Murine Parainfluenza Virus Persists in Lung Innate Immune Cells Sustaining Chronic Lung Pathology.

Respiratory viruses including the human parainfluenza viruses (hPIVs) are a constant burden to human health, with morbidity and mortality frequently increased after the acute phase of the infection. Although is proven that respiratory viruses can persist in vitro, the mechanisms of virus or viral products persistence, their sources, and their impact on chronic respiratory diseases in vivo are unknown. Here, we used Sendai virus (SeV) to model hPIV infection in mice and test whether virus persistence associates with the development of chronic lung disease. Following SeV infection, virus products were detected in lung macrophages, type 2 innate lymphoid cells (ILC2s) and dendritic cells for several weeks after the infectious virus was cleared. Cells containing viral protein showed strong upregulation of antiviral and type 2 inflammation-related genes that associate with the development of chronic post-viral lung diseases, including asthma. Lineage tracing of infected cells or cells derived from infected cells suggests that distinct functional groups of cells contribute to the chronic pathology. Importantly, targeted ablation of infected cells or those derived from infected cells significantly ameliorated chronic lung disease. Overall, we identified persistent infection of innate immune cells as a critical factor in the progression from acute to chronic post viral respiratory disease.

SARS-CoV-2-triggered neutrophil extracellular traps mediate COVID-19 pathology.

Severe COVID-19 patients develop acute respiratory distress syndrome that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that neutrophil extracellular traps (NETs) have been described as important mediators of tissue damage in inflammatory diseases, we investigated whether NETs would be involved in COVID-19 pathophysiology. A cohort of 32 hospitalized patients with a confirmed diagnosis of COVID-19 and healthy controls were enrolled. The concentration of NETs was augmented in plasma, tracheal aspirate, and lung autopsies tissues from COVID-19 patients, and their neutrophils released higher levels of NETs. Notably, we found that viable SARS-CoV-2 can directly induce the release of NETs by healthy neutrophils. Mechanistically, NETs triggered by SARS-CoV-2 depend on angiotensin-converting enzyme 2, serine protease, virus replication, and PAD-4. Finally, NETs released by SARS-CoV-2-activated neutrophils promote lung epithelial cell death in vitro. These results unravel a possible detrimental role of NETs in the pathophysiology of COVID-19. Therefore, the inhibition of NETs represents a potential therapeutic target for COVID-19.

Circulation profile of respiratory viruses in symptomatic and asymptomatic children from Midwest Brazil.

Acute respiratory infection (ARI) is a major cause of morbidity and mortality worldwide. Most of these infections are caused by viruses. Infections pose as important triggers of acute episodes of chronic respiratory diseases (CRD). This study sought to evaluate the frequency and circulation profile of respiratory viruses among ARI symptomatic patients and completely asymptomatic children in Midwest Brazil. The study enrolled symptomatic children with and without ARI symptoms. During 1 year, 225 nasal respiratory samples were obtained from patients aged 4-14 years old. The samples were screened by multiplex nested-PCR for 16 common respiratory viruses. From 225 samples, 42 had at least one virus detected. Samples from four different patients had multiple viruses detected. The viral detection rate in symptomatic (20.1%) and asymptomatic patients (14.8%) showed no significant difference. The most frequent viruses detected were rhinovirus (28.6%), FLUA (11.9%), adenovirus (11.9%), human bocavirus (HBoV) (11.9%), and respiratory syncytial virus (RSV) antigenic group A (9.5%). Monthly detection rate was higher during the rainy season. RSVs were detected during the months with higher rainfall indexes and higher air humidity, while FLU and HBoV were detected during the winter months. The obtained results reinforce the importance of viral pathogens in pediatric population, emphasizing similar viral occurrence in symptomatic and asymptomatic children.

Detection of Influenza A(H3N2) Virus RNA in Donated Blood.

Influenza A virus infection has rarely been documented to cause viremia. In 28 blood donations in Brazil that were deferred because of postdonation information, we identified influenza A(H3N2) virus RNA in 1 donation using metagenomic analysis. Our finding implies theoretical risk for viremia and transfusion transmission.