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E Math's avatar

I think the concern following the results in the Harvard/Brigham paper is that they have shown that there is S1 in the plasma, i.e. not confined simply to expression on the surface of cells. When people have expressed concern about the vaccines in terms of "is spike by itself dangerous", the expert answer has been "the spike only appears partially extruded on a cell surface", i.e. it can't get to the lungs, the vascular epithelium, etc. The paper shows that is not correct, which in turn suggests we don't completely know all the downstream consequences.

The larger theoretical concern, in my view, with the mRNA vaccines is that the set of cells that can be "transfected" by the lipid nanoparticles (LPNs) is essentially all cells, in distinction to the SARS2 virus, which can only infect cells with ACE2 receptors. In other words, any cell that the LPNs reach can end up expressing spike on its surface, and thereby invite immune attack. So it matters very much that the belief is that this will be mainly local muscle, and next most-likely local lymph nodes. But we also know that with decreasing probability (per animal study) the LPNs reach essentially every organ including the brain and the bone marrow. The other thing I find interesting is that the kinds of adverse events that are beginning to emerge as related (I have more ideas about how to do that analysis better) are of the type and range you might expect if caused by comparatively uncommon but diverse instances of mRNA getting around: eg myocarditis (heart cells), thrombosis (vascular epithelium, platelets, perhaps bone marrow), various forms of neuritis (ocular, vestibular, peripheral) via nerve cells, and so on. To get a handle on the range of adverse effects you need to collate all of these, since they each present as a unique type of relatively rare event. But they do have in common the potential mechanism of targeted inflammation and/or cell damage that would be caused by spike expression in a particular cell type.

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Amagnono's avatar

All of this jives with my casual exploration of the data. The vaccine seems quite safe for most in the short term. For those with significant risk factors for poor Covid outcomes, the vaccine seems a very reasonable option. The question of both long-term efficacy and long-term negative effects is still in question, particularly for those cohorts excluded from the initial trials, i.e. the young, pregnant women, those who have had Covid, etc.

It is truly remarkable that we were able to develop this vaccine so quickly and that it appears to have such a high level of efficacy. It is however unconscionable that governments, public health officials, businesses and schools would advise those with low risks or (and more disturbingly) compel *anyone,* regardless of their risk profile, to accept what is still a very new bit of technology.

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