More than two years on from the realisation that we are dealing with a novel pandemic, we are still nervously wondering what comes next. In the UK, Covid infection rates appear to have fallen to their lowest level since the summer of 2021, as has the number of deaths the virus is causing, but we know that new variants are still likely to emerge. So when will the end of this pandemic come, and what might it look like?
This is a very difficult question, because we won’t know we have passed the end of the pandemic until some time has elapsed. The expectation is that eventually the disease will reach endemic levels, meaning immunity in the population will balance out the reproduction of the virus, resulting in a stable level of infection year on year. That stability could include regular, repeatable fluctuations such as seasonality, but we won’t know that stability has been achieved unless the same pattern of infections is observed for more than one consecutive year.
There are two big unknowns in attempting to determine how soon the end of the pandemic may arrive and what it might look like. The first is: how durable will our immunity be, particularly against severe disease but also against infection? And the second is: how fast will the Sars-CoV-2 virus evolve, in particular with respect to overcoming our immune defences? To answer these questions, we need to look at the lessons the pandemic has taught us so far.
The year of the Sars-CoV-2 virus was very much 2020, when it caused high levels of mortality and disease, and changed lives around the world. We saw a virus transmit into humans and began to observe some evolution, but thanks to the relatively slow rate of evolution of Sars-CoV-2 compared with other RNA viruses, we did not observe much change beyond the immediate public health impact until the very end of the year, with the emergence initially of the Alpha, Beta and Gamma variants.
Looking back, 2021 appears to have been the year of the variant. The Alpha variant rapidly displaced the initial strain of the virus: it was more transmissible and more likely to cause severe disease and death, necessitating far more robust public health responses including the reimposition of restrictions in the UK and elsewhere. The degree of adaptation was staggering; the Alpha variant was more than 50% more transmissible in humans compared with the original virus, a leap of adaptation that has never previously been observed in real time. The Beta and Gamma variants also displayed a degree of immune escape, a brief glimpse into the possibility that these viruses might be able to, at least in part, evade defences we had built against previous forms of the virus, whether by infection or vaccination. And of course, these variants were succeeded by the Delta variant, which was about 50% more transmissible than the Alpha variant, and also more severe, bringing another wave of disease and devastation.
Towards the end of 2021 we were hit by another variant, Omicron, which brought its own unique challenges and lessons in viral evolution. Omicron is highly evasive of the antibodies that vaccination and prior infection confer, and thereby can breach our immune defences. Fortunately, protection against hospitalisation and death is not eroded to the same extent, though protection against severe disease has declined. And of course, Omicron is capable of reinfecting individuals who have previously been exposed to other forms of the virus. The idea that viral infection is a “one and done” risk – that you can get it over with by being infected – has well and truly been dispelled by Omicron. Thus, if 2021 was the year of the variant and the vaccine, 2022 so far appears to be the year of reinfection.
We don’t yet know how severe reinfections will be going forward – presumably there will be some decline on average between primary infections and reinfections. However, as immunity wanes and the virus keeps evolving and changing, will the gap in severity between secondary and primary infections be eroded, increasing levels of mortality? We also don’t know to what extent secondary infections bring reduced risks of morbidity, such as long Covid. And we don’t know how the importance of reinfections varies across risk groups. We will almost certainly see the further erosion of immune protection as the virus continues to evolve, and the need to redouble vaccination campaigns as well as research and development is as pressing as it ever has been – we cannot take the earlier success of vaccines for granted.
We may know how the end of the pandemic might occur in theory, and the patterns to look out for to determine whether we are approaching endemicity. What is a lot less clear is what our future with this virus will look like when Covid is no longer at pandemic levels. For now, we are experiencing multiple waves per year, each with a substantial burden of disease and death. Will endemicity continue to involve multiple waves of infection, with potentially high severity each year? How frequently will variants like Omicron, capable of partial breaching our immune defences, arise, and will this eventually include variants that can escape the protection that vaccines induce, at least in part, against hospitalisation and death?
The pandemic will not end this year, but the behaviour of this virus in highly vaccinated countries across the world may offer a glimpse of what the endpoint may look like: low risk of severe disease from any given infection, a better understanding of the cumulative disease toll of reinfections, an idea of the likelihood of further Omicron-like immune escape events and whether disease severity is further restored, and data available to guide further vaccination strategies.
Aris Katzourakis is a professor of evolution and genomics specialising in viral evolution at the University of Oxford
