Intranasal infection of k18-hACE2 mice with SARS-CoV-2 recapitulates the clinical characteristics present in severe COVID-19. Here, we present a protocol for intranasal administration of SARS-CoV-2 to k18-hACE2 mice and their subsequent daily monitoring. We describe steps for intranasal inoculation of SARS-CoV-2 and the collection of clinical scores on weight, body condition, hydration, appearance, neurological symptoms, behavior, and respiratory movements. This protocol contributes to the establishment of a model of severe SARS-CoV-2 infection that minimizes animal suffering. For complete details on the use and execution of this protocol, please refer to Gonçalves et al. (2023)..
