Inconsistent Increase in Age at Respiratory Syncytial Virus Hospitalization of Children Aged <2 Years During the Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic: A Retrospective Multicenter Study in 4 European Countries.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic disrupted respiratory syncytial virus (RSV) seasonality. To optimize the use and evaluation of RSV infant immunization strategies, monitoring changes in RSV epidemiology is essential. METHODS: Hospitalizations for acute respiratory infections (ARIs) and RSV-coded ARI in children <2 years were extracted in 4 European hospitals, according to predefined case definitions (International Classification of Diseases, Tenth Revision codes). Prepandemic RSV seasons (2017-2018 to 2019-2020) were compared to 2021-2022 and 2022-2023. RESULTS: In 2021-2022 and 2022-2023, the peak number of RSV hospitalizations was higher than prepandemic peaks after short periods of RSV circulation, and lower than prepandemic peaks after long periods of RSV circulation. A greater proportion of RSV hospitalizations occurred in children 1 to <2 years in 2021-2022 in the Netherlands (18% vs 9%, P = .04). No increase in age was observed elsewhere. High-risk children represented a greater proportion of RSV hospitalizations during the pandemic. The proportion of pediatric intensive care unit admissions did not increase. CONCLUSIONS: A decrease in population immunity has been linked to older age at RSV hospitalization. We did not observe an increase in age in 3 of the 4 participating countries. Broad age categories may have prevented detecting an age shift. Monitoring RSV epidemiology is essential as Europe implements RSV immunization.

Natural variability of TRAIL, IP-10, and CRP in healthy adults - The "HERACLES" study.

A novel host-protein score (called MMBV) helps to distinguish bacterial from viral infection by combining the blood concentrations of three biomarkers: tumour necrosis factor related apoptosis inducing ligand (TRAIL), interferon gamma induced protein 10 (IP-10), and C-reactive protein (CRP). These host biomarkers are differentially expressed in response to bacterial versus viral acute infection. We conducted a prospective study, with a time series design, in healthy adult volunteers in the Netherlands. The aim was to determine the variability of TRAIL, IP-10, and CRP and the MMBV score in healthy adults across time. Up to six blood samples were taken from each healthy volunteer over a period of up to four weeks. In 77 healthy participants without recent or current symptoms, MMBV scores (maximal) were bacterial in 1.3 % and viral (or other non-infectious etiology) in 93.5 % of participants. There was little variation in the mean concentrations of TRAIL (74.5 pg/ml), IP-10 (113.6 pg/ml), and CRP (1.90 mg/L) as well as the MMBV score. The variability of biomarker measurement was comparable to the precision of the measurement platform for TRAIL, IP-10, and CRP. Our findings establish the mean values of these biomarkers and MMBV in healthy individuals and indicate little variability between and within individuals over time, supporting the potential utility of this novel diagnostic to detect infection-induced changes.

A systematic review on global RSV genetic data: Identification of knowledge gaps.

Respiratory syncytial virus (RSV) is a major health problem. A better understanding of the geographical and temporal dynamics of RSV circulation will assist in tracking resistance against therapeutics currently under development. Since 2015, the field of RSV molecular epidemiology has evolved rapidly with around 20-30 published articles per year. The objective of this systematic review is to identify knowledge gaps in recent RSV genetic literature to guide global molecular epidemiology research. We included 78 studies published between 2015 and 2020 describing 12,998 RSV sequences of which 8,233 (63%) have been uploaded to GenBank. Seventeen (22%) studies were performed in low- and middle-income countries (LMICs), and seven (9%) studies sequenced whole-genomes. Although most reported polymorphisms for monoclonal antibodies in clinical development (nirsevimab, MK-1654) have not been tested for resistance in neutralisation essays, known resistance was detected at low levels for the nirsevimab and palivizumab binding site. High resistance was found for the suptavumab binding site. We present the first literature review of an enormous amount of RSV genetic data. The need for global monitoring of RSV molecular epidemiology becomes increasingly important in evaluating the effectiveness of monoclonal antibody candidates as they reach their final stages of clinical development. We have identified the following three knowledge gaps: whole-genome data to study global RSV evolution, data from LMICs and data from global surveillance programs.