As with influenza, they find a 'ladder-like' phylogenetic tree, suggesting that new variants emerge, become dominant, then are gradually replaced by subsequent new variants. (Influenza A/H3N2 below right from: nature.com/articles/natur…) 3/
Likewise, they find antibodies in historical samples are progressively less effective against more recent viruses (below left), much like flu responses are less effective against strains that circulated before individuals were born (below right, from journals.plos.org/plospathogens/…) 4/
Second, it's worth reading this paper by Katie Kistler and @trvrb, which provides evidence of adaptive evolution in spike protein of two seasonal coronaviruses (OC43 and 229E), as we'd expect if virus was undergoing antigenic drift. elifesciences.org/articles/64509 5/
Like influenza, it's therefore plausible that vaccine updates will be needed in long-term to ensure good immune responses against circulating viruses. The frequency of updates will depend on rate of evolution, waning, and how well vaccines prevent disease for new variants. 6/
Finally, reposting this thread by @michaelmina_lab as a reminder that although we have much to learn about SARS-CoV-2, we shouldn't view antigenic evolution as a totally new evolutionary or immunological problem that we have no understanding of. 7/7
Suppose we have a SARS-CoV-2 variant that is inherently more transmissible, and another that is more likely to reinfect people who've previously developed immunity. Which will spread more easily? A thread... 1/
We know we can measure transmission using R, but it helps to break R down into four components - duration, opportunities, transmission probability and susceptibility - or 'DOTS' for short. As below describes, R = D x O x T x S. 2/
For example, if have a variant (call it V1) that is inherently better at transmitting during social interactions, it would mean an increase in 'T'. If it was 50% more likely to transmit per contact, we'd replace 'T' with '1.5 x T'... 3/
Specifically, many will move from high COVID-19 prevalence but little prior immunity (& hence little advantage for variants that can escape this immunity to some extent), to lower prevalence and higher immunity (& hence more advantage for variants that can escape immunity) 2/
As you can see, the highest rate of adaptation (labelled '3' in the plot below) occurs during the intermediate phase, when there is still enough transmission to generate new variants as well as enough immunity to create an advantage for variants than can evade this immunity. 3/
I've noticed people sometimes use 'herd immunity' to mean 'pathogen fades to zero and stays there' rather than the technical definition (i.e. R drops below 1 because of accumulated immunity, without NPIs). Why is the distinction important? 1/
If we're talking about 'fades to zero', we're really talking about elimination or eradication as a result of accumulated immunity. So has this ever occurred in the absence of a vaccine? 2/
There are no examples of eradication (i.e. no infections globally) as a result of accumulated natural immunity, rather than from a vaccine-induced immunity or NPIs (like smallpox). 3/
These “COVID rankings” are being widely shared, but I think it illustrates why it’s unhelpful to try and precisely score countries in this way at a specific point mid-pandemic (first 36 weeks in this case)... interactives.lowyinstitute.org/features/covid… 1/
The study uses cases, deaths and testing data to rank countries. But compare the case curves of Cyprus (ranked 5th), Latvia (9th), Uruguay (12th), Singapore (13th) and Finland (17th). Things have changed a lot since first half of 2020: 2/
Or look at Philippines (79th) and Oman (91st) - if we’re judging on COVID metrics alone (as the ranking does), is it really plausible to say they’ve had worse epidemic than Austria (42nd), Ireland (43rd), Portugal (63rd) and UK (66th)? 3/
Two (currently unclear) factors that will shape COVID dynamics over coming years:
A. Impact of vaccines on reducing transmission (i.e. whether or not vaccine-driven elimination feasible)
B. Global evolutionary risk (i.e. range of possible new variants) 1/
A: If vaccines don't substantially reduce onwards transmission, then even if 100% population vaccinated, could still see outbreaks if other measures lifted (although widespread vaccination would still reduce disease impact from such outbreaks):
B: We've seen new variants can reduce ability of post-infection immune responses to neutralise virus (e.g. below). The frequency & diversity of emergent variants will affect how much of a problem this is, and what it might mean for vaccine updates:
A few people have asked "do new variants mean vaccines won't work"? Important to avoid simple categories of 'works' and 'doesn't work'. Some variants may alter the extent of protection (and some probably won't) and question is whether this change matters (and at what scale)... 1/
A change in the virus won't necessarily mean change in all aspects of protection. For example, it might increase post-infection/post-vaccination probability of infection or extent of infectiousness by some amount, but not the extent of disease. 2/
In such an example, expected individual-level disease outcomes wouldn't change, but at population-level, transmission might persist for longer than a simple SIR dynamic would predict (and hence standard definition of vaccine herd immunity threshold won't necessarily apply). 3/