A new pre-print study in BioRxIv by a team of Japanese researchers, plus emerging data from the UK and South Africa, point in the same direction: that the Omicron variant BA.2 is not just outcompeting “original” Omicron, variant BA.1, but is also more pathogenic.
The article estimated BA.2 as 1.4 times as contagious as BA.1, which is consistent with BA.2 managing to gain a lot of ground against an already fabulously contagious variant. From the abstract:
Statistical analysis shows that the effective reproduction number of BA.2 is 1.4-fold higher than that of BA.1. Neutralisation experiments show that the vaccine-induced humoral immunity fails to function against BA.2 like BA.1, and notably, the antigenicity of BA.2 is different from BA.1. Cell culture experiments show that BA.2 is more replicative in human nasal epithelial cells and more fusogenic than BA.1. Furthermore, infection experiments using hamsters show that BA.2 is more pathogenic than BA.1. Our multiscale investigations suggest that the risk of BA.2 for global health is potentially higher than that of BA.1.
This study is consistent with worrisome real-world BA.2 sightings, such as:
Omicron: BA2, South Africa, the deaths rise almost perfectly in line with the dominance of BA2: pic.twitter.com/GmJZjvvHuZ
— Chris Turnbull (@EnemyInAState) February 16, 2022
CFR is not that far away from previous peaks now: pic.twitter.com/EG9uli1TFT
— Chris Turnbull (@EnemyInAState) February 16, 2022
If you read the thread, you will also see that South African officials were nevertheless trying to spin BA.2 as no worse than “mild” BA.1.
And from the UK:
UK Health Security Agency has reported that BA.2 has an “increased growth rate” compared with the original omicron variant (BA.1) in all regions of England where there were enough cases to assess.
“the apparent growth advantage is currently substantial.” https://t.co/E6tm9OuygF
— Dr. Claudia William MD, MScHAL ?? (@DrCSWilliam) February 16, 2022
This writer is unhelpfully melodramatic, but the simple point is BA.2 is on the march in countries credited with heretofore doing a pretty good job of Covid containment:
1) There are at least two jurisdictions that are now in the grip of rising #COVID deaths from the so-called #Omicron stealth variant BA.2 – Denmark and Hong Kong. Each has taken a different approach to managing the #pandemic. In this thread, I will show the failings of each. pic.twitter.com/kF0JbA9MkP
— Aaron Derfel (@Aaron_Derfel) February 17, 2022
Now to the new paper, which is getting a lot of media play. Keep in mind that this study performed a considerable number of in vitro tests to try to understand the mechanics of BA.2, plus also infected hamsters to approximate in vivo effects in humans. So on the one hand, these findings are not yet dispositive. But on the other, these various tests pointed generally in the same direction, that BA.2 is both more evasive of existing immunity (vaccine and infection conferred) and more dangerous than BA.1. Consider this discussion:
BA.2 was almost completely resistant to two therapeutic monoclonal antibodies, Casirivimab and Imdevimab, and was 35-fold more resistant to another therapeutic antibody, Sotrovimab, when compared to the ancestral D614G-bearing B.1.1 virus (Fig. 2d). Moreover, both BA.1 and BA.2 were highly resistant to the convalescent sera who had infected with early pandemic virus (before May 2020; Fig. 2e), Alpha (Extended Data Fig. 3a) and Delta (Extended Data Fig. 3b). These data suggest that, similar to BA.1, BA.2 is highly resistant to the antisera induced by vaccination and infection with other SARS-CoV-2 variants as well as three antiviral therapeutic antibodies.
Admittedly, humans may be less susceptible to BA.2 lung damage than hamsters, but the hamster results indicate that BA.2 attacks the lungs more than BA.1 did. We could be back to the old normal of long stays in hospitals to try to contain Covid-induced viral pneumonia:
As shown in Fig. 4b, viral RNA loads in the two lung regions, hilum and periphery, of BA.2-infected hamsters were significantly higher than those of BA.1-infected hamsters…. These data suggest that BA.2 is more rapidly and efficiently spread in the lung tissues than BA.1…
To investigate the pathogenicity of BA.2, the right lungs of infected hamsters were collected at 1, 3, and 5 d.p.i. and used them for haematoxylin and eosin (H&E) staining and histopathological analysis12, 23. All histopathological parameters including bronchitis/bronchiolitis, haemorrhage, alveolar damage, and the levels of type II pneumocytes, of BA.2-infected hamsters were significantly higher than those in BA.1
Recall that it was not just the number of Covid infections but also their duration that pushed hospitals to the brink during pre-Omicron-BA.1 surges. Covid cases then were often hospitalized for 2-3 weeks, tying up capacity and draining staff, not just due to worry about contracting Covid but also due to the acute distress these patients often exhibited.
As scientist GM put it:
As suspected, BA.2 is more severe than BA.1.
And to be noted, this is just the spike, they don’t have a clinical isolate for BA.2 so just cloned the spike into whatever virus they had. So whatever effect the ORF6 mutation has, it’s not in this comparison.
What wasn’t suspected is how much more severe it is, at least in hamsters. I suspect this is actually an exaggerated difference relative to the difference in BA.1/BA.2 severity in actual people, but the hamsters are not vaccinated, while the people mostly are, so that might have something to do with it.
And it is more fusogenic, but not because of increased cleavage, it’s some other mechanism.
So the trend towards worse variants is resuming.
Basically evolution just resumed its usual course for these viruses.
BA.1 seems to have benefited initially from a founder effect relative to BA.2, although they appeared around the same time. Those early superspreader events in Pretoria must have been all BA.1, and from then on it got an early start around the world.
And it swept through because of its gigantic advantage on immune escape. It is not actually more contagious than Delta in a naive population (there was a study from Denmark on secondary attack rates in unvaccinated households, and that was shown there), it’s just that Delta never encountered a naive population — in India itself half the population had been infected prior to the Delta wave, and everywhere else it went, it found a population that had been some combination of infected+vaccinated. And with Delta you do get a 50-80% (depending on the time point and the age group) protection from reinfection, so vaccines did actually reduce transmission. And NPIs had not yet been completely dropped.
So you never saw it exploded the way it could have, the R_t was always dampened by a factor of at least two.
Then BA.1 comes and it has a shorter serial interval but actually has a lower viral load and it’s not all that fit of a variant in absolute terms, but it is a complete escape variant. And it encounters a population that has given up on NPIs and relies entirely on vaccines, vaccines that now have precisely zero effect in terms of infection control.
So it spreads like wildfire and looks unstoppable — because nobody tried to stop it (curiously the Chinese are not having all that much difficulty putting out the fires with their usual methods).
But that is the new starting point, from here on the trend is toward higher viral load, once again back to more cell-to-cell fusion, and thus more severity. Because higher viral load means both more transmissibility and higher severity.
And thus BA.2 displaces BA.1
What comes next is anyone’s guess.
So even assuming not all of the negative findings in this study pan out, two things do seem clear. First, BA.2 is more contagious and just about entirely scapes current vaccines and prior infection. That alone translates into a new big wave of infections which will overload hospitals by virtue of raw number. Second, BA.2 is more severe, which means on the same number of infections, more hospitalization and probably other morbidity. Even “not that much worse” will have a big impact.
With this background, it’s hard to find words sufficiently caustic to describe the abject negligence of officials who have the temerity to depict themselves as in the business of public health.
There was already evidence that BA.2 was more contagious than BA.1, and no reason to think it was less dangerous, public health officials were prepping citizens to get ready to eat, drink, and be merry because BA.1 was abating.
Some are willing to call out the mismanagement and the bad incentives behind it:
BA2 is looking more pathogenic than omicron. And more intrinsically contagious. But still no talk in the West on how to make our countries resilient to the constant threat of new VOCs as we open up. Endemic delusion continues.
— Dr. Lisa Iannattone (@lisa_iannattone) February 16, 2022
It is. They actually want people to take masks off because they (Zients/Klain) think it's bad optics bad for the economy. Reality is DEAD people are bad for the economy. Chronically ill people are bad for the economy
— Melpomene (@MelpomeneMel) February 17, 2022
Based on how public health officials and politicians are responding to Omicron, and Covid generally, it’s hard to think that what we call civilization has actually advanced. The key actors genuinely seem to believe that reality will deliver up their most optimistic scenario. They might as well be New Age prosperity hucksters: if you visualize and believe, the Universe will deliver what you desire. From their Panglossian hit parade:
Getting Covid would confer durable immunity (a nonsensical idea to anyone who had done cursory research on coronaviruses)
The vaccines would protect recipients from infection, even when clinical trial data said no such thing
A two-shot, and then recall per Fauci, a three shot regime would provide immunity (refer again to the statements above)
The Covid death count is not so bad, so why should we change our lives?
Covid will (soon) evolve into something harmless, as in mere nuisance level for most people
Delta would be the last variant
But the public is not as dumb as those in charge think. The dogs are less willing to eat the dog food. A new Pew survey found that only 29% of Americans have a great deal of confidence that medical scientists to act in the best interests of the public. That’s a fall from 40% in November 2020, although this new level is on par with January 2019.
It’s as if we are collectively caught in a pastiche of movie cliches: looming monster about to devour extraneous cast member meets “Don’t go into the haunted house” meets Groundhog Day. But we don’t get to flip the dial.