The Omicron situation, Week 2

An update on the escape variant

I’m not going to do one of these every week, but since the situation is still evolving fast, I thought last week’s post about the Omicron variant deserved a follow-up. The reason is that we now have more evidence about the virus than we did just a week ago; South African public health and medical authorities have been providing us with a wealth of epidemiological data, and scientists have been racing to study the new variant. As with last week’s post, this will be a summary of what the experts are saying, followed by my own thoughts. If you want to get the news directly from the experts, check out my list of coronavirus experts on Twitter.

If you haven’t been following the Omicron situation, virologist Muge Cevik has a long and very explanatory thread that’s a good primer to get you up to speed:

Muge Cevik @mugecevik

🦠 There’s a lot we don’t yet understand about Omicron, including its impact on immunity and what it means for vaccines. New data will be emerging over the next few wks, which could be misinterpreted w/o context. What we might expect & how to interpret the emerging data? 🧵(1/n)

But just in the last couple of days, events have progressed, and our data has increased by leaps and bounds.

Point 1: There is going to be a big Omicron wave in the U.S. soon.

Covid has been defined by super-spreader events, and Omicron is no different. An anime convention in NYC has been identified as one important such event. Three apparently unrelated cases have emerged in Washington state. There are reported cases of Omicron transmission between fully vaccinated people. At this point a major U.S. Omicron outbreak is totally unavoidable. It will happen, and it will happen very soon.

Remember, even when a variant spreads fast, it can take months for it to ramp up to a major nationwide outbreak. Trevor Bedford, a top epidemiologist, has a thread in which he argues that we should expect a big Omicron wave in the U.S. and other countries in about eight weeks.

Trevor Bedford @trvrb

As a broad analogy if it took ~8 weeks for Omicron to grow from initial spark into local epidemic in South Africa, I would expect very roughly 8 weeks from today for secondary epidemics to begin to manifest. 4/6

But when it ramps up, this wave could get bigger much faster than Delta. Bedford has another thread citing South African data to show that Omicron is spreading much faster than Delta did — indeed, even with widespread existing immunity and mitigation measures like masks and social distancing in place, Omicron is spreading as fast or faster than the original Covid did in the U.S. before we had any immunity or any distancing measures!

Trevor Bedford @trvrb

This estimate of Rt around 3 or 3.5 will become more precise for South Africa in the coming days, but even Rt of 3 is very high. Initial Rt of Delta in South Africa and the US was about 1.5. 16/19

Trevor Bedford @trvrb

A more rigorous analysis of variant-specific Rt by @marlinfiggins that partitions @CDCgov case counts across states in the US by sequencing data from @GISAID shows that Mu was maintaining Rt > 1 in most states in July 2021 when Alpha, Beta and Gamma had dropped below 1. 4/9 https://t.co/LX6BYA6Zwo

So buckle up, folks, we’re in for a bumpy ride here.

Point 2: Omicron has substantial resistance to existing immunity.

Scientists and public health experts strongly agree that Omicron has significant ability to escape the immunity conferred by both vaccines and by prior infection. Initially, this was based entirely on analysis of the mutations in the new variant — and this was powerful evidence, since scientists understand a whole lot about how this virus works.

Now, though, we’re starting to get epidemiological evidence to back up scientists’ theories. For example, Omicron is spreading rapidly in the UK, which has a very high rate of vaccination.

Epidemiologist Christian Althaus has a thread summarizing the emerging epidemiological evidence that Omicron is resistant to existing immunity. He stresses that there’s a lot of uncertainty here — the new variant could be as little as 31% resistant, or as much as 93%.

Christian Althaus @C_Althaus

The mutational profile of Omicron suggests a potentially significant transmission advantage. But can we already say something about increased transmissibility or immune evasion? I'll give it a try. Warning: Preliminary and based on VERY limited data. 1/15

And a study found that Omicron is about three times as likely to cause reinfection as Delta.

Matthew Herper @matthewherper

COVID-19 reinfection study from South Africa yields ominous data about Omicron

science.orgCOVID-19 reinfection study from South Africa yields ominous data about OmicronNew variant is better at evading immunity from past infection—and perhaps from vaccination

And here is a thread from biologist Tom Wenseleers explaining why Omicron’s rapid takeover from the Delta variant is almost certainly due to immune escape. If it were coming only from increased infectiousness (as was the case with Delta), Omicron would have to be 3 times as contagious as the most contagious virus we’ve ever found:

Tom Wenseleers @TWenseleers

Clearly an R0 of 6.5*6.2=40 would be highly implausible. That of measles is 12-18 and that's virtually a record. Immune escape then? What would a priori be most likely: increased infectiousness (R0) or greater immune escape?

So at this point, it’s very clear that Omicron has substantial escape ability, even if we don’t quite know the exact numbers yet.

Point 3: Omicron is less deadly in South Africa so far, but there are several theories as to why.

Omicron is spreading like wildfire in South Africa’s Gauteng province, but so far there hasn’t been a big wave of deaths to match the big wave of cases:

In previous waves, deaths started rising about a month after cases did. This time, it’s been longer than a month and deaths still aren’t rising, so that’s good. One note of caution here is that hospitalizations in Gauteng are increasing fast:

David States @statesdj

Hospitalizations in Gauteng SA continue to double weekly

So deaths are pretty sure to rise eventually to some degree. But hopefully the fact that they haven’t risen yet means that the Omicron wave is going to kill fewer of the people it puts in the hospital. And a hopeful sign is that a large percent of the hospitalizations so far are incidental detections in children hospitalized for other reasons (South Africa is testing very vigorously for Omicron).

Some have speculated that this is because Omicron is less deadly than other variants, and this theory is still going around:

Helen Branswell @HelenBranswell

Lots of caveats; too soon to know. But early info from South Africa provide tantalizing hints that #Omicron may trigger milder illness. With thoughts from @MarionKoopmans, @AmeshAA & @PeterHotez.

statnews.comEarly South Africa data hints Omicron may cause less severe Covid, but more research neededEarly data from South Africa on Omicron hints it may cause less severe Covid, but more studies are needed for a full picture of the variant.

In fact, there might be some lab evidence to support this. Some scientists theorize that Omicron shares genes with the common cold, which they think could make it both more transmissible and less deadly.

On the more pessimistic end of the spectrum, Omicron cases in Gauteng might be milder because they’re skewing much younger so far:

This is pessimistic because it could mean that A) Omicron is so infectious that it’s much more able to infect young people than previous variants, and B) when Omicron finally spreads from the young to the old, severity could increase and death rates could soar again.

But experts seem to be converging on a third explanation for Gauteng’s low death rate: Most people in Gauteng simply had some pre-existing immunity, either from vaccination or from prior infection, and that this is making their illnesses more mild. This is supported by early evidence in the U.S., where people who’ve caught Omicron so far have mild cases and were fully vaccinated. There are good scientific reasons for this — even if the virus can evolve to evade antibodies, it’s harder for variants to escape the additional immunity conferred by T-cells:

Eric Topol @EricTopol

Another reason for optimism: the T cell response to vaccines is far less influenced by variants, and is tied to protection from severe illness. The reason why the @BioNTech_Group statement here may well turn out to be true wsj.com/articles/omicr… by @bopanc

T-cell immunity is basically a second line of defense that won’t stop you from getting infected, but will stop you from dying or getting a severe case of the disease. Here is a great explainer thread from the Bertoletti Lab, explaining why T-cell immunity is harder for variants to evade:

Bertoletti Lab @bertoletti_lab

So, there is a new variant Omicron (B.1.1.529) 30AA substitutions, 3 deletions, 1 insertion in the Spike protein Great concern about escaping Spike-specific antibodies! This is important; but what about T cells? They might not protect from infection, but likely from disease: 🧵

All of which suggests that Omicron is not entirely resistant to existing immunity; vaccination might not stop you from catching Omicron, but it’ll probably reduce your risk of dying by quite a lot.

So go get that booster shot if you haven’t already. There’s very strong evidence that boosters are highly effective, including against earlier variants that showed some immune escape ability.

Eric Topol @EricTopol

Big (order of magnitude) 3rd shot impact of J&J or Pfizer vaccine after 2 doses of Pfizer for both neutralizing antibody and T-cell response vs Delta medrxiv.org/content/10.110… confirms powerful booster effect and extends to J&J, cellular immune response

My thoughts

I have two thoughts this week. The first is about the end of the Covid pandemic. Mass vaccination back in early 2021 gave us the hope that the end of this global nightmare was finally in sight, and people are certainly tired of things like masking, social distancing, and (especially) school closures. Delta, with its increased infectiousness, pushed the date of the end of the pandemic further out. But Omicron, with its immune escape properties, is raising the question of whether this will ever be over in any meaningful sense. Even if we make variant boosters against each new variant that comes out, that would still be an eternal battle if the virus keeps evolving to escape each booster. Are we going to have to spend the rest of our lives wearing masks and sending our kids to school over Zoom?

No. First of all, if we keep weathering new variants, eventually we’ll just have so many different kinds of antibodies and T-cells built up that new escape variants will be less and less deadly, and Covid will become like the flu — a yearly danger, but not something that alters the face of our society. This will happen even faster if Covid actually does evolve to become less deadly, as some predict. The four endemic coronaviruses that cause common colds probably are each the remnant of a long-ago Covid-type pandemic; in a few decades we may simply have five.

But a few decades is a long long time — the remainder of many of our lives. In the meantime, we can speed Covid on its way out the door by developing pan-sarbecovirus vaccines. Eric Topol, whom I interviewed the other day, has been one of the leading proponents of this approach, and it’s a good one. We just need to fund and coordinate it. The Biden administration should be pursuing a pan-sarbecovirus vaccine with as much vigor and determination as the Trump administration pursued Operation Warp Speed to develop the initial vaccine. The failure to do this so far is a failure of leadership, and more people need to be making noise about this. We need that supervaccine, and we need it ASAP.

In the meantime, since new therapeutic drugs are still not being manufactured in sufficient quantities, our best tool against the virus remains vaccine boosters. And here it’s becoming ever clearer that U.S. public health authorities have dropped the ball, and badly. A big reason that America lagged the rest of the developed world in booster shots was that our public health authorities, including the CDC, failed to encourage third doses.

Even as Israel quashed the Delta wave with a swift and effective booster campaign, some American public health officials were actively downplaying boosters in order to appear more concerned about ensuring vaccine supplies for the developed world. Paul Romer, an economist who has followed this issue closely and argued vigorously for a big expansion in vaccine manufacturing, minces few words here:

Paul Romer @paulmromer

The anti-boooster rebels said that 1 dose is good; 2 doses is great; and 3 does is selfish, immoral, evil. They left left logic and fact behind. They moved onto the realm of performative morality that I cannot comprehend; and to which, I know not how to respond. 3/N

A general recognition of this failure is starting to sink in.

In other words, this looks to have been an elite virtue signaling campaign that ended up costing a significant number of lives. And with Omicron on the way, it’s now clear that our national failure on boosters is going to cost more lives than the complacent public health people predicted. Public health people are now starting to question the anti-booster approach, but this is too late for many, and of course no one will be held accountable. And a few extremely irresponsible voices in public health are still sending out an anti-booster message, even in the face of Omicron!

This failure should cause us as a nation to rethink a couple of things. First, it should serve as yet one more reminder — as if we needed another! — that our CDC and FDA are deeply damaged institutions that need to be thoroughly rebuilt. But also, the symbolic and ideological nature of the anti-booster campaign should illustrate how our nation’s political unrest has compromised our effectiveness in preserving the safety of our people. The right-wing antivax movement — a politically motivated campaign of symbolic defiance — has caused the tragic deaths of hundreds of thousands. But the anti-booster movement shows that progressive politics is not blameless here either. We need to focus on going back to being a nation that puts pragmatism and safety before symbolism and signaling, as we were back in the days when we vaccinated everyone against polio.

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