May 22, 2022

Omicron: how much to worry about the BA.2 subvariant?

Spotted mainly in Denmark and also spreading in Great Britain, the Omicron BA.2 sub-variant is currently under the magnifying glass of epidemiologists and virologists who are scrutinizing its characteristics. Should we be worried about this new sub-variant? Will he change the situation concerning the evolution of the epidemic in France, in Europe? Will it push back the expected peak by a few days or weeks or will it single-handedly create a new wave by supplanting BA.1? Today, many questions and uncertainties remain.

Let’s try to take stock by remembering that the mutations at the origin of the emergence of variants are in the order of things in the evolution of this coronavirus, and that not all variants necessarily constitute a new threat.

If at present BA.2 raises questions, it is because of Denmark. The country acts as a pilot fish for Europe with regard to this pandemic, and in particular at the level of this wave linked to Omicron which arrived on its soil a week before France, last December. Denmark had hoped to reach an epidemic peak of its wave of the BA.1 subvariant of Omicron around mid-January. Because if this peak seemed to be emerging in the first days of January, it is now taking a certain delay.

Worse, the epidemic is now flaring up again, and Denmark is reaching European records in terms of new contaminations per inhabitant, with a weekly incidence of nearly 6,000 cases per 100,000 inhabitants expected in the next seven days. The Covid-19 mortality curve is also starting to rise again, with more than twenty deaths per day. This country, whose population is equivalent to that of Occitania, now exceeds its peak in mortality for spring 2020 (fifteen daily deaths) and is preparing to reach that of last January (thirty deaths per day).

A strain in three acts

Omicron is a variant of SARS-CoV-2 initially detected in Botswana and South Africa in November 2021. This strain has three sub-variants: BA.1, BA.2 and BA.3. The first, BA.1, is the one we now know well, since it has hit France and the rest of Europe, but also North America since mid-December. BA.1 causes a real avalanche of new contaminations. And for good reason: it is far more contagious than all previous variants (300% to 400% more than Delta, which was itself 50% more contagious than Alpha).

Omicron’s BA.1 variant escapes humoral immunity, that expressed by our circulating antibodies, and can thus infect people even who have been vaccinated three times or people who have already contracted Covid-19 with other strains of the virus. Omicron, on the other hand, seems less virulent, with several hypotheses that could add up.

It would infect the upper ENT area more and our lungs less often. Or it would infect our entire respiratory tree less due to lower viral loads. A third hypothesis is that he would now meet more and more people immunized by the vaccine or by recent Covid infections, whose cell-mediated immunity would have been reinforced and would allow them to avoid serious forms.

BA.2 has a structure quite close to BA.1: it is of the same line, but has twenty-eight mutations different from those of BA.1, in particular mutations on the Spike protein, which could be at the origin of changes in terms of contagiousness and virulence. For its part, BA.3 seems discreet and does not, for the moment, attract the attention of specialists.

The mysterious BA.2

What is the situation in France today? Hard to say exactly. Indeed, if the PCR tests detect BA.2 well as they are positive for SARS-CoV-2, it happens that, depending on the screening methods used, it goes off the radar when it comes to to distinguish it from BA.1.

Explanation (a bit technical) from a medical biologist: “For three weeks, we have been entering a new letter, D, during screening. Unlike the others, we have the choice of the molecular target to fill in this value (we choose the mutation we are going to look at). However, all the mutations present in Omicron are not always 100% present. This is the case of a mutation (del 69-70) present only in the BA.1 subclone of Omicron (ultra majority in France), but absent in BA.2. However, if we use the del 69-70 target to enter the letter D (and thus display “Omicron” in the screening result), in fact we only detect Omicron BA.1. The Omicron BA.2, with this technique, appear as “another variant”.

Thus, the current coding of the tests carried out in the laboratory and the targets used do not always make it possible to distinguish BA.2 from any variant, or even from BA.1. This can lead to underestimating the impact of BA.2.

Still, contrary to what could be written a little quickly, BA.2 is not a “stealth variant”: it does not escape the tests, and the carriers tested do indeed remain positive.

BA.2 has become the majority by supplanting BA.1 in Denmark, and is taking this path in the United Kingdom, Norway, as is already the case in the Philippines and India. We can therefore postulate, without being 100% positive, that BA.2 is more contagious than BA.1, but various other factors may come into play. For example, why does the decline continue in the United Kingdom, which already announces 20% of BA.2 subvariants among its isolated viruses? Will the British trend in turn reverse and rise again?

Will BA.2 be a game changer like it seems to be doing in Denmark and Norway?

We will of course know more in the coming weeks, and today we can only observe what is happening in Denmark, Norway and the United Kingdom. Of course, some scientists venture to predict the expected characteristics of the variant based on its mutations alone, but this remains a highly discussed exercise within the profession, and we prefer to refrain from such bets.

Is Denmark experiencing a simple postponement of its peak by a few days? An extension of its autumn-winter wave by a few weeks? Or even the beginning of a new wave, which would come to support itself on that BA.1 even before it reached its peak, a little like the Omicron wave had done on Delta? Hard to say at the moment.

Flare or drain

The question also arises in France, where a peak was hoped for before the end of January. If the contaminations remain massive, the reproduction rate slowly converges towards the value 1, ie the curve seems to be heading towards a peak or a plateau. BA.2 will it be a game-changer as it seems to be doing in Denmark and Norway, or will the power of the recession come to drain the country’s coronavirus reservoirs as it seems to be doing effectively in UK or Ireland?

To find out, we will have to be attentive to the evolution of the effective reproduction rate, the famous Re. If it goes below the value 1 soon, then we will be heading towards a decline. Remember that at 0.9 the number of cases is halving every month, and at 0.7 every week. But currently, it remains above 1 at the national level, with some rare but notable regional differences.

The number of new contaminations therefore continues to rise everywhere in metropolitan France, except in Île-de-France and Corsica, which have had a reproduction rate flirting with the value 1 for more than a week. These two regions are in unstable equilibrium on the top of their curve, without us understanding very well why, and without knowing very well which way the balance will end up tipping. Reunion, for its part, has a dynamic that resembles that of Denmark. To be explored closely.

Certainties and gray areas

Let’s get back to our sheep, finally to Omicron and BA.2 and to the questions that remain unanswered to this day:

  • Is BA.2 more contagious? It is probable, as we said.
  • Will BA.2 benefit from immune escape from BA.1? In other words, is the new sub-variant likely to infect people who have already been infected with BA.1? Very recent cases of reinfections have indeed been reported by Denmark, but it is difficult to say for the moment if they are only anecdotal or if the situation will become frequent. One can hope that the structural proximity of the two sub-variants will prevent this.
  • Will BA.2 evade cell-mediated immunity and cause severe cases more often, including in people who are triply vaccinated? This very pessimistic assumption seems very unlikely nowadays.

As you can see, there are still a number of gray areas today regarding the new BA.2 sub-variant. The first concerns the very evaluation of the phenomenon in France, a country which really sequences its viral strains too rarely and too slowly. But the disaster scenarios seem at least ruled out so far.

Isn’t it anachronistic to announce reductions in measures, going against the epidemic curve?

However, we find it worrying that the government, like many others in Europe, does not take the measure of the uncertainty surrounding the epidemiological situation today. How, in such a context, can we design a timetable for lifting health measures based on fixed dates and not on health indicators?

All eggs in one basket

In addition, the French strategy seems to focus almost exclusively on the vaccination pass. While this may have long-term benefits such as encouraging the booster dose and protecting the unvaccinated by keeping them away from places at risk, its effectiveness remains very limited on the very circulation of the virus in the population. Worse, this strategy seems to ignore the protection of immunocompromised or immunosenescent people, as well as children whose number of hospitalizations is currently at record highs.

Everyone is fed up with this pandemic and would like to hear that it is on the way to extinction. But is it not anachronistic to announce reductions in measures, contrary to the epidemic curve which continues to climb without seeming to worry about the proximity of national elections, while the Scientific Council recommends caution? Shouldn’t the generalization of FFP2 masks be promoted in an attempt to limit the spread of the virus?

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Children are the drivers of the current growth in the number of new infections. Shouldn’t National Education propose that the upcoming February holidays be used to substantially improve the quality of indoor air in classrooms and canteens? Such an initiative on the part of the government would be welcomed by the majority of the population, and would make it possible to attack the root of the problem, that is to say contaminations where they occur in greatest number.