Challenges. The incidence of cardiovascular diseases (CVD) increases after infections, but causal mechanisms are not understood yet. Pneumonia, which can be acquired in the community (such as flu and COVID-19) or during hospitalization, is a leading cause of infectious diseases. The main idea of the Homi-lung project is to investigate the causal relationship between CVD progression and the immune and microbiome alterations observed after pneumonia. Objectives. During the Homi-lung project, we aim to i) define the medical and societal, and patient needs; ii) increase medical doctor’s knowledge of the physiological processes linking pneumonia and CVD; iii) enable early identification of patients at risk of CVD progression; and iv) preclinically develop new treatments. Implementation. The Homi-lung project will address this challenge by comparing CVD rates between patients cured of pneumonia and matched patients who had not developed pneumonia during a prospective 3-year follow-up. We will analyze longitudinal samples collected in these populations and develop new algorithms by artificial intelligence to associate host-microbiome interactions with CVD progression. We will also demonstrate the causal link between CVD progression and host-microbiome interactions in preclinical pneumonia models. The interdisciplinary and ambitious Homi-lung project brings together 8 partners from 5 EU countries, with expertise in pneumonia, CVD, immunology, microbiome, and artificial intelligence and is uniquely placed to reach these objectives. Impacts. The project will provide clinicians with robust evidence contributing to identifying patients at risk of CVD after pneumonia. By developing new biomarkers and preclinical validating treatments to TRL4, the project will contribute to improving patients’ recovery and reducing the burden of infections. This project, particularly timely after the COVID-19 pandemic crisis, will also increase European preparedness for the next pandemic.