Proinflammatory IgG Fc structures in patients with severe COVID-19
Chakraborty S, Gonzalez J, Edwards K, Mallajosyula V, Buzzanco AS, Sherwood R, Buffone C, Kathale N, Providenza S, Xie MM, Andrews JR, Blish CA, Singh U, Dugan H, Wilson PC, Pham TD, Boyd SD, Nadeau KC, Pinsky BA, Zhang S, Memoli MJ, Taubenberger JK, Morales T, Schapiro JM, Tan GS, Jagannathan P, Wang TT
Severe acute respiratory syndrome coronavirus 2 infections can cause coronavirus disease 2019 (COVID-19), which manifests with a range of severities from mild illness to life-threatening pneumonia and multi-organ failure. Severe COVID-19 is characterized by an inflammatory signature, including high levels of inflammatory cytokines, alveolar inflammatory infiltrates and vascular microthrombi. Here we show that patients with severe COVID-19 produced a unique serologic signature, including an increased likelihood of IgG1 with afucosylated Fc glycans. This Fc modification on severe acute respiratory syndrome coronavirus 2 IgGs enhanced interactions with the activating Fcγ receptor FcγRIIIa; when incorporated into immune complexes, Fc afucosylation enhanced production of inflammatory cytokines by monocytes, including interleukin-6 and tumor necrosis factor. These results show that disease severity in COVID-19 correlates with the presence of proinflammatory IgG Fc structures, including afucosylated IgG1.