Thread by @TimothyChase

@lalani_safina (1/n) They actually*replicate* in a host, but transmission, at least by droplets or aerosols tends to work better at lower temperatures because the air is dryer (the humidity of saturation roughly doubles with every 10°C, droplets tend to lose moisture, virus particles...

@lalani_safina (2/n) and remain aloft longer. Or at least that is how it works with the flu. But if everyone is immunologically naive to the pathogen then transmission can remain high even in warm weather. This is, is I remember correctly, with the "Spanish" flu that started in Kansas...

@lalani_safina (3/n) during it's second wave. And it has been what we have been seeing so far with the SARS-CoV-2, which so far has shown less dependence upon the season. At the same time, there is another seasonal effect, one less dependent upon the absolute humidity: the extent...

@lalani_safina (4/n) to which we tend to remain indoors. this often coincides with temperature, but not always. for example, Brazil had it's big wave with P.1 (Gamma) during it's summer. But it was the heat that drive people inside. Oh, and lest I forget, flu season, according to...

@lalani_safina (5/n) one recent study at least, terms to start with cooler weather, that is where the maximum temperature is sufficiently close to freezing for several days, but once it starts it it's less dependent upon temperature.

It is also worth noting that, at least according to...

@lalani_safina (6/n) another recent study the flu had adapted to cooler temperatures, being better able to withstand them without drying out.

@lalani_safina (7/n) SARS-CoV-2 may be less hearty in this regard. But another thing that may be working in Delta's favor is it's especially strong binding binding due to its T478K mutation with it's especially high binding free energy as well as L453R. B.1.617, B.1.617.1 and B.1.617.3...

@lalani_safina (8/n) all had E484Q which had nearly the same immune escape as E484K, but unlike the latter it is neutral and binds to the receptor by means of weak hydrogen bonds. Additionalyl, we had worried that it's immune escape and that of L452R would be additive. But in fact while...

@lalani_safina (9/n) the combination have a slightly higher immune escape than either mutation in isolation from the other, it is by no means additive and does not make up for the weaker binding to the ACE2 receptor by the E485Q substitution.

@lalani_safina (10/n) L452R does to some extent, but only partially. Losing the E484Q in favor of T478K, B.1.617.2 binds more strongly to the receptor and has more immune escape due to its positive charge.

@lalani_safina (11/n) the big mutation that has fueled the success of the B.617[.*] lineages has been the P681R mutation. The other Variants of Concern are better able to create syncytia in the lungs than the earlier variants, where syncytia are multinucleated cells in which the virus...

@lalani_safina (12/n) the virus is able to replicate, and which also give the virus the la kill mechanism that it is able to use against some white blood cells (both CD8+ and CD4+ bit preferentially the former), but B.1.617.2 is especially good at this. This is due to its ability to...

@lalani_safina (13/n): cleave the spike (poly-)protein into the S1 and S2 proteins where the first attached to the receptor but the second fuses the capsid and cell membranes. This ability to cleave the two fusion proteins results in quicker growing, larger and more numerous syncytia...

@lalani_safina (14/n) that are widely believed to lead to more severe disease. This also likely leads to more virions in aerosols produced in the lungs. However, the more efficient cleavage undoubtedly plays the central role in achieving high viral loads in the nasal cavity and...

@lalani_safina (15/n) and upper throat. 1000(+)X that of the original lineage. According to several recent studies, the viral loads (measured indirectly by means of PCR based amplification CT (cycle thresholds) for measuring the presence of the virus , vaccinated and unvaccinated...

@lalani_safina (16/n) cases of infection have roughly the same viral load in the nasal cavity. (Another study, in this case, large scale had concluded that levels are somewhat lower with vaccinated individuals.) As peak transmission occurs with the onset of symptoms, at least with...

@lalani_safina (17/n) subclinical and symptomatic individuals, rate of transmission is thought to be roughly the same during this period. And given that rate of transmission is so high for non-asymptomatic fully-vaccinated individuals (and to a lesser extent, asymptomatic nonvaccinated and...

@lalani_safina (18/n) fully vaccinated. Now early on in the infection the nose and to a lesser extent upper throat serve as the beachead for the viral invasion. This is partly due to the high density of ACE2 receptors. The virus is better able to establish infection there, then follows...

@lalani_safina (19/n) a diminishing gradient to the lungs. In contrast, there are low levels of antibodies in the upper respiratory system and a rising gradient as one approaches the lungs.This is why vaccines are less effective at preventing symptomatic infection and mild illness to...

@lalani_safina (20/n) the vaccinated with effectiveness against infection at 50% and mild infection at 60%, at least according to one recent study with results that lie between other studies.

@lalani_safina (21/n) In any case, with these advantages, Delta has a high transmissibility, conservatively 45% higher that Alpha (b.1.1.7) which itself has a much higher transmissibility than the original lineage, conservatively 60% above, which means that the transmissibility of Delta...

@lalani_safina (22/n) is roughly 230% that of the original ("wild type") lineage. This combined with it's greater ability to infect fully vaccinated individuals, better hide from antibodies, and use lysosomes (high pH organelles) for cell-in-cell killing of t-cell CD8+ and CD4+ in syncytia...

@lalani_safina (23/n) and immune escape results in a higher r0, where r0 is the average number of individuals an infected individual infects. This is I believe roughly somewhere between 6 and 9, currently, even given the current rate of vaccination in the United States.

@lalani_safina (24/n) In any case, so far the virus keeps reinventing itself, and as such had avoided becoming season, at least so far. However, there are a few antibodies effective against the major variants of concern that were recently discovered in early convalescent plasma, one of...

@lalani_safina (25/n) of which appears especially effective against Delta, there is another bank-antibody found in llamas, which (presumably) could be cheaply made-produced, and there are different approaches to vaccines, including pan-betacoronavirus antibody based that target highly...

@lalani_safina (26/n) conserved epitopes, t-cell based vaccines, and of delivery: the combination of periodic nasal spray antibody delivery with the the traditional muscle injection.

@lalani_safina PS I believe that was the last of the thread.

@lalani_safina CORRECTION to 24... "season" should have been "seasonal". Touch screen swypo.

@lalani_safina CORRECTION to (20/n) "mild infection" should have been "mild illness".

@lalani_safina CORRECTION to (25/n) "bank" should have been "nano". Using a touch screen with swype keyboard. Occasional weird word substitutions are essentially "swypos".