The novel coronavirus SARS-CoV2 causes COVID-19, a pandemic threatening millions. As protective immunity does not exist in humans and the virus is capable of escaping innate immune responses, it can proliferate, unhindered, in primarily infected tissues. Subsequent cell death results in the release of virus particles and intracellular components to the extracellular space, which result in immune cell recruitment, the generation of immune complexes and associated damage. Infection of monocytes/macrophages and/or recruitment of uninfected immune cells can result in massive inflammatory responses later in the disease. Uncontrolled production of pro-inflammatory mediators contributes to ARDS and cytokine storm syndrome. Antiviral agents and immune modulating treatments are currently being trialled. Understanding immune evasion strategies of SARS-CoV2 and the resulting delayed massive immune response will result in the identification of biomarkers that predict outcomes as well as phenotype and disease stage specific treatments that will likely include both antiviral and immune modulating agents.

The association between severe bronchiolitis and dual infection by human metapneumovirus (hMPV) and human respiratory syncytial virus (hRSV) was investigated in <2-year-old infants with bronchiolitis who were admitted to the hospital during the 2001-2002 winter season. hMPV in nasopharyngeal aspirate and/or cells and fluid collected by nonbronchoscopic bronchoalveolar lavage was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). hRSV was detected in nasopharyngeal aspirate and/or cells and fluid collected by nonbronchoscopic bronchoalveolar lavage by enzyme immunoassay, tissue culture, and RT-PCR. Dual infection with hMPV and hRSV confers a 10-fold increase in relative risk (RR) of admission to a pediatric intensive-care unit for mechanical ventilation (RR, 10.99 [95% confidence interval, 5.0-24.12]; P<.001, by Fisher exact test). Dual infection by hMPV and hRSV is associated with severe bronchiolitis.

Reverse transcription-polymerase chain reaction was used to detect segments of the M (matrix), N (nucleoprotein), and F (fusion) genes of human metapneumovirus in bronchoalveolar fluid from 30 infants with severe respiratory syncytial virus bronchiolitis. Seventy percent of them were coinfected with metapneumovirus. Such coinfection might be a factor influencing the severity of bronchiolitis.

BackgroundAcute respiratory infection (ARI) is a leading cause of morbidity and mortality in children worldwide. This study aimed to determine the viral and atypical bacterial causes of different severities and clinical manifestations of ARI in preschool children from low-income families in North-East Brazil.MethodsClinical/demographic data and nasopharyngeal aspirates (NPA) were prospectively collected from children <5 years presenting with ARI over one year to a paediatric A&E department. Disease severity was grouped according to presence of lower respiratory tract signs, need for hospital admission and need for oxygen. Clinical manifestation of ARI was based on discharge diagnosis from hospital with four conditions predominating: bronchiolitis, pneumonia, episodic viral wheeze/asthma and upper respiratory tract infection. Multiplex PCR was used to detect 17 common respiratory viral and atypical bacterial pathogens in NPA.Findings407 children with a median age of eight months were recruited. Pathogens were detected in 85·5% samples with co-infection being particularly common (39·5%). Respiratory Syncytial Virus (RSV; 37%), Adenoviruses (AdV; 25%), Rhinoviruses (hRV; 19%), Bocavirus (hBoV; 19%), human Meta-pneumovirus (hMPV; 10%) and Mycoplasma pneumoniae (Mpp; 10%) were most prevalent. Detection and co-infection rates were similar in all severities and clinical manifestations of ARI apart from RSV, which was associated with more severe disease and specifically more severe cases of bronchiolitis, and Mpp, which was associated with more severe cases of pneumonia. Mpp was detected in 17% of children admitted to hospital with pneumonia.InterpretationThis study underlines the importance of viral and atypical bacterial pathogens in ARI in pre-school children and highlights the complex epidemiology of these pathogens in this age group. Generally, viruses and atypical bacteria were detected in all severities and clinical manifestations of ARI but RSV and Mpp were associated with more severe cases of bronchiolitis and pneumonia respectively.

Aim:To examine over time, the cellular response within the lungs of infants ventilated with respiratory syncytial virus (RSV) bronchiolitis and to compare this response in infants born at term with those born preterm. Methods: Non-bronchoscopic bronchoalveolar lavage (BAL) samples were taken from 47 infants (24 born at term and 23 born preterm) who were ventilated for RSV positive bronchiolitis and 10 control infants. BAL cellularity and differential cell counts were calculated using standard techniques. Results: Total cellularity in BAL over the first four days of ventilation in infants with RSV bronchiolitis was greater in term infants (median 2.2 (IQR 4.27) × 10 6 cells/ml) compared with preterm infants (0.58 (1.28) × 10 6 cells/ml). The magnitude of the cellular response in preterm infants with bronchiolitis was similar to that in the control group measured on day 1 (0.62 (0.77) × 10 6 cells/ml). BAL cellularity decreased progressively from the time of intubation in term infants, but remained relatively constant in preterm infants up to seven days after intubation. Conclusions: There are differences in the magnitude and type of pulmonary cellular response in term and preterm infants ventilated with RSV bronchiolitis. The cellular response in term infants with bronchiolitis differs from that in a control group of infants. These differences may reflect variations in cellular recruitment in the lung and/or variations in airway calibre.

AimAcute bronchiolitis is the commonest cause for hospitalisation in infancy. Supportive care remains the cornerstone of current management and no other therapy has been shown to influence the course of the disease. It has been suggested that adding nebulised hypertonic saline to usual care may shorten the duration of hospitalisation. To determine whether hypertonic saline does have beneficial effects we undertook an open, multi-centre parallel-group, pragmatic RCT in ten UK hospitals.MethodsInfants admitted to hospital with a clinical diagnosis of acute bronchiolitis and requiring oxygen therapy were randomised to receive usual care alone or nebulised 3% hypertonic saline (HS) administered 6-hourly. Randomisation was within 4 h of admission. The primary outcome was time to being assessed as ‘fit’ for discharge with secondary outcomes including time to discharge, incidence of adverse events together with follow up to 28 days assessing patient centred health related outcomes.ResultsA total of 317 infants were recruited to the study. 158 infants were randomised to HS (141 analysed) and 159 to standard care (149 analysed). There was no difference between the two arms in time to being declared fit for discharge (hazard ratio: 0−95, 95% CI: 0.75−1.20) nor to actual discharge (hazard ratio: 0.97, 95% CI: 0.76−1.23). There was no difference in adverse events. One infant in the HS group developed bradycardia with desaturation.ConclusionThis study does not support the use of nebulised HS in the treatment of acute bronchiolitis over usual care with minimal handlings.ClinicalTrials.gov registration numberNCT01469845.

CXC chemokines predominate within the RSV-infected lung. Much of this response comes from inflammatory cells within the lower respiratory tract. Chemokine response patterns vary over time, possibly indicating different cellular sources for individual chemokines in the RSV-infected lung.

Respiratory syncytial virus (RSV) is a leading cause of severe respiratory infection in infants and children. RSV is an RNA virus whose genome encodes 10 proteins. The G protein is responsible for viral attachment to cells whilst the F protein promotes syncytia formation. These proteins are also important in the immune response to RSV. Both the innate and adaptive arms of the cellular immune system are involved in the immunological response to RSV. The cytopathic effects of the virus explain many of the pathological findings in RSV disease. However, there is compelling evidence to suggest that the host cell immune response also has a prominent role in disease pathogenesis. Non-immunological factors may also be important.