όμικρον

Around the middle of this past week I was having trouble finding some interesting news to include for this week's blog. At the same time, scientists in South Africa were first confirming the alarming facts about what is now known as the omicron variant, and as a result I ended up with too much to cover this week. I hope I can help cut through some questions and inaccuracies circulating about this newest variant of concern.

I'll devote all of today's blog to omicron, it's that important, but I want to stress one point first. The government of South Africa has one of the premier pandemic monitoring systems in the world that has given the rest of the world a bit of a lead time to prepare in case omicron turns out to be the next game-changer in the pandemic. We'll probably never know the origins of this variant, but we already know a lot about it thanks to South Africa. Furthermore, much of what I'll be relaying below comes from a press conference in South Africa! Our sound-bite specialists in the US should take a page out of their book: let the actual scientists tell the story with their own words and graphs.

The Beginning of Omicron

As part of South Africa's surveillance system (set up in February 2020, by the way), epidemiologists noted a sharp increase in COVID-19 cases from districts in the province of Guateng. When samples taken November 12-20 were analyzed it became clear that this was a different variant containing many mutations in the spike protein genome. Some were well-known, others had not been described previously, but the main concern was the sheer number affecting a region of the genome that could dramatically change the behavior of the virus.

Looking at the gene diagrams from the press conference, I count 35 separate mutations in the spike protein gene of omicron. Scarier still is the fact that 10 of those are in the receptor binding domain (RBD), a key portion of the genome with regard to many phenotypic properties of SARS-CoV-2. By comparison, the delta variant has 2 mutations in the RBD. So, we need to look very carefully for evidence of how omicron behaves with regard to transmissibility, detectability, immune escape (evading immunity from natural infection and vaccines, poor response to monoclonal antibody or convalescent plasma therapy), and disease severity.

With respect to transmissibility, it is very likely that omicron has heightened ability to spread within a population. Preliminary data from Gauteng suggest a reproductive number of 1.93, not off the charts but pretty healthy. Note this estimate could change significantly because it is based on so few cases in just one country. More concerning is that in just a couple weeks it appears that omicron is replacing delta as the predominant strain in Gauteng and possibly in other provinces as well. The latter information comes from an interesting property of the variant that can be detected by PCR testing rather than waiting for the more technically-difficult and time-consuming method of whole genome sequencing (WGS). A new variant with increased transmissibility and multiple mutations that could affect other viral behavior makes omicron a great concern.

Omicron displays what is called "S gene dropout" where the S gene is so different that it tests negative for that gene in conventional PCR testing. Most PCR tests look at more than one gene, usually the nucleoprotein (N) and open reading frame (ORF) genes in addition to S. So, a specimen that is strongly positive for N or ORF but negative for S could very likely be omicron. As you might surmise, any PCR test that looks only at S gene will likely miss omicron altogether. Still, this property of omicron has allowed South African scientists to hypothesize that this new variant isn't just a fluke in one province but likely has extended across South Africa. What they are now seeing is this same S gene dropout in their newer cases elsewhere. WGS studies now in progress are needed to confirm this, and we should have those answers in the next several days.

Immune escape is a feared property of any variant. Delta expressed this to some degree; in general our vaccines and immune-based therapies don't work quite as well for delta as for the original SARS-CoV-2 strain, but they still provide decent protection from severe disease. At this point we just don't know if this is happening with omicron. We will know, likely within 1-2 weeks, how individual sera from people previously infected or vaccinated can neutralize omicron. It will take much longer to understand how innate immunity and the rest of the immune system behaves with this new variant. Every vaccine manufacturer is now scurrying to look at this and prepare new prototype vaccines in case they are needed for protection from omicron.

Does omicron cause more severe disease? That also will take a bit of time to know. In general, new outbreaks tend to affect younger and healthier populations; they are the ones more out and about to be exposed. So, we can be misled early on into thinking that this new variant is associated with milder disease. If it does spread more extensively we'll end up with a broader population infected and will have the answer to the question of disease severity. Unfortunately there isn't a reliable method to determine this in the laboratory.

What to Do Now?

In the US we may have a little lead time, although I'd be very surprised if we don't eventually learn that omicron is already here. First and foremost, we need to vaccinate the unvaccinated. Yes, it may be that the current vaccines turn out to be less effective against omicron, but based on everything we know about this virus it is clear that partial protection is far better than no protection. Second, everyone who is eligible for a booster should get one now. We do know that neutralizing antibody titers measured one month after a booster dose are very high; this can help overcome some slight decrease in effectiveness against omicron. Don't wait for a new vaccine tailored to omicron; this will take at least three months to see the light of day.

Third, we need to go back to those non-pharmaceutical interventions (NPIs) that have proved so successful in the past: masking especially for indoor activities, social distancing, good hand hygiene, and avoiding large gatherings. We already likely will have a spike in cases from Thanksgiving holiday activities; let's not aggravate an already problematic situation by ignoring NPIs.

Notice that I didn't mention travel bans among the NPIs. That's because they likely aren't effective in the long run. I guess one could argue that this ban on travel from 8 countries in southern Africa gives us another week or two to prepare for omicron.

I'll be watching immunization rates very closely the next couple of weeks; maybe we've learned our lesson and those who have been hesitant will come forward in larger numbers to start their vaccine series.

No One is Safe Until We All are Safe

The Johns Hopkins Coronavirus Resource Center tracks, among other topics, vaccination coverage across the world. It's very clear where the haves and have-nots reside. In Africa only one country, the small island nation of Mauritius, has a fully vaccinated rate of 72% that is above the world average. South Africa's rate is listed as 24% (compare to US of 60% which is pretty dismal itself), but South Africa actually has more vaccine doses available than it does residents seeking vaccine. However, many African countries are in the single digits and do not have access to vaccines. I reiterate that we need to remove all barriers to COVID-19 vaccination across the world. We are running out of Greek letters, but more importantly we are losing lives needlessly.