Effects of neutrophil extracellular traps during human respiratory syncytial virus infection in vitro

The human respiratory syncytial virus (hRSV) is the most common cause of severe lower respiratory tract diseases in young children worldwide, leading to a high number of hospitalizations and significant expenditures for health systems. Neutrophils are massively recruited to the lung tissue of patients with acute respiratory diseases. At the infection site, they release neutrophil extracellular traps (NETs) that can capture and/or inactivate different types of microorganisms, including viruses. Evidence has shown that the accumulation of NETs results in direct cytotoxic effects on endothelial and epithelial cells. Neutrophils stimulated by the hRSV-F protein generate NETs that are able to capture hRSV particles, thus reducing their transmission. However, the massive production of NETs obstructs the airways and increases disease severity. Therefore, further knowledge about the effects of NETs during hRSV infections is essential for the development of new specific and effective treatments. This study evaluated the effects of NETs on the previous or posterior contact with hRSV-infected Hep-2 cells. Hep-2 cells were infected with different hRSV multiplicity of infection (MOI 0.5 or 1.0), either before or after incubation with NETs (0.5–16 μg/mL). Infected and untreated cells showed decreased cellular viability and intense staining with trypan blue, which was accompanied by the formation of many large syncytia. Previous contact between NETs and cells did not result in a protective effect. Cells in monolayers showed a reduced number and area of syncytia, but cell death was similar in infected and non-treated cells. The addition of NETs to infected tissues maintained a similar virus-induced cell death rate and an increased syncytial area, indicating cytotoxic and deleterious damages. Our results corroborate previously reported findings that NETs contribute to the immunopathology developed by patients infected with hRSV.

Bovine Respiratory Syncytial Virus (BRSV) Infection Detected in Exhaled Breath Condensate of Dairy Calves by Near-Infrared Aquaphotomics

Bovine respiratory syncytial virus (BRSV) is a major contributor to respiratory disease in cattle worldwide. Traditionally, BRSV infection is detected based on non-specific clinical signs, followed by reverse transcriptase-polymerase chain reaction (RT-PCR), the results of which can take days to obtain. Near-infrared aquaphotomics evaluation based on biochemical information from biofluids has the potential to support the rapid identification of BRSV infection in the field. This study evaluated NIR spectra (n = 240) of exhaled breath condensate (EBC) from dairy calves (n = 5) undergoing a controlled infection with BRSV. Changes in the organization of the aqueous phase of EBC during the baseline (pre-infection) and infected (post-infection and clinically abnormal) stages were found in the WAMACS (water matrix coordinates) C1, C5, C9, and C11, likely associated with volatile and non-volatile compounds in EBC. The discrimination of these chemical profiles by PCA-LDA models differentiated samples collected during the baseline and infected stages with an accuracy, sensitivity, and specificity >93% in both the calibration and validation. Thus, biochemical changes occurring during BRSV infection can be detected and evaluated with NIR-aquaphotomics in EBC. These findings form the foundation for developing an innovative, non-invasive, and in-field diagnostic tool to identify BRSV infection in cattle.

Clinico-Epidemioogical and Radiological Profile of Broncholitis at Sher-E-Bangla Medical College Hospital in Barishal, Bangladesh

Background: Bronchiolitis, caused mostly by Respiratory syncytial virus (RSV) virus is the leading cause of lower respiratory tract infection in infants. The disease is mostly presents with cough runny nose, fever, breathing difficulties and respiratory failure This infection usually affects children up to age of 24 months, with younger infants often more severely affected and is the most prevalent cause of hospitalization in infants under the age of 12 months. The treatment is supportive; therefore, epidemiology, clinical, laboratory, and radiologic findings can help to ensure appropriate diagnosis and proper treatment.Methods:This descriptive cross-sectional observation study was conducted at Paediatrics department of Sher-E-Bangla Medical College & Hospital (SBMCH), Barishal, Bangladesh between October 2018 to March 2019To find out the clinico-epidemiological and radiological profile of Bronchiolitis. Children below 24 months of age diagnosed as bronchiolitis were studied.Results:200 children were evaluated, including 150 boys and 50 girls; Infants below 6 months accounted for the highest proportion (60%). All the bronchiolitis patients had cough or cold with respiratory distress. Other symptoms were fever (98.0%), restlessness (63.0%), poor feeding (60%) and fast breathing. On examination lower chest indrawing and rhonchi were found in all cases. Hyperinflation was the most prevalent radiological finding (60%) and more than half (55%) patients had lymphocytosis on CBC.Conclusion:Most children present with typical clinical and radiological feature of bronchiolitis which can help the clinicians to clinically identify this disease more efficiently.

4′-Fluorouridine is an oral antiviral that blocks respiratory syncytial virus and SARS-CoV-2 replication

Preparing antiviral defenses Antiviral drugs are an important tool in the battle against COVID-19. Both remdesivir and molnupiravir, which target the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase, were first developed against other RNA viruses. This highlights the importance of broad-spectrum antivirals that can be rapidly deployed against related emerging pathogens. Sourimant et al . used respiratory syncytial virus (RSV) as a primary indication in identifying further drugs that target the polymerase enzyme of RNA viruses. The authors explored derivatives of molnupiravir and identified 4′ fluorouridine (EIDD-2749) as an inhibitor of the polymerase of RSV and SARS-CoV-2. This drug can be delivered orally and was effective against RSV in mice and SARS-CoV-2 in ferrets. —VV

IFN-γ Attenuates Eosinophilic Inflammation but Is Not Essential for Protection against RSV-Enhanced Asthmatic Comorbidity in Adult Mice

The susceptibility to respiratory syncytial virus (RSV) infection in early life has been associated with a deficient T-helper cell type 1 (Th1) response. Conversely, healthy adults generally do not exhibit severe illness from RSV infection. In the current study, we investigated whether Th1 cytokine IFN-γ is essential for protection against RSV and RSV-associated comorbidities in adult mice. We found that, distinct from influenza virus, prior RSV infection does not induce significant IFN-γ production and susceptibility to secondary Streptococcus pneumoniae infection in adult wild-type (WT) mice. In ovalbumin (OVA)-induced asthmatic mice, RSV super-infection increases airway neutrophil recruitment and inflammatory lung damage but has no significant effect on OVA-induced eosinophilia. Compared with WT controls, RSV infection of asthmatic Ifng−/− mice results in increased airway eosinophil accumulation. However, a comparable increase in eosinophilia was detected in house dust mite (HDM)-induced asthmatic Ifng−/− mice in the absence of RSV infection. Furthermore, neither WT nor Ifng−/− mice exhibit apparent eosinophil infiltration during RSV infection alone. Together, these findings indicate that, despite its critical role in limiting eosinophilic inflammation during asthma, IFN-γ is not essential for protection against RSV-induced exacerbation of asthmatic inflammation in adult mice.

Respiratory Syncytial Virus (RSV) Diseases

The respiratory syncytial virus (RSV) is an RNA virus that causes annual ARI outbreaks during winter with mild URTI in the general population, but with severe LRTI particularly among young children (bronchiolitis), patients with underlying diseases and people >65 years of age. RSV does not induce a long-lasting protective immunity and repeated infections throughout life are the norm. Basically, all children have been infected by 2 years of age and of those hospitalized, >50% are <3 months and 75% are <6 months of age. The overall CFR is 1/500. For adults ≥65 years, RSV hospitalization rates are 90–250/105. There is no specific therapy, general preventive measures include general hygiene and isolation/separation of patients. A monoclonal anti-F-protein antibody is available for passive immunization of selected high-risk children. It requires monthly injections, comes at a high cost and has limited efficacy (50% against RSV hospitalization). Active immunization failed in the past, probably as the post-fusion conformation of the F-protein was used. Long-acting monoclonal antibodies (for infants) as well as stabilized pre-fusion F-protein vaccines (for immunization of pregnant women, children, older adults) produced on various platforms are in late stages of clinical development.