Our data suggest that interactions between RSV and nasopharyngeal microbiota might modulate the host immune response, potentially affecting clinical disease severity.

Summary Severe disease of SARS-CoV-2 is characterized by vigorous inflammatory responses in the lung, often with a sudden onset after 5–7 days of stable disease. Efforts to modulate this hyperinflammation and the associated acute respiratory distress syndrome rely on the unraveling of the immune cell interactions and cytokines that drive such responses. Given that every patient is captured at different stages of infection, longitudinal monitoring of the immune response is critical and systems-level analyses are required to capture cellular interactions. Here, we report on a systems-level blood immunomonitoring study of 37 adult patients diagnosed with COVID-19 and followed with up to 14 blood samples from acute to recovery phases of the disease. We describe an IFNγ-eosinophil axis activated before lung hyperinflammation and changes in cell-cell co-regulation during different stages of the disease. We also map an immune trajectory during recovery that is shared among patients with severe COVID-19.

Oseltamivir treatment started within 24 hours of symptom onset provides substantial benefits to children with influenza A infection. Clinical trials registration. ClinicalTrials.gov identifier: NCT00593502.

Rationale: Rhinoviruses (RVs) are a major cause of symptomatic respiratory tract infection in all age groups. However, RVs can frequently be detected in asymptomatic individuals.Objectives: To evaluate the ability of host transcriptional profiling to differentiate between symptomatic RV infection and incidental detection in children.Methods: Previously healthy children younger than 2 years old (n = 151) were enrolled at four study sites and classified into four clinical groups: RV2 healthy control subjects (n = 37), RV1 asymptomatic subjects (n = 14), RV1 outpatients (n = 30), and RV1 inpatients (n = 70). Host responses were analyzed using whole-blood RNA transcriptional profiles.Measurements and Main Results: RV infection induced a robust transcriptional signature, which was validated in three independent cohorts and by quantitative real-time polymerase chain reaction with high prediction accuracy. The immune profile of symptomatic RV infection was characterized by overexpression of innate immunity and underexpression of adaptive immunity genes, whereas negligible changes were observed in asymptomatic RV1 subjects. Unsupervised hierarchical clustering identified two main clusters of subjects. The first included 93% of healthy control subjects and 100% of asymptomatic RV1 subjects, and the second comprised 98% of RV1 inpatients and 88% of RV1 outpatients. Genomic scores of healthy control subjects and asymptomatic RV1 children were similar and significantly lower than those of RV1 inpatients and outpatients (P , 0.0001).Conclusions: Symptomatic RV infection induced a robust and reproducible transcriptional signature, whereas identification of RV in asymptomatic children was not associated with significant systemic transcriptional immune responses. Transcriptional profiling represents a useful tool to discriminate between active infection and incidental virus detection.