SARS-CoV-2-antibodies may promote severe COVID-19
According to a new study by Willianne Hoepel and colleagues from Amsterdam UMC, serum taken from patients with severe COVID-19 had an increased level of anti-spike IgG that helped trigger an overactive immune response in alveolar macrophages. Glycosylation with fucose was also less common in these anti-spike antibodies, making them more pro-inflammatory. Hoepel et al. also identify fostamatinib, an approved small molecule inhibitor of the protein Syk, as a drug that can counteract the hyper-inflammatory response observed in macrophages exposed to SARS-CoV-2-specific IgG.
The findings here help explain why some patients with COVID-19 become critically ill just as their bodies begin to produce antibodies against the virus. In further lab experiments, the researchers also demonstrated that macrophages that are activated by the anti-spike antibodies can disrupt lung cells in vitro and trigger tiny blood clots, similar to symptoms associated with severe COVID-19.
It is still unclear how severe SARS-CoV-2 infections lead to abnormal IgG levels and lower levels of fucosylation, but Hoepel et al. do note that these factors return to normal a few weeks after the hyperinflammatory response. This return to IgG normalcy could help explain why people who are diagnosed with COVID-19 twice do not have the same hyperinflammatory response the second time. The findings potentially also have implications for the use of convalescent plasma for treating patients with COVID-19, since that plasma may still contain the hyperinflammatory versions of IgG, the researchers conclude.
The hyperinflammatory response only occurred when the M2 carried either an FcγRI, FcγRIIa,or FcγRIII receptor. The clinical monoclomal antibody COR-101, developed by German CORAT Therapeutics thus does not carry such Fcγ receptors.