Since Omicron first emerged in late November, teams of scientists in the UK and beyond have been racing to understand it. The results so far suggest that this new variant is producing a very different epidemic – which may mean that our approach to it needs to change too. Omicron immediately caused concern in the scientific community because it had 50 mutations compared with the original virus, many of which were known to produce significant changes in other variants. These were focused on the spike protein, which sits on the virus particle and acts as the key to allow it to enter human cells. With fellow scientists at the MRC-University of Glasgow Centre for Virus Research (CVR), I worked on a study that suggests such a vast shift in the structure of the spike is very likely to affect the protection we get from vaccines. We (and others) found that two doses of the AstraZeneca, Pfizer and Moderna vaccines were significantly less effective against Omicron than other variants. This might in part explain why it is more transmissible than some other variants, given all our licensed vaccines to date are based on raising immunity to the spike protein of the earliest variant of the virus that emerged in Wuhan in December 2019. However, the response to three vaccines was markedly improved. Therefore, the UK’s strategy of ramping up the booster rollout after Omicron’s discovery was a good one, and will have had a huge impact on the number of severe cases presenting to hospitals in the coming weeks. Unfortunately this will not be enough to prevent the NHS coming under severe pressure as hospitalisations and deaths are still not fully decoupled from the large numbers of cases we are seeing in the UK. There is also the added pressure of staff shortages as a result of isolation following infection or exposure to infection. Meanwhile, people who are older or have underlying health conditions remain at a higher risk of severe illness. Those changes to the spike protein don’t just affect Omicron’s response to vaccines. One unexpected finding in our study and another study from Imperial College London was that Omicron has fundamentally changed the way it enters cells in the human body. Early reports are also suggesting that Omicron may cause a slightly less severe illness, which may be related to this change in the life cycle of the virus. We found that while previous variants enter human cells by fusing with the cell membrane, which may cause severe disease by allowing cell-to-cell transmission of the virus, Omicron is instead enveloped by the cell membrane inside a capsule which is then injected inside the cell. It has to escape from this capsule with the help of different proteins in the cell called cathepsins before it can divide and then infect other cells. These findings have now been confirmed by researchers from Imperial College London, who also went on to show that Omicron may preferentially infect cells in the nose and is less likely to infect lung cells. Further research will help us understand if we should upgrade our measures to prevent respiratory transmission of the virus as a result. The best way to optimise our immunity against this new variant would most likely be vaccines aimed at Omicron (and other variants that have not yet evolved). These would need to be tested in clinical trials and may be reserved for those most at risk given the expense and speed required to roll them out. Importantly, the finding that three doses of vaccine is far superior to two doses has bought us time. The emergence of new variants, which will probably continue, means that Covid requires us to be nimble in our research and response to the virus – whatever form it takes in future. Emma Thomson is a professor in infectious diseases at the MRC-University of Glasgow Centre for Virus Research