On Omicron, and What We Do Now

[citation needed] The Third

Before you start: I’m not actually panicking about this! I’m concerned, and cautious, but it’s early days, the NGS-SA was extremely responsible and proactive in notifying the global community, and plans are being rapidly mobilized to address the situation. It probably won’t be pretty, but if you’ve been being careful already, staying careful is the right call. If you haven’t been being careful, well, you know what I’m going to say anyway. Onward:

Yesterday morning, November 25, Prof. Tulio de Oliveira and Richard Lessells at the Network for Genomic Surveillance in South Africa (NGS-SA) put out an urgent briefing regarding a newly-identified variant of Covid-19: B.1.1.529. You may see this identified online as both Nu and Omicron; the official name given by the WHO is Omicron. As of today (November 26), this variant has been detected in Gauteng and other parts of South Africa, Botswana, and a few other isolated cases (mostly travel-related). We have cause to assume the variant is already present in many other places and not yet identified, as many countries do not routinely sequence positive samples, but we fully expect to see cases cropping up globally in the coming days. The NGS-SA numbers are based on samples collected 12-20 November; in Gauteng nearly 100% of positive cases are currently attributed to this variant.

What We Know

The newly-identified variant has a high number of mutations concerning for predicted immune evasion and transmissibility:

  • There are 10 mutations on the ACE-2 receptor, and 30 mutations on the infamous spike protein. Most variants have one or two mutations, so these are BIG changes. Many of these mutations are either known to us because of other variants, or we can infer their potential impact based on their location in the sequence. Those that we can identify are almost all concerning, and other mutations may have effects we can’t predict. This list from Jeffrey Barrett on twitter shows the full list, colour-coded based on what we know about them:

  • Notably, there are mutations associated with resistance to neutralizing antibodies and our existing therapeutic monoclonal antibodies. These are the antibodies that people either have because they’ve been infected or vaccinated, or the antibody-based treatments we’ve been creating from the blood of recovered individuals. We don’t have cause to think we’re going to have no protection from these things (so it is absolutely still worth it to get vaccinated and you absolutely should), but we do have cause to think they’ll be weakened, perhaps significantly.

  • There are also mutations we know to be associated with more efficient cell entry, which means they cause the variants with these mutations to be more contagious.

  • There is some concern about a mutation that may evade not only neutralizing antibodies but also innate immunity, or our bodies’ ability to recognize and fight the virus due to previous infection and/or vaccination. If you’ve heard people talking about T cells and B cells with regard to vaccines, this is part of that. We don’t expect total escape, but you may be less protected against this variant than against the others we know about.

What We Don’t Know

  • While we know what some of the mutations can do, we don't necessarily know what they will do; we don't know what some of the others do at all or what they'll do in combination. That said, we do have pretty solid guesses, and what we know is definitely cause for concern and caution.

  • The variant can't be well assessed against vaccines due to South Africa's low vaccination rates, but the guesses based on the mutations are informed by existing data.

  • For the same reason, the variant is also not well assessed against Delta; data will become clearer over time, but current situation suggests it may become dominant very quickly. That said, this is not the first time SA and other areas have seen a significant spike of a variant only to have it drop (for example, Alpha - B.1.1.7 - also had a steep but brief climb against Delta). The current R0, or measure of how many people an infected person will infect, in Gauteng is 1.67-2.19 (which means the average infected person will infect between 1 and 3 people), and quickly climbing. For the Delta variant, R0 is 3.2-8, with an average of 5. The R0 data from South Africa is still very early, though, and some knowledgeable people estimate that the R0 for Omicron could be much higher, meaning Omicron will become dominant. The variant with the higher R0 will become dominant. However, the case identified in Hong Kong suggests high estimates are likely correct.

  • We currently have no data not currently available on severity for this variant. It’s possible, though highly unlikely, that it may be more transmissible but less severe (you’re going to see the “it’s possible” idea, but please be cautious about it—we don’t have any reason to believe it any more than any other scenario). At this moment, the only known hospitalized case is in Hong Kong, where all positive cases are hospitalized as part of their routine procedure. The case currently remains asymptomatic.

The Good News

There’s not much positive here, but the one bright point is that a specific gene marker means the variant is trackable by PCR assay without full genetic sequencing, so we can follow outbreaks fairly easily even in areas that do not sequence. This is a good thing, as very few countries are fully-sequencing positive cases as a routine measure.

Another positive note is that both Moderna and Pfizer have made clear that they have protocols in place in the event of an immune-evasive variant. Moderna expects to be able to create an adjusted formula quickly, and Pfizer says they are already working and, if this variant proves to be immune-evasive, should be able to ship out doses of an updated vaccine within 100 days.

What We Need to Do

For now, at least until we know more, the advice hasn’t changed:

  • Get your full dose of vaccinations. That means first, second, and if you’re eligible, third shots for anybody currently eligible. Don’t wait. Yes, you. YOU KNOW WHO YOU ARE.

  • Be cautious. The holiday season is coming in hot, which means everybody’s about to have more new contacts than average. School and workplace exposures will be crossing back and forth between groups in ways they don’t often do. This isn’t ideal! Please be aware and careful about these cross-exposures whenever you can. The smaller your total number of cross-exposures, the better.

  • Wear good quality masks and ventilate when around people outside your household. Gather outdoors if possible, and if you have to be inside, do whatever else you can for good air flow and air exchange, and to minimize breathing other people’s breath. Covid aerosols work more or less exactly like secondhand smoke, with the infected person an invisible smoker. If you can smell the smoke or your clothes would smell like cigarettes after you left that room, it needs more airflow. A properly-fitted and -filtered mask will actually keep most odors from your mouth and nose, so if you’re masked but you can still smell the air around you, your mask isn’t doing its job.

  • If you have access to rapid testing, use it. A rapid test taken the day of a gathering is an excellent measure of whether or not you’re currently contagious. In a perfect world we’d be able to take rapid tests every three days (and if you have ready access to free tests, you can protect others by doing so!). In the real world, tests are expensive and difficult to obtain, but those day-of-event testing measures can make a big difference.

  • Targeted travel bans aren’t supported by science. They punish countries for being transparent about cases and variants, which is the opposite of what we want. Instead, universal precautions, while unpopular, are the most effective. Testing on departure and arrival, “bubbling,” and other infection control measures are better for reducing the risk of community spread, and that does buy us time to get plans in place when things change.

  • Global vaccine equity is critical. Until the whole world has good, reliable access to our best vaccines, this is going to keep happening. That means both that we need to “send” vaccines to more places and that we need to enable countries around the world to establish local production and distribution for their own populations. The first year of vaccination has been an abysmal failure, and that needs to be remedied immediately. If you’re in a position to advocate for that in any way, please do.

Finally, we owe a huge debt to the relentless efforts of African scientists who have been doing the work of sequencing and studying the virus and its variants. They deserve our gratitude and recognition.

Jeffrey Barrett, “Took a Look at the Spike Mutations in B.1.1.529 This Evening, and Colour Coded Them (Details below)...There Is...Not Much Green.🧵 Https://T.Co/YNHM55oTTH.”

Jetelina, Katelyn. “New Concerning Variant: B.1.1.529.” Substack newsletter. Your Local Epidemiologist (blog), November 26, 2021.

John Carroll, “$PFE $BNTX Say They Can Ship a New Vaccine ‘within 100 Days’ @JohnCendpts, 26 Nov. 2021. Https://T.Co/UpvuzskhUr.”

Pai, Madhukar, and Ayoade Olatunbosun-Alakija. “Vax the World.” Science 374, no. 6571 (November 26, 2021): 1031–1031. https://doi.org/10.1126/science.abn3081.

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