In vitro complement activation via nucleocapsid and spike proteins of SARS-CoV-2 in COVID-19 patients

In the overactivation of the complement, the role of classical pathway is still not thoroughly investigated in COVID-19. Our aim was to examine the connection between SARS-CoV-2-specific antibodies, in vitro complement activation, and in vivo complement profiles in COVID-19 severity groups. Significant differences were detected in the in vitro complement deposition (C3b and C4b) between patients with or without SARS-CoV-2-specific antibodies in each COVID-19 severity group. Interestingly, we could detect in vitro complement depositions via nucleocapsid (N) protein without N-specific antibodies. Furthermore, no differences were detected in the levels of specific antibodies among the whole COVID-19 groups. In vitro complement activation by spike (S) protein was only detected with high S-specific IgG. Next, in vivo complement biomarkers were compared in samples with low or high C3b, C4b depositions. Although, SARS-CoV-2-specific IgG and IgM were strongly associated with in vitro complement deposition, it was only C3a and factor B that was elevated in samples with high in vitro N-induced C3b deposition. In conclusion, in vitro C3b and C4b depositions by S- and N-proteins were associated with the presence of SARS-CoV-2-specific antibodies. Furthermore, convalescence and severely ill patients with specific antibodies showed slight difference in in vitro C4b deposition via nucleocapsid protein.