Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity

Mads Delbo Larsen, Erik L de Graaf, Myrthe E Sonneveld, H Rosina Plomp, Jan Nouta, Willianne Hoepel, Hung-Jen Chen, Federica Linty, Remco Visser, Maximilian Brinkhaus, Tonći Šuštić, Steven W de Taeye, Arthur E H Bentlage, Suvi Toivonen, Carolien A M Koeleman, Susanna Sainio, Neeltje A Kootstra, Philip J M Brouwer, Chiara Elisabeth Geyer, Ninotska I L DerksenGertjan Wolbink, Menno de Winther, Rogier W Sanders, Marit J van Gils, Sanne de Bruin, Alexander P J Vlaar, Theo Rispens, Jeroen den Dunnen, Hans L Zaaijer, Manfred Wuhrer, C Ellen van der Schoot, Gestur Vidarsson, Amsterdam UMC COVID-19, M Bugiani

Research output: Contribution to journalArticleAcademicpeer-review


Immunoglobulin G (IgG) antibodies are crucial for protection against invading pathogens. A highly conserved N-linked glycan within the IgG-Fc tail, which is essential for IgG function, shows variable composition in humans. Afucosylated IgG variants are already used in anticancer therapeutic antibodies for their increased activity through Fc receptors (FcgRIIIa). Here, we report that afucosylated IgG (approximately 6% of total IgG in humans) are specifically formed against enveloped viruses but generally not against other antigens. This mediates stronger FcgRIIIa responses but also amplifies brewing cytokine storms and immune-mediated pathologies. Critically ill COVID-19 patients, but not those with mild symptoms, had high concentrations of afucosylated IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), amplifying proinflammatory cytokine release and acute phase responses. Thus, antibody glycosylation plays a critical role in immune responses to enveloped viruses, including COVID-19.

Original languageEnglish
Article numberabc8378
Issue number6532
Publication statusPublished - 26 Feb 2021

Cite this