fter a difficult year of battling Covid-19, we are now beginning to see the rollout of many effective vaccines across the world, including the Oxford/AstraZeneca vaccine, which I helped to develop. It’s therefore to be expected that people might begin to ask, “When will life return to normal?” The main indication of this will be when the pressure begins to ease on public health systems. So far, the signs are good as the Oxford/AstraZeneca, Johnson & Johnson, Novavax, Moderna and Pfizer/BioNTech vaccines all show almost complete protection against hospitalisation, even in countries with new variants. This remains hugely good news, but it is tempered by the fact that we have so many unvaccinated vulnerable populations around the world. We urgently need to get vaccines out to them to prevent severe disease. We, and our politicians, must break down barriers to distribution rather than putting them up. This is especially pertinent as we have seen the rise of new variants. These mutations appear to have arisen in populations where a high proportion of individuals have been infected and there is a reasonably high level of background immunity already, so the virus had to change to survive. The mutations we are seeing in South Africa and Brazil specifically make it easier for the virus to infect people who are already immune by evading the neutralising antibodies that humans make following natural infections or vaccination. Despite this worrisome observation, there should be some optimism that immunity against the virus from vaccines or after infection just might prevent severe disease, even while spread continues. After all, the virus isn’t here to kill us. Its raison d’être is to spread, and it needs us alive to best do that. Indeed, the immune system is highly complex and other important functions are preserved even when faced with variants that can avoid neutralising antibodies. In response to infection and vaccination, most people produce strong T-cell responses (important for controlling infection once it starts) and other types of binding antibodies (which can target infected cells and clear them). These T-cells and binding antibodies may play an important role in preventing severe disease and should be little affected by the mutations we are seeing. However, ongoing transmission of new variants is likely to occur both in naturally infected and vaccinated populations for years to come. New mutations allow ongoing infection in the nose and throat so that the virus can survive. Coronaviruses are very common in humans, and almost all of us will have had coronavirus infections in childhood, but we still get reinfected and develop “colds” with them throughout life. This is a very likely future pattern for the pandemic coronavirus. We need to understand whether this thesis is correct as it will tell us how best to respond to the virus as it changes. Because of the virus’s ability to mutate, we may have to find ways of adapting to living with it as it continues to transmit in the population, causing mild symptoms of upper respiratory infections in most, and more severe disease among the small population of people who are non-immune or whose immunity is flagging. If this proportion is small, it may be manageable by healthcare systems such as the NHS, as is the case with seasonal influenza. We may perhaps need annually updated vaccines to manage changes in the virus or waning immunity over time. If protection against severe disease and hospitalisation can be sustained in the future through the current generation of vaccines, we may well have contained the problem of pressures on our health systems, and the end of the pandemic, in that sense, could be in sight. While we evaluate the real-world impact of the current vaccines against hospital admissions, developers are already working on next-generation vaccines, aimed at controlling the new variants better, in case they turn out to be needed. There definitely is cause for hope, but it is not a time for us to become complacent. Andrew Pollard is head of the Oxford Vaccine Group at the University of Oxford, and chief investigator of the ChAdOx1 nCoV-19 coronavirus vaccine trial, now gathering data from nearly 24,000 volunteers in the UK, Brazil and South Africa The fee for this article has been donated to charity