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Why do #COVID19 patients often become critically ill around 1.5 weeks? Our latest work (now on @biorxivpreprint) may provide an explanation (and therapy) for this: aberrant IgG antibodies. A thread on why we think this could be (very) important: https://www.biorxiv.org/content/10.1101/2020.07.13.190140v1 1/7
First, we identified that anti-Spike IgG from serum of severely ill COVID-19 patients induces a hyper-inflammatory response by lung macrophages. This closely resembles the previously described ‘cytokine storm’ observed in COVID-19 patients. Yet, it does more. 2/7
The macrophages also induce (1) long-lasting permeabilization (‘leaking’) of pulmonary blood vessels, an important cause of edema, and (2) microvascular thrombosis. Both are main symptoms of severe COVID-19. 3/7
But why are these anti-Spike antibodies so pathogenic? It turns out to be the glycosylation (sugar groups) on the IgG. Previous manuscripts already hinted towards this, check out those too: https://www.biorxiv.org/content/10.1101/2020.05.18.099507v1 and https://www.medrxiv.org/content/10.1101/2020.05.15.20103341v1 4/7
So is there any way we prevent this? Yes, there may be! We found that the drug fostamatinib can specifically counteract all of these effects. And this drug is both FDA and EMA approved, so it can be repurposed to treat COVID-19 patients. 5/7
Now what to do next? Perhaps first get fostamatinib into a clinical trial ( @RigelPharma)? Apart from that, further uncovering of this pathogenic mechanism may identify additional drugs to treat severe COVID-19. 6/7
Big thanks to all co-authors incl @WillianneHoepel @vanGilsLab @gesturv, but also the COVID-19 scientists on Twitter for their thoughts and ideas: @florian_krammer @Marc_Veld @EricTopol @p_openshaw @MiriamMerad @MC_Nawijn and most of all: @VirususImmunity. 7/7
