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(1/10) What genomic features make SARS-CoV2 more pathogenic? A study in PNAS looked into this: https://www.pnas.org/content/117/26/15193. "Distinct inserts in the spike glycoprotein are associated with high case fatality rate of some coronaviruses as well as the host switch from animals to humans"
(2/10) The role of this 12 nucleotide enzymatic furin cleavage site insertion in the spike protein of SARS-CoV2 has been much discussed, because earlier gain-of-function research showed that such a FCS insertion also made SARS more infectious, https://www.pnas.org/content/106/14/5871.
(3/10) The presence of this insertion does not imply a lab-origin of SARS-CoV2 as 4 out 7 coronaviruses known to infect humans (OC43, HKU1, MERS and SARSCoV2) carry a furin cleavage site in their spike protein & it can arise through natural evolution, https://link.springer.com/article/10.1007/s00705-020-04750-z.
(4/10) The fact that it had been a focus of earlier gain-of-function research, and given the controvery of some of this research, it caused some to speculate though about this possibility, https://medium.com/@yurideigin/lab-made-cov2-genealogy-through-the-lens-of-gain-of-function-research-f96dd7413748. Though that's pure speculation at this point.
(5/10) More important is that SARS-CoV2 mutants that lack the furin cleavage site insertion in their genome (which accumulate after passage in Vero E6 monkey kidney cells) have now indeed been shown to be less pathogenic in a hamster model... @BoudewijnsR
(6/10) ...while infection with these low pathogenic deletion mutant strains produced robust immunity and protected the hamsters against the more pathogenic wild-type: https://www.biorxiv.org/content/10.1101/2020.08.26.268854v1.abstract https://www.biorxiv.org/content/10.1101/2020.08.24.264192v1.abstract
(7/10) Another mutant with a deletion in the ORF8 gene that naturally occurs at low frequency in some parts of Asia has also been shown to be less pathogenic: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31757-8/fulltext https://www.nature.com/articles/s41598-020-70812-6
(8/10) At first glance, one might think these mutants would offer an easy route to an oral attenuated vaccine, in the style of the oral polio vaccine, which now caused wild polio to be eradicated from Africa. Though safety requirements and public acceptance would be a bottleneck.
(9/10) Strange in a way, since reaching herd immunity naturally, causing ca. 60% of all people to get naturally infected, as was the initial aim of the Swedish experiment, or going for a "living with the virus"-strategy, is in many ways much more dangerous...
(10/10) Only difference is that if you get infected by a natural strain then it's merely nature's fault. Even if it would be indirectly the fault of politicians that made the wrong policy choices. While pharma companies would be sued if things would go wrong with a vaccine.
