Viral Lower Respiratory Tract Illness Research Articles

Risk of persistent and new clinical sequelae among adults aged 65 years and older during the post-acute phase of SARS-CoV-2 infection: retrospective cohort study

ObjectiveTo characterize the risk of persistent and new clinical sequelae in adults aged ≥65 years after the acute phase of SARS-CoV-2 infection.DesignRetrospective cohort study.SettingUnitedHealth Group Clinical Research Database: deidentified administrative...

POSA197 Modeled Impact of Nirsevimab Against Respiratory Syncytial Virus (RSV) Among UK Infants Experiencing Their First RSV Season

Respiratory syncytial virus (RSV) is the leading cause of viral lower respiratory tract illness (LRTI) in young children and is associated with significant morbidity, especially among infants. Nirsevimab is a monoclonal antibody being developed as a passive immunization for the prevention of medically attended RSV-LRTI (RSV MALRTI). Understanding its health economic impact under different scenarios is important to determine the optimal implementation strategy to protect all infants entering their first RSV season.

POSB191 Modeled Impact of Nirsevimab Against Respiratory Syncytial Virus (RSV) Among French Infants Experiencing Their First RSV Season

Respiratory syncytial virus (RSV) is the leading cause of viral lower respiratory tract illness (LRTI) in young children and is associated with significant morbidity, especially among infants, and important burden on health care systems. Nirsevimab is a monoclonal antibody being developed as a passive immunization for the prevention of medically attended RSV-LRTI (RSV MALRTI). Understanding its health economic impact under different scenarios is important to determine the optimal implementation strategy to protect infants entering their first RSV season.

PIN29 Cost-Effectiveness of Nirsevimab Against Respiratory Syncytial VIRUS (RSV) Among US Infants Experiencing Their First RSV Season

Respiratory syncytial virus (RSV) is the leading cause of viral lower respiratory tract illness (LRTI) in young children, such as bronchiolitis or pneumonia. It is associated with significant morbidity, especially among infants. New prophylactic options are currently in late-development stages, notably nirsevimab, a monoclonal antibody developed as a passive immunization intervention for the prevention of RSV-LRTI. Understanding its potential health economic impact is important to define the intervention strategy of protecting all infants experiencing their first RSV season.

Risk of clinical sequelae after the acute phase of SARS-CoV-2 infection: retrospective cohort study

ObjectiveTo evaluate the excess risk and relative hazards for developing incident clinical sequelae after the acute phase of SARS-CoV-2 infection in adults aged 18-65.DesignRetrospective cohort study.SettingThree merged data sources from...

The anti-respiratory syncytial virus activity of methanol leaf extract of Aspilia africana

Respiratory syncytial virus (RSV), to date, is still the most frequent cause of infantile and childhood cause of viral lower respiratory tract illness on a global scale, and at the same time, causing significant impact in the elderly. Presently, there is no licensed vaccine or safe and specific antiviral agent that could be used against the virus. Medicinal plants are known to be a promising source for the discovery of utilizable anti-RSV treatments. In this present study, we screened the anti-RSV and cell cytotoxicity activities of methanol extract of A. Africana by virus plaque reduction and corresponding cell viability methods in Hep-2 and Vero cells of human and mammalian origin respectively. The corresponding set up for analyses of A. Africana extract on cell viability were performed by the reduction of thiazolyl blue tetrazolium bromide (MTT) in the Hep-2 cells following the established method. The results of an evaluation of the extract of A. africana showed anti-RSV activities with inhibition of RSV at IC50, 42.5 ± 8.89, while the cell cytotoxic effect in Hep2 cells recorded was TC50, 121.4. ± 7.21. Therefore, our results show that the methanol extract of AA exhibited anti-RSV activities and has a moderate effect on the cell viability of the recipient host cell, indicating that target molecular substances against RSV can be developed from the extract.

Time to Say Goodbye to Bronchiolitis, Viral Wheeze, Reactive Airways Disease, Wheeze Bronchitis and All That.

The diagnosis and management of infants and children with a significant viral lower respiratory tract illness remains the subject of much debate and little progress. Over the decades various terms for such illnesses have been in and fallen out of fashion or have evolved to mean different things to different clinicians. Terms such as “bronchiolitis,” “reactive airways disease,” “viral wheeze,” and many more are used to describe the same condition and the same term is frequently used to describe illnesses caused by completely different dominant pathologies. This lack of clarity is due, in large part, to a failure to understand the basic underlying inflammatory and associated processes and, in part, due to the lack of a simple test to identify a condition such as asthma. Moreover, there is a lack of insight into the fact that the same pathology can produce different clinical signs at different ages. The consequence is that terminology and fashions in treatment have tended to go around in circles. As was noted almost 60 years ago, amongst pre-school children with a viral LRTI and airways obstruction there are those with a “viral bronchitis” and those with asthma. In the former group, a neutrophil dominated inflammation response is responsible for the airways' obstruction whilst amongst asthmatics much of the obstruction is attributable to bronchoconstriction. The airways obstruction in the former group is predominantly caused by airways secretions and to some extent mucosal oedema (a “snotty lung”). These patients benefit from good supportive care including supplemental oxygen if required (though those with a pre-existing bacterial bronchitis will also benefit from antibiotics). For those with a viral exacerbation of asthma, characterized by bronchoconstriction combined with impaired b-agonist responsiveness, standard management of an exacerbation of asthma (including the use of steroids to re-establish bronchodilator responsiveness) represents optimal treatment. The difficulty is identifying which group a particular patient falls into. A proposed simplified approach to the nomenclature used to categorize virus associated LRTIs is presented based on an understanding of the underlying pathological processes and how these contribute to the physical signs.

Prevention of Pediatric Respiratory Syncytial Virus Lower Respiratory Tract Illness: Perspectives for the Next Decade.

The landscape of infant bronchiolitis and viral pneumonia may be altered by preventive interventions against respiratory syncytial virus under evaluation today. Pediatric wards in 2018 in developing countries may differ from those attended by future generation pediatricians who may not witness the packed emergency rooms, lack of available beds, or emergency situations that all physicians caring for children with RSV experience every year. In this review, we describe and discuss different prevention strategies under evaluation to protect pediatric patients. Then, we outline a number of potential challenges, benefits, and concerns that may result from successful interventions after licensure.

EGFR Interacts with the Fusion Protein of Respiratory Syncytial Virus Strain 2-20 and Mediates Infection and Mucin Expression.

Respiratory syncytial virus (RSV) is the major cause of viral lower respiratory tract illness in children. In contrast to the RSV prototypic strain A2, clinical isolate RSV 2–20 induces airway mucin expression in mice, a clinically relevant phenotype dependent on the fusion (F) protein of the RSV strain. Epidermal growth factor receptor (EGFR) plays a role in airway mucin expression in other systems; therefore, we hypothesized that the RSV 2–20 F protein stimulates EGFR signaling. Infection of cells with chimeric strains RSV A2-2-20F and A2-2-20GF or over-expression of 2–20 F protein resulted in greater phosphorylation of EGFR than infection with RSV A2 or over-expression of A2 F, respectively. Chemical inhibition of EGFR signaling or knockdown of EGFR resulted in diminished infectivity of RSV A2-2-20F but not RSV A2. Over-expression of EGFR enhanced the fusion activity of 2–20 F protein in trans. EGFR co-immunoprecipitated most efficiently with RSV F proteins derived from “mucogenic” strains. RSV 2–20 F and EGFR co-localized in H292 cells, and A2-2-20GF-induced MUC5AC expression was ablated by EGFR inhibitors in these cells. Treatment of BALB/c mice with the EGFR inhibitor erlotinib significantly reduced the amount of RSV A2-2-20F-induced airway mucin expression. Our results demonstrate that RSV F interacts with EGFR in a strain-specific manner, EGFR is a co-factor for infection, and EGFR plays a role in RSV-induced mucin expression, suggesting EGFR is a potential target for RSV disease.

Advances in RSV vaccine research and development – A global agenda

Respiratory syncytial virus (RSV) is an important cause of viral lower respiratory tract illness in infants and children globally, but no vaccine is currently available to protect these vulnerable populations. Live-attenuated vaccine approaches have been in development for decades, but achieving the appropriate balance between immunogenicity and safety has proven difficult. Immunoprophylaxis with the neutralizing monoclonal antibody palivizumab is limited to high-risk infants, but cost requirements for multiple dosing make its use impractical in low- and middle-income countries. A growing number of RSV vaccine candidates using a variety of technologies and targeting diverse populations has emerged in recent years. There are now 60 RSV vaccine candidates in development that target pediatric and elderly populations. While most are at a preclinical stage, 16 candidates are in clinical development. This review summarizes current RSV vaccine research and development, including an overview of the vaccine platforms being used, the development stage of individual vaccine candidates, and gaps to be addressed to facilitate use of these vaccines to meet global health needs.

Serum Procalcitonin Measurement and Viral Testing to Guide Antibiotic Use for Respiratory Infections in Hospitalized Adults: A Randomized Controlled Trial.

Background. Viral lower respiratory tract illness (LRTI) frequently causes adult hospitalization and is linked to antibiotic overuse. European studies suggest that the serum procalcitonin (PCT) level may be used to guide antibiotic therapy. We conducted a trial assessing the feasibility of using PCT algorithms with viral testing to guide antibiotic use in a US hospital. Methods. Three hundred patients hospitalized with nonpneumonic LRTI during October 2013–April 2014 were randomly assigned at a ratio of 1:1 to receive standard care or PCT-guided care and viral PCR testing. The primary outcome was antibiotic exposure, and safety was assessed at 1 and 3 months. Results. Among the 151 patients in the intervention group, viruses were identified in 42% (63), and 83% (126) had PCT values of <0.25 µg/mL. There were no significant differences in antibiotic use or adverse events between intervention patients and those in the nonintervention group. Subgroup analyses revealed fewer subjects with positive results of viral testing and low PCT values who were discharged receiving antibiotics (20% vs 45%; P = .002) and shorter antibiotic durations among algorithm-adherent intervention patients versus nonintervention patients (2.0 vs 4.0 days; P = .004). Compared with historical controls (from 2008–2011), antibiotic duration in nonintervention patients decreased by 2 days (6.0 vs 4.0 days; P < .001), suggesting a study effect. Conclusions. Although antibiotic use was similar in the 2 arms, subgroup analyses of intervention patients suggest that physicians responded to viral and biomarker data. These data can inform the design of future US studies. Clinical Trials Registration. NCT01907659.

Identification of potential human respiratory syncytial virus and metapneumovirus T cell epitopes using computational prediction and MHC binding assays

Human respiratory syncytial virus (RSV) and human metapneumovirus (MPV) are two of the most common causes of serious viral lower respiratory tract illness in humans. CD8+ T cells have been shown to be important in animal models and human clinical studies for the clearance of viral infection, and they may contribute in part to protection against severe disease during reinfections. Precise enumeration and accurate phenotyping of RSV- or MPV-specific CD8+ T cells in humans is currently limited by the relatively small number of T cell epitopes that have been mapped with accompanying identification of MHC restriction patterns. We sought to expand the number of potential RSV and MPV epitopes for use in clinical and translational studies by identifying an expanded set of MHC-binding peptides based on RSV and MPV wild-type virus strain protein sequences. We interrogated the full protein sequences of all 9 or 11 proteins of MPV or RSV respectively using four established epitope prediction algorithms for human HLA A*0101, A*0201, or B*0702 binding and attempted to synthesize the top-scoring 150–152 peptides for each of the two viruses. Synthesis resulted in 442 synthesized and soluble peptides of the 452 predicted epitopes for MPV or RSV. We then determined the binding of the synthetic peptides to recombinant human HLA A*0101, A*0201 or B*0702 molecules with the predicted restriction using a commercially available plate-based assay, iTopia. A total of 230 of the 442 peptides tested exhibited binding to the appropriate MHC molecule. The binding results suggested that existing algorithms for prediction of MHC A*0201 binding are particularly robust. The binding results also provided a large benchmarking data collection for comparison of new prediction algorithms.

Chest Computed Tomographic Imaging Characteristics of Viral Acute Lower Respiratory Tract Illnesses

This study aimed to determine whether computed tomographic (CT) findings can distinguish viral lower respiratory tract illness (LRTI) from other conditions. Three radiologists reviewed CT images of patients with LRTI who underwent testing for respiratory viral infection. Imaging findings in subjects with positive viral assays were compared with subjects with negative assays. Of 334 subjects, 93 were positive for viral LRTI. Tree-in-bud opacities and bronchial wall thickening were observed more often in subjects with viral LRTI (P < 0.05). Multifocal airspace disease occurred with similar frequency in both groups. Diffuse airspace opacification was negatively associated with viral LRTI. Pleural effusion was observed more often among subjects without viral LRTI (P < 0.001). Airway inflammatory changes such as tree-in-bud opacities, bronchial wall thickening, and peribronchiolar consolidation are associated with community-acquired viral LRTI. Recognition of these findings should prompt testing for viral infection. Multifocal consolidation is commonly found in cases of viral LRTI but is nonspecific.

Serious Early Childhood Wheezing After Respiratory Syncytial Virus Lower Respiratory Tract Illness in Preterm Infants

Background Respiratory syncytial virus (RSV) lower respiratory tract infection (LRI) in early life has been associated with sustained airway hyperreactivity during childhood; however, corresponding data in premature infants are sparse. Objective The objective of this study was to determine whether RSV-LRI during early infancy of preterm infants was associated with an increased risk for serious early childhood wheezing (SECW) by age 3 years. Methods A retrospective cohort study was conducted using data from a large (∼14 million members) US health plan database. The study population included infants ≤6 months of age born at ≤36 weeks' gestational age or weighing <2500 g, or both. Preterm infants with any medically attended RSV-LRI from May 2001 through April 2004 with 3 years of continuous eligibility were selected and propensity matched with ≤3 control infants. SECW was defined as >3 office, outpatient, or emergency department (ED) visits with asthma or wheezing; ≥1 office, outpatient, or ED visit with asthma or wheezing plus treatment with systemic corticosteroids within 7 days; ≥1 inpatient stay with asthma or wheezing; or ≥150 days' supply of asthma-control medications. The presence of SECW between ages 2 and 3 years was compared between infants with and without RSV-LRI using univariate and multivariate methods. Health care costs for patients with SECW were explored. Results A total of 378 infants with RSV were matched to 606 controls. The prevalence of SECW between ages 2 and 3 years was 16.7% in the RSV-LRI group versus 8.6% in the control group ( P < 0.001). Logistic regression showed that preterm infants with RSV in early life were 2.52-fold (95% CI,1.65–3.85) more likely to present with SECW between ages 2 and 3 years ( P < 0.001). Patients with SECW had a mean SECW-related cost of US $1378 (95% CI, $939–$1816) and total health care cost of $7138 (95% CI, $5087–$9189) compared with $37 (95% CI, $24–$51) and $2521 (95% CI, $1789–$3253), respectively, for patients without SECW. After adjusting for possible confounders, patients with SECW had a significantly higher total health care cost than did patients without evidence of SECW ( P < 0.001). Conclusions The development of RSV-LRI in infancy in preterm infants was associated with an increased prevalence of SECW between ages 2 and 3 years. Patients with SECW had higher total health care costs than those who did not have SECW.

Respiratory Syncytial Virus lower respiratory tract illness in infancy and subsequent morbidity

Respiratory Syncytial Virus lower respiratory tract illness in infancy and subsequent morbidity

Respiratory Syncytial Virus Bronchiolitis

Respiratory syncytial virus (RSV) is the most important cause of viral lower respiratory tract illness in infants and children worldwide and is responsible for over 120 000 annual hospitalizations in infants in the US alone. RSV is also recognized as a major respiratory viral pathogen in the elderly and other high-risk populations. Bronchiolitis, pneumonia, apnea, respiratory failure, and death are well known manifestations of severe acute RSV disease. RSV infection has also been associated with recurrent wheezing in children, but the mechanisms involved in this association are not completely understood. The host immune response plays a significant role in controlling the infection but is likely also involved in augmenting the disease through pathways that have not been completely identified. The treatment options for RSV infection are very limited. Ribavirin, corticosteroids, and bronchodilators are not used routinely because they have not proven to be sufficiently effective. Education of caregivers, strict handwashing, and avoidance of exposure to environmental factors associated with severe forms of RSV infection are among the most effective preventive means. Passive immunization with monoclonal antibodies provides protection against severe RSV disease in high-risk children. Clinical trials to evaluate the safety and efficacy of a second-generation monoclonal antibody are underway. Efforts to develop a safe and effective RSV vaccine have continued despite the poor outcomes observed following the administration of formalin-inactivated formulations in the 1960s. In the last decade, live attenuated vaccines (including those developed by recombinant techniques) and purified subunit vaccines have all been evaluated in humans. Results of clinical trials have been encouraging, but the availability of a safe and effective RSV vaccine is not a reality yet. Better prevention strategies will have an impact, not only on acute morbidity caused by RSV, but will also likely have an effect on ameliorating the chronic consequences of this disease.

The future of respiratory syncytial virus vaccine development.

Respiratory syncytial virus (RSV) is the leading cause of viral lower respiratory tract illness in infants and children and is an important cause of lower respiratory tract illness in other populations. Despite decades of research there are currently no licensed vaccines for prevention of RSV disease. A review of the obstacles to RSV vaccine development; current live, attenuated and subunit RSV vaccines in clinical development; and the potential for developing additional vaccine candidates based on recombinant technology. A number of biologically derived live attenuated RSV vaccines were evaluated in Phase I clinical trials in adults and children, and one vaccine (cpts 248/404) was evaluated in infants as young as 1 month of age. These vaccines displayed a spectrum of attenuation, with cpts 248/955 being the least attenuated and cpts 248/404 being the most attenuated candidate vaccine. None of these was sufficiently attenuated for young infants. The ability to generate recombinant RSV vaccines has led to the development of large numbers of candidate vaccines containing combinations of known attenuating point mutations and deletions of nonessential genes. Clinical evaluation of many of these candidates is in progress. Three types of RSV subunit vaccines have recently been evaluated in clinical trials: purified F glycoprotein vaccines (PFP-1, PFP-2 and PFP-3), BBG2Na and copurified F, G and M proteins. Additional studies of the F/G/M protein vaccine are being conducted. During the past 10 years, considerable progress has been made in RSV vaccine development. It is likely that different RSV vaccines will be needed for the various populations at risk.

Progress in the development of respiratory syncytial virus and parainfluenza virus vaccines.

Respiratory syncytial virus (RSV) and human parainfluenza viruses (hPIVs) are leading causes of viral lower respiratory tract illness in children and in high-risk adult populations. Despite decades of research, licensed vaccines for RSV and hPIVs do not exist. Recently, however, genetically engineered live attenuated RSV and hPIV candidate vaccines have been generated, several of which are already being evaluated in clinical trials. Recombinant technology allows candidate vaccines to be "fine-tuned" in response to clinical data, which should hasten the development of vaccines against these important respiratory pathogens.

Populations at risk for developing respiratory syncytial virus and risk factors for respiratory syncytial virus severity: infants with predisposing conditions.

According to National Vital Statistics Reports, premature infants (< 36 weeks gestation) account for approximately 7.4% of all births. During the 8 years from 1989 to 1997, multiple births steadily increased across all categories from twin to quintuplet and higher orders. During that same period low birth weight (< 2500 g) births increased almost 12%, and very low birth weight (< 1500 g) births increased approximately 20%.Attendant to these national trends in multiple and preterm births, overall gestation-specific survival rates have improved substantially. This improved outcome can be attributed in large measure to advances in neonatal care and technology. Despite the encouraging statistics on survival, infants born prematurely, at low or very low birth weights and/or with chronic conditions that predispose to lower respiratory tract illness, continue to incur serious risk of long term morbidity and the consumption of inpatient hospital services. In a recent 2-year study of US children, low and very low birth weights were found to be independent risk factors for bronchiolitis-associated mortality. In the past 14 years what defines bronchopulmonary dysplasia (BPD)/chronic lung disease (CLD) has shifted away from clinical, radiographic and pathologic findings in the preterm infant toward the pathophysiology of arrested lung development and the need for supportive care beyond 36 weeks corrected gestational age. The incidence of BPD/CLD ranges from 14 to 43%, with higher rates observed among infants of lower gestational age and birth weight. The health care team approach to the management of BPD directs its efforts toward minimizing pulmonary vascular resistance, alleviating airway obstruction and improving short term lung mechanics. Measures to prevent BPD/CLD attempt to forestall both acute and chronic lung function abnormalities. To that end researchers have investigated the early use of continuous positive airway pressure, vitamin supplementation and recombinant human copper/zinc superoxide dismutase. Despite significant gains in the survival of infants born at lower gestational ages, prematurity, low birth weight and/or underlying chronic pulmonary disease put the pediatric patient at risk for increased frequency and severity of respiratory syncytial virus lower respiratory tract illness and the potential for its long term sequelae.

Maturation of immune responses at the beginning of asthma

The prevalence of childhood asthma appears to be increasing worldwide. A critical element in the development of childhood asthma is maturation of the child’s immune system. Most asthmatic children have a history of recurrent lower respiratory tract illnesses associated with airway obstruction during the first year of life. Most infants and young children who will go on to have persistent wheezing and asthma show high IgE production and eosinophilic immune responses at the time of their first viral lower respiratory tract illness. Understanding the genetic and environmental factors that regulate the maturation of the immune response during early life will greatly enhance the development of strategies for the primary and secondary prevention of asthma. (J Allergy Clin Immunol 1999;103:355-61.)