Does Omicron Cause Milder Disease?

The numbers behind the rapid rise in Omicron cases and how this variant impacts disease
07 January 2022

Interview with 

Christina Pagel, University College London and Luke O'Neill, Trinity College Dublin

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Cases of coronavirus have been hitting record highs in the UK due to the highly transmissible Omicron variant. But levels of severe illness seen in previous waves have not been replicated. Does Omicron cause a milder form of disease? Or are we just seeing the vaccine taking effect? Chris Smith interviews mathematician and disease modeler Christina Pagel and immunologist Luke O'Neil to get some answers about this variant...

Chris - First let's kick off with COVID. Now it's been a pretty turbulent few weeks since the emergence of the Omicron variant, that spooked policy makers, the general public and the media.

BBC News - Let's begin with a full update on the new Omicron variant of coronavirus. The world health organization says it would have severe consequences for some parts of the world if it spreads. The World Health Organisation says the overall global risk related to the new variant is assessed as 'very high'. Health ministers from the G7 group of rich countries have met and say, the global community is faced with the threat of a new, highly transmissible variant of COVID 19, which requires urgent action.

Chris - But is it turning out to be the threat that some claimed it would be, and what's likely to happen in the weeks ahead? With me are immunologist Luke O'Neil, he's from Trinity College, Dublin, and mathematician and disease modeler, Christina Pagel, who's from University College London. Christina, let's start with yourself. What are the numbers looking like at the moment?

Christina - They're higher than they've ever during the pandemic. The official case counts that we're getting every day at the moment aren't telling us that much because there's been a lot of changes in testing over Christmas and New Year, plus we know that testing is maxed out at the moment. But the National Infection Survey released its latest numbers today, and they showed that up to the week ending at new year, the 31st of December, 6% of England had COVID, which is two to three times higher than we've ever seen before. And that was 10% in London.

Chris - Do we know who that 10% in London or a couple of percent of the population on the whole are? Are they any particular groups in society?

Christina - Pretty much every age group is higher than it's ever been. It is still concentrated in younger adults and school aged children. What is quite concerning in the infection survey is that over 2% of over 70's now have COVID, which again is quite high. Now, luckily that group is highly vaccinated, so it shouldn't lead to new admissions, but cases are certainly going up quite steeply in over 50's now across the country.

Chris - Because people were saying, 'Look this is a mild disease' and if we look at South Africa, there doesn't seem to be the same rate of translation of cases into severe consequences, like there have been with other variants. Could that be just a function of the fact that younger people were getting a lot of these, or were accounting for, a lot of these cases initially, and later, we're going to see it filtering into more older people who might become more unwell? Or are we pretty comfortable it is a mild disease across the age spectrum?

Christina - Certainly in South Africa, the average age is 20 years younger than in the UK. We do have an older and more vulnerable population. Part of it is that Omicron does seem to be intrinsically a bit milder than Delta. It doesn't seem to cause the same kind of lung disease that puts people on a ventilator, but because it's so infectious and it's infecting so many people, it is still causing a big burden in hospitals. Although now that burden is more on the ward than in intensive care. You've got a combination of stress on hospitals from a really big backlog of people trying to get treatment, along with lots of new COVID patients coming in and then also loads of staff being off sick. 10 to 15% of NHS staff are off sick. That's just creating these big bottlenecks. Loads of hospitals now are declaring crises, the military is going in to help, ambulance services are taking hours and hours to get to urgent cases. We are in quite an overwhelming situation just because of the amount of infection that is around right now.

Chris - So it's more a problem of 'what it's doing to our ability to run services' than actually 'what it's doing to people' per say, at the moment. Luke, bringing you in here, what are the experiments that scientists are now doing telling us about whether or not this is a more severe illness or not? Do we know yet whether it's just a function of who's getting it or whether there really is something fundamentally different about the biology of this Omicron variant that means we are weathering this storm better?

Luke - We're learning a huge amount Chris, the amount of immunology going on all over the world about this variant is startling in many ways. What we're learning on a day by day basis is lab-based. That means 'does it translate into the real world?' is one question. There's a couple of things that we're pretty confident about. One is that, as Christina said, it doesn't really affect the lungs as much as the upper airways. There's lab-based experiments, including in animals, to support that the change in the spike protein means it seems less able to latch onto your lungs. That's good because the lung infections cause severe disease. It is able to infect the upper airways massively, as much as 70-fold increase compared to Delta, for example, so something's changed there. If it stays in the upper airways, it's less of a concern for the person who's caught it unless it becomes severe, and that's a good thing. That seems to be consistent with the clinical course of this disease, with regard to Omicron and we hope that holds up. The second thing that we're more confident about is the T-cell responses holding up. The immune system has two key parts: the B-cells that make the antibodies, and the T-cells. The T-cells are still able to recognize parts of Omicron. In other words, parts haven't changed that much compared to Delta,. T cells are very good at stopping severe disease, their job in fact is to stop severe disease. It's like plan B for the immune system in a way, plan A is antibodies that can stop you getting infected and limit the spread in your body. If that fails, the T-cells kick in and they heal the virally infected cells. Therefore, the virus can't really grow very much. The evidence at the moment suggests that T-cells can still fight Omicron. That gives us hope that the clinical data, which says 'it's less severe' may be true, because we have these two aspects of the immune system that our bodies can use.

Chris - We are waiting really to gather that real world data aren't we? Which we're doing in real time. One question that's surfacing quite a bit is people are saying, 'if the vaccines haven't changed to reflect the fact that we have this new Omicron variant, why do they work at all? And why would a third dose work better than the two you've already had?' What's the immunology of that?

Luke - You learn as you go along, some vaccines are four shots. The tetanus vaccine needed four shots. That was discovered empirically by just testing it. It's now clear that this is a three shot vaccine. Why would that be? The immune system is a fascination. Every time you challenge it's almost like it's exponentially better every time. You train the troops, and train them again, and then a third time. The third time really trains them.

Chris - Have you escaped infection so far, Luke?

Luke - No, I caught COVID about four weeks ago. I was in close contact with someone, four days later I tested positive. Now, luckily it was very mild, I had three days with a bit of a sniffle and a bit of a cough. Ironically, I tested positive the day after I got my booster. It's no surprise you can get infected after you're vaccinated because the vaccines don't really work in the nose. It's very hard to get the immune system up into what's called the mucosa. So it's no surprise that you might pick up a bit and test positive. The beauty is, if it goes to your lungs, the immune system kills it. That's why vaccination is so important.

Chris - Just to finish, Christina, there's been a bit of negative press around the whole maths modelling and prediction side of what's going on at the moment with the pandemic. Now it was Neils Bhor, who was the forefather of quantum mechanics, who said “Prediction is very difficult, especially if it's about the future.” This is no different, is it? How did they manage to get it so wide of the mark? Because there were numbers that were being produced such as 6,000 deaths a day, 10,000 people going into hospital every day. We are a long way from that at the moment. Is it just that we haven't got there yet? Or was this a "worse case scenario on steroids" as one minister put it?

Christina - I don't think they have really got it wrong. What you do with modelling is you take the best available information at the time, you put it in and you see what would happen under different scenarios. Now the best available information at the time, which was early December, was that Omicron had the same kind of severity as Delta. Under that scenario, when you have the number of infections we've got now, which is 3 or 4 times higher, and you know that it can evade the vaccines, then you're in a situation where that could have been a possibility. Now it then turned out, it is a little bit milder. They updated their models, the deaths came down and what they said is, 'okay, well we still have really high hospitalizations'. And so far hospital admissions are running within their range. In fact, if anything, slightly higher than what was predicted by the SAGE models. I think what people forget is that what SAGE does is it says, 'Under this scenario, this is what we think might happen.' Then if the government says, 'Actually I don't want that scenario, so I'll change what I'm going to do.' that scenario never happens and the predictions don't come true. That's what happened, certainly in the first wave and also last December. I think people have to remember why you're modelling. Modelling is to inform policy and if policy changes, then what you modelled won't happen. It doesn't mean the model was wrong. It means it's done its job in informing policy.

Chris - Christina, thank you very much. That's Christina Pagel and also with us, Luke O'Neil. Thanks to both of them and Luke's book, which is called 'Keep Calm and Trust the Science -  An Extraordinary Year in the Life of an Immunologist.' is out now. He can also now write the sequel; 'What it's like when an Immunologist gets COVID.'

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