Proteomic profiling of neonatal herpes simplex virus infection on dried blood spots

Neonatal herpes simplex virus (HSV) infection is life-threatening, with a mortality of up to 70–80% when disseminated, often due to vague symptoms and delayed treatment. Neonatal screening using dried blood spot (DBS) samples is among the most impactful preventative health measures ever implemented, but screening for HSV has not been investigated. We investigated high throughput multiplexed proteomics on DBS samples collected on days 2–3 of life from a nationwide cohort of neonates with HSV infection (n = 53) and matched controls. We measured 2941 proteins using the Olink Explore 3072 panels and proximity extension assays, followed by differential protein expression by Analysis of Variance with post-hoc correction and functional annotation. Here, we show distinct protein profiles in neonates with disseminated HSV disease, with differences in 20 proteins compared to controls. These proteins are associated with innate and adaptive immune responses and cytokine activation. Our findings indicate the potential of neonatal screening for disseminated HSV disease to ensure early treatment and reduce the high mortality. Herpes simplex virus (HSV) infection in newborns has a 70% risk of death if infection becomes widespread in the body. Initial symptoms are often vague, leading to delayed treatment. Early dried blood spot (DBS) screening of newborns is very effective for identifying disorders present at birth, but its use to identify HSV infection has not been investigated. Here, we analysed DBS samples taken on days 2–3 of life from newborns developing HSV infection in the neonatal period. We identified 20 proteins that differed between those with widespread HSV infection compared to healthy babies. These findings suggest that HSV screening on DBS samples have the potential to detect severe infections early, enabling prompt treatment and reducing the risk of death. Dungu et al. use high throughput multiplexed proteomics on dried blood spot samples from neonates with herpes simplex virus infection. Distinct protein profiles were seen in proteins associated with innate and adaptive immune responses neonates with disseminated HSV disease compared to controls.