Anti-SARS-CoV-2 IgG from severely ill COVID-19 patients promotes macrophage hyper-inflammatory responses
Abstract
For yet unknown reasons, severely ill COVID-19 patients often become critically ill around the time of activation of adaptive immunity. Here, we show that anti-Spike IgG from serum of severely ill COVID-19 patients induces a hyper-inflammatory response by human macrophages, which subsequently breaks pulmonary endothelial barrier integrity and induces microvascular thrombosis. The excessive inflammatory capacity of this anti-Spike IgG is related to glycosylation changes in the IgG Fc tail. Moreover, the hyper-inflammatory response induced by anti-Spike IgG can be specifically counteracted in vitro by use of the active component of fostamatinib, an FDA- and EMA-approved therapeutic small molecule inhibitor of Syk.
One sentence summary Anti-Spike IgG promotes hyper-inflammation.
Competing Interest Statement
The authors have declared no competing interest.
Subject Area
- Biochemistry (11699)
- Bioengineering (8715)
- Bioinformatics (29119)
- Biophysics (14927)
- Cancer Biology (12047)
- Cell Biology (17347)
- Clinical Trials (138)
- Developmental Biology (9405)
- Ecology (14138)
- Epidemiology (2067)
- Evolutionary Biology (18261)
- Genetics (12216)
- Genomics (16760)
- Immunology (11839)
- Microbiology (27996)
- Molecular Biology (11549)
- Neuroscience (60781)
- Paleontology (450)
- Pathology (1864)
- Pharmacology and Toxicology (3228)
- Physiology (4937)
- Plant Biology (10382)
- Synthetic Biology (2876)
- Systems Biology (7332)
- Zoology (1642)