The man was travel weary. He was returning home, finally, from a long trip – Spain via Britain. Hong Kong airport, as with most major airports these days, has a rigorous COVID-19 screening program for anyone passing through. The man queued up to be throat-swabbed, perhaps with a little impatience. He did not feel sick. He had no fever, no cough.
And besides, he couldn’t have COVID-19. He’d already had COVID-19. He spent two weeks in hospital back in March, recovering. He was immune.
We can only imagine his shock, then, when his results came back positive.
And this wasn’t a false positive, nor a resurgence of the old virus. Scientists later compared the genetic code of the new virus with a sample they’d kept from the man’s first infection. The codes were different. He’d been reinfected with a different virus.
The news spread around the world. Combined with earlier studies about dropping antibody levels, it seemed to raise questions about whether we could ever be truly protected from the virus.
Scientists were less shocked.
“This is a textbook example,” Yale immunologist Akiko Iwasaki wrote on Twitter, of “of how immunity should work”.
The case of reinfection was, in a way, one of the key missing pieces in completing our understanding of what immunity to COVID-19 actually looks like. Much remains to be learnt but immunologists are now ready to confidently answer several key questions.
Do we develop immunity to COVID-19 after we are infected and, if so, what does “immune” really mean? Is herd immunity possible? What sort of immunity could a vaccine confer? And ultimately, what happens to COVID-19 in the long-term?
Hang on. Once you’ve had a virus, aren’t you immune?
Immunologists agree that almost everyone who has recovered from COVID-19 are probably immune. Here’s the problem: “immune” means something very different to immunologists than the general public.
We think of “immunity” as being unable to be reinfected. But immunologists think of several different “types” of immunity, each with different features.
What’s sterilising immunity?
Sterilising immunity means a virus cannot infect you at all. That’s the best kind of immunity, and is what most people think of when they think about being immune. This is what the human papillomavirus (HPV) vaccine confers.
“It blocks the virus from getting in. You don’t get another infection,” says Associate Professor Nathan Bartlett, head of the viral immunology and respiratory disease group at the University of Newcastle.
But this sort of immunity is hard to develop. It’s easy to understand why. You don’t just need armies of antibodies and immune cells ready to neutralise a virus; they also need to be in exactly the right place to stop a virus as soon as it tries to enter the body.
For viruses that spread through the air, such as SARS-CoV-2 – the virus that causes COVID-19 – that means your immune system needs to have set up fortifications in the nose and throat.
The immune system does this using a type of antibody known as immunoglobulin A. These antibodies actually coat the lining of the cells in your nose and throat, stopping a virus infecting them.
When you are infected with SARS-CoV-2, scientists suspect your body makes heaps of these nose-and-throat antibodies. About three weeks after you’re infected, your nose and throat are probably covered in them.
Bartlett says that process likely confers sterilising immunity to SARS-CoV-2.
Here’s the bad news: it does not appear to last.
About three weeks after you are infected, antibody levels in the blood – particularly immunoglobulin A – begin to decline, a pre-print study that is still under review shows.
Assuming what is happening in the blood is also happening in the nose, this suggests you’re likely to have true sterilising immunity for only a few months after you are infected, says Bartlett – “transient sterilising immunity”.
If SARS-CoV-2 comes along again, your nose and throat are unprotected. The virus can get into the cells there and start replicating.
“Their antibody responses have nosedived, suggesting they are going to lose that sterilising immunity. But that’s what some respiratory viruses are very good at doing,” says Bartlett.
Scientists say this is not surprising. Many respiratory viruses, such as the coronaviruses that cause the common cold, do not leave you with long-term sterilising immunity. That’s part of the reason you can keep getting reinfected.
This sounds really bad, right? But don’t panic yet. Antibodies are only one part of the picture.
“The thing that persists is immunological memory,” says Professor Heidi Drummer, head of viral entry research at the Burnet Institute.
After our bodies fight off an infection, they don’t need antibodies any more so they are allowed to diminish. That’s what the nosedive studies are showing.
“Antibodies are an inefficient way for the body to maintain immunity because it takes a lot of energy to produce them. If you have immunity in your T cells, that can be rapidly brought back into the fight,” says Dr Rob Grenfell, director of health and biosecurity at the CSIRO.
But wise countries don’t stand down their entire army after the war is won, and neither does the immune system.
What’s functional immunity?
When we are infected with a new virus, the immune system generates vast armies of B and T cells. B cells are giant antibody factories; T cells float through the blood, hunting and killing infected cells. After a virus is beaten, the body hides some B and T cells specialised to kill that virus in the bone marrow and lymph nodes, just in case the virus comes back.
This is called functional immunity. These B and T cells are able to respond to COVID-19 if it reinvades the body. They take a couple of days to kick into action – the body has to activate them and grow them into a big, virus-busting army – but when they are ready, they decimate SARS-CoV-2’s.
“But it’s not an instantaneous thing. It takes time – a couple of days to get this full-blown immunological response. So there is a bit of a window for the virus,” says Drummer.
This means any SARS-CoV-2 reinfection can probably get no further than the nose or throat – meaning you have long-term protection from falling seriously, life-threateningly-ill.
This is what scientists suspect COVID-19 immunity looks like.
So what does this mean for us?
Let’s recap the likely, although not proven, scenario. In the first few months after the infection, it is likely you are totally immune. Then, your nose and throat immunity wanes, allowing the virus to get in and infect cells there. You can get reinfected. But the virus cannot get any further than your nose and throat and you are protected against serious illness.
That’s probably what we saw in the infection in Hong Kong, says Professor Andreas Suhrbier, group leader of inflammation biology at the QIMR Berghofer Medical Research Institute and probably explains why the man had no symptoms.
“That shows he wasn’t protected against reinfection, but was protected against getting really sick. The first virus infection certainly did not produce sterilising immunity.”
Will a vaccine offer complete sterilising immunity?
Maybe. The evidence we have so far is mixed.
In animal studies, both the Oxford vaccine that Australia purchased and the University of Queensland’s vaccine both effectively stopped SARS-CoV-2 getting deep into the lungs.
That’s a really good sign.
If that translates to humans, it should stop you developing severe life-threatening illness. For most people, COVID-19 would be transformed from potential killer to mild disease, says Suhrbier.
But in the animal studies, the virus kept replicating in the nose.
“It is not triggering an immune response in the nose and throat. It’s not providing any protection against that infection in the [upper] airways,” says Bartlett.
That may indicate the vaccine, just as with the immunity you get after being infected with the virus, protects you from becoming seriously ill but does not stop you catching the virus.
“It seems sterilising immunity in the upper tract is hard to achieve,” says Professor Trent Munro, one of the team building the University of Queensland’s vaccine.
Results that scientists see in animals often don’t translate into results in humans. And the animals used in the studies were exposed to very high doses of the virus – way higher than the average human might encounter. Possibly, a vaccine will give us enough sterilising immunity to cope with the normal doses of virus we encounter.
Other vaccines being developed by biotech companies Moderna, Sinovac, and NovaVax, appeared to offer protection in the nose as well as in the lungs. We’re a long way from knowing whether a vaccine will provide sterilising immunity, says James Triccas, a professor of medical microbiology at the University of Sydney.
“I don’t think we have enough evidence to say ‘we cannot make a vaccine that will give you complete protection’.”
And the lack of protection in the nose is not a huge setback for vaccines, scientists emphasised. That’s not the focus for the first generation of vaccines.
“The most urgent need at the moment is to stop people getting severely ill and dying,” says Drummer.
A vaccine that turns COVID-19 into a mild cold would be a huge win, and save many millions of lives.
“But if the virus can still replicate a little bit, and be spread, that is an opportunity for the virus to continue spreading in the community.”
Will the vaccine stop the virus spreading? When does COVID-19 go away?
It’s common to think a vaccine will bring all this to an end. The virus will vanish, and we can resume our old lives.
That may be wishful thinking, says Suhrbier.
“The vaccine may not be the total solution that everyone wants. Many people still die from influenza every year, despite a vaccination campaign.”
Elimination – having no virus transmitting in Australia – could be a plausible scenario if we get a vaccine that provides absolute, 100 per cent sterilising immunity in 100 per cent of the population. The virus will have nowhere to go.
That’s possible. The human papillomavirus (HPV) vaccine appears to provide long-term sterilising immunity; so does the polio vaccine and that disease is now on the cusp of global eradication.
But scientists say a more likely scenario is a vaccine that protects against serious illness but does not provide total sterilising immunity – as with the flu vaccine.
“We have not really got to the point where we can readily develop those vaccines. It’s not something we have been good at,” says Suhrbier.
And SARS-CoV-2 is a particularly tricky virus to combat because it can jump so quickly from one person to another – a metric known as the “latent period”.
“The latent period for this virus can be astronomically short. You are infected, and 2½ days later you can be infectious. That’s an extremely short period,” says Suhrbier.
Let’s think about the implications of that.
If the virus can replicate in the nose and mouth, it only needs to survive for a couple of days before it is ready to jump to another person. Unfortunately, it takes at least a couple of days for the body’s T and B cells to arm up. That gives it a (small) chance to spread. “The virus could thus still circulate and infect people, even in a well-vaccinated population” says Suhrbier.
Indeed, by reducing the severity of the infection via a vaccine, you could turn everyone into asymptomatic spreaders.
“We basically make everyone who is vaccinated an asymptomatic spreader. That’s the worst-case scenario,” says Suhrbier.
It also means you can forget about herd immunity. “Not possible. Herd immunity will not be possible,” says Bartlett. If everyone can spread the virus, there’s no way we can get there.
That could pose a big problem for certain groups in our community, such as those with weakened immune systems and the elderly.
We don’t yet know how effective a vaccine is likely to be for them, but generally vaccines are less effective in those groups. We do know that around 1 in 10 people aged over 80 who get the virus die from it.
If the virus continued to circulate, it would continue to pose a mortal risk to vulnerable groups. Consider our ongoing battle with the flu. For young, healthy people, the flu is generally not fatal. And we have a vaccine. But the virus continues to circulate. And so every year it finds its way into people who are vulnerable. Some 902 people died in Australia from the flu last year.
“It will be a bit like flu, where we see seasonal outbreaks,” says Drummer. “I think the most likely scenario for this is this virus will be around with us forever.”