In order to better understand the importance and role of C5a/C5aR1 signaling on the pathophysiology of COVID-19, we moved to a well-established preclinical mouse model used to study this disease, the K18-hACE2 Tg mice (Tg mice) infected with SARS-CoV-2 (37, 38) (Figure 3A). Here, C5AR1 is linked to COVID-19.