SARS-CoV-2 Thoughts

SARS-CoV-2 is known to be a seasonal virus because the amount of viral transmission depends critically on the temperature . There are higher loads of viral inoculum that are transmitted greater distances when it's cold and absolute humidity is lower, and people are more likely to gather inside together for warmth. https://www.frontiersin.org/articles/10.3389/fpubh.2021.650493/full This is true of all strains, and we are entering autumn with a higher case count than we had last year. Also, last winter, Alpha was dominant nearly entirely alone, and it's not antigenically very distant from the original S protein. Instead, today, we now have many antigenically distant strains and variants of concern(VoCs). Check the dot plot for cross-immunoreactivity between strains in the following article. https://www.sciencemag.org/news/2021/08/new-sars-cov-2-variants-have-changed-pandemic-what-will-virus-do-next Through those two factors, we should see new domestic highs in case co...

SARS-CoV-2 caught most experts off guard with its evolutionary alacrity , but it always should have been expected to be very good at evolution despite a relatively low mutation rate . The progenitor virus(or, at least, the majority of its genome) came from bats. Bats have amazing immune systems due to their colony lifestyle in cramped quarters and their high metabolic rate. Further, coronaviruses have the longest genomes of any known +ssRNA viral family, and viruses are under constant evolutionary pressure to keep their genomes small. The genome of SARS-CoV-2 is about 30kb in length. The value of the genome was evidently great enough to compensate for that pressure. There is more highly conserved genetic material in coronaviruses than others, which in SARS-CoV-2's case means a lot of finely tunable accessory genes that screw up the immune system badly and even vicious microRNA's outside the coding regions of actual genes . SARS-CoV-2 has absolutely ingenious replicatio...

The Delta strain of SARS-CoV-2 has a longer asymptomatic period than earlier strains: around a day more. This is because it becomes detectable by PCR in 1.5 fewer days than previous strains, on average, but that is slightly counterweighted by faster symptom onset. Thus, although overall, symptoms present themselves slightly more quickly than in other strains, this still allows for longer aymptomatic transmission. https://www.nature.com/articles/d41586-021-02259-2 Although these mutations probably just generally facilitate spread, they demonstrate that the virus has the ability to adapt itself to our quarantine strategies. SARS-CoV-2 has now demonstrated that it can modify both of these timepoints -- seroconversion and symptom onset -- independently, and it can probably modify each timepoint in either direction. It's not clear just how long it can make its incubation or asymptomatic phases, though, because extension of that time could come at the cost of pathogenicity over...

Masks, in an ideal setting, produce an immense reduction in the amount of virus that passes through them, on the order of 98-99%. https://pubmed.ncbi.nlm.nih.gov/33441205/ The major issues are people not wearing them properly and people wearing poor ones, which didn't matter much early in the pandemic, where surgical or even cloth masks sufficed. https://pubmed.ncbi.nlm.nih.gov/32673300/ More infectious strains change the calculus because either a smaller number of virions is sufficient for infection or there are just more virions being expelled, and masks are a percentage reduction. A population educated on how to do a proper fit test with an N95 (or KN95) mask should see a dramatic decrease in transmission even with Alpha or Delta, although preliminary data out of Israel, where masking is mandatory indoors and outdoors, indicates that compliance or proper masking is not comprehensive or that surgical masks might not be effective enough anymore. Here is a great review ...

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...

Initially, SARS-CoV-2's focus was on improved infectiousness.  However, as the virus continues to spread, that may become less relatively important, unless it were antigenically drifting enough, in which case the focus would remain on transmissivity.  But we're seeing trends in isolates that immune escape is becoming relatively more important.  That may abruptly flip if sufficient antigenic drift occurs or the virus somehow evolves the ability to evade antibodies created against it well enough..  This will be particularly true if it exhibits better ADE through mutations. https://www.ncbi.nlm.nih.gov/ pmc/articles/PMC7943455/ Anyway, with more antibodies from vaccination and natural infection accumulating but sufficient escape from them to mutate, the virus will want to start working on the adaptive immune response so that it can reside in the body longer for better transmission, especially with its ability to form syncytia and the rapid mutation that occurs...