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Did the Omicron variant jump to humans from mice?

The Omicron variant has already spread all over the world, causing an enormous number of infections in many countries, including all-time records in the US, UK, Australia, and many places in Europe. Although it appears to be milder than previous coronavirus variants, its high transmissibility – as well as its ability to partly evade antibodies gained after prior infection or vaccination – could still lead to high rates of hospitalization and deaths.

One of the most puzzling aspects of this variant is the high number of mutations that it acquired compared to previous strains such as the wild-type virus first found in Wuhan in 2019. Since Omicron is clearly not a direct descendent of other variants of concern such as Alpha, Beta, or Delta, scientists want to know where this variant originated and how it managed to gain such an extraordinary contagiousness.

One of the hypotheses regarding Omicron’s origin is that it started circulating in mid-2020 in a location without much genetic monitoring or testing capacity (possibly an African country), and that a year and a half later it managed to pick up so many mutations that it practically “exploded onto the scene” in November, in South Africa’s Gauteng province. However, this theory is unlikely considering that such a contagious coronavirus strain would have probably been noticed much earlier.

Another hypothesis is that one of SARS-CoV-2’s previous variants (or perhaps even the Wuhan wild-type) has infected a severely immunocompromised person (possibly an untreated HIV patient). The virus was not lethal, but remained in the individual’s body long enough to acquire a vast number of mutations. The most troubling question with this theory, however, is how the variant was not spread by this person sooner.

A new study published in the Journal of Genetics and Genomics is offering a fascinating alternative hypothesis. According to a research team led by the Chinese Academy of Sciences, the rapid accumulation of mutations in the Omicron variant that enabled its fulminant global outbreak suggests that its proximal origin may have been an animal rather than a human host – most likely mice.

“The molecular spectrum of mutations acquired by the progenitor of Omicron was significantly different from the spectrum for viruses that evolved in human patients but resembled the spectra associated with virus evolution in a mouse cellular environment,” the study authors wrote.

“Furthermore, mutations in the Omicron spike protein significantly overlapped with SARS-CoV-2 mutations known to promote adaptation to mouse hosts, particularly through enhanced spike protein binding affinity for the mouse cell entry receptor.” 

Thus, it seems highly possible that, at some point during 2020, the virus jumped from humans to mice, where it rapidly accumulated this staggering number of mutations, then jumped back into humans towards the end of 2021, “indicating an inter-species evolutionary trajectory for the Omicron outbreak.”

If this hypothesis will turn out to be true, it will add to the evidence that the hope of a final eradication of SARS-CoV-2 becomes increasingly less probable the more we learn about this virus. While animal populations remain susceptible to SARS-CoV-2 infection, there is always the possibility that the virus will spill back into humans at some point, probably in highly mutated forms. And whether these new strains will turn out to be more or less pathogenic will most likely be a matter of pure luck (or bad luck), an evolutionary gambit.      

By Andrei Ionescu, Staff Writer

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