Several people asked me for highlights of the #longcovid Keystone conference #KSLongCoVID24. I’ll mention a few, personal, highlights. 1/x #KSLongCoVID24 highlight #1. First, the fact that we finally have a dedicated #longcovid meeting! Really feels like this research field has finally started, with scientists meeting each other for the 1st time. Let’s hope many meetings will follow (@KeystoneSymp 😉) 2/x

We previously showed that IgG antibodies strongly promote inflammation in severe COVID-19. But what about IgG induced by mRNA vaccines? Fortunately, no pathogenic IgG response there: biorxiv.org/content/10.110…. A thread. 1/7 In severe COVID-19, IgG induces inflammation because of two things: (1) different glycosylation of the antibody’s Fc tail (low fucose, high galactose) (2) enormous amounts of this IgG. Upon mRNA vaccination, these both happen, BUT: not simultaneously. 2/7

Why do #COVID19 patients become critically ill after around 1.5 weeks? Our @ScienceTM publication provides an explanation (and potential therapy). See our movie+article+thread for why we think this could be (very) important: 1/14 Super-short summary: We found (1) Why we become so sick (-> aberrant antibodies against Spike) (2) A drug that can counteract this (-> fostamatinib). Paper: stm.sciencemag.org/lookup/doi/10.… Now let’s go for some more detail. 2/14

Aberrant #glycosylation of anti-Spike antibodies promotes #thrombosis as observed in severely ill #COVID19 patients. Very interesting work from our collaborators in the UK: biorxiv.org/content/10.110…. A few thoughts on why this could be important. 1/4 Severely ill patients make IgG with aberrant glycosylation. We previously showed that this (over)activates lung macrophages, which in turn activates endothelium, which in turn activates platelets. But this paper shows that the antibodies (over)activate platelets directly! 2/4

IgG subclasses (IgG1/2/3/4) promote pathogen-specific immunity: jimmunol.org/content/early/…. Congratulations @WillianneHoepel @sona_all on this great work @J_Immunol. A small thread to summarize these findings and their potential implications 1/6 IgG antibodies come in 4 different flavors, known as subclasses: IgG1/2/3/4. According to the current paradigm, IgG3 is the most inflammatory subclass, while IgG2 and IgG4 are sometimes even considered to be anti-inflammatory. But that paradigm now seems to be outdated. 2/6

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: biorxiv.org/content/10.110… 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