DEFCON Omicron? Scientists report that Omicron evades antibodies. Here's what that might really mean.

Antibody escape isn’t great news, but it has no direct relationship to key clinical outcomes for Covid-19.

New research shows that the Omicron variant diminishes the protection that neutralizing antibodies from prior infections or vaccines offer. Data from laboratory experiments were shared online by at least two different groups of scientists in the last day.

Neutralizing antibodies help fend off infections. Does this mean that our vaccines won’t work?

I’m convinced that the newly emerging neutralizing antibody data from laboratory studies of Omicron are meaningful. But these findings should primarily alarm the unvaccinated...

No. At least not in the ways that matter most. Yes, antibody “escape” or immune “evasion” by the Omicron variant will likely lead to more infections, including among people who have already had Covid-19, those who are vaccinated, and even in those who are boosted. (We'll see.) While we can’t make a direct estimate of how much lower vaccine-derived protection against infection will be when confronted with Omicron, we can reasonably infer from lower neutralizing antibody activity in the laboratory that vaccine effectiveness (i.e. real-world data) will decrease yet again. To what extent, we can’t guess, despite numbers you may have read claiming that Omicron is such-and-such more infectious or such-and-such more contagious than Delta. Right now, all of these estimates are non-sequiturs. The only way we will learn this is through large real-world epidemiology, not laboratory experiments or small reports from one isolated region or two.

But fortunately, despite some viral social media posts, antibody escape should have little to no bearing on vaccine effectiveness against severe disease, long-term effects, hospitalization, and death. That’s because the part of our immune system that protects us against those outcomes is separate from the activity of neutralizing antibodies. The fact that some of my science and medicine colleagues seem to not realize (or remember) this is pretty disappointing, if I am being forthcoming.

Vaccines spark our bodies to generate neutralizing antibodies which we keep in circulation for a finite period. Naturally, these levels fall, as we’ve seen in many studies since the vaccine rollout began. But that’s not the whole story. Our immune systems also create a “memory” of viruses (or vaccines mimicking parts of them). That means that even after neutralizing antibody levels fade, our immune systems can “mobilize the sleeping troops” if another infection occurs. As time goes on, repeated infections (including among the vaccinated) become more likely because of fading antibody levels. Fortunately, protection against poor outcomes are likely to hold steady, though. It’s almost as if our bodies “know” not to waste energy by keeping high levels of antibodies around; our bodies seem to understand that repeat infections no longer carry the same threat they once did. Our immune systems are battle-hardened, and battle-ready.

•••

If this sounds familiar, it’s because it parallels what we found during the early days of the Delta variant outbreak. In tests similar to the Omicron studies now being shared, Delta was also found to evade neutralizing antibodies more than the variants that preceded it. We later learned that once infection occurred, though, the risk of serious outcomes was virtually unchanged for people with intact immune systems.

If Delta foretells what Omicron will bring and the latest Delta booster data from Israel remains applicable, here is what we might expect from Omicron:

1. More infections among the unvaccinated; unvaccinated individuals are likely to experience approximately the same rates of severe illness that we’ve seen throughout the pandemic.

2. More infections among recovered Covid-19 patients; more infections among the vaccinated than were caused by earlier variants, and likely even more infections among boosted individuals than we’ve seen before.

3. Somewhat higher rates of severe disease among unboosted people starting around age 50 among those who get infected compared to previous variants (both the boosted and unboosted rates of severe disease get markedly worse by decade, especially those over ages 70 and 80); no major change in the rates severe disease for unboosted people under 40 who get infected compared to previous variants. For people ages 40-49, the data are murkier. In the latest study, researchers in Israel lumped severe disease outcomes for those ages 40-49 and 50-59 together; but when I analyzed just the data for those ages 40-49, I found no compelling signal suggesting that boosting prevented severe illness among the infected in that younger subset.

•••

In addition, in the past couple of days scientists have also answered two other interesting questions with their research. First, one group tested whether or not Omicron uses the same mode of entry to infect our cells (i.e. the viral spike protein attaches to “ACE2” receptors found on the surfaces of some of our cells). This is interesting because Omicron evades vaccine- and infection-derived antibodies so well (which were designed to mimic spike protein) that many of us wondered if Omicron’s spike protein might be so different that it might fail to attach to ACE2 receptors. However, that’s off the table. The variant indeed still uses the ACE2 doorway. That could be good news, though. Remember, for those of us who are vaccinated, the “memory” of a prior infection that protects us against severe disease comes from our previous encounter with the spike protein fake-out that our vaccines delivered. That means our immune systems will likely be activated by Omicron and will spring into action in time to keep most of us from becoming very sick.

The other interesting finding we learned is that, regarding protection from infection, the neutralizing activity of antibodies taken from people who had experienced both a prior infection and been vaccinated outperformed samples from people who had been vaccinated but not infected. So, “hybrid” immunity continues to show signs of providing the most robust protective against infection. That said, to have hybrid immunity, one must successfully recover from a previous SARS-CoV-2 infection and be lucky enough to have avoided the dangers of that infection.

•••

I’m convinced that the newly emerging neutralizing antibody data from laboratory studies of Omicron are meaningful. But these findings should primarily alarm the unvaccinated, especially adults. As Delta did, Omicron will mostly punish the unvaccinated. I also think that the new data on Omicron, combined with the latest booster data from Israel, again strongly indicate that older and immune-compromised people need a third dose to achieve maximal protection against severe illness in the short-term. (We'll see about whether a 4th dose is necessary and for whom). And while most of my colleagues have grown tired of reading the literature on this topic for themselves, I continue to find absolutely no data to support boosting adults ages 18-40 in an effort to stop severe illness. In fact, if even boosters turn out to be useless in preventing Omicron infections, but both the 2- and 3-dose vaccine series continue to hold up against severe disease among young adults, the case for boosting individuals under 40 will collapse.

However, if unlike Delta, though, Omicron causes a decrease in vaccine effectiveness against severe disease among those infected in any age group, and less protection from long-term effects, hospitalization, and death, Omicron-specific vaccines may become necessary.

So, what's our Omicron DEFCON level as of now (with DEFCON 1 being doomsday and DEFCON 5 being a lovely picnic)? I’d say we remain squarely at DEFCON 2.5.

•••

❓💡🗣️ What are your questions? Comments? Join the conversation below!

Follow me on Twitter, Instagram, and on Facebook and help me share accurate frontline medical information!

📬 Subscribe to Inside Medicine here and get updates from the frontline at least twice per week.