PT  - JOURNAL ARTICLE
AU  - Mads Delbo Larsen
AU  - Erik L. de Graaf
AU  - Myrthe E. Sonneveld
AU  - H. Rosina Plomp
AU  - Federica Linty
AU  - Remco Visser
AU  - Maximilian Brinkhaus
AU  - Tonći Šuštić
AU  - Steven W. de Taeye
AU  - Arthur E.H. Bentlage
AU  - Jan Nouta
AU  - Suvi Natunen
AU  - Carolien A. M. Koeleman
AU  - Susanna Sainio
AU  - Neeltje A. Kootstra
AU  - Philip J.M. Brouwer
AU  - Rogier W. Sanders
AU  - Marit J. van Gils
AU  - Sanne de Bruin
AU  - Alexander P.J. Vlaar
AU  - Amsterdam UMC COVID-19 biobank study group
AU  - Hans L. Zaaijer
AU  - Manfred Wuhrer
AU  - C. Ellen van der Schoot
AU  - Gestur Vidarsson
TI  - Afucosylated immunoglobulin G responses are a hallmark of enveloped virus infections and show an exacerbated phenotype in COVID-19
AID  - 10.1101/2020.05.18.099507
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.05.18.099507
4099  - http://biorxiv.org/content/early/2020/05/18/2020.05.18.099507.short
4100  - http://biorxiv.org/content/early/2020/05/18/2020.05.18.099507.full
AB  - 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 for their elevated binding and killing activity through Fc receptors (FcγRIIIa). Here, we report that afucosylated IgG which are of minor abundance in humans (∼6% of total IgG) are specifically formed against surface epitopes of enveloped viruses after natural infections or immunization with attenuated viruses, while protein subunit immunization does not elicit this low fucose response. This can give beneficial strong responses, but can also go awry, resulting in a cytokine-storm and immune-mediated pathologies. In the case of COVID-19, the critically ill show aggravated afucosylated-IgG responses against the viral spike protein. In contrast, those clearing the infection unaided show higher fucosylation levels of the anti-spike protein IgG. Our findings indicate antibody glycosylation as a potential factor in inflammation and protection in enveloped virus infections including COVID-19.Competing Interest StatementThe authors have declared no competing interest.