Pandemic: Rebooted

Part 2: Omicron declares ‘Check!”

Yesterday’s post was fairly negative and I woke up thinking that legitimacy would best be served by acknowledging the sources I had used. But by the time I lumbered into the kitchen in a post-Thanksgiving Monday morning stupor, most media outlets were already reporting what I had posted last night: namely, community spread is already occurring and travel bans are not likely to have much impact on spread. It was not prescience on my part to say so last night. Rather, I probably just read the same sources as the professional journalists who get paid for this. For last night’s post, these included:

1. Trevor Bedford- computational biologist. I believe he is at the University of Washington (Seattle). He maintains the NextStrain database and tracks the evolution of many viruses of which Covid is only the most recent addition. He is one of the people responsible for helping to identify the Covid pandemic in January 2020. He also identified its arrival in the US and tracked its subsequent spread and mutation.

2. Angela Rasmussen- virologist in Saskatoon

3. Eli Perencevich- Epidemiologist at the University of Iowa

But I should apologize for provocatively writing yesterday that researchers have a dirty little secret, that they already know whether or not Omicron will escape vaccination. While I intended it to be provocative, it kind of sounds conspiratorial which is not how I meant it. As penance, I will open by fully discussing immune escape and follow with the topics of Omicron’s rate-of-spread and its fitness relative to Delta.

Vaccine Escape.

By now, you have probably read that researchers are saying they will know in a few weeks if Omicron can escape the vaccines. “They already know,” I wrote yesterday. But they haven’t done the experiments yet so what did I mean?

I have written before about the many parts of the vertebrate immune system. There is innate and adaptive immunity. Adaptive immunity can be divided into cellular and humoral immunity. Of the latter, antibodies are but one part (albeit a large and important one). Finally, antibody function can be described in terms of neutralizing, opsonizing, and agglutinating antibodies. These are not different kinds of antibodies (isotypes) but antibody ‘behaviors’ that may be observed in *any* antibody.

The only tests that can be completed in “a few weeks” are tests of humoral immunity, specifically tests of neutralizing antibodies. And no one really doubts that these neutralizing antibody tests will show significant reductions in neutralizing antibody activity. So the headlines Christmas week are going to be depressing: “Omicron variant 20 times less sensitive to neutralizing antibodies” or something like that.

But as far as immune escape in a whole organism is concerned, neutralizing antibodies tell a woefully inadequate story. Remember that delta also showed an 87% reduction in neutralizing antibody activity. Yet, cellular immunity (T-cells) was still robust in the laboratory. And in 3 randomized controlled trials all conducted during delta predominance the clinical effectiveness of the vaccines for preventing illness also remained above 90% despite the 8-fold reduction in neutralizing antibody activity.

So, yes. The story next month is going to be that Omicron escapes. But I don’t plan to make much of that news. 3–6 months later (because it takes longer to study cellular immunity and the “sum total” of the immune response than it does to study humoral immunity in isolation) we will have better data about whether the virus truly escapes immunity in whole organisms rather than just the part of us that can fit in a test tube. On that point, I have no guess what those studies are likely to show.

As far as efficacy of monoclonal antibodies against Omicron, there too, I have no idea and no basis for formulating a guess. At the time I was studying immunobiology in the 1990s there was only one licensed therapeutic monoclonal antibody and only a handful in development.

How fast is Omicron spreading?

South Africa’s chief epidemiologist said today that we will know in a few weeks how fit Omicron is versus Delta. As you know, Delta is so infectious that it has put every other variant that has stepped into the octagon with it into a submission hold. It might seem, therefore, that the appearance of Omicron in multiple countries means that it can outcompete Delta. But this is not necessarily true. At this time, we do not know where it came from or in what stew of variants it evolved. It does have many mutations in common with Delta that contribute to Delta’s extreme infectiousness. That may put it on equal footing with Delta or even give it an advantage.

There are ways of guessing at the rate of spread but they suffer from problems that make them susceptible to both overestimation and underestimation. Trevor Bedford discusses this in a 13 part Twitter post dated 11/26. Here, too, I confess my lack of expertise. I was unable to follow his argument. Bedford’s conclusion however was that we should take a couple weeks to “settle into a baseline” and then measure the spread of Omicron from there for a few weeks. So we should know in early January how fit Omicron is compared to Delta.

Several months ago When Delta was first in the news I wrote that its emergence had changed the game. Endemicity, which had long been the likely outcome, was now inevitable. Delta soon became the dominant strain worldwide. Then when Mu was all over the news I recommended ignoring it. And soon Mu, like so many others, succumbed to Delta’s submission hold. But now Omicron has my attention. You may wonder, why am I paying atention to omicron when I ignored mu.

Even without knowing if Omicron makes people sicker than delta or if it can escape vaccines or if it is more infectious than Delta, Omicron has changed the game and brought something back to the fight we have not seen since early 2020. When the pandemic began, faulty test manufacturing meant we did not know where Covid was, how much of it there was, or how fast it was spreading. Without a good test we could not get a handle on core epidemiological numbers like R0, and the case fatality rate (cfr). We knew that asymptomatic and presymptomatic spread were occurring but not how much. We did not know if the pandemic was being driven by droplets, aerosols, or fomites, or whether any mask other than an N95 would block transmission. I wrote on September 8 in “Covid-19: Endgame” “[M]ake no mistake, [the endgame] will be a long drawn out one with plenty of surprises from our opponent.” Well, SURPRISE! It’s been about 18 months since we’ve been in a fog-of-war situation with the pandemic, but we’re back there with Omicron.

More than any particular virulence property that Omicron possesses, a return to the fog-of-war has been Omicron’s real sneak-attack.

-Credit to Carl T. Bergstrom for “It’s been about 18 months since we’ve been in a fog-of-war situation with the pandemic, but we’re back there with Omicron”.