The virus-antibody complexes formed during COVID-19 infection, ligate Fc receptors, activate complement, cause inflammation and trigger type III hypersensitivity. I summarize the results for FcR signaling in the activation of CD4+ T cells, platelets, and a likely contribution to brain cells. FcRs engagement by the immune complexes (ICs) triggers thrombosis and neurological disease. Anaphylatoxins C3a, and C5a produced post complement activation by the ICs cause inflammation and cell death. FcR signaling in CD4+ T cells and platelets, overly induce the gene expression of signaling pathways that drive cellular activation and differentiation. Further understanding of these mechanisms is required for understanding the pathology and the development of therapies required to manage long-term symptoms of COVID-19 disease.