SARS-CoV-2 Thoughts

https://github.com/cov-lineages/pango-designation/issues/188 This was always to be expected as Delta encountered a larger, more densely vaccinated population, but it's still happening with remarkable speed. There is still no change in the RBD, as I had predicted, but S:L5F is unique. It's in the signal sequence for the S protein and thought to increase viral secretion further. It is a part of B.1.526(Iota). https://europepmc.org/article/PPR/PPR180476 https://outbreak.info/situation-reports?muts=S%3AL5F Most of the others are in the S2 subunit, indicating that Delta is taking full advantage of P681R and syncytia. N1074S appears to be becoming fixed, and it had appeared in no lineage before B.1.617.2. Its increased viability is almost certainly tied to P681R given its position in the S2 subunit. https://outbreak.info/situation-reports?muts=S%3AN1074S Q613H never appeared in a really dominant A or B strain, but it was theorized to have worked in roughly the same ...

Why am I COVID-19 vaccine resistant? I believe the current versions of SARS-CoV-2 vaccines are poor, and it was always inevitable that they would become poor because of slow global vaccination rates and a use of a single, highly mutable gene, S, which makes escape easier. https://www.sciencemag.org/news/2021/08/grim-warning-israel-vaccination-blunts-does-not-defeat-delta Further, they will probably only get worse given the rate of evolution in SARS-CoV-2 today. That rate is likely to only accelerate unless we get R below 1 for all strains, which is nearly impossible if we're starting from R0's around 8 . There looms the spectre of antibody-dependent enhancement(ADE), which is a property of other betacoronaviruses. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943455/ I think other vaccines hold better promise and will not need to be administered nearly as frequently because they target other parts of the immune system or virus, and their safety profi...

The inability of Delta serum to protect against Beta/B.1.621 virus indicates that, as SAGE predicted, sufficient antigenic drift has occurred since the beginning of the pandemic such that only a bivalent vaccine can provide protection today. This is not surprising when considering that the two strains took qualitatively different paths towards immune evasion.  Delta increased the distance between two beta sheets in the RBD by 1.5 angstroms, making the energy required for antibodies to inactivate the virus greater.  Beta and B.1.621 directly modified their epitopes and relied on electrostatic, hydrophobic, or other properties to make the antibodies unable to bind.  We do not know how many other qualitatively different paths there are out there, but it's safe to assume, "a lot." This means we can't just amp up the immunogenicity of the vaccine to compensate for the evolution of the virus.  It must be bivalent as of today.  We will try to find a new t...