Single-cell genome-wide association reveals that a nonsynonymous variant in confers increased susceptibility to influenza virus.

During pandemics, individuals exhibit differences in risk and clinical outcomes. Here, we developed single-cell high-throughput human susceptibility testing (scHi-HOST), a method for rapidly identifying genetic variants that confer resistance and susceptibility. We applied this method to influenza A virus (IAV), the cause of four pandemics since the start of the 20 century.

Divergent age-related humoral correlates of protection against respiratory syncytial virus infection in older and young adults: a pilot, controlled, human infection challenge model.

Background: Respiratory viral infections are typically more severe in older adults. Older adults are more vulnerable to infection and do not respond effectively to vaccines due to a combination of immunosenescence, so-called inflamm-ageing, and accumulation of comorbidities. Although age-related changes in immune responses have been described, the causes of this enhanced respiratory disease in older adults remain poorly understood.

Wearable Sensor-Based Detection of Influenza in Presymptomatic and Asymptomatic Individuals.

Background: The COVID-19 pandemic highlighted the need for early detection of viral infections in symptomatic and asymptomatic individuals to allow for timely clinical management and public health interventions.

Methods: Twenty healthy adults were challenged with an influenza A (H3N2) virus and prospectively monitored from 7 days before through 10 days after inoculation, using wearable electrocardiogram and physical activity sensors. This framework allowed for responses to be accurately referenced to the infection event.

Assessment of the Feasibility of Using Noninvasive Wearable Biometric Monitoring Sensors to Detect Influenza and the Common Cold Before Symptom Onset.

Importance: Currently, there are no presymptomatic screening methods to identify individuals infected with a respiratory virus to prevent disease spread and to predict their trajectory for resource allocation.

Objective: To evaluate the feasibility of using noninvasive, wrist-worn wearable biometric monitoring sensors to detect presymptomatic viral infection after exposure and predict infection severity in patients exposed to H1N1 influenza or human rhinovirus.

Design, Setting, And Participants: The cohort H1N1 viral challenge study was conducted during 2018; data were collected from September 11, 2017, to May 4, 2018.

Innate-like Gene Expression of Lung-Resident Memory CD8 T Cells during Experimental Human Influenza: A Clinical Study.

Suboptimal vaccine immunogenicity and antigenic mismatch, compounded by poor uptake, means that influenza remains a major global disease. T cells recognizing peptides derived from conserved viral proteins could enhance vaccine-induced cross-strain protection. To investigate the kinetics, phenotypes, and function of influenza virus-specific CD8 resident memory T (Trm) cells in the lower airway and infer the molecular pathways associated with their response to infection .

Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19.

While it is now widely accepted that host inflammatory responses contribute to lung injury, the pathways that drive severity and distinguish coronavirus disease 2019 (COVID-19) from other viral lung diseases remain poorly characterized. We analyzed plasma samples from 471 hospitalized patients recruited through the prospective multicenter ISARIC4C study and 39 outpatients with mild disease, enabling extensive characterization of responses across a full spectrum of COVID-19 severity. Progressive elevation of levels of numerous inflammatory cytokines and chemokines (including IL-6, CXCL10, and GM-CSF) were associated with severity and accompanied by elevated markers of endothelial injury and thrombosis.

Epitope-specific airway-resident CD4+ T cell dynamics during experimental human RSV infection.

BACKGROUNDRespiratory syncytial virus (RSV) is an important cause of acute pulmonary disease and one of the last remaining major infections of childhood for which there is no vaccine. CD4+ T cells play a key role in antiviral immunity, but they have been little studied in the human lung.METHODSHealthy adult volunteers were inoculated i.