t’s hard to believe, but Covid-19 has been with us for more than a year, and like the rest of us, it is beginning to adapt. It isn’t unique in this regard – we know that viruses mutate all the time as they make mistakes during replication. Once a virus has entered a human host, it needs to find the right cell type in which it can replicate. During this process, it is exposed to human immune responses that exert pressure on it in various ways, causing mutations to develop. This often occurs in parts of the virus that are most exposed to the immune system, such as the outer protein. In the case of Covid-19, this is the spike protein that binds it to host cells, allowing the virus to enter and replicate. The UK variant initially appeared last autumn in Kent with a mutation in the spike protein, along with a couple of amino acid deletions. This appeared to be more transmissible, but not any more clinically severe, and was later found not to impact significantly on the effectiveness of our then main Pfizer/BioNTech vaccine. Shortly after, we heard about the emergence of a new variant that contained a different pattern of mutations in the spike protein, which appeared to be spreading quickly throughout the South African population. The more worrying thing about the South African variant is that it has been shown to significantly reduce the neutralising efficacy of spike protein-specific antibodies, such as those induced by the current generation of vaccines, including those developed by Pfizer/BioNTech, Moderna, Oxford-AstraZeneca and Novavax. It has also been shown to hinder the effectiveness of antibodies contained in plasma obtained from people who were previously infected with the older, Wuhan strain of the virus. Similar patterns of mutations have been reported in Brazil. The Brazilian variant is considered to be more transmissible, and research has shown that it is able to partially evade vaccine responses. Although cases of this variant have not yet been identified in the UK, that does not mean it isn’t present in the population – remember that the Covid-19 Genomics UK Consortium team can only sequence about 5%-10% of all positive samples. In addition, the recent E484K mutation in the UK variant is worrying as this particular mutation seems to be the main one that is responsible for the vaccine-escape properties. This mutation is already present in both the Brazilian and South African variants. Given the increased transmissibility of the UK and South African variants and the E484K mutation, how worried should we be? Perhaps not so much. Don’t forget that exposure to any of these variants will produce a natural response from your immune system against all the viral proteins, not just to the spike protein targeted by most of the Covid-19 vaccines. If the virus has some mutations in the spike protein that may reduce vaccine effectiveness, your natural immune response will also act against all the other viral proteins to defend you further against these variant viruses. Even a partially protective vaccine, together with your natural immune response, may reduce the risk of more severe Covid-19 that requires hospitalisation. This does not mean that we should be complacent. To reduce the emergence of viral variants we need to reduce the viral replication in the population overall. Viruses can only mutate if they are allowed to replicate, so with large numbers of people being infected in the UK, the virus has a greater chance to mutate and evolve into these more transmissible, vaccine-escaping variants. This means that we need to continue with the current masking, social distancing and stay-at-home restrictions to slow down the spread of the viruses, while continuing the mass Covid-19 vaccination programme. To some extent, the appearance of these variants is inevitable, especially in the first few years of a new, emerging virus as it spreads to infect a host population. After many years living with this Covid-19 virus across the whole population, we will have built up years of immunological experience and protection, so that any clinical disease is likely to be milder – as we see with the seasonal common cold coronaviruses and, to some extent, seasonal influenza. This may mean vaccine boosters each year, as for flu, as well as some ongoing social-distancing measures, such as masks on public transport and indoor public spaces, well into the future. For a while at least, we will need to learn to live with the virus. Julian Tang is a clinical virologist and honorary associate professor in the respiratory sciences department at the University of Leicester