Respiratory Syncytial Virus Co-infection Research Articles

Respiratory syncytial virus in pediatric patients admitted to a tertiary center in Amman: clinical characteristics, and age-related patterns

BackgroundRespiratory 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.MethodsThis 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.ResultsA 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).ConclusionThe 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.

Risk Factors for Severe COVID-19 Among Children and Adolescents Enrolled in Acute Respiratory Infection Sentinel Surveillance in South Africa, 2020-2022.

Identifying children at risk for severe COVID-19 disease from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may guide future mitigation interventions. Using sentinel surveillance data, we aimed to identify risk factors for SARS-CoV-2-associated hospitalisation among patients aged ≤ 18 years with respiratory illness. From April 2020 to March 2022, patients meeting study case definitions were enrolled at four outpatient influenza-like illness (ILI) and five inpatient severe respiratory infection (SRI) surveillance sites and tested for SARS-CoV-2 infection using polymerase chain reaction (PCR). Each ILI clinic shared a catchment area with its corresponding SRI hospital. Potential risk factors for SARS-CoV-2-associated hospitalisation were analysed using multivariable logistic regression by comparing inpatient versus outpatient SARS-CoV-2 cases. Of 4688 participants aged ≤ 18 years, 4556 (97%) with complete PCR and HIV data were included in the analysis. Among patients with ILI and SRI, 92/1145 (8%) and 154/3411 (5%) tested SARS-CoV-2 positive, respectively. Compared to outpatients, hospitalised SARS-CoV-2 cases were associated with age < 6 months ([adjusted odds ratio (aOR) 8.0, 95% confidence interval (CI) 2.7-24.0] versus 1-4 years); underlying medical condition other than HIV [aOR 5.8, 95% CI 2.3-14.6]; laboratory-confirmed Omicron BA.1/BA.2 or Delta variant ([aOR 4.9, 95% CI 1.7-14.2] or [aOR 2.8, 95% CI 1.1-7.3] compared to ancestral SARS-CoV-2); and respiratory syncytial virus coinfection [aOR 6.2, 95% CI 1.0-38.5]. Aligning with previous research, we identified age < 6 months or having an underlying condition as risk factors for SARS-CoV-2-associated SRI hospitalisation and demonstrated the potential of sentinel surveillance to monitor COVID-19 in children.

Neutrophil-to-Lymphocyte Ratio and the Systemic Immune-Inflammation Index: Biomarkers in Infants with Bronchiolitis: a Cross-Sectional Study.

The use of a novel inflammatory indicator, the systemic immune-inflammatory index (SII), in pediatric patients with bronchiolitis remains unreported. Therefore, this study investigated the relationship between the SII and the neutrophil-to-lymphocyte ratio (NLR) in patients with respiratory syncytial virus (RSV) and non-RSV bronchiolitis and clinical severity prediction. This study analyzed the data of 155 patients aged <2 years who were hospitalized for viral bronchiolitis caused by RSV and/or other viral pathogens. The SII (platelet count × [neutrophil/lymphocyte]) was calculated and compared among patients with RSV mono-infections, other viral mono-infections, and RSV co-infections. Severity was defined by the number of days of supplemental oxygen treatment. The NLR and SII were significantly higher in the non-RSV mono-infection group than in the RSV mono-infection group, and the number of days of supplemental oxygen therapy was significantly higher in the RSV mono-infection group. No significant differences in the NLR, SII, or days of supplemental oxygen therapy were found between the RSV mono-infection and RSV co-infection groups. Although patients with RSV mono-infection showed more severe clinical findings than those without non-RSV mono-infection, the NLR and SII values were significantly higher in the non-RSV mono-infection group. Therefore, the NLR and SII do not appear to be very useful measurements for determining the severity of acute bronchiolitis attacks; however, lower NLR and SII values in the RSV group compared to the non-RSV group may be potential biomarkers for RSV infection. Therefore, further studies are warranted.

Severe Influenza Virus and Respiratory Syncytial Virus Infections in Intensive Care Over the Last 15 Years.

Influenza virus is a common agent of pediatric infections. Most cases are mild, but severe illness and death can occur. We aimed to analyze severe cases associated the influenza virus and compare it with respiratory syncytial virus(RSV). This is a retrospective study of 0-17-year-old patients admitted to the intensive care unit (ICU) of Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra (Pediatric Hospital, Coimbra Hospital and University Center), a tertiary pediatric hospital in Coimbra, Portugal, over the last 15 years (2008-2022) due to influenza virus infection. Clinical presentation, severity, and evolution were analyzed. A comparison of children with RSV infection admitted in the same period was performed. We identified 47 cases of influenza virus infection (34% coinfection with other viruses), median age of 2.3 years (interquartile range (IQR) 6.1), and 38% had comorbidities. The median admissions were three/year (maximum 11 in 2019). Influenza A was identified in 96%. Ninety-six percent had respiratory symptoms, 38% had neurologic symptoms, and 28% had sepsis. The main reason for admission was respiratory failure (68%). The mean pediatric index of mortality 2 (PIM2) at admission was 9±15.9%. Ventilatory support was necessary in 66%, vasoactive support in 19%, and blood products in 17%. The median length of stay was four days (IQR 5). There were four (8.5%) deaths. During the same study period, there were 171 RSV-related admissions. When comparing influenza (group A, without RSV coinfection) and RSV (group B), the first had a higher PIM2 on admission, greater need of ventilatory support, more complications, and higher mortality (p=0.001). The number of influenza virus infections admitted to ICU was much lower than RSV. However, influenza was more severe and associated with all deaths registered.

Epidemiology and Clinical Features of Human Metapneumovirus and Respiratory Syncytial Viral Infections in Children.

Human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are 2 common causes of acute respiratory tract infections in infants and young children. The objective of this study is to compare the demographics and outcomes of children hospitalized with HMPV and RSV infections in the United States. We performed a retrospective cohort analysis of children 1 month to less than 3 years old discharged during 2016 with HMPV or RSV infection using the Kids' Inpatient Database. Children with HMPV and RSV coinfection were excluded. Data were weighted for national estimates. There were 6585 children with HMPV infection and 70,824 with RSV infection discharged during the study period. The mean age of children with HMPV infection was higher than that of children with RSV infection (0.73 ± 0.8 vs. 0.42 ± 0.7 years; P < 0.05). The mortality rate was significantly higher in children with the presence of any complex chronic conditions compared to those without, in both HMPV [odds ratio (OR): 32.42; CI: 9.931-105.857; P < 0.05] as well as RSV (OR: 35.81; CI: 21.12-57.97; P < 0.05) groups. The adjusted median length of stay was longer (4.64 days; CI: 4.52-4.76 days vs. 3.33 days; CI: 3.31-3.35 days; P < 0.001) and total charges were higher ($44,358; CI: $42,145-$46,570 vs. $22,839; CI: $22,512-$23,166; P < 0.001), with HMPV infection. The mortality rate was similar in HMPV infection compared to RSV infection on multivariable analysis (OR: 1.48; P > 0.05). In hospitalized children in the United States, HMPV infection is less common than RSV infection. Complex chronic conditions are more prevalent in children hospitalized with HMPV infection. Hospitalization with HMPV is associated with longer length of stay and higher hospital charges. The adjusted mortality is similar with both infections.

Severe SARS-CoV-2 and respiratory syncytial virus co-infection in two children.

The Coronavirus Disease 2019 (COVID-19) caused by a novel coronavirus (SARS-CoV-2) affects mainly older adults. Those with comorbidities are at a higher risk of severe disease and even death. The symptomatic infection rate of children is lower, manifestations are milder, and severe forms are scarce. We present here two children with severe COVID-19 and a respiratory syncytial virus, with the goal of emphasizing the possibility of coinfection with a severe course and a different result. The microbiological diagnosis was made using multiplex PCR. This assay not only provided an early and accurate diagnosis but also aided in the implementation of contact precautions. Further research should be done to determine the influence of coinfection on the clinical course and outcome of pediatric patients.

Clinical Presentation and Severity of SARS-CoV-2 Infection Compared to Respiratory Syncytial Virus and Other Viral Respiratory Infections in Children Less than Two Years of Age

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the implementation of restrictive measures led to a dramatic reduction in respiratory syncytial virus (RSV) occurrence together with rare and mild bronchiolitis induced by SARS-CoV-2. We described the respiratory picture of SARS-CoV-2 infection and evaluated the frequency and the severity of SARS-CoV-2 bronchiolitis comparing it with other respiratory viral infections in children less than two years of age. The severity of respiratory involvement was evaluated based on the need for oxygen therapy, intravenous hydration, and the length of hospital stay. A total of 138 children hospitalized for respiratory symptoms were enrolled: 60 with SARS-CoV-2 and 78 with RSV. In the group of SARS-CoV-2-infected children, 13/60 (21%) received a diagnosis of co-infection. Among the enrolled children, 87/138 (63%) received a diagnosis of bronchiolitis. The comparative evaluation showed a higher risk of the need for oxygen therapy and intravenous hydration in children with RSV infection and co-infection compared to children with SARS-CoV-2 infection. In the children with a diagnosis of bronchiolitis, no differences in the main outcomes among the groups were observed. Although children with SARS-CoV-2 infection have less severe respiratory effects than adults, the pediatrician should pay attention to bronchiolitis due to SARS-CoV-2, which could have a severe clinical course in younger children.

Coinfection by influenza A virus and respiratory syncytial virus produces hybrid virus particles.

Interactions between respiratory viruses during infection affect transmission dynamics and clinical outcomes. To identify and characterize virus-virus interactions at the cellular level, we coinfected human lung cells with influenza A virus (IAV) and respiratory syncytial virus (RSV). Super-resolution microscopy, live-cell imaging, scanning electron microscopy and cryo-electron tomography revealed extracellular and membrane-associated filamentous structures consistent with hybrid viral particles (HVPs). We found that HVPs harbour surface glycoproteins and ribonucleoproteins of IAV and RSV. HVPs use the RSV fusion glycoprotein to evade anti-IAV neutralizing antibodies and infect and spread among cells lacking IAV receptors. Finally, we show that IAV and RSV coinfection in primary cells of the bronchial epithelium results in viral proteins from both viruses co-localizing at the apical cell surface. Our observations define a previously unknown interaction between respiratory viruses that might affect virus pathogenesis by expanding virus tropism and enabling immune evasion.

Factors Associated With Severe Illness in Patients Aged

To describe coronavirus disease 2019 (COVID-19)-related pediatric hospitalizations during a period of B.1.617.2 (Δ) variant predominance and to determine age-specific factors associated with severe illness. We abstracted data from medical charts to conduct a cross-sectional study of patients aged <21 years hospitalized at 6 United States children's hospitals from July to August 2021 for COVID-19 or with an incidental positive severe acute respiratory syndrome coronavirus 2 test. Among patients with COVID-19, we assessed factors associated with severe illness by calculating age-stratified prevalence ratios (PR). We defined severe illness as receiving high-flow nasal cannula, positive airway pressure, or invasive mechanical ventilation. Of 947 hospitalized patients, 759 (80.1%) had COVID-19, of whom 287 (37.8%) had severe illness. Factors associated with severe illness included coinfection with respiratory syncytial virus (RSV) (PR 3.64) and bacteria (PR 1.88) in infants; RSV coinfection in patients aged 1 to 4 years (PR 1.96); and obesity in patients aged 5 to 11 (PR 2.20) and 12 to 17 years (PR 2.48). Having ≥2 underlying medical conditions was associated with severe illness in patients aged <1 (PR 1.82), 5 to 11 (PR 3.72), and 12 to 17 years (PR 3.19). Among patients hospitalized for COVID-19, factors associated with severe illness included RSV coinfection in those aged <5 years, obesity in those aged 5 to 17 years, and other underlying conditions for all age groups <18 years. These findings can inform pediatric practice, risk communication, and prevention strategies, including vaccination against COVID-19.

A Pilot Study on Aetiology of Acute Lower Respiratory Tract Infections Among Children Hospitalized of Respiratory Illness at a Rural Hospital in South Coastal Karnataka

Objective: Aetiological diagnosis can significantly impact the clinical management and outcome of acute lower respiratory tract infections (LRTI) in children. There is a paucity of data on etiological agents of acute LRTI among children in Karnataka, especially in Udupi district. Present study provides an insight into the pathogens associated with acute LRTI among children in Udupi district of south coastal Karnataka. Methods: A cross sectional study was performed at a rural hospital in south coastal Karnataka, A total of 50 children clinically diagnosed for acute LRTI and admitted in paediatric ward were enrolled for the study. Nasopharyngeal/throat swab specimens were collected, and nucleic acid was extracted, and Multiplex real-time PCR was performed for detection of bacterial and viral aetiology. Results: S. pneumoniae was detected in 16% (8/50), followed by ‎ Respiratory syncytial virus (RSV) 14% (7/50), H. influenzae 8 % (4/50) and M. pneumoniae 2% (1/50). Mixed infection was detected in 28% (14/50) of children. S. pneumoniae and H. influenzae was the most prevalent co-infection and was detected in 10% (5/50) followed by H. Influenzae and RSV (4%, 2/50) co-infection. Conclusion: S. pneumoniae and RSV were the most predominant bacterial and viral pathogens respectively associated with LRTIs among paediatric population in present study. Further we found very high number of cases with mixed infections which signifies the urgent need of much elaborate studies for elucidating the clinical significance of these infections as well as for better understanding of epidemiology of LRTI among children in this region.

Severe acute respiratory syndrome coronavirus 2 and respiratory syncytial virus coinfection in children.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has infected many people around the world. Children are considered an important target group for SARS-CoV-2, as well as other viral infections such as respiratory syncytial virus infection. Both SARS-CoV-2 and respiratory syncytial virus can affect the respiratory tract. Coinfection of SARS-CoV-2 and respiratory syncytial virus can pose significant challenges in terms of diagnosis and treatment in children. This review compares the symptoms, diagnostic methods, and treatment of COVID-19 and respiratory syncytial virus infection in children.

Respiratory Syncytial Virus Co-infection in the Era of COVID-19 Pandemic

Respiratory Syncytial Virus Co-infection in the Era of COVID-19 Pandemic

Exacerbation of Influenza A Virus Disease Severity by Respiratory Syncytial Virus Co-Infection in a Mouse Model.

Influenza A virus (IAV) and respiratory syncytial virus (RSV) are leading causes of childhood infections. RSV and influenza are competitive in vitro. In this study, the in vivo effects of RSV and IAV co-infection were investigated. Mice were intranasally inoculated with RSV, with IAV, or with both viruses (RSV+IAV and IAV+RSV) administered sequentially, 24 h apart. On days 3 and 7 post-infection, lung tissues were processed for viral loads and immune cell populations. Lung functions were also evaluated. Mortality was observed only in the IAV+RSV group (50% of mice did not survive beyond 7 days). On day 3, the viral loads in single-infected and co-infected mice were not significantly different. However, on day 7, the IAV titer was much higher in the IAV+RSV group, and the RSV viral load was reduced. CD4 T cells were reduced in all groups on day 7 except in single-infected mice. CD8 T cells were higher in all experimental groups except the RSV-alone group. Increased airway resistance and reduced thoracic compliance were demonstrated in both co-infected groups. This model indicates that, among all the infection types we studied, infection with IAV followed by RSV is associated with the highest IAV viral loads and the most morbidity and mortality.

Molecular epidemiology of Respiratory Syncytial Virus in children in sub‐Saharan Africa

This study investigated the molecular epidemiology of respiratory syncytial virus (RSV) among febrile children with acute respiratory tract infection in Ghana, Gabon, Tanzania and Burkina Faso between 2014-2017 as well as the evolution and diversification of RSV strains from other sub-Saharan countries. Pharyngeal swabs were collected at four study sites (Agogo, Ghana: n=490; Lambaréné, Gabon: n=182; Mbeya, Tanzania: n=293; Nouna, Burkina Faso: n=115) and analysed for RSV and other respiratory viruses using rtPCR. For RSV positive samples, sequence analysis of the second hypervariable region of the G-gene was performed. A dataset of RSV strains from sub-Saharan Africa (2011-2017) currently available in GenBank was compiled. Phylogenetic analysis was conducted to identify the diversity of circulating RSV genotypes. In total, 46 samples tested RSV positive (Ghana n=31 (6.3%), Gabon n=4 (2.2%), Tanzania n=9 (3.1%), Burkina Faso n=2 (1.7%)). The most common RSV co-infection was with rhinovirus. All RSV-A strains clustered with genotype ON1 strains with a 72-nucleotide duplication and all RSV-B strains belonged to genotype BAIX. Phylogenetic analysis of amino acid sequences from sub-Saharan Africa revealed the diversification into 11 different ON1 and 22 different BAIX lineages and differentiation of ON1 and BAIX strains into potential new sub-genotypes, provisionally named ON1-NGR, BAIX-KEN1, BAIX-KEN2 and BAIX-KEN3. The study contributes to an improved understanding of the molecular epidemiology of RSV infection in sub-Saharan Africa. It provides the first phylogenetic data for RSV from Tanzania, Gabon and Burkina Faso and combines it with RSV strains from all other sub-Saharan countries currently available in GenBank.

Molecular epidemiology of respiratory syncytial virus in children in sub-Saharan Africa.

This study investigated the molecular epidemiology of respiratory syncytial virus (RSV) among febrile children with acute respiratory tract infection in Ghana, Gabon, Tanzania and Burkina Faso between 2014 and 2017 as well as the evolution and diversification of RSV strains from other sub-Saharan countries. Pharyngeal swabs were collected at four study sites (Agogo, Ghana: n=490; Lambaréné, Gabon: n=182; Mbeya, Tanzania: n=293; Nouna, Burkina Faso: n=115) and analysed for RSV and other respiratory viruses using rtPCR. For RSV-positive samples, sequence analysis of the second hypervariable region of the G gene was performed. A dataset of RSV strains from sub-Saharan Africa (2011-2017) currently available in GenBank was compiled. Phylogenetic analysis was conducted to identify the diversity of circulating RSV genotypes. In total, 46 samples were tested RSV positive (Ghana n=31 (6.3%), Gabon n=4 (2.2%), Tanzania n=9 (3.1%) and Burkina Faso n=2 (1.7%)). The most common RSV co-infection was with rhinovirus. All RSV A strains clustered with genotype ON1 strains with a 72-nucleotide duplication and all RSV B strains belonged to genotype BAIX. Phylogenetic analysis of amino acid sequences from sub-Saharan Africa revealed the diversification into 11 different ON1 and 22 different BAIX lineages and differentiation of ON1 and BAIX strains into potential new sub-genotypes, provisionally named ON1-NGR, BAIX-KEN1, BAIX-KEN2 and BAIX-KEN3. The study contributes to an improved understanding of the molecular epidemiology of RSV infection in sub-Saharan Africa. It provides the first phylogenetic data for RSV from Tanzania, Gabon and Burkina Faso and combines it with RSV strains from all other sub-Saharan countries currently available in GenBank.

Clinical impact of respiratory syncytial virus infection on children hospitalized for pertussis

BackgroundAlthough Respiratory syncytial virus (RSV) is one of the common pathogens in children with pertussis and viral coinfection, the clinical impact of RSV infection on pertussis remains unclear. We compared clinical characteristics and sought differences between infants with single Bordetella pertussis (B. pertussis) infection and those with RSV coinfection.MethodsWe enrolled 80 patients with pertussis who were hospitalized in Shenzhen Children’s Hospital from January 2017 to December 2019. Respiratory tract samples were tested for B. pertussis with real-time polymerase chain reaction and respiratory viruses with immunofluorescence assay. Clinical data were obtained from hospital records and collected using a structured questionnaire.ResultsThirty-seven of 80 patients had B. pertussis infection alone (pertussis group) and 43 had RSV-pertussis coinfection (coinfection group). No significant differences were found with regard to sex, body weight, preterm birth history, pertussis vaccination, symptoms, presence of pneumonia, or lymphocyte count between the 2 groups. Univariate analysis showed patients with RSV coinfection were older (median, 4.57 months vs 4.03 months, p = 0.048); more commonly treated with β-lactam antibiotics (21% vs 5%, p = 0.044); had higher rates of wheezes (40% vs 14%, p = 0.009) and rales (35% vs 14%, p = 0.028) on chest auscultation, a higher rate of readmission (40% vs 11%, p = 0.004), and a longer hospital stay (median, 10 days vs 7 days, p = 0.002). In the further binary logistic regression analysis, patients with RSV coinfection had higher rates of wheezes (OR = 3.802; 95% CI: 1.106 to 13.072; p = 0.034) and readmission (OR = 5.835; 95% CI: 1.280 to 26.610; p = 0.023).ConclusionsRSV coinfection increases readmission rate in children hospitalized for pertussis. RSV infection should be suspected when wheezes are present on auscultation of the chest in these patients. Early detection of RSV may avoid unnecessary antibiotic use.

SARS-CoV-2 and Respiratory Syncytial Virus Coinfection in Hospitalized Pediatric Patients.

In this study, children under 24 months of age hospitalized with respiratory compromise due to COVID-19 were retrospectively analyzed according to the event of coinfection with respiratory syncytial virus. Of 32 patients, 18.7% had coinfection and these had a significantly longer length of stay. There were no differences regarding need for intensive care, mechanical ventilation or mortality rates.

Severity of influenza virus and respiratory syncytial virus coinfections in hospitalized adult patients

Abstract Background With the introduction of molecular diagnostic techniques over the past decades, different kinds of viral pathogens in the same sample are detected simultaneously more frequently. Nevertheless, influenza virus (Flu) and respiratory syncytial virus (RSV) coinfection in adults was reported only occasionally. Moreover, the clinical implications of Flu/RSV coinfection in the respiratory tract of adults remain unclear. Methods This retrospective study analyzed adult patients with acute respiratory infection from January 2017 to June 2019 in China-Japan Friendship Hospital. Results A total of 574, 235 and 113 patients were positive for influenza A-only (FA-only), influenza B-only (FB-only) and RSV-only in influenza seasons (from Nov 2017 to Mar 2018 and from Nov 2018 to Mar 2019), respectively. Of these, 19 cases were coinfected by Flu and RSV and admitted to this hospital. Compared with 809 Flu-only infected patients and 113 RSV-only infected patients, both the rates of intensive care unit(ICU) admission and use of invasive mechanical ventilation in Flu/RSV coinfected patients were higher (ICU admission: 47.4% vs. 20.1%, P=0.004; 47.4% vs. 22.1%, P=0.020; invasive mechanical ventilation: 47.4% vs.13.2%, P Conclusion The findings of this study suggest that coinfection of Flu/RSV in adults is associated with a high adverse outcome. Thus, Flu/RSV coinfections should be increasingly appreciated and given appropriate management.

The role of viral co-infections in the severity of acute respiratory infections among children infected with respiratory syncytial virus (RSV): A systematic review and meta-analysis.

BackgroundRespiratory syncytial virus (RSV) is the predominant viral cause of childhood pneumonia. Little is known about the role of viral-coinfections in the clinical severity in children infected with RSV.MethodsWe conducted a systematic literature review of publications comparing the clinical severity between RSV mono-infection and RSV co-infection with other viruses in children under five years (<5y). Clinical severity was measured using the following six clinical outcomes: hospitalisation, length of hospital stay, use of supplemental oxygen, intensive care unit (ICU) admission, mechanical ventilation and deaths. We summarised the findings by clinical outcome and conducted random-effect meta-analyses, where applicable, to quantitatively synthesize the association between RSV mono-infection/RSV co-infection and the clinical severity.ResultsOverall, no differences in the clinical severity were found between RSV mono-infection and RSV co-infection with any viruses, except for the RSV-human metapneumovirus (hMPV) co-infection. RSV-hMPV coinfection was found to be associated with a higher risk of ICU admission (odds ratio (OR) = 7.2, 95% confidence interval (CI) = 2.1-25.1; OR after removal of the most influential study was 3.7, 95% CI = 1.1-12.3). We also observed a trend from three studies that RSV-hMPV coinfections were likely to be associated with longer hospital stay.ConclusionOur findings suggest that RSV-hMPV coinfections might be associated with increased risk for ICU admission in children <5y compared with RSV mono-infection but such association does not imply causation. Our findings do not support the association between RSV coinfections with other viruses and clinical severity but further large-scale investigations are needed to confirm the findings.Protocol registrationPROSPERO CRD42019154761.

Epidemiological study on respiratory syncytial virus-caused respiratory infection in children and preliminary analysis of changes in immune function

Objective To analyze the epidemiological characteristics of respiratory syncytial virus (RSV)-caused respiratory diseases in children in Hebei Province and the changes in peripheral blood lymphocyte subsets and inflammatory indexes. Methods A total of 9 491 sputum specimens and 9 491 paired peripheral blood specimens were collected from children admitted to Hebei Children′s Hospital for respiratory infection in 2018. RSV-positive sputum specimens were screened by multiple detection reagents for 13 kinds of respiratory pathogens. Flow cytometry was uses to detect T and B lymphocytes and NK cells in peripheral blood samples of randomly screened RSV-positive children. Procalcitonin (PCT) was measured by Roche E411 luminescence analyzer. Hypersensitive C-reactive protein (hs-CRP) was detected by Roche Cobas 8000 C701 biochemical analyzer. White blood cells (WBC) were measured by Sysmex XN-BN3 hematometer. Results The positive rate of RSV in children with respiratory diseases was 13.08% in Hebei Province in 2018. There were significant differences in RSV-positive rates among different age groups (χ2=479.297 6, P<0.000 1). The positive rate of RSV decreased gradually with age (χ2=-20.282 7, P<0.000 1) and was higher in male than in female (χ2=34.552 7, P<0.000 1). The incidence of co-infection of RSV with other respiratory pathogens was 29.49% (366/1 241), mainly caused by human rhinovirus (HRV, 150/1 241) and adenovirus (ADV, 40/1 241). The main epidemic seasons of RSV infection were winter and spring. The epidemic trends of simple RSV infection and co-infection were consistent. There were significant differences in inflammatory indexes, WBC (P<0.01), CD4+ (P=0.015) and CD4+ /CD8+ cells (P=0.016) between simple RSV infection and co-infection groups. Conclusions RSV was a common pathogen causing respiratory diseases in children in Hebei Province. The younger the children were, the more likely they were to be infected with RSV. RSV infection was easily complicated by HRV or ADV infection. The epidemic seasons of RSV infection in Hebei were winter and spring. Both simple infection and co-infection of RSV might result in immune dysfunction. Key words: Respiratory syncytial virus; Lymphocyte subsets; Molecular epidemiology; Immunity