replicating virus with an obvious respiratory tract tropism. This approach will not only pave the way for a nasal delivery approach aimed at reducing respiratory viral illness but also controlling aerosol virus transmission.

Antiviral Effect of Ferula Plants and their Potential for Treatment of COVID-19: A Comprehensive Review.

Viral diseases have always been a threat to mankind throughout history, and many people have lost their lives due to the epidemic of these diseases. In recent years, despite the progress of science, we are still witnessing a pandemic of dangerous diseases such as COVID-19 all over the world, which can be a warning for humanity. Ferula is a genus of flowering plants commonly found in Central Asia, and its species have shown antiviral activity against a variety of viruses, including respiratory syncytial virus, Herpes simplex virus type 1, influenza, human immunodeficiency virus, hepatitis B, and coronaviruses. In this study, we intend to review the antiviral effects of Ferula plants, emphasizing the therapeutic potential of these plants in the treatment of COVID-19. Google, PubMed, Web of Science, and Scopus databases were searched to review the relevant literature on the antiviral effect of Ferula or its isolated compounds. The search was performed using the keywords Ferula, antiviral, Coronaviruses, respiratory syncytial virus, Herpes simplex virus type 1, influenza, human immunodeficiency virus, and hepatitis B. According to the reviewed articles and available scientific evidence, it was determined that the plants of this genus have strong antiviral effects. Also, clinical studies have shown that some species, such as Ferula assa-foetida, can be used effectively in the treatment of COVID-19. Ferula plants have inhibitory effects on various viruses, making them an attractive alternative to conventional antiviral agents. Therefore, these plants are a natural source of valuable compounds that can help us fight infectious diseases.

Randomized, Open-Label Phase 3 Study Evaluating Immunogenicity, Safety, and Reactogenicity of RSVPreF3 OA Coadministered with FLU-QIV-HD in Adults Aged ≥ 65.

INTRODUCTION: Respiratory syncytial virus (RSV) and influenza pose major disease burdens in older adults due to an aging immune system and comorbidities; seasonal overlap exists between these infections. In 2023, the RSV prefusion protein F3 older adult (RSVPreF3 OA) vaccine was first approved in the USA as a single dose for prevention of lower respiratory tract disease due to RSV in adults aged ≥ 60 years. The vaccine has since been approved in the European Union and elsewhere. RSVPreF3 OA and FLU-QIV-HD could be coadministered if immunogenicity, safety, and reactogenicity are not affected. METHODS: This open-label, randomized (1:1), controlled, phase 3 study in 1029 adults aged ≥ 65 years in the USA evaluated the immunogenicity (up to 1 month after last vaccine dose) and safety (up to 6 months after last vaccine dose) of RSVPreF3 OA coadministered with FLU-QIV-HD (co-ad group) versus FLU-QIV-HD alone followed by RSVPreF3 OA at a separate visit 1 month later (control group). Non-inferiority criterion was defined as an upper limit of the two-sided 95% confidence interval of the geometric mean titer (GMT) group ratio (control/co-ad) ≤ 1.5. Secondary endpoints included safety and reactogenicity. RESULTS: Proportions of participants across age categories between groups and proportions of male (50.4%) and female (49.6%) participants were well balanced; most participants were white (68.7%). Group GMT ratios for RSV-A neutralizing titers, hemagglutination inhibition titers for four influenza vaccine strains, and RSV-B neutralizing titers were non-inferior in the co-ad group versus the control group. No clinically meaningful differences in local or systemic solicited and unsolicited adverse events (AEs), serious AEs, and potential immune-mediated diseases were identified. The most common solicited AEs in both groups were injection-site pain and myalgia. CONCLUSION: In adults aged ≥ 65 years, coadministration of RSVPreF3 OA and FLU-QIV-HD was immunogenically non-inferior to the sequential administration of both vaccines 1 month apart, and had clinically acceptable safety and reactogenicity profile. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05559476.

Adults aged 65 years or older are vulnerable to infections caused by influenza and respiratory syncytial viruses, due to an aging immune system and other underlying conditions. Infections with both viruses increase during autumn and winter seasons in temperate climates. In 2023, a vaccine against respiratory syncytial virus, called RSVPreF3 OA, was first approved for use in adults aged 60 years or older in the USA; the vaccine has since also been approved in the European Union and elsewhere. Giving RSVPreF3 OA in the same vaccination visit (coadministration) with a high-dose influenza vaccine, called FLU-QIV-HD, which is given to adults aged 65 years or older, could help protect against both respiratory syncytial virus and influenza. This article reports the results of a phase 3 trial comparing coadministration of the RSVPreF3 OA and FLU-QIV-HD vaccines with sequential administration (FLU-QIV-HD followed by RSVPreF3 OA 1 month later) in 1029 adults aged 65 years or older in the USA. Proportions of participants across age categories between groups, and the proportions of male (50.4%) and female (49.6%) participants were well balanced; most participants were white (68.7%). Immune response to both the vaccines among participants in the coadministration arm was non-inferior to that in the sequential arm. Coadministration was well tolerated, with no meaningful differences in adverse reactions to the vaccines compared with sequential administration. The most common adverse reactions were pain at the injection site and muscle aches. This study supports the coadministration of RSVPreF3 OA and FLU-QIV-HD in adults aged 65 years or older.

Graphene Multiplexed Sensor for Point-of-Need Viral Wastewater-Based Epidemiology.

Wastewater-based epidemiology (WBE) can help mitigate the spread of respiratory infections through the early detection of viruses, pathogens, and other biomarkers in human waste. The need for sample collection, shipping, and testing facilities drives up the cost of WBE and hinders its use for rapid detection and isolation in environments with small populations and in low-resource settings. Given the ubiquitousness and regular outbreaks of respiratory syncytial virus, SARS-CoV-2, and various influenza strains, there is a rising need for a low-cost and easy-to-use biosensing platform to detect these viruses locally before outbreaks can occur and monitor their progression. To this end, we have developed an easy-to-use, cost-effective, multiplexed platform able to detect viral loads in wastewater with several orders of magnitude lower limit of detection than that of mass spectrometry. This is enabled by wafer-scale production and aptamers preattached with linker molecules, producing 44 chips at once. Each chip can simultaneously detect four target analytes using 20 transistors segregated into four sets of five for each analyte to allow for immediate statistical analysis. We show our platform's ability to rapidly detect three virus proteins (SARS-CoV-2, RSV, and Influenza A) and a population normalization molecule (caffeine) in wastewater. Going forward, turning these devices into hand-held systems would enable wastewater epidemiology in low-resource settings and be instrumental for rapid, local outbreak prevention.

Filling two needs with one deed: a combinatory mucosal vaccine against influenza A virus and respiratory syncytial virus.

Influenza A Virus (IAV) and Respiratory Syncytial Virus (RSV) are both responsible for millions of severe respiratory tract infections every year worldwide. Effective vaccines able to prevent transmission and severe disease, are important measures to reduce the burden for the global health system. Despite the strong systemic immune responses induced upon current parental immunizations, this vaccination strategy fails to promote a robust mucosal immune response. Here, we investigated the immunogenicity and efficacy of a mucosal adenoviral vector vaccine to tackle both pathogens simultaneously at their entry site. For this purpose, BALB/c mice were immunized intranasally with adenoviral vectors (Ad) encoding the influenza-derived proteins, hemagglutinin (HA) and nucleoprotein (NP), in combination with an Ad encoding for the RSV fusion (F) protein. The mucosal combinatory vaccine induced neutralizing antibodies as well as local IgA responses against both viruses. Moreover, the vaccine elicited pulmonary CD8+ and CD4+ tissue resident memory T cells (TRM) against the immunodominant epitopes of RSV-F and IAV-NP. Furthermore, the addition of Ad-TGFß or Ad-CCL17 as mucosal adjuvant enhanced the formation of functional CD8+ TRM responses against the conserved IAV-NP. Consequently, the combinatory vaccine not only provided protection against subsequent infections with RSV, but also against heterosubtypic challenges with pH1N1 or H3N2 strains. In conclusion, we present here a potent combinatory vaccine for mucosal applications, which provides protection against two of the most relevant respiratory viruses.

Economic Burden of Medically Attended Respiratory Syncytial Virus Infections Among Privately Insured Children Under 5 Years of Age in the USA.

BACKGROUND: The cost of medically attended RSV LRI (lower respiratory infection) is critical in determining the economic value of new RSV immunoprophylaxes. However, most studies have focused on intermittent RSV encounters, not the episode of care that captures the entirety of RSV illness. METHODS: We created age- and condition-specific cohorts of children under 5 years of age using MarketScan® data (2015-2019). We contrasted aggregating healthcare costs over RSV-LRTI episodes to ascertaining costs based on RSV-specific encounters only. Economic burden was estimated by multiplying costs per encounter or per episode by their respective incidence rates. RESULTS: Average cost was higher per episode than per encounter regardless of settings (inpatient: $28,586 vs. $18,056 and outpatient/ED: $2099 vs. $407 for infants). Across ages, the economic burden was highest for infants and RSV-LRTI requiring inpatient care, but the burden in outpatient/ED settings was disproportionately higher than costs due to higher incidence rates (for inpatient vs. outpatient episodes: $226,403 vs. $101,269; for inpatient vs. outpatient encounters: $151,878 vs. $38,819 per 1000 infant-years). For high-risk children, cost and burden were up to 3-10 times higher, respectively. CONCLUSIONS: With a comprehensive stratification by settings and risk condition, the encounter- versus episode-based estimates provide a robust range for policymakers' economic appraisal of new RSV immunoprophylaxes.

Cold-adapted influenza vaccine carrying three repeats of a respiratory syncytial virus (RSV) fusion glycoprotein epitope site protects BALB/c mice and cotton rats against RSV infection.

Respiratory syncytial virus is the major cause of respiratory viral infections, particularly in infants, immunocompromised populations, and the elderly (over 65 years old), the prevention of RSV infection has become a priority. In this study, we generated a chimeric influenza virus, termed LAIV/RSV/HA-3F, using reverse genetics technology which contained three repeats of the RSV fusion protein neutralizing epitope site II to the N terminal in the background of the hemagglutinin (HA) gene of cold adapted influenza vaccine A/California/7/2009 ca. LAIV/RSV/HA-3F exhibited cold-adapted (ca) and attenuated (att) phenotype. BALB/c mice immunized intranasally with LAIV/RSV/HA-3F showed robust immunogenicity, inducing viral-specific antibody responses against both influenza and RSV, eliciting RSV-specific humoral, cellular and mucosal immune responses. LAIV/RSV/HA-3F also conferred protection as indicated by reduced viral titers and improved lung histopathological alterations against live RSV virus challenge. Mechanismly, single-cell RNA sequencing (scRNA-seq) and single-cell T cell antigen receptor (TCR) sequencing were employed to characterize the immune responses triggered by chimeric RSV vaccine, displaying that LAIV/RSV/HA-3F provided protection mainly via interferon-γ (IFN-γ). Moreover, we found that LAIV/RSV/HA-3F significantly inhibited viral replication in the challenged mouse lung and protected against subsequent RSV challenge in cotton rats without causing lung disease. Taken together, our findings demonstrated that LAIV/RSV/HA-3F has potential as a promising bivalent vaccine with dual purpose candidate for the prevention of influenza and RSV, and preclinical and clinical studies warrant further investigations.

Passive Immunization Strategies to Prevent Severe Respiratory Syncytial Virus Infection Among Newborns and Young Infants.

Newborns and young infants are at risk for severe respiratory syncytial virus (RSV) lower respiratory tract infection. Passive immunity is the mainstay of infection prevention in this cohort. Transplacental transfer of maternal antibodies provides the newborn with immediate protection from life-threatening infections, however, is dependent upon gestational age, birth weight, mother's age, recent maternal vaccination, maternal nutritional status, maternal immunocompetence and medical conditions, and placental integrity. Efficient transplacental transfer of RSV-neutralizing antibodies have led to the development and approval of maternal RSV immunization for the protection of the newborn. Additionally, administration of RSV-specific antibodies to infants leads to high serum titers of RSV-neutralizing antibodies and further protection from severe disease.

Temporal trends in respiratory pathogens following the COVID-19 pandemic and climate variables: A unicentric retrospective evaluation of 24 pathogens in a temperate subtropical region.

Temperature and humidity are studied in the context of seasonal infections in temperate and tropical zones, but the relationship between viral trends and climate variables in temperate subtropical zones remains underexplored. Our retrospective study analyzes respiratory pathogen incidence and its correlation with climate data in a subtropical zone. Retrospective observational study at Moinhos de Vento Hospital, South Brazil, aiming to assess seasonal trends in respiratory pathogens, correlating them with climate data. The study included patients of all ages from various healthcare settings, with data collected between April 2022 and July 2023. Biological samples were analyzed for 24 pathogens using polymerase chain reaction and hybridization techniques; demographic variables were also collected. The data was analyzed descriptively and graphically. Spearman tests and Poisson regression were used as correlation tests. Tests were clustered according to all pathogens, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza viruses, rhinovirus, and respiratory syncytial virus (RSV). Between April 2022 and July 2023, 3329 tests showed a 71.6% positivity rate. Rhinovirus and RSV predominated, exhibiting seasonal patterns. Temperature was inversely correlated with the viruses, notably rhinovirus, but SARS-CoV-2 was positively correlated. Air humidity was positively correlated with all pathogens, RSV, rhinovirus, and atmospheric pressure with all pathogens and rhinovirus. Our results showed statistically significant correlations, with modest effect sizes. Our study did not evaluate causation effects. Despite the correlation between climate and respiratory pathogens, our work suggests additional factors influencing transmission dynamics. Our findings underscore the complex interplay between climate and respiratory infections in subtropical climates.

Diagnostic accuracy of Savanna RVP4 (QuidelOrtho) for the detection of Influenza A virus, RSV, and SARS-CoV-2.

Seasonal increase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza virus A/B (Flu A/B), and respiratory syncytial virus (RSV) require rapid diagnostic test methods for the management of respiratory tract infections. In this study, we compared the diagnostic accuracy of Savanna RVP4 (RVP4, QuidelOrtho) with Xpert Xpress Plus SARS-CoV-2/Flu/RSV (Xpert, Cepheid). Nasopharyngeal swabs from patients treated at a tertiary care hospital (Germany) were tested for SARS-CoV-2, Flu A/B, and RSV by RVP4 to assess diagnostic accuracy (reference standard: Xpert). The intra and inter assay precision of Ct-values was assessed by repeated test in triplicates (on day 1) and duplicates (days 2-3). All patients with a physician's order for a multiplex test for SARS-CoV-2, Flu, and RSV test were included. Duplicate swabs from the same patient, samples with a total volume ≤1 mL, or inappropriate shipment/storage were excluded. In total, 229 swabs were included between September 2023 and February 2024. The concordance between both tests was 96.5% (SARS-CoV-2), 98.7% (Flu A), and 99.6% (RSV). Flu B was not detected by both tests. The RVP4 test had a sensitivity of 85%-95% and a specificity of 100% for the detection of SARS-CoV-2, Flu A, and RSV. The intra and inter assay precision of Ct-values from RVP4 was 3% and 2% (SARS-CoV-2), 5% and 4% (Flu A), and 0% and 3% (RSV), respectively. The Savanna RVP4 has a favorable diagnostic accuracy for the detection of SARS-CoV-2, Flu A, and RSV. IMPORTANCE: We assessed the diagnostic accuracy of a new point-of-care test for the rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza virus A/B (Flu A/B), and respiratory syncytial virus (RSV). The new test has a concordance with the reference standard of 96.5% (SARS-CoV-2), 98.7% (Flu A), and 99.1% (RSV). The sensitivity of 85%-95% and specificity of 100% for the detection of SARS-CoV-2, Flu A, and RSV is comparable with similar nucleic acid amplification-based point of care tests but at lower costs.

Severe acute respiratory infections: An epidemiological analysis of surveillance data in Bahrain, 2018-2022.

Background: Severe acute respiratory tract infections (SARI) pose a health threat to children and adults worldwide. The SARI surveillance program was initiated in 2018 in Bahrain to monitor the activity of respiratory pathogens. Salmaniya Medical Complex (SMC) was chosen as the sentinel site for the SARI surveillance program. This study aimed to describe the epidemiology of SARI patients admitted to SMC from 2018 to 2022. Methods: Patients meeting the World Health Organization definition of SARI and presenting with cough and fever within the last 10 days and admitted to SMC from January 2018 until December 2022 were included in the study. Epidemiological data on SARI cases were collected from SARI surveillance data and analyzed using SPSS version 25 and Excel. Results: A total of 1362 SARI cases were enrolled from January 2018 to the end of December 2022; the majority were males (57.7%, n = 786). The highest SARI incidence rates were recorded among individuals over 65 years old (155.5 per 100,000) in 2021 and among those under 5 years old (887 per 100,000) in 2020. About half of the patients had at least one comorbidity (54.0%, n = 735), with diabetes (23.0%, n = 313) and hypertension (17.2%, n = 234) being the most common. The highest number of cases was observed in 2021 (27%, n = 373), followed by 2018 (20%, n = 267). A viral pathogen was detected in 30.7% (n = 418) of the SARI patients. The most prevalent pathogen was influenza A (11.5%, n = 156), followed by SARS-CoV-2 (9.7%, n = 132), respiratory syncytial virus (RSV) (5.1%, n = 69), and influenza B (3.9%, n = 53). The highest percentage of SARI cases was recorded in the winter months, mainly January (17%, n = 236). The percentages of influenza A and RSV cases were highest in December, at 22% (n = 39) and 14% (n = 25), respectively. Influenza B cases were recorded predominantly in March (9%, n = 11). Conclusion: The incidence of SARI was highest among patients above 65 years old. The majority had comorbidities. Influenza and respiratory syncytial viruses were the most frequent causes of SARI, with influenza A being the most prevalent. December and January were the months with the highest SARI cases and viral detection rates. Promoting vaccination, timely testing, and prompt treatment, especially for the elderly and those with comorbidities, is key to reducing SARI-related morbidity and mortality, especially during peak seasons.

Post-infectious pityriasis rubra pilaris in pediatric patients. / Pitiriasis rubra pilaris posinfecciosa en pacientes pediátricos.

Pityriasis rubra pilaris (PRP) is a rare skin condition. The etiology of PRP is unknown; however, it has been associated with infections, autoimmune diseases, and neoplasms. Here we describe the cases of 2 pediatric patients with PRP triggered by a respiratory syncytial virus infection concurrently with obstructive bronchial syndrome. PRP resolved after treatment with topical emollients, topical corticosteroids, and calcineurin inhibitors.

La pitiriasis rubra pilaris (PRP) es una enfermedad dermatológica poco frecuente. Se desconoce su etiología, sin embargo, se ha asociado a infecciones, enfermedades autoinmunes y neoplasias. Se describen los casos de dos pacientes pediátricos que presentaron PRP gatillada por una infección por virus sincicial respiratorio mientras cursaban un síndrome bronquial obstructivo. Los cuadros de PRP remitieron luego del tratamiento tópico con emolientes, corticoesteroides tópicos e inhibidores de la calcineurina.

Virus neutralization assays for human respiratory syncytial virus using airway organoids.

Neutralizing antibodies are considered a correlate of protection against severe human respiratory syncytial virus (HRSV) disease. Currently, HRSV neutralization assays are performed on immortalized cell lines like Vero or A549 cells. It is known that assays on these cell lines exclusively detect neutralizing antibodies (nAbs) directed to the fusion (F) protein. For the detection of nAbs directed to the glycoprotein (G), ciliated epithelial cells expressing the cellular receptor CX3CR1 are required, but generation of primary cell cultures is expensive and labor-intensive. Here, we developed a high-throughput neutralization assay based on the interaction between clinically relevant HRSV grown on primary cells with ciliated epithelial cells, and validated this assay using a panel of infant sera. To develop the high-throughput neutralization assay, we established a culture of differentiated apical-out airway organoids (Ap-O AO). CX3CR1 expression was confirmed, and both F- and G-specific monoclonal antibodies neutralized HRSV in the Ap-O AO. In a side-by-side neutralization assay on Vero cells and Ap-O AO, neutralizing antibody levels in sera from 125 infants correlated well, although titers on Ap-O AO were consistently lower. We speculate that these lower titers might be an actual reflection of the neutralizing antibody capacity in vivo. The organoid-based neutralization assay described here holds promise for further characterization of correlates of protection against HRSV disease.