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Whereas most infants infected with respiratory syncytial virus (RSV) show no or only mild symptoms, an estimated 3 million children under five are hospitalized annually due to RSV disease. This study aimed to investigate biological mechanisms and associated biomarkers underlying RSV disease heterogeneity in young infants, enabling the potential to objectively categorize RSV‐infected infants according to their medical needs. Immunophenotypic and functional profiling demonstrated the emergence of immature and progenitor‐like neutrophils, proliferative monocytes (HLA‐DRLow, Ki67+), impaired antigen‐presenting function, downregulation of T cell response and low abundance of HLA‐DRLow B cells in severe RSV disease. HLA‐DRLow monocytes were found as a hallmark of RSV‐infected infants requiring hospitalization. Complementary transcriptomics identified genes associated with disease severity and pointed to the emergency myelopoiesis response. These results shed new light on mechanisms underlying the pathogenesis and development of severe RSV disease and identified potential new candidate biomarkers for patient stratification. [ABSTRACT FROM AUTHOR]

Respiratory viruses are a common cause of morbidity and mortality around the world. Viruses like influenza, RSV, and most recently SARS‐CoV‐2 can rapidly spread through a population, causing acute infection and, in vulnerable populations, severe or chronic disease. Developing effective treatment and prevention strategies often becomes a race against ever‐evolving viruses that develop resistance, leaving therapy efficacy either short‐lived or relevant for specific viral strains. On June 29 to July 2, 2022, researchers met for the Keystone symposium "Respiratory Viruses: New Frontiers." Researchers presented new insights into viral biology and virus–host interactions to understand the mechanisms of disease and identify novel treatment and prevention approaches that are effective, durable, and broad. [ABSTRACT FROM AUTHOR]

Complement, a critical defence against pathogens, has been implicated as a driver of pathology in COVID‐19. Complement activation products are detected in plasma and tissues and complement blockade is considered for therapy. To delineate roles of complement in immunopathogenesis, we undertook the largest comprehensive study of complement in COVID‐19 to date, comprehensive profiling of 16 complement biomarkers, including key components, regulators and activation products, in 966 plasma samples from 682 hospitalized COVID‐19 patients collected across the hospitalization period as part of the UK ISARIC4C (International Acute Respiratory and Emerging Infection Consortium) study. Unsupervised clustering of complement biomarkers mapped to disease severity and supervised machine learning identified marker sets in early samples that predicted peak severity. Compared to healthy controls, complement proteins and activation products (Ba, iC3b, terminal complement complex) were significantly altered in COVID‐19 admission samples in all severity groups. Elevated alternative pathway activation markers (Ba and iC3b) and decreased alternative pathway regulator (properdin) in admission samples were associated with more severe disease and risk of death. Levels of most complement biomarkers were reduced in severe disease, consistent with consumption and tissue deposition. Latent class mixed modelling and cumulative incidence analysis identified the trajectory of increase of Ba to be a strong predictor of peak COVID‐19 disease severity and death. The data demonstrate that early‐onset, uncontrolled activation of complement, driven by sustained and progressive amplification through the alternative pathway amplification loop is a ubiquitous feature of COVID‐19, further exacerbated in severe disease. These findings provide novel insights into COVID‐19 immunopathogenesis and inform strategies for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to assess the impact of treatment with dexamethasone, remdesivir or both on neurological complications in acute coronavirus diease 2019 (COVID‐19). Methods: We used observational data from the International Severe Acute and emerging Respiratory Infection Consortium World Health Organization (WHO) Clinical Characterization Protocol, United Kingdom. Hospital inpatients aged ≥18 years with laboratory‐confirmed severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) infection admitted between January 31, 2020, and June 29, 2021, were included. Treatment allocation was non‐blinded and performed by reporting clinicians. A propensity scoring methodology was used to minimize confounding. Treatment with remdesivir, dexamethasone, or both was assessed against the standard of care. The primary outcome was a neurological complication occurring at the point of death, discharge, or resolution of the COVID‐19 clinical episode. Results: Out of 89,297 hospital inpatients, 64,088 had severe COVID‐19 and 25,209 had non‐hypoxic COVID‐19. Neurological complications developed in 4.8% and 4.5%, respectively. In both groups, neurological complications were associated with increased mortality, intensive care unit (ICU) admission, worse self‐care on discharge, and time to recovery. In patients with severe COVID‐19, treatment with dexamethasone (n = 21,129), remdesivir (n = 1,428), and both combined (n = 10,846) were associated with a lower frequency of neurological complications: OR = 0.76 (95% confidence interval [CI] = 0.69–0.83), OR = 0.69 (95% CI = 0.51–0.90), and OR = 0.54 (95% CI = 0.47–0.61), respectively. In patients with non‐hypoxic COVID‐19, dexamethasone (n = 2,580) was associated with less neurological complications (OR = 0.78, 95% CI = 0.62–0.97), whereas the dexamethasone/remdesivir combination (n = 460) showed a similar trend (OR = 0.63, 95% CI = 0.31–1.15). Interpretation: Treatment with dexamethasone, remdesivir, or both in patients hospitalized with COVID‐19 was associated with a lower frequency of neurological complications in an additive manner, such that the greatest benefit was observed in patients who received both drugs together. ANN NEUROL 2023;93:88–102 [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the association of obesity with in-hospital coronavirus disease 2019 (COVID-19) outcomes in different ethnic groups.Methods: Patients admitted to hospital with COVID-19 in the United Kingdom through the Clinical Characterisation Protocol UK (CCP-UK) developed by the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) were included from February 6 to October 12, 2020. Ethnicity was classified as White, South Asian, Black, and other minority ethnic groups. Outcomes were admission to critical care, mechanical ventilation, and in-hospital mortality, adjusted for age, sex, and chronic diseases.Results: Of the participants included, 54,254 (age = 76 years; 45.0% women) were White, 3,728 (57 years; 41.1% women) were South Asian, 2,523 (58 years; 44.9% women) were Black, and 5,427 (61 years; 40.8% women) were other ethnicities. Obesity was associated with all outcomes in all ethnic groups, with associations strongest for black ethnicities. When stratified by ethnicity and obesity status, the odds ratios for admission to critical care, mechanical ventilation, and mortality in black ethnicities with obesity were 3.91 (3.13-4.88), 5.03 (3.94-6.63), and 1.93 (1.49-2.51), respectively, compared with White ethnicities without obesity.Conclusions: Obesity was associated with an elevated risk of in-hospital COVID-19 outcomes in all ethnic groups, with associations strongest in Black ethnicities. [ABSTRACT FROM AUTHOR]

The first report to detail infection in children found only 9 cases of COVID-19 in children; 7 were female and none required intensive care support, potentially indicating that children may be less susceptible to infection and/or symptomatic disease [[10]]. Like SARS-CoV-2, SARS and MERS coronaviruses are thought to have originated from bats and transmitted to humans from an intermediate host, civets and dromedary camels respectively. There are currently no specific anti-COVID-19 therapies but over 80 clinical treatment trials have been initiated to tackle COVID-19 [[18]]. The SARS and MERS epidemics have put us in a better position to respond to COVID-19. [Extracted from the article]