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The complement system is the first defensive response by the host innate immune system to viral pathogens, including SARS-CoV-2. SARS-CoV-2 entry results in the release of pro-inflammatory cytokines and chemical mediators to create a \u201ccytokine storm\u201d. Endothelial cell (EC) dysfunction and cell-mediated injury are also present. These factors cause an exacerbated inflammatory state. During HIV infection and PE, various complement components are elevated, causing a hyper-inflammatory state. Furthermore, EC dysfunction and cell-mediated injury are also present. The similarities in pathological aspects of these three disorders may emanate from excessive complement activation. 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