IgG antibodies are crucial for protection against invading pathogens. A highly conserved N-linked glycan within the IgG-Fc-tail, essential for IgG function, shows variable composition in humans. Afucosylated IgG variants are already used in anti-cancer therapeutic antibodies due to elevated binding and killing activity through Fc receptors (Fc?RIIIa). Here, we show that afucosylated IgG which are of minor abundance in humans (~6% of total IgG) are specifically formed against surface epitopes of enveloped viruses, including the S-protein of COVID-19. Furthermore, a large gap segregates intensive care patients from convalescent blood bank donors with mild symptoms and resolving symptoms unaided. This strongly suggests altered anti-COVID-19 IgG-glycosylation to be responsible for the aggravated immune response and being for morbidity and mortality. This mechanism of antibody-dependent enhancement of disease has been described by us earlier in pregnancy responses, and for Dengue virus by others, another enveloped virus with typical clinical exacerbation of immune responses leading to strong morbidity and mortality due to overactive antibody-mediated immune-responses. Here we will determine the full clinical course in hospitalized patients with relationship to outcome, link this to functional readouts, develop diagnostic tools, that can be used to optimize convalescent antibody treatment (Plasma or IVIg) of both health workers and patients.