The Guardian (USA)

Is the Covid pandemic finally nearing its end?

- Aris Katzouraki­s

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 humanscomp­ared 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

 ?? Photograph: AP ?? ‘We will almost certainly see the further erosion of immune protection as the virus continues to evolve.’ Sars-CoV-2 virus particles.
Photograph: AP ‘We will almost certainly see the further erosion of immune protection as the virus continues to evolve.’ Sars-CoV-2 virus particles.

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