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International Journal of Environmental... Jan 2020Respiratory viruses are a common cause of respiratory tract infection (RTI), particularly in neonates and children. Rapid and accurate diagnosis of viral infections...
Respiratory viruses are a common cause of respiratory tract infection (RTI), particularly in neonates and children. Rapid and accurate diagnosis of viral infections could improve clinical outcomes and reduce the use of antibiotics and treatment sessions. Advances in diagnostic technology contribute to the accurate detection of viruses. We performed a multiplex real-time polymerase chain reaction (PCR) to investigate the viral etiology in pediatric patients and compared the detection rates with those determined using traditional antigen tests and virus cultures. Fifteen respiratory viruses were included in our investigation: respiratory syncytial virus A/B (RSV), influenza virus A (FluA) and influenza virus B (FluB), human metapneumovirus (MPV), enterovirus (EV), human parainfluenza virus (PIV) types 1-4, human rhinovirus (RV), human coronavirus OC43, NL63, and 229E, human adenovirus (ADV), and human bocavirus (Boca). In total, 474 specimens were collected and tested. Respiratory viruses were detected more frequently by PCR (357, 75.3%) than they were by traditional tests (229, 49.3%). The leading pathogens were RSV (113, 23.8%), RV (72, 15.2%), PIV3 (53, 11.2%), FluA (51, 10.8%), and ADV (48, 10.1%). For children younger than 5 years, RSV and RV were most prevalent; for children older than 5 years, FluA and ADV were the most frequently detected. Of the specimens, 25.8% (92/357) were coinfected with two or more viruses. RV, Boca, PIV2, FluB, and PIV4 had higher rates of coinfection; MPV and PIV1 had the lowest rates of coinfection (9.1% and 5.3%). To conclude, the detection power of PCR was better than that of traditional antigen tests and virus cultures when considering the detection of respiratory viruses. RSV and RV were the leading viral pathogens identified in the respiratory specimens. One-quarter of the positive specimens were coinfected with two or more viruses. In the future, further application of PCR may contribute to the rapid and accurate diagnosis of respiratory viruses and could improve patient outcomes.
Topics: Child; Child, Preschool; Coinfection; Female; Humans; Infant; Infant, Newborn; Male; Microbiological Techniques; Real-Time Polymerase Chain Reaction; Respiratory Tract Infections; Virus Diseases
PubMed: 31952364
DOI: 10.3390/ijerph17020564 -
Open Forum Infectious Diseases Nov 2021Respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and influenza are respiratory pathogens leading to hospitalization in adults. Our understanding of the...
Risk Factors and Medical Resource Utilization of Respiratory Syncytial Virus, Human Metapneumovirus, and Influenza-Related Hospitalizations in Adults-A Global Study During the 2017-2019 Epidemic Seasons (Hospitalized Acute Respiratory Tract Infection [HARTI] Study).
BACKGROUND
Respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and influenza are respiratory pathogens leading to hospitalization in adults. Our understanding of the disease burden is limited to data from single-center or 1-season studies in elderly patients. The HARTI study allows comparison of risk factors for progression to severe disease and medical resources utilization (MRU) during and post-hospitalization in adults diagnosed with influenza, RSV, or hMPV.
METHODS
This was a prospective global study in adults hospitalized with acute respiratory tract infection (40 centers, 12 countries). Participants with influenza, RSV, or hMPV were enrolled in a substudy and followed for up to 3 months postdischarge.
RESULTS
Overall, 366 influenza, 238 RSV, and 100 hMPV-infected participants enrolled in the substudy. RSV participants were older and had greater frequency of risk factors and longer duration of symptoms before hospitalization than influenza participants. The RSV and hMPV groups received more bronchodilators, corticosteroids, and oxygen supplementation. No significant differences in intensive care unit admissions or complications were observed. Readmission occurred in 20%-33% of patients within 3 months postdischarge, with the highest rates for RSV and hMPV. In-hospital death occurred in 2.5% of RSV, 1.6% of influenza, and 2% of hMPV participants. In multivariate analyses, length of stay was independently associated with country, renal disease, and increased age; probability of receiving supplemental oxygen was associated with pathogen (hMPV > RSV > influenza), abnormal chest x-ray, and increased age.
CONCLUSIONS
Although influenza is more frequent, the HARTI study demonstrates greater frequency of underlying risk factors and MRU for RSV and hMPV vs influenza in hospitalized adults, indicating a need for effective interventions.
PubMed: 35559130
DOI: 10.1093/ofid/ofab491 -
Clinical Infectious Diseases : An... Jul 2022Respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (hMPV) are increasingly associated with chronic lung allograft dysfunction (CLAD)... (Meta-Analysis)
Meta-Analysis
Respiratory Syncytial Virus, Human Metapneumovirus, and Parainfluenza Virus Infections in Lung Transplant Recipients: A Systematic Review of Outcomes and Treatment Strategies.
BACKGROUND
Respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (hMPV) are increasingly associated with chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTR). This systematic review primarily aimed to assess outcomes of RSV/PIV/hMPV infections in LTR and secondarily to assess evidence regarding the efficacy of ribavirin.
METHODS
Relevant databases were queried and study outcomes extracted using a standardized method and summarized.
RESULTS
Nineteen retrospective and 12 prospective studies were included (total 1060 cases). Pooled 30-day mortality was low (0-3%), but CLAD progression 180-360 days postinfection was substantial (pooled incidences 19-24%) and probably associated with severe infection. Ribavirin trended toward effectiveness for CLAD prevention in exploratory meta-analysis (odds ratio [OR] 0.61, [0.27-1.18]), although results were highly variable between studies.
CONCLUSIONS
RSV/PIV/hMPV infection was followed by a high CLAD incidence. Treatment options, including ribavirin, are limited. There is an urgent need for high-quality studies to provide better treatment options for these infections.
Topics: Humans; Lung; Metapneumovirus; Parainfluenza Virus 1, Human; Parainfluenza Virus 2, Human; Paramyxoviridae Infections; Prospective Studies; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Retrospective Studies; Ribavirin; Transplant Recipients
PubMed: 35022697
DOI: 10.1093/cid/ciab969 -
Influenza and Other Respiratory Viruses Mar 2022The frequency and clinical profile of respiratory syncytial virus (RSV)-acute respiratory disease (ARD) in older adults in Japan has not been well-characterized. (Observational Study)
Observational Study
Occurrence and disease burden of respiratory syncytial virus and other respiratory pathogens in adults aged ≥65 years in community: A prospective cohort study in Japan.
BACKGROUND
The frequency and clinical profile of respiratory syncytial virus (RSV)-acute respiratory disease (ARD) in older adults in Japan has not been well-characterized.
METHODS
This was a multicenter prospective observational cohort study to evaluate the occurrence rate of ARD in 1000 older adult participants (≥65 years) for 52 weeks during the 2019 to 2020 season. A multiplex polymerase chain reaction panel was used for pathogen detection in nasopharyngeal swab from participants diagnosed with ARD. Symptoms and impact of ARD was assessed using the Respiratory Infection Intensity and Impact Questionnaire (RiiQ™). The study was registered at UMIN (https://www.umin.ac.jp/ctr/): UMIN000037891.
RESULTS
RSV-ARD was detected in 24/1000 (2.4%) participants and RSV-lower respiratory tract disease in 8/1000 (0.8%) participants. The median duration of RSV-ARD was 18 days. All 24 participants had utilized the medical services of outpatient visits and only 1 (4.2%) participant was hospitalized for RSV-ARD. The most common viruses other than RSV that caused ARD (detected in >10 participants) were human rhinovirus/enterovirus, parainfluenza 3, coronavirus OC43, human metapneumovirus, and influenza A/H1. The most frequent symptoms of RSV-ARD were cough, sore throat, nasal congestion, and expectoration.
CONCLUSIONS
RSV was reported as a major pathogen for respiratory infections in older adults in Japan.
Topics: Aged; Cost of Illness; Humans; Infant; Japan; Metapneumovirus; Prospective Studies; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections
PubMed: 34730287
DOI: 10.1111/irv.12928 -
The Lancet. Global Health Jan 2021Human metapneumovirus is a common virus associated with acute lower respiratory infections (ALRIs) in children. No global burden estimates are available for ALRIs...
BACKGROUND
Human metapneumovirus is a common virus associated with acute lower respiratory infections (ALRIs) in children. No global burden estimates are available for ALRIs associated with human metapneumovirus in children, and no licensed vaccines or drugs exist for human metapneumovirus infections. We aimed to estimate the age-stratified human metapneumovirus-associated ALRI global incidence, hospital admissions, and mortality burden in children younger than 5 years.
METHODS
We estimated the global burden of human metapneumovirus-associated ALRIs in children younger than 5 years from a systematic review of 119 studies published between Jan 1, 2001, and Dec 31, 2019, and a further 40 high quality unpublished studies. We assessed risk of bias using a modified Newcastle-Ottawa Scale. We estimated incidence, hospital admission rates, and in-hospital case-fatality ratios (hCFRs) of human metapneumovirus-associated ALRI using a generalised linear mixed model. We applied incidence and hospital admission rates of human metapneumovirus-associated ALRI to population estimates to yield the morbidity burden estimates by age bands and World Bank income levels. We also estimated human metapneumovirus-associated ALRI in-hospital deaths and overall human metapneumovirus-associated ALRI deaths (both in-hospital and non-hospital deaths). Additionally, we estimated human metapneumovirus-attributable ALRI cases, hospital admissions, and deaths by combining human metapneumovirus-associated burden estimates and attributable fractions of human metapneumovirus in laboratory-confirmed human metapneumovirus cases and deaths.
FINDINGS
In 2018, among children younger than 5 years globally, there were an estimated 14·2 million human metapneumovirus-associated ALRI cases (uncertainty range [UR] 10·2 million to 20·1 million), 643 000 human metapneumovirus-associated hospital admissions (UR 425 000 to 977 000), 7700 human metapneumovirus-associated in-hospital deaths (2600 to 48 800), and 16 100 overall (hospital and community) human metapneumovirus-associated ALRI deaths (5700 to 88 000). An estimated 11·1 million ALRI cases (UR 8·0 million to 15·7 million), 502 000 ALRI hospital admissions (UR 332 000 to 762 000), and 11 300 ALRI deaths (4000 to 61 600) could be causally attributed to human metapneumovirus in 2018. Around 58% of the hospital admissions were in infants under 12 months, and 64% of in-hospital deaths occurred in infants younger than 6 months, of which 79% occurred in low-income and lower-middle-income countries.
INTERPRETATION
Infants younger than 1 year have disproportionately high risks of severe human metapneumovirus infections across all World Bank income regions and all child mortality settings, similar to respiratory syncytial virus and influenza virus. Infants younger than 6 months in low-income and lower-middle-income countries are at greater risk of death from human metapneumovirus-associated ALRI than older children and those in upper-middle-income and high-income countries. Our mortality estimates demonstrate the importance of intervention strategies for infants across all settings, and warrant continued efforts to improve the outcome of human metapneumovirus-associated ALRI among young infants in low-income and lower-middle-income countries.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Acute Disease; Child, Preschool; Cost of Illness; Female; Global Health; Humans; Infant; Infant, Newborn; Linear Models; Male; Metapneumovirus; Paramyxoviridae Infections; Respiratory Tract Infections
PubMed: 33248481
DOI: 10.1016/S2214-109X(20)30393-4 -
MMWR. Morbidity and Mortality Weekly... Oct 2022The New Vaccine Surveillance Network (NVSN) is a prospective, active, population-based surveillance platform that enrolls children with acute respiratory illnesses...
The New Vaccine Surveillance Network (NVSN) is a prospective, active, population-based surveillance platform that enrolls children with acute respiratory illnesses (ARIs) at seven pediatric medical centers. ARIs are caused by respiratory viruses including influenza virus, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human parainfluenza viruses (HPIVs), and most recently SARS-CoV-2 (the virus that causes COVID-19), which result in morbidity among infants and young children (1-6). NVSN estimates the incidence of pathogen-specific pediatric ARIs and collects clinical data (e.g., underlying medical conditions and vaccination status) to assess risk factors for severe disease and calculate influenza and COVID-19 vaccine effectiveness. Current NVSN inpatient (i.e., hospital) surveillance began in 2015, expanded to emergency departments (EDs) in 2016, and to outpatient clinics in 2018. This report describes demographic characteristics of enrolled children who received care in these settings, and yearly circulation of influenza, RSV, HMPV, HPIV1-3, adenovirus, human rhinovirus and enterovirus (RV/EV),* and SARS-CoV-2 during December 2016-August 2021. Among 90,085 eligible infants, children, and adolescents (children) aged <18 years with ARI, 51,441 (57%) were enrolled, nearly 75% of whom were aged <5 years; 43% were hospitalized. Infants aged <1 year accounted for the largest proportion (38%) of those hospitalized. The most common pathogens detected were RV/EV and RSV. Before the emergence of SARS-CoV-2, detected respiratory viruses followed previously described seasonal trends, with annual peaks of influenza and RSV in late fall and winter (7,8). After the emergence of SARS-CoV-2 and implementation of associated pandemic nonpharmaceutical interventions and community mitigation measures, many respiratory viruses circulated at lower-than-expected levels during April 2020-May 2021. Beginning in summer 2021, NVSN detected higher than anticipated enrollment of hospitalized children as well as atypical interseasonal circulation of RSV. Further analyses of NVSN data and continued surveillance are vital in highlighting risk factors for severe disease and health disparities, measuring the effectiveness of vaccines and monoclonal antibody-based prophylactics, and guiding policies to protect young children from pathogens such as SARS-CoV-2, influenza, and RSV.
Topics: Adolescent; Antibodies, Monoclonal; COVID-19; COVID-19 Vaccines; Child; Child, Preschool; Humans; Infant; Influenza, Human; Metapneumovirus; Prospective Studies; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; SARS-CoV-2; United States; Viruses
PubMed: 36201373
DOI: 10.15585/mmwr.mm7140a1 -
Cell Host & Microbe Aug 2023Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections pose a significant health burden. Using pre-fusion conformation fusion (F) proteins, we...
Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections pose a significant health burden. Using pre-fusion conformation fusion (F) proteins, we isolated a panel of anti-F antibodies from a human donor. One antibody (RSV-199) potently cross-neutralized 8 RSV and hMPV strains by recognizing antigenic site III, which is partially conserved in RSV and hMPV F. Next, we determined the cryoelectron microscopy (cryo-EM) structures of RSV-199 bound to RSV F trimers, hMPV F monomers, and an unexpected dimeric form of hMPV F. These structures revealed how RSV-199 engages both RSV and hMPV F proteins through conserved interactions of the antibody heavy-chain variable region and how variability within heavy-chain complementarity-determining region 3 (HCDR3) can be accommodated at the F protein interface in site-III-directed antibodies. Furthermore, RSV-199 offered enhanced protection against RSV A and B strains and hMPV in cotton rats. These findings highlight the mechanisms of broad neutralization and therapeutic potential of RSV-199.
Topics: Humans; Metapneumovirus; Antibodies, Neutralizing; Antibodies, Viral; Cryoelectron Microscopy; Respiratory Syncytial Virus, Human; Immunoglobulin Variable Region; Viral Fusion Proteins
PubMed: 37516111
DOI: 10.1016/j.chom.2023.07.002 -
Clinical Infectious Diseases : An... Aug 2022To combat the coronavirus disease 2019 (COVID-19) pandemic, nonpharmaceutical interventions (NPIs) were implemented worldwide, which impacted a broad spectrum of acute... (Observational Study)
Observational Study
BACKGROUND
To combat the coronavirus disease 2019 (COVID-19) pandemic, nonpharmaceutical interventions (NPIs) were implemented worldwide, which impacted a broad spectrum of acute respiratory infections (ARIs).
METHODS
Etiologically diagnostic data from 142 559 cases with ARIs, who were tested for 8 viral pathogens (influenza virus [IFV], respiratory syncytial virus [RSV], human parainfluenza virus [HPIV], human adenovirus [HAdV], human metapneumovirus [HMPV], human coronavirus [HCoV], human bocavirus [HBoV], and human rhinovirus [HRV]) between 2012 and 2021, were analyzed to assess the changes in respiratory infections in China during the first COVID-19 pandemic year compared with pre-pandemic years.
RESULTS
Test-positive rates of all respiratory viruses decreased during 2020, compared to the average levels during 2012-2019, with changes ranging from -17.2% for RSV to -87.6% for IFV. Sharp decreases mostly occurred between February and August when massive NPIs remained active, although HRV rebounded to the historical level during the summer. While IFV and HMPV were consistently suppressed year-round, RSV, HPIV, HCoV, HRV, and HBoV resurged and went beyond historical levels during September 2020-January 2021, after NPIs were largely relaxed and schools reopened. Resurgence was more prominent among children <18 years and in northern China. These observations remain valid after accounting for seasonality and long-term trend of each virus.
CONCLUSIONS
Activities of respiratory viral infections were reduced substantially in the early phases of the COVID-19 pandemic, and massive NPIs were likely the main driver. Lifting of NPIs can lead to resurgence of viral infections, particularly in children.
Topics: COVID-19; Child; Human bocavirus; Humans; Metapneumovirus; Orthomyxoviridae; Pandemics; Parainfluenza Virus 1, Human; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Virus Diseases; Viruses
PubMed: 34788811
DOI: 10.1093/cid/ciab942 -
Frontiers in Immunology 2022Respiratory tract infections are a leading cause of morbidity and mortality in newborns, infants, and young children. These early life infections present a formidable... (Review)
Review
Respiratory tract infections are a leading cause of morbidity and mortality in newborns, infants, and young children. These early life infections present a formidable immunologic challenge with a number of possibly conflicting goals: simultaneously eliminate the acute pathogen, preserve the primary gas-exchange function of the lung parenchyma in a developing lung, and limit long-term sequelae of both the infection and the inflammatory response. The latter has been most well studied in the context of childhood asthma, where multiple epidemiologic studies have linked early life viral infection with subsequent bronchospasm. This review will focus on the clinical relevance of respiratory syncytial virus (RSV), human metapneumovirus (HMPV), and rhinovirus (RV) and examine the protective and pathogenic host responses within the neonate.
Topics: Child; Child, Preschool; Humans; Immunity; Infant; Infant, Newborn; Metapneumovirus; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Viruses
PubMed: 35493465
DOI: 10.3389/fimmu.2022.863149 -
The Lancet. Microbe May 2023Respiratory disease is a major cause of morbidity and mortality; however, surveillance for circulating respiratory viruses is passive and biased. Wastewater-based...
Wastewater concentrations of human influenza, metapneumovirus, parainfluenza, respiratory syncytial virus, rhinovirus, and seasonal coronavirus nucleic-acids during the COVID-19 pandemic: a surveillance study.
BACKGROUND
Respiratory disease is a major cause of morbidity and mortality; however, surveillance for circulating respiratory viruses is passive and biased. Wastewater-based epidemiology has been used to understand SARS-CoV-2, influenza A, and respiratory syncytial virus (RSV) infection rates at a community level but has not been used to investigate other respiratory viruses. We aimed to use wastewater-based epidemiology to understand community viral respiratory infection occurrence.
METHODS
A retrospective wastewater-based epidemiology surveillance study was carried out at a large wastewater treatment plant located in California, USA. Using droplet digital RT-PCR, we measured RNA concentrations of influenza A and influenza B viruses, RSV A and RSV B, parainfluenza (1-4) viruses, rhinovirus, seasonal coronaviruses, and metapneumovirus in wastewater solids three times per week for 17 months (216 samples) between Feb 1, 2021, and June 21, 2022. Novel probe-based RT-PCR assays for non-influenza viral targets were developed and validated. We compared viral RNA concentrations to positivity rates for viral infections from clinical specimens submitted to California Sentinel Clinical Laboratories (sentinel laboratories) to assess concordance between the two datasets.
FINDINGS
We detected RNA from all tested viruses in wastewater solids. Human rhinovirus (median concentration 4300 [0-9500] copies per gram dry weight) and seasonal human coronaviruses (35 000 [17 000-56 000]) were found at the highest concentrations. Concentrations of viral RNA correlated significantly and positively with positivity rates of associated viral diseases from sentinel laboratories (tau 0·32-0·57, p<0·0009); the only exceptions were influenza B and RSV A, which were rarely detected in wastewater solids. Measurements from wastewater indicated coronavirus OC43 dominated the seasonal human coronavirus infections whereas parainfluenza 3 dominated among parainfluenza infections during the study period. Concentrations of all tested viral RNA decreased noticeably after the omicron BA.1 surge suggesting a connection between changes in human behaviour during the surge and transmission of all respiratory viruses.
INTERPRETATION
Wastewater-based epidemiology can be used to obtain information on circulation of respiratory viruses at a localised, community level without the need to test many individuals because a single sample of wastewater represents the entire contributing community. Results from wastewater can be available within 24 h of sample collection, generating real time information to inform public health responses, clinical decision making, and individual behaviour modifications.
FUNDING
CDC Foundation.
Topics: Humans; Influenza, Human; Metapneumovirus; Rhinovirus; Wastewater; Nucleic Acids; Seasons; Pandemics; Retrospective Studies; Respiratory Tract Infections; COVID-19; SARS-CoV-2; Respiratory Syncytial Virus, Human; Paramyxoviridae Infections; Virus Diseases; Respiratory Syncytial Virus Infections; Influenza B virus; RNA, Viral
PubMed: 36965504
DOI: 10.1016/S2666-5247(22)00386-X