Epidemiological and genetic factors affecting severe epizootic hemorrhagic disease in Spanish Holstein cattle during the Southern Europe outbreak of 2023

Epizootic hemorrhagic disease (EHD) is a non-contagious viral infection that can cause important economic losses in dairy farms. This study aimed to identify epidemiological and genetic factors influencing the susceptibility and severity of EHD in Holstein dairy cattle during the 2023 outbreak in Spain. Data from 2852 animals in 7 affected farms from 5 Spanish provinces were used. Symptoms were categorized in 5 categories: no symptoms, mild symptoms, severe symptoms and recovered, severe symptoms with aftereffects (sequelae) and severe symptoms followed by death. All animals were genotyped using the Illumina EuroG MD SNP array, and imputation to whole genome sequenced was carried out using the 1000 bull genomes data set as reference. Risk factors for EHD were explored using linear mixed effects models, as well as the loss of milk yield and culling risk probability due to severe EHD. Around 66% of animals showed EHDV antibodies, although only 25% of the sample in this study showed severe symptoms and a death rate of 2-3%. Results indicated that age was the main risk factor for severe EHD, with older cows showing higher susceptibility. Production losses were significant in cows with moderate to severe symptoms, especially if the outbreak occurred mid-lactation (up to -9 kg/d). Cows exhibiting severe symptoms demonstrated a markedly increased likelihood of being culled, with odds ratio of 10.86 (95% CI: 6.08-19.41) for cows with severe symptoms. The genetic component of EHD was evaluated using REML procedures, and a genome-wide association study was conducted to investigate genomic regions associated to the disease. A heritability of 0.08 was estimated, with some genes (AOC1, BST1, CD38, DPP6, DPYS, HOGA1, KMT2C, PIK2A, PIK3, PI4K2A) associated with the disease that were involved in immunity processes and the development of the pulmonary tree. This study underscores the genetic and epidemiological factors influencing EHD severity in dairy cattle, providing insights for managing future outbreaks and mitigating economic losses in affected regions.