Minimize the number of times you get Covid. Your body will thank you.
Not only can repeat infections inflict Long Covid, they also, as @zalaly has shown, increase the risk of a multitude of ailments, such as cardiovascular events. 1/5
You'll repeatedly acquire immunity one way or another. The more you get through vaccination, the less you'll get through infection.
Would you like to suffer more illness & higher risk of long-term health issues? Or would you prefer less of both? It's not a hard call. 3/5
And thanks to the magic of affinity maturation, even an imperfect shot is valuable. Exposure to a large variety of spike can, over the long term, grant you an effective antibody response even against variants that don't yet exist. 4/5
Anthropomorphized Delta, channeling Mark Twain: "Reports of my death are greatly exaggerated."
That's 66 private mutations for those keeping count. 1/6
Like the legendary Indonesian Delta, it has the extremely rare S:R452L reversion.
Unlike that one—but like most Deltas—it has few RBD mutations, meaning it would be unlikely to survive in the current immune environment, even if it were to transmit. 2/6
I spend a lot of time analyzing and documenting outlier SARS-CoV-2 sequences. Recently, I’ve noticed a fascinating pattern: the repeated appearance of paired mutations in two narrow NSP12 regions >2400 nucleotides distant from each other. 1/45
NSP12 is the RNA-dependent RNA polymerase (RdRp), part of the SARS-CoV-2 replication complex, which also includes NSP7-10 and NSP13-14. I discussed some basics of the RdRp & coronavirus genome replication previously. 2/45
The first two-thirds of the SARS-CoV-2 genome consists of ORF1a & ORF1b. When the full genome enters a ribosome, the cell protein-making machine, only ORF1a is translated ~75% of the time. The ribosome hits a stop codon & cuts loose. No ORF1b. 3/45
GW.5 is my favorite XBB* lineage. It's always pulling crazy tricks, like deleting entire genes or adding 5-7 AA mutations at once. Here's it's latest antic: grabbing a chunk of the nucleocapsid gene (top) and stuffing it into the spike NTD (bottom). 1/4
These two sequences share two other mutations not found in other related sequences and are from different labs on opposite sides of the world, so this is real, not an artifact. 2/4
Incredibly, this exact insertion, in the exact same location, has occurred once before, and in a completely unrelated sequence—an XBC.1.2.1 from Denmark collected in December 2022. (XBC is a "Deltacron" lineage now mainly circulating in Australia.) 3/4
What’s new in the world of SARS-CoV-2 accessory proteins? In this 🧵, I’ll recap their evolution so far & describe a possible new trend: partial or total deletion of ORF7a, ORF7b, & ORF8—particularly in GW.5.1.1, an XBB.1.19 + FLip lineage—plus an ORF9b/N bonus TRS surprise! 1/45
The SARS-CoV-2 accessory proteins are ORF3a, ORF6, ORF7a, ORF8, ORF9b, and N* (the last absent from Delta). While the non-structural & structural proteins are absolutely essential for replication, accessory proteins are not. 2/45
In cell culture & in mice, deleting each accessory protein (one at a time) causes only slight-to-moderate reductions in viral replication & pathogenesis. ORF3a & ORF6 seem more crucial than ORF7a, ORF7b, and ORF8. (ORF9b & N* are excluded from these studies). 3/45
I think this preprint, by @Stuartturville, is potentially one of the more important recent SARS-CoV-2 papers. It promises to unwrap some of the most mystifying aspects of Omicron surrounding cell entry, TMPRSS2 use, & reduced lung invasion/pneumonia. 1/48
When BA.1 emerged, it was apparent it did not cause the same degree of pneumonia or disease severity as Delta (though unprecedented levels of infection resulted in similarly large numbers of hospitalizations & deaths in many areas). h/t @mike_famulare 2/48
Many studies showed this was attributable to Omicron’s impaired ability to infect lung cells & reduced cell-cell fusion (syncytia formation). But what accounted for these attributes of Omicron?
(Image 1 from paper by @GuptaR_lab, @veeslerlab @sigallab @SystemsVirology) 3/48
Charles Chaplin, ultra-influential author and public health official in the early 1900s, said almost the exact same thing. If disease is airborne, people will despair & not be properly sanitary. Therefore, we must tell them disease is not airborne. 1/3 thebaffler.com/salvos/airborn…
Chaplin's view was influential—not because the evidence favored droplet transmission but because his views led to politically acceptable conclusions. With droplet transmission no public action or business regulation was required. @BenEhrenreich: 2/3 thebaffler.com/salvos/airborn…
It's hard to put it any better than @jljcolorado: "Droplets & surfaces are very convenient for people in power—all the responsibility is on the individual. ...if you admit it is airborne, institutions, governments, & companies have to do something." 3/3
(Credit to @mdc_martinus)