Stuff.co.nz

October, 2021

 

Most of the world has accepted this Covid-19 pandemic will end in a particular way. What does that look like, and what does it mean for Aotearoa? Keith Lynch explains.

The race is on. Mass vaccination will save lives, it’ll protect the health system, it’ll mean fewer restrictions, particularly lockdowns, which have a devastating effect on the economy.

Right now, the government is focused on the journey. But it’s also worth asking, what’s the destination? Where are we headed? How does this all end?

In August – before the current outbreak – Prime Minister Jacinda Ardern outlined a future where mass vaccination, contact tracing and tight (but not closed) borders would allow for the continuation of the elimination strategy.

Yes, Covid would pop up, but we’d stamp it out when it does. The critique of this plan was straightforward: New Zealand would end up in a messy and costly ‘forever war’ with Delta, which would inevitably leak in.

Now, after more than 1500 cases of Delta, the government hasn’t really clearly articulated what the long-term strategy is. Of course, everyone has a plan until they get punched in the face. At the 1pm press conferences, officials hint at a new normal of “some Covid”. Yet, it appears plenty of New Zealanders are viewing this pandemic through that 2020 lens – it’s eliminate or bust.

Ultimately, it may be that New Zealand had no real choice. The Delta variant was a devastating twist that turned the pandemic on its head. If we are forced to follow Singapore, which is seeing thousands of cases every day, the road will not be easy. There’ll be deaths, there may be lockdowns. But after that, then what? What’s waiting on the other side? What are the alternatives?

Let’s start by talking about the bind we’re in

The common cold is also caused by a coronavirus, and with that we mostly manage OK. The reason this particular coronavirus is creating so many problems is that it’s new. This means our immune system has not encountered it before and our bodies simply do not know how to respond.

Then there’s the sheer infectiousness of Delta.

Sure, the original strain and the Alpha variant were both infectious and dangerous, but it was thought high vaccination rates would allow us to achieve what’s called population or herd immunity.

The original variant had a basic Reproduction number, or R number, of about 2.5. This meant, on average, one person would infect between two and three people. We expected high vaccination rates would put up enough roadblocks to stop the virus from spreading far and wide.

Simply put, if enough people were immune to the virus it’d hit a wall and die out.

But then the Delta variant came along. Its R number is about 6. This is incredibly high and while the vaccines significantly reduce the risk of infection, they are not perfect. They alone will not lead us to the promised land of no-Covid.

For example, in June modelling from Te Pūnaha Matatini suggested 97 per cent of the population needs to be vaccinated to stop the spread of new Covid-19 variants. The key caveat was the modelling assumed no waning immunity. (This was reasonable, by the way. At the time we were still learning about how the vaccines stood up against the virus.)

The latest batch of Te Pūnaha Matatini modelling, presented by Prof Shaun Hendy recently during a 1pm Covid-19 press conference, also contained a range of assumptions. One of those was that the Pfizer vaccine was 70 per cent effective at stopping spread after two doses. Again, this is wholly reasonable, but crucially that model also assumed no waning immunity.

But the efficacy of the vaccine – that is, how effective it is at stopping spread – does appear to wane over time.

A recent study published in the Lancet found: “effectiveness against infections declined from 88 per cent during the first month after full vaccination to 47 per cent after 5 months”.

And it noted: “Reduction in vaccine effectiveness against SARS-CoV-2 infections over time is probably primarily due to waning immunity with time rather than the Delta variant escaping vaccine protection.”

(This is good news by the way, and we’ll get back to it.)

Crucially, and I can’t emphasise this enough, the study found the vaccines were incredibly effective at protecting people from going to hospital or dying – and that kind of protection lasts for a much longer period of time. This really is what matters most.

What does that immunity look like?

When a person is infected, or vaccinated, the body creates little molecules called antibodies which can both fight off intrusions of SARS-CoV-2, the virus that causes Covid-19. These antibodies dissipate over time. That’s perfectly normal.

But there’s another layer of immunity that’s longer lasting. This is called immune memory. As Dr Fran Priddy, clinical Director of Vaccine Alliance Aotearoa New Zealand, previously told Stuff, what’s called B cells and T cells file away the blueprints to make antibodies until they

“When your body is exposed to that infection later, once it recognises that infection, it then signals to your memory B cells, ‘Hey, make that antibody you previously made’. It keeps a record. It goes in the file cabinet and says ‘Oh, I know this one’. And then it starts to turn out antibodies. But that takes a period of time.”

So while a range of studies (and real world data) suggest that antibody numbers drop off and therefore people are more likely to be infected, that doesn’t necessarily mean the vaccines’ effectiveness against serious illness and disease diminishes.

Yes, the virus might bypass that first line of defence and infect someone, but the B and T cells kick in and fight back.

So what this means is that over time the vaccine may not necessarily stop every infection, but it will still stop the vast majority of people from getting very sick over a longer period.

That’s not to say that those most at risk – like elderly and immunocompromised – won’t need boosters, or a top-up of antibodies, to keep the virus away and protect them from serious illness.

And by the way, Dr Priddy also tells me getting vaccinated even after an infection provides much better lasting protection.

How does this all end, then?

As epidemiologist Michael Baker says, there’s really only two ways the pandemic ends: elimination or endemic Covid.

New Zealand is only one of a handful of countries where zero-Covid remains within the realm of possibility – even though that now seems unlikely.

But even if this outbreak is somehow stopped, the current vaccines alone will not be enough in the long-term. Ongoing elimination would likely mean public health restrictions and tight borders, supplementing world-class contact tracing. It might even need lockdowns from time to time. And there’s no guarantee all of that promises no Covid.

The brutal reality is the rest of the world has kind of boxed us into a corner. In January this year, the science journal Nature published a piece where they asked 100 Covid experts if the virus could be wiped out. Almost all of them said the virus would become endemic. This is where the world is at.

So what does that actually mean?

US publication The Atlantic published an article in August that explains this: “the pandemic ends when almost everyone has immunity, preferably because they were vaccinated or alternatively because they were infected and survived”.

The piece suggests that once everyone has been vaccinated or encountered the virus, we’ll enter a new stage of endemic Covid-19. The virus will still do the rounds, people will still catch it, it will still cause severe illness in some, but it should be less of a problem because of that immunity that vaccines and infections provide.

The big question when it comes to endemic Covid then, as Harvard Professor Yonatan Grad asks in this blog, is: will vaccination or infection protect against severe illness in the long-term?

A lot of this depends on what the virus does next. And on that, we just cannot be sure.

Some people offer an optimistic view. Others, of course, are a touch more pessimistic.

It’s probably worth keeping in mind that a transition from this pandemic to endemic does not necessarily equate to going from bad to good, as Wellington immunologist Graham Le Gros tells me.

On this, Baker says reaching endemic Covid would take years and getting there would be “awful and harsh”. Next winter could be particularly difficult, he says.

And remember, endemic Covid doesn’t replace an existing disease. It’s another one to add to the pile.

The flu, for example, is pretty much endemic. It kills tens of thousands of people in the US alone every year. It kills about 500 New Zealanders in a typical year.

What happens if the collective immunity holds?

Then Covid may well be neutered somewhat – but only for those who have been vaccinated or survived an infection.

In a recent blog post, management firm McKinsey & Company wrote of the devastating impact of the virus in a partially vaccinated country: “Covid-19 hospitalisation and mortality rates in June and July were nearing the ten-year average rates for influenza but have since risen.”

Yet, there’s another vital piece of information in this post (with significant caveats): “Today (September 15), the burden of disease caused by Covid-19 in vaccinated people in the United States is similar to, or lower than, the average burden of influenza over the last decade, while the risks from Covid-19 to unvaccinated people are significantly higher.”

Data this week from the UK also showed reinfections from Covid are rare. Between July 2020 and September 2021 in just over 20,000 people, 296 reinfections were discovered, and only 137 of those were classed as likely to cause serious illness. (The risk did appear to creep upwards though when Delta appeared.)

Paul Hunter, a professor in medicine at the University of East Anglia and an expert in infectious diseases, wrote in a piece for The Conversation earlier this year on the end the pandemic. His take is broadly hopeful.

“Protection against severe disease – generated either by immunisation or natural infection – is much longer lasting [than protection against infection],” he wrote.

“It also doesn’t appear to be lost when facing new variants. Indeed, for the other human coronaviruses, the vast majority of infections are either asymptomatic or at worst a mild cold. The signs are there to suggest that Covid-19 may end up being the same.”

Professor Dale Fisher, senior consultant at Singapore’s National University Hospital (NUH) Division of Infectious Diseases, also told me the journey to endemic Covid would be rocky and could take years. Then there may be stable case numbers, you’ll know roughly when the waves hit, you’ll know the impact on health services.

There would be, he says, good and bad years but with “some degree” of predictability.

“But eventually, you settle in a place where the virus circulates. Every now and then people get sick, there’ll probably be regular vaccinations, but that’ll be a little like the flu vaccine and for older age groups, because by and large most people are getting exposed to Covid because it circulates around, and it’s asymptomatic most of the time.”

Some argue these mild infections would top up people’s immunity. Others worry all those infections will give the virus a chance to mutate.

Again, keep in mind reaching this kind of equilibrium would not be easy. For example, in countries where there are small pockets of people who are not vaccinated, the virus will hit hard. For them the virus will be novel.

“Virtually everyone who has not been vaccinated is likely to catch the virus. When infected, they will be as much at risk of severe disease and death (depending on their age and medical status) as at any time during the pandemic,” Hunter says.

‘ALWAYS thinking about Covid’

In a recent social media thread, Assistant Professor of Epidemiology, Boston University Public Health, Dr Ellie Murray struck a cautionary note, emphasising that endemic Covid doesn’t mean we pat ourselves on the back and move on.

She writes: “Endemic doesn’t mean ‘never think about Covid again’. It’s exactly the opposite! Endemic means someone is ALWAYS thinking about Covid. Endemic means public health is always monitoring disease and always intervening when cases cross the ‘acceptable’ level.”

The key word is ‘acceptable’. Society accepts death every day – and now may be time to think about what burden we’re willing to accept – which is ultimately a political or societal decision.

Let’s go back to the flu and the 500 Kiwis it kills. First, I need to point out that it’s not as if we do nothing about that. The country constantly monitors flu, it offers annual vaccinations, but 500 deaths has never been enough to enforce lockdowns or shut borders.

Indeed, in the highly vaccinated UK – which may offer a glimpse of endemic Covid – about 100 people a day are dying of the virus. This sounds terrifying, doesn’t it? It’s comparable to a very bad flu season.

“[But] Flu is not good benchmark,” Baker says. “We’d eliminate flu if we could.”

Also in the UK, the respiratory syncytial virus (RSV), which caused major problems this winter in Aotearoa, is circulating. It, as the BBC reports, leads to 30,000 hospital admissions every winter among the under-fives – six times what that country has seen so far from Covid-19.

Society as a whole simply does not pay the same level of attention to these diseases. This is why a range of public health professionals think it may be time to reconsider what we view as ‘acceptable’.

Le Gros also urges caution here. His key point is we simply can’t be sure what damage the virus will do to people in the long-term. If the government has no choice but to accept endemic Covid, it needs to prepare accordingly.

And what if the virus changes?

There is also the concern that the virus mutates again and becomes something worse.

Let’s unpack this for a moment. A lot has been written about what the coronavirus will do next, but the reality is that no-one really knows for sure.

One little talked about benefit of the vaccines, however, is the pressure they put on the virus. They not only stop the virus from finding a host, they stop the virus from replicating wildly when it finds itself in the human body doing its thing.

According to this (pre-print) study from July which looked at 1.8m genomes (or versions) of the virus from around the world, the authors found: “the first known evidence that Covid-19 vaccines are fundamentally restricting the evolutionary and antigenic escape pathways accessible to SARS-CoV-2”.

This sounds complicated. But it’s very simple. Vaccination may muffle the virus’ ability to change.

That said, about half the world has still not been vaccinated – there are billions of vulnerable people, in particular, in poorer countries with no immunity.

This is the reason a number of experts, for example, believe there’s no incentive right now for the virus to seek to evade our immune response. There are an awful lot of hosts out there, so for a virus that simply wants to create more virus, speed may be what matters most.

The Beta variant, for example, had characteristics that may have helped it dodge our immune response, but Delta has very much outdone that.

I asked Hunter what he expects. He notes no-one can be sure of what lies ahead and says there are two key issues to look for: the speed of the virus and its ability to avoid our immune system.

“I think of this as a lock and key – the virus (key) evolves to get the best fit to the lock (us). When it gets the best fit, the infectiousness increases [and often the virulence or seriousness of the disease].” We saw this, he says, with the emergence of the Alpha and Delta variants.

In his view, the evidence is that the Delta variant represents a fantastic fit so we are unlikely to see another variant arise that gives as big a boost to infectivity and so case numbers.

“Indeed we have not seen any other variant that looks close to being able to take on Delta for months. Delta is spreading globally and pretty much eradicating every other variant. In the UK, Alpha is now pretty much extinct and in South Africa, [the] Beta [variant] is now close to extinction.”

But what about the nightmare scenario of a variant that sidesteps our defences? This would essentially be another ‘novel’ virus and this whole mess would kick off again. Could this happen?

Again, anything could happen. Coronaviruses evolve all the time, throwing up what’s called “escape mutations” that seek to sidestep our protection. Coronavirus, however, mutates at a slower rate than influenza viruses, like the flu. (If this pandemic was being caused by an influenza virus it may be a whole lot worse).

The good news, Hunter says, is that coronaviruses don’t really change up all at once. They don’t go from being one thing to being something totally different that essentially ignores all that immunity we have built up. It’s more likely they drift across lanes, rather than suddenly veer.

“For the other endemic coronaviruses it takes multiple escape mutations to lead to complete escape and can take up to 20 years, but of course we have been infected several times and so are still reasonably up to date with protection.

“We can already see this in Covid-19 where protection by vaccine against severe disease from new variants is pretty much unaffected, even though mild infection is less well protected.”

Essentially, we can expect the virus to continue to evolve but not necessarily all at once in a way that makes the immunity we’ve gained obsolete.

It’ll likely be slow and steady, and it may mean we have to continuously counter it with boosters and, where necessary, public health measures. It may be, as The New York Times reported this week, that Covid-19 could become much like the flu over time. Or, as another scientist told the paper, it could become like the common cold.

Or, of course, maybe something else happens.

So that’s it then?

Well, not quite. There are other alternatives.

I asked Australian epidemiologist Tony Blakely about how he thought the pandemic would end.

I’ll summarise his thoughts below:

1. The most likely future is endemic Covid – some form of what I’ve outlined above.
2. The world eradicates the virus. This is unlikely to happen unless vaccines that stop transmission in the long-term emerge. Then it may be possible to, as Blakely says, “exit the pandemic on humans’ terms – with global herd immunity”.
3. The vaccines get better. For example, they confer five or more years of immunity against infection. Yes, there are flare-ups now and then, but life is pretty much back to normal.
4. The virus mutates. It becomes less deadly. This would be great. But there’s no reason to suggest this will happen. Instead, the virus could mutate and become more deadly. Again, this could happen. We don’t know. This would obviously be a disaster.
5. The other plausible route for New Zealand is to suppress the virus hard for now – in the hope that better vaccines (and treatments) are around the corner.

If the only way out is endemic Covid, Blakely says it’s reasonable to ask: “Why are you public health folk stopping us getting infected if vaccinated? Don’t we just need to get on with it, and live with it?”

He’s also sympathetic to this viewpoint. But the reality is living with the virus is not just a case of opening up and moving on. We can see this in Singapore at the moment. A move towards endemic Covid will take some time. It will need public health measures. It will mean a lot of pain, particularly in the unvaccinated and most vulnerable. Elimination certainly bought us time to vaccinate; if it’s inevitable here, it’ll certainly be less painful than what we saw in the rest of the world.

But it would, according to Blakely’s Covid modelling, take at least a year to build up enough immunity within a population. And over that time, almost everyone would encounter the virus. For a lot of those people, particularly the unvaccinated, the outcomes will be far from ideal.

And after that, the pain won’t necessarily end, but it should be less awful, and maybe more acceptable.