Symptomatic SARS-CoV-2 infections display specific IgG Fc structures
Authors: Saborni Chakraborty et al.
Journal/ Pre-Print: posted on medRxiv on 18th May, 2020
Tags: Clinical, Immunology/Immunity
1. Adult symptomatic COVID-19 patients generate antibodies against SARS-CoV-2 spike RBD domain with reduced fucosylation of the Fc fragment, which can enhance binding to FcγRIIIa (CD16a).
Chakraborty and colleagues characterize antibodies against SARS-CoV-2 spike RBD domain from serum of COVID-19 patients. Isotype distribution analysis revealed that adult patients have higher titers of IgM, IgA and IgG anti-RBD antibodies in comparison with seropositive asymptomatic children. They demonstrate IgG1 anti-RBD Ab from adults have significantly reduced fucosylation in the Fc region compared to paediatric samples, specific IgG1 Ab from influenza A virus patients, and total IgG1 from healthy controls. In consequence, adult anti-RBD IgG1 show increased binding affinity to FcγRIIIa (CD16a), an Fc receptor expressed by NK cells and macrophages, as assessed by biolayer interferometry.
Impact for SARS-CoV2/COVID19 research efforts
Understand the immune response to SARS-CoV2/COVID19
Clinical symptoms and pathogenesis of SARS-Cov2/COVID19
· In vitro study
· Patient Case study
Strengths and limitations of the paper
Novelty: Symptomatic COVID-19 patients produce IgG1 Ab against viral proteins with a distinct post-translational modification that can enhance Fc receptor binding and could lead to augmented innate immune cell activation.
Standing in the field: Exacerbation of the severity of viral-induced diseases by antibodies have been so far only reported in dengue fever. Further work is required to assess if observed post-translational modification has functional consequences for the severity of COVID-19.
Appropriate statistics: Yes.
Viral model used: Serum from COVID-19 patients with SARS-CoV-2 infection confirmed by PCR
Serum samples from the controlled influenza A virus challenge study were used as a control
Recombinant SARS-CoV-2 spike RBD and full length recombinant SARS-CoV-2 spike protein used for ELISA
Translatability: Requires extensive further work for potential translation to clinical applications.
Main limitations: No functional data on Fc receptor expressing cell activation.
No data on correlation between Ab titer and Fc modification with disease severity. Comparison of severe and asymptomatic adult patient samples would be very informative.
As authors admit themselves, reduced fucosylation of IgG1 Abs might not be triggered by infection itself, but rather an inherent characteristic of susceptible individuals. It would be interesting to examine fucosylation of total IgG1 fraction from COVID-19 patients, in the course of infection and post recovery.
Only characterised glycosylation on the IgG1 isotype, not other IgG isotypes.