Determining the protection an individual has to SARS-CoV-2 variants of concern (VoC) is crucial for future immune surveillance, vaccine development and understanding the changing immune response. We devised a more informative assay to current ELISA based serology using multiplexed, baited, targeted-proteomics for direct detection of multiple proteins in the SARS-CoV-2 anti-spike antibody immunocomplex. Serum from individuals collected after infection, or first and second dose vaccination demonstrate this approach shows concordance with existing serology and neutralisation. Our assays show altered responses of both immunoglobulins and complement to the Alpha (B.1.1.7), Beta (B.1.351) and Delta (B.1.617.1) VoC. and a reduced response to Omicron (B1.1.1529). We were able to identify individuals who had prior infection, and observed that C1q is closely associated with IgG1 (r>0.82) and may better reflect neutralisation to VoC. Analysing additional immunoproteins beyond IgG, provides important information about our understanding of the response to infection and vaccination.