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Variant Omicron du SARS-CoV-2: que sait-on et faut-il s’inquiéter ?

Olivia Vong 744 Comments 20 likes
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Variant Omicron du SARS-CoV-2: que sait-on et faut-il s’inquiéter ?

Sylvain Brisse1,2,* et Federica Palma2
Membres du comité de Direction de la Section Epidémiologie et Génomique des Populations de la SFM
1 Unité Biodiversité et Epidémiologie des Bactéries Pathogènes, Institut Pasteur, Paris
2 Centre de Resources Biologiques de l’Institut Pasteur, Paris
* sbrisse@pasteur.fr

Qu’est ce que Omicron?

Omicron est un variant du virus SARS-Cov-2, qui représente une nouvelle lignée phylogénétique appelée B.1.1.529 dans la nomenclature scientifique Pango (voir Nommer les souches de SARS-CoV-2). Cette lignée est caractérisée par de multiples mutations génétiques par rapport à la souche ancestrale de SARS-CoV-2. Ce variant a été classé par l’OMS comme un variant préoccupant (VOC), en raison d’inquiétudes concernant l’échappement immunitaire et sa transmissibilité potentiellement accrue par rapport au variant Delta, actuellement dominant en Europe et dans les autres parties du monde. Omicron a été détecté pour la première fois au Botswana le 11 novembre 2021 (ECDC, 2021).

Pourquoi cet emballement médiatique ?

Auparavant, la lenteur dans la reconnaissance du danger posé par le variant Delta (plus de six mois avant d’être classifié comme VOC) avait mis en évidence l’importance d’agir plus rapidement pour mieux contrôler les nouveaux variants potentiellement dangereux. De nombreux experts considèrent Omicron comme “le variant le plus inquiétant que nous ayons vu” étant donné que cette souche comporte un nombre exceptionnel de mutations, étant le plus divergent jusqu’à présent. La souche présente environ 60 mutations (50 non-synonymes, 8 synonymes et 2 non codantes) dont une trentaine dans le gène de la protéine Spike, qui sert au virus à entrer dans les cellules et est la cible des vaccins. Une fraction importante de ces mutations sont non-synonymes, ce qui suggère une sélection positive et donc une adaptation du variant. Il pourrait avoir une transmissibilité augmentée, réduire l’efficacité des vaccins et/ou être plus virulent. Mais on sait peu de choses pour l’instant, et la vitesse à laquelle le variant Omicron a été désigné VOC contraste avec le peu de données disponibles.

Comment l’a-t-on identifié?

Par séquençage génomique des souches. Actuellement (au 1er décembre 2021), plus de 260 séquences du variant ont été rendues publiques, et ce chiffre augmente exponentiellement au fil des jours. Ces séquences permettent de cartographier les mutations du virus, de géolocaliser sa transmission et d’en comprendre la dynamique évolutive ainsi que de quantifier les paramètres de transmission et d’efficacité vaccinale. L’OMS souligne qu’il est essentiel d’améliorer les efforts de surveillance et de séquençage, ainsi que de rendre publiques les données génomiques et contextuelles, afin de mieux comprendre les variants circulants du SARS-CoV-2 de manière coordonnée au sein de la communauté internationale. L’Afrique du Sud a été félicitée de sa transparence lorsqu’elle a rapporté le nouveau variant (Hodcroft, Twitter), mais la réponse de nombreux autres pays de limiter les voyages depuis ce pays lanceur d’alerte apparaît comme une réponse largement inappropriée (Rambaut, Twitter). En effet, même si cela limite légèrement la diffusion, cela ne l’empêche pas, ou intervient trop tard, et d’autres mesures comme des aides à la vaccination ou la surveillance en Afrique du Sud pourraient être mises en place (Topol, Twitter).

Où est-il maintenant ?

23 pays ont rapporté l’avoir détecté (au 1er décembre), et ce nombre ne cesse d’augmenter. Mais la capacité de séquencer rapidement les virus à partir des échantillons testés positifs est concentrée dans les pays avec plus de ressources, ou mieux organisés pour le séquençage génomique, ce qui signifie que les premières données sur la propagation d’Omicron sont largement biaisées (Brito et al. medRxiv).

Et en France ?

Au 13 décembre 2021, 170 cas confirmés d’infection par le variant Omicron (B.1.1.529) ont été rapportés selon le Ministère des solidarités et de la santé.
(Nombre cumulé de personnes testées positives (RT-PCR et test antigénique) et dont le résultat de séquençage confirme un variant B.1.1.529)
https://www.santepubliquefrance.fr/dossiers/coronavirus-covid-19/coronavirus-chiffres-cles-et-evolution-de-la-covid-19-en-france-et-dans-le-monde
https://www.santepubliquefrance.fr/dossiers/coronavirus-covid-19/coronavirus-circulation-des-variants-du-sars-cov-2

D’où vient-il, géographiquement ?

Difficile à dire vu la vitesse de diffusion des souches et l’intensité des voyages internationaux. Les premiers pays à l’avoir rapporté et rendu public sont l’Afrique du Sud et le Botswana. Cela ne veut pas dire que le virus ait émergé dans ces pays. Il aurait pu évoluer ailleurs et être détecté d’abord là. Le ministre de la santé du Botswana a précisé que la plupart de cas détectés viennent de l’étranger, sans divulguer la provenance de ces cas.  Comme la grippe « espagnole », dont on sait maintenant qu’elle venait des USA, mais qui avait d’abord été rendue publique en Espagne, pays neutre pendant la première guerre mondiale.

D’où vient-il, évolutivement?

Ses caractéristiques génomiques suggèrent qu’il évoluait depuis longtemps (2020) à partir d’autres lignées du virus SARS-CoV-2, difficiles à définir exactement, sans avoir été détecté auparavant. La diversité des souches omicron échantillonnées pour l’instant permet d’estimer le début de la diffusion inter-individuelle vers août 2021, et celui de l’épidémie avant la mi-octobre (voir The mystery of where omicron came from — and why it matters).

Est-il plus dangereux ?

On ne sait pas encore s’il cause des infections plus sévères. Les données cliniques existantes sont très limitées. Elles ne montrent pas de formes plus sévères a priori, mais pourraient être insuffisantes pour le montrer même si c’était le cas. Il faut attendre des données complémentaires.

Est-il plus transmissible et pourquoi?

La diffusion rapide du variant Omicron dans la province du Gauteng en Afrique du Sud pourrait suggérer, mais ne signifie pas nécessairement, qu’il est plus transmissible que d’autres variants. Là aussi les données sont trop limitées. Il semble se répandre extrêmement rapidement dans les populations surveillées jusqu’à présent, qui sont restreintes en nombre et en taille. Mais il est difficile de dire si c’est dû à une caractéristique propre au virus (transmissibilité intrinsèque accrue) et/ou un effet de situation (événement “super-spreader” par exemple), à une couverture vaccinale faible, ou encore un échappement à l’immunité préexistante contre le SARS-CoV-2 (Bedford, Twitter). Cette dernière est fortement soupçonnée à cause de ses nombreuses mutations (Topol, Twitter).

Échappe-t-il au diagnostic ?

Les tests PCR ciblent le matériel génétique du virus. Les variants peuvent donc échapper à la détection par ces méthodes (test faux négatifs). C’est le cas des tests qui visent une mutation (∆69-70) présente dans le gène Spike du variant Omicron qui cause un « S-gene-drop-out » ou « S-gene-target-failure (SGFT) » (i.e., ce gène cible n’est pas détecté). D’autres variants (Alpha, identifié pour la première fois en Grande-Bretagne ou Bêta, détecté en Afrique du Sud) possèdent également cette mutation. Mais comme ces variants ne circulent plus beaucoup ou ont été remplacés par Delta, la présence de SGFT peut être utilisé comme marqueur indirect du variant Omicron, en attendant la confirmation par séquençage, selon l’OMS.

Pourquoi n’a-t-il pas été détecté avant novembre 2021 ?

Trois hypothèses sont évoquées. D’abord, la possible circulation dans des populations humaines qui échappent à la surveillance génomique. Deuxièmement, une circulation chez l‘animal, contaminé par l’homme (zoonose inverse), puis repassage chez l’homme récemment. C’est une hypothèse avancée par le virologue Kristian Andersen (Twitter). Enfin, une infection chronique (de plusieurs mois) d’un patient chez lequel le virus aurait eu le temps de muter sans être détecté. Ces hypothèses sont discutées ici : Where did ‘weird’ Omicron come from?.

Les vaccins resteront ils efficaces ?

C’est le point d’inquiétude majeur. Les fabricants de vaccins ne sont pas nécessairement d’accord sur ces points, ce qui montre l’incertitude actuelle. Les virologues évaluent la capacité des anticorps neutralisants, c’est-à-dire bloquant le virus, déclenchés par une infection ou une vaccination antérieure, à empêcher Omicron d’infecter les cellules. Toutefois, même si Omicron échappait partiellement aux anticorps neutralisants, cela ne signifie pas que les réponses immunitaires déclenchées par la vaccination et une infection antérieure n’offrent aucune protection contre le variant. Des études sur l’immunité suggèrent en effet que des niveaux relativement faibles d’anticorps neutralisants peuvent protéger contre les formes graves de COVID-19. Si cela s’avérait nécessaire, la fabrication d’un nouveau vaccin dédié à Omicron prendrait quelques mois a minima.

Les possibles scénarios

Le variant Omicron présente peu de mutations dans les protéines autres que Spike, qui sont potentiellement associées à une plus grande transmissibilité chez les autres variants (Obermeyer et al. medRxiv). Un scénario optimiste serait celui d’une souche peu virulente mais très transmissible : elle aurait la vertu, en contaminant un grand nombre de personnes, d’immuniser contre l’infection par d’autres souches plus virulentes. Un scénario pessimiste, voire catastrophe, serait que Omicron soit aussi virulent que Delta, tout en étant plus transmissible et en échappant aux vaccins.

Quelle réponse apporter?

Il faudra plusieurs semaines aux scientifiques pour tracer un portrait plus complet d’Omicron et pour comprendre sa transmissibilité et sa dangerosité, ainsi que sa capacité à échapper aux vaccins et à provoquer des ré-infections. En attendant, il est important de renforcer et respecter les gestes barrières, et d’accélérer la vaccination des populations. Par exemple, l’ECDC dans un rapport sur Omicron (ECDC, 2021) recommande d’accélérer la vaccination de toutes les personnes cibles non encore vaccinées, tandis que la FDA a approuvé un vaccin pour les enfants.

L’émergence et la diffusion rapide d’Omicron est un rappel violent que le monde ne sera à l’abri, que lorsque tout le monde sera à l’abri. Ce qui appelle à plus de solidarité internationale dans l’accès aux vaccins, actuellement très limité en Afrique. La plupart des personnes hospitalisées en Afrique du Sud, où Omicron a été détecté, n’étaient pas vaccinées contre SARS-CoV-2. Seulement un quart des habitants de l’Afrique du Sud ont été vaccinés, et 6% en moyenne en Afrique.

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