West Nile virus transmission in Europe is critically driven by spring temperature

West Nile Virus (WNV), a flavivirus that was first isolated in Uganda in 1937, is one of the most recent emerging mosquito-borne pathogens in Europe. While its main enzootic cycle occurs between mosquitoes and birds, humans might act as incidental hosts. About 25% of the human infections develop symptoms such as fever and headache and less than 1% more severe neurological diseases, which eventually might be fatal. WNV is now endemic in many European countries, causing hundreds of human cases every year, usually towards the end of summer, with a high spatial and temporal heterogeneity. WNV transmission is largely affected by temperature. In fact, it affects mosquito population dynamics by influencing survival and developmental times. Temperature is also paramount at shaping viral circulation: warmer conditions might increase the mosquito biting rate and decrease the incubation period of the virus, thus accelerating WNV transmission. Previous studies, carried out in northern Italy, have suggested that spring temperature might play a key role at shaping WNV transmission. Specifically, warmer temperatures in April-May might amplify WNV circulation, thus increasing the risk for human transmission later in the year. To test this hypothesis, we collated publicly available data, collected by the European Centre for Disease Prevention and Control, on the number of human infections recorded in Europe between 2011 and 2019. For each region of interest and year between 2003 and 2019, daily average temperature data were obtained from the gap-free Moderate Resolution Imaging Spectroradiometer (MODIS) Land Surface Temperature (LST) maps. We quantified the relationship between human cases and spring temperature, considering both average conditions (over years 2003-2010) and deviations from the average for subsequent years (2011-2019), by applying generalized linear models. We found a significant positive association both spatially (average conditions) and temporally (deviations). The former indicates that WNV circulation is higher in usually warmer regions while the latter implies that an increase in spring temperature is positively associated with an increase of WNV transmission and could therefore be considered as an early warning to enhance surveillance and vector control. We also found a positive association between human cases and WNV detection during the previous year, which can be interpreted as an indication of the reliability of the surveillance system but also of WNV overwintering capacity. Our findings highlight that weather anomalies at the beginning of the mosquito breeding season might act as an early warning signal for public health authorities, enabling them to strengthen in advance ongoing surveillance and prevention strategies