Thread by @NAChristakis

There’s a new COVID19 variant that has people worried. Let’s talk about “omicron.” This assessment must necessarily be very preliminary, since we are in very early days (partly thanks to South Africa generously sounding the alarm!). 1/

Three key issues are whether omicron is 1) more transmissible, 2) more deadly, and 3) more capable of evading current vaccines (or, somewhat analogously, whether it evades current antibody treatments or immunity conferred by prior natural infection, aka “immune escape”). 2/

Based on currently available technical data and on news reports from around the world, here is a *preliminary* opinion about these three issues, along with my level of confidence in these guesses. 3/

The omicron #SARS2 variant is probably roughly as transmissible or somewhat more transmissible than the delta variant. The Wuhan strain had an R0 of 3, the delta variant an R0 of 6, and the omicron might have an R0 in the range of 4-8. I am very confident about this feature. 4/

Part of the explosion of cases of the omicron variant may relate, however, not to a higher intrinsic transmissibility (R0) but rather to its capacity (given its other known mutations) to partially evade existing immunity in the population and infect otherwise immune people. 5/

The omicron variant is probably not intrinsically more deadly than the delta variant (which was perhaps 30% more intrinsically deadly than the original Wuhan strain). I am somewhat confident about this. 6/

The omicron variant might materially reduce vaccine efficacy re transmission; however, it might *not* meaningfully subvert vaccine efficacy re death. I am not very confident about this yet. It’s just too early to know if and by how much omicron evades current vaccines. 7/

The @WHO designated omicron as a "variant of concern" on November 26, just three days ago. who.int/news/item/26-1…. The WHO noted that the earliest known confirmed case was on November 9. Other news reports say that the first case was noted in Botswana on November 11. 8/

The omicron variant likely arose much earlier than when it came to our notice, probably in early October.

Genomic analyses suggest an emergence of the variant on a median date of October 7 (range: September 19 to October 21) according to @trvrb.

https://twitter.com/trvrb/status/1464353262119776258?s=20

9/

Thus, omicron has had >30 days to circulate internationally. Judging from the COVID19 pandemic so far, and given its likely R0, we may assume omicron is everywhere and that border closures are of little use (whether they will be easy to undo, politically, is another matter). 10/

Prior work re the difficulty of using border closures to stop (or even materially delay) respiratory pandemics of this kind, via @neil_ferguson et al, is here: nature.com/articles/natur… @Nature 11/

The omicron variant has already been detected in many countries (with community transmission, and not just importation). There are reports from South Africa, UK, Israel, Netherlands, Hong Kong, Belgium, Italy, Canada, etc. Running list via @BNONews: bnonews.com/index.php/2021… 12/

So #omicron is simply going to spread worldwide. It will inevitably be identified in the USA, probably in early December. 13/

This image from @trvrb suggests that omicron did not descend from previous variants of concern. @GISAID /14

The >1 year branch indicates either (1) long period of omicron circulation in places w poor genomic surveillance (ie, not South Africa but perhaps nearby), or (2) evolution in chronically infected (likely immunocompromised) individual before moving to population (more likely) 15/

The omicron variant is the most (relevantly) mutated form of the SARS2 virus discovered thus far. See assets.publishing.service.gov.uk/government/upl… (where the variant is called Nu) and this nice summary via @jcbarret. 16/

Many of the mutations in omicron are known to facilitate transmissibility of the SARS2 virus. Others are suggestive of a capacity to evade immunity or cause more serious disease. Here is a nice @Nature paper published this past week re delta: nature.com/articles/s4158… 17/

Based on anecdotal evidence, genomics, and (to some extent) situation in South Africa of rapidly rising cases, I suspect the R0 of this variant is between 4-8 (original Wuhan strain had an R0 of 3 and delta had an R0 of 6). But precise R0 of omicron is just a guess at present 18/

Cases in South Africa have jumped up from ~550 per day in the middle of November to ~4,000 per day at present, and test positivity has risen to 10%, all suggestive that there is a new and more infectious variant present. Updates at @nicd_sa:.

https://twitter.com/nicd_sa/status/1465365031005077518?s=20

19/

The ease of omicron transmission is also indicated by some fascinating case reports. One is reminiscent of the famous 2003 SARS1 super-spreading event, as discussed in Apollo’s Arrow (amazon.com/Apollos-Arrow-…), one of the most famous case studies in epidemiology. 20/

With SARS2 in 2021, two guests *already in quarantine in Hong Kong* appear to have transmitted omicron variant when one guest briefly opened his door to the hallway un-masked on November 13 or 14, and the virus floated into the room across the hall. news.gov.hk/eng/2021/11/20… 21/

If omicron has been in South Africa longer but not yet caused a (very) material rise in death, that's reassuring. On the other hand, South Africa has a young pop (median age 27.6; USA is 38.1), and case & death counts are still low in absolute terms, so it’s hard to be sure. 22/

With respect to mortality, it’s also interesting to me that we have had many anecdotes of patients with mild or no symptoms with omicron worldwide, but no reports, yet, of deaths (though of course we will see such deaths before long). 23/

In a recent @Telegraph article, it was reported that, prior to November 18, a South African doctor had observed ~24 cases of COVID-19 that had an unusual clinical presentation (eg, intense fatigue). That is, omicron presentation may be different than typical COVID19. 24/

This doctor also noted that half of the patients who tested positive for omicron were vaccinated. She did not mention that these patients went on to become very sick, despite a couple of weeks of follow-up. telegraph.co.uk/global-health/… [thread continues...] 25/

At present time, vaccination rate in South Africa is ~43% (many w adenovirus vaccines). This case series would thus suggest that vaccines are not especially effective at preventing infection. But the real benefit of vaccination is preventing progression to serious illness. 26/

There were also 13 cases found by testing in Netherlands (on a flight from South Africa), and these people were also not reported to be seriously ill. bbc.com/news/world-eur… The 13 omicron cases were among 61 people found to be COVID positive in two planes (~600 people). 27/

Presumably, all those people who tested positive for SARS2 on arrival in the Netherlands would have had to have negative tests and/or vaccination in order to board their flight (government.nl/topics/coronav…). This also hints vaccination might not stop omicron infection. 28/

But this case series is fascinating, because, if true, it suggests that there may be a large prevalence of omicron in South Africa already (13 out of 600 travelers), and, if there's not yet been spike in deaths in SA, the variant may not be more deadly than prior variants. 29/

Importantly, even if the omicron variant is not more deadly than delta on a per-case basis, its higher infectiousness alone could cause a large spike in deaths on a population level (because it could cause many more people to get sick quickly). 30/

Concerns re vaccine evasion are high because many cases so far have been in vaccinated people. But without the base rates, it is impossible to know whether omicron materially evades the vaccines and, if so, with respect to what outcomes (infection, serious illness, or death). 31/

Remember that the delta variant also reduced vaccine efficacy to a limited and relatively not worrisome extent (lowering mRNA efficacy from ~95 to ~90%). So perhaps omicron will be like this? One review is here: tandfonline.com/doi/full/10.10… 32/

Moderna has said it will immediately investigate whether participants in its active trials of novel boosters targeting other COVID19 variants have made antibodies that, in vitro, are effective against omicron. businesswire.com/news/home/2021… 33/

Moderna is already (unsurprisingly) developing bespoke boosters targeting omicron that could be ready for clinical testing in 60-90 days. Phase 3 RCTs could be waived for such boosters; so, after brief testing in humans, the only factor will be speed of manufacturing doses. 34/

An important paper published in @Nature in September 2021 by Fabian Schmidt & @PaulBieniasz et al suggests that many mutations are required to fully evade the vaccines nature.com/articles/s4158…. It’s too early to be sure, but omicron variant may not have reached that threshold. 35/

It’s possible that triply vaccinated people may actually be well protected against omicron, but it is also too early to be sure. If I had to guess, I do think that such a high level of vaccination would be at least moderately protective. 36/

Regardless of the clinical and epidemiological details, the economic and political impact of omicron could still be large, as we are seeing with the border closures, stock market volatility, and fear (an ancient companion to plagues, as discussed in #ApollosArrow). 37/

Finally, the international community will have to figure out a way to do worldwide monitoring for pandemic diseases in a way that doesn’t disincentivize countries from quickly reporting new variants. 38/

If we close borders and harm the economy of reporting countries, then we won’t get early warnings. This is discussed in the new afterword to #ApollosArrow amazon.com/Apollos-Arrow-… and by @michaelmina_lab et al in elifesciences.org/articles/58989 39/

Correction: vaccination rates in South Africa is 24% fully vaccinated (h/t @Streitapfel), which affects anecdotal assessment of vaccine efficacy in one case series mentioned above. Without details, it's impossible to be sure. 40/

Bonus fact: The last named variant of concern was Mu, but the WHO skipped the next two Greek letters, Nu and Xi to name Omicron. "The Greek letter Xi bears a similarity to the Chinese surname Xi -- as in Chinese leader Xi Jinping." Sheesh! cnn.com/2021/11/29/hea… 41/

Moderna CEO confirms that, as expected, vaccine effectiveness against omicron will likely be reduced (more than it was for delta): "I think it's going to be a material drop. I just don't know how much because we need to wait for the data." cnn.com/2021/11/30/inv… 42/

In keeping with genomic data and *very* preliminary epidemiological assessments, it seems omicron was already in Europe by mid-November. Today, Netherlands says patient samples dating from Nov 19 & 23 were found to contain the variant. apnews.com/article/corona… 43/

Right on schedule, omicron is diagnosed in the USA today. Patient arrived from SA on 11/22, became symptomatic 11/29. The person was fully vaccinated and is experiencing "mild symptoms, which are improving at this point.” cnn.com/2021/12/01/hea… 44/

Another possible explanation for emergence of omicron is that the virus spent a long time in an animal; it could have indeed spread from humans to an animal & then back to humans (esp given the mutations seen). statnews.com/2021/12/02/som… via @HelenBranswell h/t @aleszubajak 45/

Another anecdote re R0 of omicron: Of 120 healthy vaccinated ppl in Oslo party, two came from South Africa positive w omicron. Now ~90 are PCR pos, 13 so far confirmed omicron. Some of those infected were not at party but just at the same restaurant. reuters.com/world/europe/o… 46/

This fine thread & paper via @sigallab illustrate possibility that omicron evolved via tenure in an immunocompromised individual.

It’s vitally important we vaccinate as much of world population as possible to reduce the risk of emergence of more worrisome strains of SARS2. 47/

https://twitter.com/sigallab/status/1468623699951734788