The passengers of these two flights had been tested upon arrival because of the newly imposed restrictions (which were set in place during their flight), after which 61 tested positive for SARS-CoV-2.

Entry into the Netherlands generally required having been vaccinated or PCR-tested, or having recovered. Confirmation of a further 5 cases among these passengers followed later. On 28 November, 13 cases were confirmed in the Netherlands among the 624 airline passengers who arrived from South Africa on 26 November. On 27 November, two cases were detected in the United Kingdom, another two in Munich, Germany and one in Milan, Italy. All three initial confirmed and suspected cases reported from Israel occurred among fully vaccinated individuals, as did a single suspected case in Germany. On 26 November, Belgium confirmed its first case an unvaccinated person who had travelled from Egypt via Turkey on 11 November. All four initial cases reported from Botswana occurred among fully vaccinated individuals. On 25 November, one confirmed case was identified in Israel from a traveler returning from Malawi, along with two who returned from South Africa and one from Madagascar. When WHO was alerted on 24 November, Hong Kong was the only place outside Africa that had confirmed a case of Omicron one person who traveled from South Africa on 11 November, and another traveler who was cross-infected by this case while staying in the same quarantine hotel. Likely Omicron (SGTF) samples had occurred on 4 November 2021 in Pretoria, South Africa. The first confirmed specimens of Omicron were collected on 8 November 2021 in South Africa and on 9 November in Botswana. South African scientists were first alerted by samples from the very beginning of November where the PCR tests had S gene target failure (occurs in a few variants, but not in Delta which dominated in the country in October) and by a sudden increase of COVID-19 cases in Gauteng sequencing revealed that more than 70 percent of samples collected in the province between 14 and 23 November were a new variant. On 24 November 2021, the variant was first reported to the WHO from South Africa based on samples that had been collected from 14 to 16 November. One hypothesis to explain the novel mutations is that SARS-CoV-2 was transmitted from humans to mice and mutated in a population of mice sometime between mid-2020 and late 2021 before reinfecting humans. HIV prevention could be key to reducing the risk of uncontrolled HIV driving the emergence of SARS-CoV-2 variants. This is the case in HIV patients in South Africa, who represent about 14% of the population (as of 2017). Indeed, in order to be affected by such a high number of mutations, the virus must have been able to evolve a long time without killing its host, which can occur in people with a weakened immune system who receive enough medical care to survive. Ī link with HIV infection may explain a large number of mutations in the sequence of the Omicron variant. This is not entirely unexpected - at times, viruses within the body acquire and swap segments of genetic material from each other, and this is one common means of mutation. One origin hypothesis is that various mutations in the Omicron variant, comprising a 9- nucleotide sequence, may have been acquired from another coronavirus (known as HCoV-229E), responsible for the common cold. Omicron did not evolve from any other variant but instead on a distinct track diverging in perhaps mid-2020. As of 6 January 2022, the variant has been confirmed in 149 countries.

The first known cases outside of South Africa were two people who travelled on 11 November: one who flew from South Africa to Hong Kong via Qatar, and another who travelled from Egypt to Belgium via Turkey. The first known samples were collected in Johannesburg, South Africa on 8 November. Omicron was first detected on 22 November 2021 in laboratories in Botswana and South Africa based on samples collected on 11–16 November. On 26 November 2021, WHO designated B.1.1.529 as a variant of concern and named it 'Omicron', after the fifteenth letter in the Greek alphabet. Mutation data from WHO, structure from PDB: 6VYB.

In this trimeric structure, two monomers (gray and light blue) have their receptor-binding domains in the 'down' conformation while one (dark blue) is in the 'up' or 'open' conformation. Illustration of the locations of the Omicron mutations in the spike protein, top view (left) and side view (right), showing amino acid substitutions (yellow), deletions (red), and insertions (green).

Omicron greek letter