Originariamente Scritto da
Gianni78ba
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Perlecano @
burian br @
barry @
snowaholic @
jack9
Il seguente articolo è opera di soggetto ultraspecializzato. Non le solite robe da 2 lire che si leggono in giro nei blog e sui giornali o peggio in tv.
COVID lessons I have learned in 2021 – la bottega
alcuni estratti per me più importanti:
All of the most important variants – certainly all of those who became dominant – have not developed linearly from each other. Delta did not arise from Alpha and Omicron did not arise from Delta (or Beta). That was not a predictable development by any means but it does carry some important implications in terms of vaccinology. We knew Delta had acquired some decent properties of immune escape towards all the vaccines and in the Autumn of 2021 most scientists would have welcomed a vaccine update based on Delta’s Spike sequence, based on the assumption that any future variant would have evolved on Delta’s backbone. However, given how omicron evolved, it is now reasonable to assume that a Delta specific vaccine would not have helped towards omicron – in fact, it is even possible to speculate the opposite: a Delta specific vaccine may confer less protection toward omicron than the vaccines currently available!
The first variants (Alpha, Delta) were selected against a very different landscape. Pressure for those was linked to their sheer contagious ability, not on immune escape. Omicron (with Lambda and Beta) on the other hand evolved in a different setting in which pressure was mostly towards immune evasion. Some had proposed that Delta represented “peak fitness” of the virus (Burioni et al) but, as population geneticists know well, it is not appropriate to talk about peak fitness when the fitness landscape changes continuously. What should we expect then? Given that immunity seems to be extremely short lasted, we should expect a continuous change of fitness landscape that will select new escape variants.
We should certainly expect that the virus now has a much larger evolutionary pressure towards immune escape and the evanescent nature of immune protection, with waining manifesting itself after a few weeks, creates perfect conditions for further selection.
I would also command extreme caution towards the idea that the evolutionary landscape is restricted to ACE2 binding. We have multiple solid evidence of co-receptors and/or alternative receptors involved in cell entry of Sars-Cov-2 and we do know that other beta-coronaviruses do not use ACE2 at all (MERS-CoV, for instance, uses DPP4 as its main receptor).
The unprecedented evolutionary pressure toward Spike implies that tropism could change and, with it, the disease profile (including symptomatology and the age/severity profile). The remarkable number of residues changes in the RBD of omicron’s Spike is an alarming sign that this could happen.
One aspect of omicron’s severity was not discussed as required: omicron descends from the original strain and therefore its severity should be compared to the original strain, not to Delta. Is omicron’s virulence higher or lower than the original Wuhan strain? Alpha doubled the risk of hospitalization compared to the original strain and Delta doubled the risk of hospitalization compared to Alpha. Omicron has evolved from the original strain, not from Delta, so the narrative of the virus getting milder is rather unsupported if we compare omicron severity to Delta’s severity.
Mio pensiero:
per me ha senso quest'anno programmare richiami ogni 4 mesi in attesa che (mi sbilancio: in un annetto) vengano risolti i problemi di cui all'articolo postato nella rincorsa alla variante. Gli studi ci sono e non sono in alto mare.
Nonostante le mazzate nell'articolo io tendo ad avere fiducia che il prossimo Natale non avremo questi pensieri.
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