Skip to content

By Roger Highfield on

COVID-19: Beyond Omicron to the Next Pandemic

Although Omicron is milder than first feared, there is a failure of political imagination when it comes to the implications for pandemic preparedness. Roger Highfield, Science Director, looks beyond Omicron with the government’s influential life sciences advisor, Sir John Bell.

The Omicron variant is smashing COVID-19 infection records across Europe, North America, Africa, and Australia, though there is evidence it may have peaked in the UK.

I talked to Sir John Bell, the Canadian immunologist and geneticist who is Regius Chair of Medicine at the University of Oxford and previously Chair of the Office for Strategic Coordination of Health Research and an early member of the Vaccine Taskforce.  His edited responses are shown in italics.

What has been the impact of Omicron?

The bottom line is that whether it’s Omicron itself or the fact that most of the population has had at least two doses of a good vaccine, we are not seeing a lot of pressure on hospital intensive care units.

Data from South Africa suggested Omicron put one-third as many people in the hospital as the Delta variant. Despite initial concerns that previous infections and the country’s relatively young population may have curbed severe cases, the finding that Omicron was milder was initially discounted but ultimately borne out by the team from Imperial College London and follow up studies in South Africa.

We’re following the South African path, despite lots of people suspecting at first we could be different. There’s a distinct separation between disease incidence and hospitalisations in both countries and I think a very large percentage of the population will have been exposed to Omicron, which is highly infectious. Lots and lots of people have had it either asymptomatically or with mild symptoms.

What concerns you the most?

One of my biggest worries now is that decision makers don’t have much imagination because the one thing that Omicron has showed us is how quickly a new variant, which is highly infectious, can go around the world. You have a big problem if you have Omicron on steroids – by that I mean imagine if avian flu, which has mortality between 30 and 50%, could spread as fast as Omicron.

I think people just lack the imagination to see what bad really looks like. By that standard, what we just had in the last six weeks is not bad at all. But you can now see some of the scenarios where bad is writ large. The whole world would grind to a halt and we would have devastating effects for a generation. I don’t really understand why people are not taking pandemic preparedness a bit more seriously, because to be honest, they’re not.

Why is Omicron milder?

Research suggests Omicron lurks in the upper respiratory tract, so it is expelled more readily into the surrounding air to spread but is less linked with serious infection of the longs.

One study at the University of Hong Kong – supported by work at Imperial – found Omicron was better at infecting the airways, but worse at getting into the deep tissues of the lungs, where it is able to do more damage.

Bar chart comparing different SARS-CoV-2 strains and how the infect the human bronchus and lungs. © 2021 Li Ka Shing Faculty of Medicine, The University of Hong Kong.

Another study, conducted at the University of Cambridge found the variant was not as good at fusing lung cells together, which happens in the lungs of people who become severely ill.

But it is early days when it comes to understanding Omicron and the idea that very high transmissibility may be related to excessive amounts of virus in the upper airway might not be right, according to work by Prof Isabella Eckerle and colleagues in Geneva.

Other details may be important. SARS-CoV-2 has two entry routes, one by binding to ACE2, a receptor protein on surface of human cells, or by fusing with human cells directly. Lab studies by Prof Emma Thomson of the MRC-University of Glasgow Centre for Virus Research, UK and colleagues show Omicron is less able to take the direct route.

That’s a fair assessment but I think people have dramatically undervalued and underestimated the role of different aspects of the immune response to vaccines, for example, in protecting you against those deep pneumonias. They’re very atypical pneumonia, and I suspect that protection against those may well be mediated by cellular immunity and not related to neutralizing antibodies. Those responses tend to be durable, and they are clearly long lived in this circumstance because we made our way through Delta without any boosters and without very many people sitting in intensive care who had been doubly vaccinated.  

Do the new antiviral drugs for COVID-19 (Paxlovid and Molnupiravir) currently make much difference?

We don’t really have access to them yet and, besides, a single therapy against viruses is a bad idea because the first thing you get is lots of resistance. I think we’ll need to wait for the next generation of new protease inhibitors, which target other parts of SARS-CoV-2, and other new replication inhibitors to come along, and then we’ll have a mix of drugs to try on patients (similar to how we treat HIV). And if you’ve got four or five, then that is well worth having.

What do you say to those, like Sir Jeremy Farrar, who argue that mutants such as Omicron are what we would expect with the patchy international vaccination campaign and we can expect to see more problematic mutants?

It depends on how you think Omicron occurred. One hypothesis, which is fair, given the large number of mutations in Omicron that seemed to come out of nowhere, is that the virus may have gone off and lived in another species, say monkeys for some period, built up a whole set of mutations and then came back into the human. Another is that it has been sitting in an HIV patient or an immunosuppressed patient, which is eminently possible in Africa where HIV rates are high and most of the immunosuppressed people haven’t had two vaccines yet.

Rather than evolve from Alpha or Delta, Omicron appears to have evolved in parallel—and likely diverged from other strains in mid-2020.  Either the virus could have multiplied and evolved in a population with little surveillance and sequencing, gestated in a chronically infected COVID-19 patient, as is thought to have happened with Alpha, or evolved in a nonhuman species, such as mice or white-tailed deer, from which it then spilled back into people.

Do we need “prototype” vaccines against important families of viruses, to speed up vaccine development in case of emergency?

The big thing that happened before COVID-19 was that the platforms – both adenovirus and RNA vaccines – had been developed and matured to a point at which you could flip the SARS-CoV-2 spike protein into both within days or weeks. And then you were off to the races trying to see whether it would work or not.

Yes, absolutely the right thing to be doing is to have the constructs ready to some extent so that you can flip the genetic code for new pathogens in and out.

This also means it is possible to tune the existing COVID-19 vaccine to new variants. A booster tailored to Omicron would likely offer better protection, according to vaccinologist Prof Florian Krammer of the Icahn School of Medicine in New York City:  “Omicron emerged very quickly and took over very, very quickly and it would be important not just to have technical solutions to update the vaccines quickly – which we have – but get fast approval from regulatory agencies too.”

Rather than customising vaccines to SARS-CoV-2 variants another approach is to develop a more universal coronavirus vaccine that would aim to protect against every new mutant of SARS-CoV-2.

A ‘pan coronavirus’ vaccine that covers every type would be a tall order but one that deals with the SARS-CoV-2 strains is ‘low hanging fruit,’ said Prof Krammer, who has completed early (phase one and two) trials of a universal influenza vaccine which produces antibodies that target the part of a surface protein of the influenza virus, using “chimeric” proteins, a patchwork quilt built from different flu strains. ‘It looks pretty good and does what we wanted it to do, so there’s no reason to think this could not work for coronaviruses,’ he said.

Evidence a universal vaccine may be possible for coronaviruses comes from a study in Nature Communications led by Prof Ajit Lalvani of Imperial College London which found that high levels of pre-existing T cells, immune cells created by the body when infected with other human coronaviruses like the common cold, can protect against COVID-19 infection.

These T cells targeted internal proteins within the SARS-CoV-2 virus, rather than the spike protein on the surface, to protect against infection. Prof Lalvani said that – alongside our existing effective spike protein-targeting vaccines – these internal proteins offer a new vaccine target that could provide long-lasting protection because T cell responses persist longer than antibody responses which wane within a few months of vaccination.

Glass vial from the first doses of the Oxford-AstraZeneca COVID-19 vaccine used in the UK rollout, 4th Jan 2021

How important is rapid testing?

We’ve got really good at testing in the UK – the lateral flow tests have been revolutionary. I think it’s been pretty transformational over the last 6 to 8 months to be honest and no other country in the world has such an impressive access to lateral flow tests, but not only that, a week or so ago we rolled out 19 million. That’s a third of the population!

When we started the validation stuff, and we took the first tests through MHRA approval for self-use, we knew that the first time people used it, they wouldn’t use it very well and you’d lose quite a lot of sensitivity. But now everybody in the country knows how to do it really well, and the quality of the data that comes back is extremely high. So, we are in a different world now that they’re procured very cheaply.    

If you had one of these scenarios where you had a variant which was much nastier than Omicron, you would absolutely want widespread lateral flow tests out there and ready to go. I’m a big of a fan of lateral tests because I am very familiar with their characteristics as I chaired the group that did all the lateral flow test validation. Basically, we solved Boris’ ‘moon shot’ problem.  

There is much talk of COVID-19 becoming endemic. What does that mean, endemic in a similar way to influenza, which still causes many deaths, or like a regular cold?

 It is possible in fact it might even be likely that we we’ve now achieved sufficiently high levels of herd immunity in the UK, whatever that is, that subsequent variants are going to get bounced back and we will get the odd head cold and it’ll gradually become endemic, and I think that’s by far the likeliest outcome.  

It’s just I’m worried about an unpredictable and severe mutant, one more likely than a Black Swan event, an unpredictable event beyond normal expectations, and that we don’t really have a global surveillance system to identify it. We were lucky ’cause the South Africans picked up Omicron quickly but in 80% of the world a new variant would run and run for months before anybody even knew it was there.

We still don’t know the full story of the origins of COVID – – with bats, or even laboratory experiments being implicated. If we did, would that help?

Toiling away to find out is unproductive unless you are interested in the blame game. It could have come from the bat or the lab. I don’t think it makes any difference at this moment. It’s not as if we don’t have enough problems to deal with without spending time trying to sort that out.

Thanks to vigilant COVID-19 testing in South Africa, we do know the origins of Omicron, which was detected on 23 November 2021 and designated B.1.1.529 on 24 November 2021.  On 26 November 2021, the World Health Organisation designated this variant of concern Omicron.

What do you think we should do to protect ourselves from the next pandemic?

That’s a hot potato and is the central question in my view. There are a few things that the global community could do to get ourselves set up to deal with the next pandemic.

There are two things that I’ve been working on: one is helping to develop an analytical tool that allows viral genetic code to be captured straight off sequencers and put in the cloud so that they are aligned and ready to analyse.  

You can make it possible for scientists in the Democratic Republic of the Congo, where they don’t have 400 bioinformaticians to put pathogen sequences in the cloud and you don’t have anybody handling in sequence data at scale. There’s certainly one solution to that which we’ve been working on, and that’s now getting traction globally, and I think that will help a lot.

Obviously, they’re the two other ends of that initiative – getting enough sequencers out there and government labs or public health labs in every African country so you know what is happening, and ensuring Governments are able to use the data to make policy decisions.

The second thing which is a global issue, is that I think it would be a real shame if the vaccine capacity that we will build up, both in terms of manufacturing and other things, gets lost post COVID. Thanks to the new vaccine platforms developed for COVID we have already got a whole set of new vaccines, against malaria, TB and Dengue vaccines that look great. We’ll get new flu vaccines and will be able to manufacture those at scale using this global new manufacturing network which is growing so it is less patchy – I can think of about four or five African countries that are going to develop vaccine manufacture, along with Indonesia and Thailand.   

I am a real believer in local capacity. I know several international pharma companies have said ‘just leave it to us – It’ll all be fine’ but that is not plausible.

However, I think it’s easy to underestimate what it takes for developing countries to develop vaccine deployment capability, they need IT and more. They have done it but developing more local vaccine manufacture still needs a bit more attention.

The other thing is that every country in the world now has a deployment mechanism for adolescent and adult vaccines. Somehow, we must stabilize that and make sure it doesn’t disappear because it’s our best defence.

We can use all that infrastructure to try and manage the chronic endemic diseases like TB and malaria. Then if we get another acute pandemic from a respiratory virus or whatever, we can then pivot all those facilities and use it for manufacturing vaccines locally at scale.

There are attempts to predict the way viruses will evolve. Do you think we will one day predict how they behave too?

Well, I can tell you some scientists got it completely wrong with Omicron.

The initial concern about the Omicron variant focused on how it had an unprecedented 37 mutations in the spike protein that it uses to invade human cells —  three to five times more mutations than any previous variant.

Atomic structure of the Omicron variant spike protein (purple) bound with the human ACE2 receptor (blue). Image from The University of British Columbia, Faculty of Medicine.

Some predicted the world was going to end but I think that they forgot that there are two sides to this, the viral biology and there’s immunology. The prediction was gloomy, gloomy, gloomy but the reality was not because these people haven’t thought about the immunology problem. Ultimately, you need data from epidemiologists and laboratory experiments on the virus.

That capacity to predict the behaviour of a virus in the body from the genetic code is not there. It has been interesting; I can say that. There have been some heroic moments for science but there have been some slightly embarrassing times too where we have screwed it up. It’s always good to be humble and we should not pretend we know more than we do.


The latest picture of how far the pandemic has spread can be seen on the Johns Hopkins Coronavirus Resource Center or Robert Koch-Institute.

You can check the number of UK COVID-19 lab-confirmed cases and deaths along with figures from the Office of National Statistics.

There is more information in my earlier blog posts (including some in German by focusTerra, ETH Zürich, with additional information on Switzerland), from the UK Research and Innovation, UKRI, the EUUS Centers for Disease ControlWHO, on this COVID-19 portal and Our World in Data.