Infants display reduced NK cell responses in RSV and increased inflammatory responses in SARS-CoV-2 infections

Caution: This preprint is a work in progress that has not been peer-reviewed. It should not be relied upon to guide clinical practice or health behaviors, and it should not be reported in news media as established information. We will update this web page if this preprint becomes a peer-reviewed publication. (Not all research reports move past the preprint stage.)

View Preprint on PubMed

Published

January 2025

Journal

Research Square

Abstract

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection hospitalizations in infants and poses a significantly higher risk of respiratory failure than SARS-CoV-2. The mechanisms underlying these differences remain unclear. We analyzed blood samples from infants (median age 2.3 months) with SARS-CoV-2 (n = 30), RSV (n = 19), and healthy controls (n = 17) using single-cell transcriptomics and epigenomics, and cytokine profiling. Both viruses triggered comparable interferon responses across PBMC subsets but differed in NK cell and inflammatory responses. Severe RSV cases showed reduced NK cell frequencies, lower IFNG expression, and decreased chromatin accessibility at T-BET and EOMES binding sites. RSV infections were also associated with increased CD4+ TEMRA, memory Treg and transitional B cells. In contrast, SARS-CoV-2 was characterized by stronger pro-inflammatory signatures, including increased NFKB pathway activity and higher serum TNF concentrations. These findings highlight distinct immune responses to RSV and SARS-CoV-2, providing insights that may inform clinical decisions.

Authors

Duygu Ucar, Asa Thibodeau, Asuncion Mejias, Djamel Nehar-Belaid, Radu Marches, Zhaohui Xu, Giray Eryilmaz, Steven Josefowicz, Silke Paust, Virginia Pascual, Jacques Banchereau, Octavio Ramilo

Keywords

Not available