A double edged-sword - The Complement System during SARS-CoV-2 infection

In the past 20 years, infections caused by coronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2 have posed a threat to public health since they may cause severe acute respiratory syndrome (SARS) in humans. The Complement System is activated during viral infection, being a central protagonist of innate and acquired immunity. Here, we report some interactions between these three coronaviruses and the Complement System, highlighting the central role of C3 with the severity of these infections. Although it can be protective, its role during coronavirus infections seems to be contradictory. For example, during SARS-CoV-2 infection, Complement System can control the viral infection in asymptomatic or mild cases; however, it can also intensify local and systemic damage in some of severe COVID-19 patients, due to its potent proinflammatory effect. In this last condition, the activation of the Complement System also amplifies the cytokine storm and the pathogenicity of coronavirus infection. Experimental treatment with Complement inhibitors has been an enthusiastic field of intense investigation in search of a promising additional therapy in severe COVID-19 patients.

Automated summary

In the past 20 years, coronavirus infections have been a threat to public health, with the Complement System playing a central role in innate and acquired immunity. The role of C3 in the severity of these infections is highlighted, showing conflicting effects on different cases of COVID-19 patients. Experimental treatment with Complement inhibitors is being investigated as a potential additional therapy for severe COVID-19 patients.