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To date there is no specific therapeutic treatment or vaccine for COVID-19 caused by the SARS-CoV-2 virus and relevant animal models that mimic human COVID-19 pathologies are lacking. We will generate two novel humanized mouse models: HuLung mice (human lung) and HIS-HuLung mice (and human immune system and human lung). Infection of HuLung and HIS-HuLung mice with SARS-CoV-2 will provide an in vivo model for viral replication and will enable the study of pathological mechanisms provoked by the anti-viral human immune responses to SARS-CoV-2.