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From the bubonic plague to the Spanish flu, pandemics are not new, but a University of Melbourne expert says the 21st century has advancements and challenges.

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A pandemic can happen when a disease spreads between countries and continents. A recent example of a pandemic is COVID-19. Read more here.

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What Coronavirus Symptoms Look Like, Day By Day

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SARS-CoV-2, the coronavirus which causes COVID-19, has infected almost 2.5 million people around the world and claimed 170,000 lives.

But some people don't even get symptoms. Recent studies suggest as many as 80% or more of those infected are "silent carriers", showing no or very mild symptoms.

It seems children and young, healthy people are more likely to be asymptomatic.

Read more: Worried about your child getting coronavirus? Here's what you need to know

But to calculate the true proportions of people who have no symptoms right through to severe illness, testing would need to be expanded across whole populations, and this hasn't been feasible yet.

We don't know exactly why some people with coronavirus are asymptomatic while others develop life-threatening illness. But here's what we know so far.

What happens when coronavirus enters your body?

Like all viruses, SARS-CoV-2 needs to get inside human cells to multiply and survive.

To do this, a particle on the outer shell of the virus latches onto a matching protein receptor, called ACE2, like a lock and key. ACE2 receptors are normally found in the lungs, kidneys, heart and the gut.

Once a person has been infected with the virus, it can take up to 14 days for symptoms to appear (if they do at all) - known as the incubation period.

The path from the point of infection can vary enormously. The body's immune system is critical for determining this.

Having a strong immune response during the incubation period can prevent the infection taking hold, reduce the actual quantity of virus in the body and prevent it from getting to the lungs.

Read more: Coronavirus: how long does it take to get sick? How infectious is it? Will you always have a fever? COVID-19 basics explained

Some immune response basics

Our immune system offers us two lines of defence against viruses.

The first is the innate system and includes physical barriers such as skin and mucous membranes (the lining of the throat and nose), various proteins and molecules found in tissues, as well as some of the white blood cells that attack invading organisms. This immune response is general, non-specific and kicks in quickly.

Children have immature immune systems, but one hypothesis to explain why they don't seem to get as sick with COVID-19 is that their innate immune response to coronavirus is greater than in adults.

This may lead to a reduced viral load - the quantity of virus particles that survive in the body - because they're able to clear the virus more quickly.

The second line of defence is the adaptive immune response. This takes longer to initiate but once established, is much more efficient at eradicating a specific infection when encountering it again.

It's thought that very specific genetic variations in some people might play a part in how sick they get. By generating an early adaptive immune response, the body seems to recognise the virus during the incubation period and fight it off.

A person also needs to be generally healthy to be able to mount an appropriate immune response to the infection.

Read more: Why are older people more at risk of coronavirus?

After the incubation period, what determines how sick you get?

If the SARS-CoV-2 virus survives beyond the point of entry to the body (nose, eyes, throat) it might then make its way down the respiratory tract into the lungs.

In the lungs, it latches onto ACE2 receptors and continues replicating itself, triggering further immune responses to clean out infected cells. The amount of virus that gets deep into the lungs may be another important factor determining how sick you get.

As the battle between virus and immune responses proceeds, infected airway linings produce large amounts of fluid that fill the air sacs, leaving less room for transferring oxygen into the bloodstream and removing carbon dioxide.

Symptoms of pneumonia appear, such as fever, cough with sputum (phlegm) and shortness of breath.

For some people, the immune response is excessive or prolonged and causes what's known as a "cytokine storm". Cytokines are a group of proteins that send signals to cells in the immune system, helping direct the response.

A cytokine storm is a catastrophic overreaction that causes so much inflammation and organ damage, it can be fatal.

In people with COVID-19, as well as the previous SARS and MERS coronaviruses, this causes acute respiratory distress syndrome (ARDS), when fluid builds up in the lungs. This is the most common cause of death from SARS-CoV-2.

Elderly people and those with chronic lung disorders are more likely to develop ARDS and therefore to die. This is currently thought to be due to these groups of people having fewer ACE2 receptors in their lungs.

Read more: What does it mean to be immunocompromised? And why does this increase your risk of coronavirus?

This seems counter-intuitive, because the virus attaches itself to these receptors. However, ACE2 receptors have an important role in regulating the immune response, particularly in managing the degree of inflammation.

So the reduced levels of ACE2 receptors in the elderly may actually make them more at risk of a cytokine storm and severe lung disease.

Conversely, children have more ACE2 receptors in their lungs which might explain why they do not get as sick.

In some cases, medications that work to suppress the immune system have successfully treated this excessive immune response in people with COVID-19.

Can people without symptoms pass it on?

Some studies have indicated people with COVID-19 tend to have a high viral load just before and shortly after they start getting symptoms.

This suggests they can transmit it when they first get sick and up to 48 hours before, while they're pre-symptomatic.

However, there is no good evidence that asymptomatic people who never develop symptoms are able to pass it on.

Researchers and clinicians are working around the clock to understand the complex relationship between humans' immune systems and SARS-CoV-2 but it remains very much a work in progress.

Read more: What the coronavirus does to your body that makes it so deadly

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Why do some people with coronavirus get symptoms while others don't?

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SARS-CoV-2, the coronavirus which causes COVID-19, has infected almost 2.5 million people around the world and claimed 170,000 lives. But some people don't even get symptoms. Recent studies suggest as many as 80% or more of those infected are "silent carriers", showing no or very mild symptoms. It seems children and young, healthy people are more likely to be asymptomatic.

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The new coronavirus pandemic is historic. But this isn't the first time a virus has sickened people around the globe. Pandemics have happened throughout history.

The most recent pandemic started just over a decade ago, in 2009, with the outbreak of a new kind of H1N1 flu called the swine flu. The illness most likely started in North America, and it quickly spread around the world.

Swine flu wasn't nearly as deadly as the coronavirus. That made it much easier to control. Governments did not have to issue stay-at-home orders like we are seeing today. By late 2009, vaccines were available to prevent people from becoming sick.

Throughout History

Before the modern era of pandemics, the United States was hit hard by yellow fever, which arrived in Philadelphia, Pennsylvania, in 1793. Yellow fever attacks a person's liver and kidneys. The disease got its name because it causes the skin to take on a yellow tint.

Back then, scientists didn't understand what caused yellow fever or how it spread, which made it difficult to stop the outbreak. But when the weather in Philadelphia cooled down in the fall, the outbreak let up. That's because yellow fever is spread by mosquitoes, which aren't active in cold weather-though scientists wouldn't learn that until a century later. Today, yellow fever can be prevented with a vaccine. The disease is no longer a concern in the U.S., but people traveling to parts of Africa and South America may be required to take precautions.

In 1918, a true pandemic hit, caused by a new kind of flu called the Spanish flu. (The disease didn't actually start in Spain, but newspapers there were among the first to report on it. So people started calling it the Spanish flu, and the name stuck.)

Experts believe that one third of the world's population was infected with the Spanish flu. Many historians have compared it to the new coronavirus. "They're similar in the way they infect people," historian John Barry told TIME for Kids. "They're similar in the way they spread." Both the coronavirus and Spanish flu can affect a person's lungs. And they both spread when a person coughs, sneezes, or talks.

Stopping the Spread

During the Spanish flu pandemic, the U.S. put in place restrictions similar to those we're seeing today. People were asked to wear face masks and encouraged to wash their hands. Officials limited large gatherings and ordered people to quarantine themselves.

"Quarantine is centuries and centuries old," says Katherine Foss. She's an author and professor who has studied pandemics throughout history. "It's the number-one practice that is used to stop an outbreak. And it works even when scientists don't know what is making people sick."

Science has come a long way since 1918. Back then, doctors didn't even have microscopes that were powerful enough to let them see the viruses that cause pandemics. Today, scientists and doctors have advanced technology to help them battle the new coronavirus. "But since we're dealing with a brand-new virus that nobody has ever seen before, it still takes time to develop vaccines and treatments using modern medicine," Barry says. "In the meantime, the only thing left to fight it with are public-health measures like quarantine."

Barry says that although there have been many pandemics throughout history, kids should understand that this one is unusually severe.

"This is something you're going to remember for the rest of your life," he says. "This is not ordinary. This is a special time that requires special courage. You have an opportunity to rise to greatness. Social distancing matters, and it saves lives."

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The new coronavirus pandemic is historic. But this isn't the first time a virus has sickened people around the globe. Pandemics have happened throughout history. The most recent pandemic started just over a decade ago, in 2009, with the outbreak...

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MILLIE, ROOKIE REPORTER: Hi, my name's Millie Chappell. I'm 11 years old and this is my brother Benji and my sister Jessie. We live in Brisbane.

MILLIE: I'm going to tell you about vaccines with help from my friends and our parents. My dad, Zoe and Lucy's Dad and Emma and Adele's Mum all work at the University of Queensland. Like many other scientists right now, they're working on a vaccine for COVID-19.

ZOE & LUCY, ROOKIE REPORTERS: What is a vaccine?

PROFESSOR TRENT MUNRO, UNIVERSITY OF QUEENSLAND: A vaccine is something that we use to try and protect people from disease.

DR. KEITH CHAPPELL, UNIVERSITY OF QUEENSLAND: It teaches your body what a disease is so then it can make a proper immune response to stop you from getting sick.
ZOE & LUCY: How does it help people?

PROFESSOR TRENT MUNRO, UNIVERSITY OF QUEENSLAND: Before vaccines people used to get a lot more diseases. Things like measles and smallpox and polio. They're diseases we don't really see much of today and it's all because of vaccines.

MILLIE: Why is it important to make a vaccine for COVID-19?

DR KEITH CHAPPELL, UNIVERSITY OF QUEENSLAND: So COVID-19 is a really severe disease that's making a lot of people sick and people are dying. If we have a great vaccine, we can stop the virus from circulating and save people's lives.

ZOE & LUCY: How do you make a vaccine?

PROFESSOR TRENT MUNRO, UNIVERSITY OF QUEENSLAND: Well Lucy, that's a really good question. Making a vaccine is actually pretty complicated and on top of that there are lots of different types of vaccines. But there's a few different ways you can make it. One is that you can actually use part of the virus and you can actually use that and make a dead version or make an inactivated version and you can give that to people to trick their body into thinking they've been exposed to the virus and then they raise immunity against it, or now there are a lot more modern techniques like the techniques we're using at the University of Queensland where we're using molecular biology and genetic engineering and cell culture and we're able to take sequences of DNA and actually turn that into a vaccine.

EMMA & ADELE, ROOKIE REPORTERS: How long does it usually take?

DR JULIA LACKENBY, UNIVERSITY OF QUEENSLAND: Normally to make a vaccine it can take anywhere up to ten to 15 years, but our lab here has a really special technology that allows us to do that in as little as 12-18 months.
PROFESSOR TRENT MUNRO, UNIVERSITY OF QUEENSLAND: We need to both understand the disease that we're trying to treat and also understand how the vaccine works and the main reason for that is because we want to make sure it's safe. Unlike a drug where you'd give a drug to someone who's already sick, a vaccine is only given to healthy people, people who are not sick, so you really need to make sure that, you know, that vaccine is very safe and that it's going to work, it's going to help protect them from the disease.

MILLIE: Can we go in the lab now?

DR KEITH CHAPPELL, UNIVERSITY OF QUEENSLAND: We sure can.

MILLIE'S SISTER AND BROTHER: Every time we go into the lab there are some safety measures we need to take. Like wearing our gloves, eye protection gloves and shoes and lab coats.

MILLIE: This lab isn't the only one working on a COVID-19 vaccine. There are heaps of others in Australia and around the world working on it too. They're using lots of different methods and everyone is hoping that one of them will work.

MILLIE: I think that making a vaccine is really important, so I'm really proud that my dad and his team are some of the world leaders in developing a vaccine for coronavirus. Hopefully they'll have some good news for everyone soon.

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MILLIE, ROOKIE REPORTER: Hi, my name's Millie Chappell. I'm 11 years old and this is my brother Benji and my sister Jessie. We live in Brisbane. MILLIE: I'm going to tell you about vaccines with help from my friends and our parents.

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Reference article: Definition and examples of a pandemic.

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FACT: Hand sanitizers can be used often

An alcohol-based sanitizer does not create antibiotic resistance. Unlike other antiseptics and antibiotics, pathogens (harmful germs) do not seem to develop resistance to alcohol-based sanitizers.

FACT: Alcohol-based sanitizers are safe for everyone to use

Alcohols in the sanitizers have not been shown to create any relevant health issues. Little alcohol is absorbed into the skin, and most products contain an emollient to reduce skin dryness. Allergic contact dermatitis and bleaching of hand hair due to alcohol are very rare adverse effects. Accidental swallowing and intoxication have been described in rare cases.

FACT: Alcohol-based sanitizers can be used in religions where alcohol is prohibited

Any manufactured substance developed to alleviate illness or contribute to better health is permitted by the Qur'an, including alcohol used as a medical agent.

FACT: The amount of alcohol-based sanitizer you use matters

Apply a palmful of alcohol-based sanitizer to cover all surfaces of your hands. Rub your hands together using the right technique until they are dry.

The entire procedure should last 20-30 seconds.

FACT: Vitamin and mineral supplements cannot cure COVID-19

Micronutrients, such as vitamins D and C and zinc, are critical for a well-functioning immune system and play a vital role in promoting health and nutritional well-being. There is currently no guidance on the use of micronutrient supplements as a treatment of COVID-19.

WHO is coordinating efforts to develop and evaluate medicines to treat COVID-19.

Is dexamethasone a treatment for all COVID-19 patients?

Dexamethasone should be reserved for patients who need it most. It should not be stockpiled.

It provided no improvement for patients with mild symptoms. Dexamethasone is a corticosteroid used for its anti-inflammatory and immunosuppressive effects. For some COVID-19 patients on ventilators, a daily 6 mg dose of dexamethasone for 10 days improved their health

Fact: Water or swimming does not transmit the COVID-19 virus

The COVID-19 virus does not transmit through water while swimming. However, the virus spreads between people when someone has close contact with an infected person.

WHAT YOU CAN DO:

Avoid crowds and maintain at least a 1-metre distance from others, even when you are swimming or at swimming areas. Wear a mask when you're not in the water and you can't stay distant. Clean your hands frequently, cover a cough or sneeze with a tissue or bent elbow, and stay home if you're unwell.

FACT: The coronavirus disease (COVID-19) is caused by a virus, NOT by bacteria

The virus that causes COVID-19 is in a family of viruses called Coronaviridae. Antibiotics do not work against viruses.

Some people who become ill with COVID-19 can also develop a bacterial infection as a complication. In this case, antibiotics may be recommended by a health care provider.

There is currently no licensed medication to cure COVID-19. If you have symptoms, call your health care provider or COVID-19 hotline for assistance.

FACT: Spraying and introducing bleach or another disinfectant into your body WILL NOT protect you against COVID-19 and can be dangerous

Do not under any circumstance spray or introduce bleach or any other disinfectant into your body. These substances can be poisonous if ingested and cause irritation and damage to your skin and eyes.

Bleach and disinfectant should be used carefully to disinfect surfaces only. Remember to keep chlorine (bleach) and other disinfectants out of reach of children.

FACT: Antibiotics CANNOT prevent or treat COVID-19

Antibiotics work only against bacteria, not viruses.

COVID-19 is caused by a virus, and therefore antibiotics should not be used for prevention or treatment.

Some people who become ill with COVID-19 can also develop a bacterial infection as a complication. In this case, antibiotics may be recommended by a health care provider.

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COVID-19 Mythbusters - World Health Organization

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Highlighting some of the misinformation circulating on COVID-19

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There are more than 100 coronavirus vaccines in the pipeline and almost a dozen that have made it to human trials so far.

But which one - if any - will be the panacea to the COVID-19 pandemic is still anyone's guess.

Researchers working to develop a SARS-CoV-2 vaccine face a unique and significant set of challenges - not to mention the fact they're trying to do it in record time.

While it will be some months before we know whether any of the proposed vaccines are effective, initial safety trials and encouraging animal studies show promising early signs.

Let's take a closer look at some of the candidates leading the race (remembering those that make it to clinical trials first will not necessarily be the most effective).

The 10 vaccines in human trials

A quick recap, according to the World Health Organization, as of May 24.

Non-replicating viral vector vaccine from CanSino (China)

RNA vaccine from Moderna (USA)

Inactivated vaccine from Wuhan Institute of Biological Products (China)

Inactivated vaccine from Beijing Institute of Biological Products (China)

Inactivated vaccine from Sinovac (China)

Non-replicating viral vector vaccine from Oxford University and AstraZeneca (UK)

Protein subunit vaccine from Novavax (US)

RNA vaccine from BioNTech and Pfizer (Germany/USA)

DNA vaccine from Inovio (US)

While vaccine developers typically follow a linear sequence (pre-clinical animal studies to Phase 1/2/3/4 human trials), the urgency of COVID-19 means many are speeding up their timelines.

In some cases, Phase 1 and 2 trials are being squashed together (testing safety and effectiveness of the vaccine at the same time), or Phase 1 human safety trials are running before animal efficacy data is in.

Genetic vaccines create buzz

This week, all eyes were on an experimental vaccine produced by American biotech company Moderna - the first coronavirus vaccine to be tested in humans back in March.

On Monday, the biotech firm announced its RNA vaccine, which was given to 45 healthy individuals in a Phase 1 trial, appeared to be safe and promote an immune response against COVID-19.

Coronavirus questions answered

Breaking down the latest news and research to understand how the world is living through an epidemic, this is the ABC's Coronacast podcast.

Read more

Unlike more traditional vaccines, which contain a weakened version of the actual virus or portions of it, Moderna's vaccine is based on a new technology that involves taking genetic material from the virus and delivering it to healthy cells.

Using messenger RNA (or mRNA), the vaccine carries instructions to the body to create the SARS-CoV-2 protein the vaccine is aiming to protect against.

The idea is that the body detects the genetic material and new protein as foreign, and mounts an immune response - producing antibodies that learn to remember and fight the virus if the body encounters it again.

Without publishing its findings in full, Moderna said preliminary data of eight people in its trial showed participants developed neutralising antibodies (which stop the virus replicating) at levels similar to people who have recovered from COVID-19.

The findings, though limited, sent the company's share price soaring. But it later dropped when Medical news website STAT reported the figures "don't mean much on their own, because critical information ... was withheld", including information about the other 37 trial participants.

Like all vaccine candidates, Moderna's findings need to be repeated in much larger Phase 2 (and eventually Phase 3) clinical trials to prove the vaccine actually works. These are expected to begin soon.

Meanwhile, two other genetic vaccines for COVID-19 have also made it to human trials - one from American biotech firm Inovio, and another jointly developed by pharmaceutical giant Pfizer and German company BioNTech.

Inovio, which has enrolled 40 people in a phase 1 trial of its DNA vaccine, is expected to publish its results in early June.

Moderna is collaborating with the US National Institute of Allergy and Infectious Diseases.(Getty Images: Boston Globe)

Pfizer, on the other hand, has begun delivering doses of its RNA vaccine to 360 volunteers in the US as part of a Phase 1/2 trial. The drug maker and its German partner said if the vaccine proved to be safe and effective, it could potentially be ready for US distribution by the end of the year.

Kylie Quinn, a vice-chancellor's research fellow at RMIT University, said although genetic vaccines are relatively easy and inexpensive to produce, none have been approved for human use before.

"We don't know how they're going to perform in humans, but the advantage of them is that they are very quick in terms of design and manufacturing, and should be relatively safe," said Dr Quinn.

Viral vector vaccines charge ahead

Using an entirely different approach, scientists at Oxford University's Jenner Institute recently announced a coronavirus vaccine they are working on appears to be protective in monkeys. The vaccine is already being tested in humans.

According to a preliminary research paper - which has not yet been peer-reviewed - the vaccine candidate provided protection in six rhesus macaque monkeys who were vaccinated and then exposed to high levels of SARS-CoV-2.

The animals had less of the virus in their lungs and airways when compared to non-vaccinated animals, and were protected from developing pneumonia.

Oxford's vaccine candidate is known as a viral vector vaccine, and is one of several being developed for COVID-19. These vaccines work by introducing a different type of virus that is engineered to include proteins of the virus the vaccine is aiming to protect against.

"You basically take a virus that is generally harmless but can infect cells and you use it like a trojan horse," Dr Quinn said.

For the Oxford vaccine, a genetically modified version of a common cold virus (known as an adenovirus) from chimpanzees is being used to carry a protein from SARS-CoV-2 to the body. The goal is to stimulate an immune response and prime the body to respond to any future infection.

Unlike most other vaccines, which begin with small clinical trials to demonstrate safety, this vaccine was fast-tracked because the research team had already tested very similar vaccines in humans for other viruses, including MERS and Ebola.

Researchers hope to test the vaccine on more than 6,000 people in the UK by the end of May, as part of a Phase 1/2 trial. If those results show the vaccine is effective, they say the first few million doses could be available as soon as September, with emergency approval from regulators.

This chart uses a logarithmic scale to highlight coronavirus growth rates. Read our explainer to understand what that means - and how COVID-19 cases are spreading around the world.

Trevor Drew, director of CSIRO's Australian Centre for Disease Preparedness, said the decision by British drug-maker AstraZeneca to partner with Oxford to manufacture and distribute the vaccine was an encouraging sign.

"The Oxford vaccine is really quite a clever one," Professor Drew said. "I think it's probably going to be one of the prime candidates."

Besides Oxford, one other viral vector vaccine has made it to human trials. It comes from Chinese vaccine company CanSino.

While CanSino is yet to publish detailed results of its Phase 1 trial, its vaccine candidate was the first to reach Phase 2 clinical trials back in April.

Tried and tested methods being used

Three of the remaining vaccines to have made it to human trials are "inactivated" vaccines, which means they contain the actual virus, but it's been killed by being exposed to ultraviolet light or chemicals.

"This is a really simple and sometimes very effective way of introducing your immune system to something without having the potential to cause disease," Dr Quinn said. "It's a very old style of vaccine."

Inactivated vaccines are slightly different to live attentuated vaccines, which involve introducing a "live" virus into the body, but one that has been weakened. Just a handful of COVID-19 vaccine candidates are using this approach, all still in pre-clinical trials.

The three inactivated vaccines that have made it to human trials are being developed in China and are in Phase 1/2 clinical trials, however data from the initial phase 1 trials is limited.

One of the vaccine candidates, developed by Chinese biopharmaceutical company Sinovac, was recently shown to be effective in rhesus macaque monkeys, who - like in the Oxford vaccine study - generated neutralising antibodies.

"It builds the case that [this vaccine] is possibly viable and worth following up on," Dr Quinn said.

Read more about coronavirus:

The final type of vaccine researchers are pursuing are called subunit or protein vaccines. These contain only a fragment of the virus, rather than the whole thing.

US biotech company Novavax recently begun Phase 1 clinical trials in Australia with a subunit vaccine that targets the "spike" protein on the surface of coronvirus particles.

It's the same technique being pursued by researchers at the University of Queensland, who are set to begin clinical trials in July.

Multiple vaccines possible

There are pros and cons to every vaccine approach, and it may be that multiple candidates are found to show some protection against COVID-19.

No vaccine is 100 per cent effective, and the vast majority of vaccines that make it to clinical trials do not succeed in getting to market.

Given the challenges of manufacturing and distributing a vaccine on a global scale, Dr Quinn said it wouldn't be a bad outcome if several candidates were ultimately used.

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"Different vaccines have very specific manufacturing requirements," she said.

"So perhaps having a few different vaccine formats that each show a level of protecting ... we can spread the weight across different manufacturing facilities."

Professor Drew said because the COVID-19 vaccine development timeline was being compressed, and some of the longer-term effects would be unknown, the decision to roll it out - if an effective vaccine was found - would likely be based on each country's individual level of risk.

"How urgent is the vaccine needed, and what are the potential benefits against some of the more minor risks?" he said.

"In the current situation with COVID-19, a lot of those decisions may be made with the acceptance [that] there may be some minor downstream issues, but certainly no worse than the current suffering that's being created by the disease itself."

What you need to know about coronavirus:

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Who are the frontrunners in the coronavirus vaccine race?

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There are more than 100 coronavirus vaccines in the pipeline and almost a dozen that have made it to human trials so far. But which one - if any - will be the panacea to the COVID-19 pandemic is still anyone's guess.

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The first coronaviruses known to infect humans were discovered more than half a century ago - so why are there no vaccines against these viruses? Should we be optimistic that an effective vaccine will be developed now?

SARS-CoV-2, the recently discovered coronavirus that causes COVID-19, is similar enough to other coronaviruses, so scientists make predictions about how our immune system might deal with it. But its novelty warrants its own careful study. Similar to Sars and Mers that cause severe acute respiratory syndrome, the novel coronavirus has emerged from animals and can cause damage to the lungs and sometimes other organs.

Why don't we have a vaccine against other human coronaviruses? The emergence of Sars and Mers, in 2002 and 2012 respectively, were either quashed relatively quickly or affected small numbers of people. Despite the interest from keen virologists, there was no economic incentive to develop a vaccine for these diseases as they posed a small threat at the time. Virologists with an interest in coronaviruses were struggling to secure funding for their research.

In contrast, COVID-19 has caused huge disruption around the world. As a result, at least 90 vaccines are under development, with some already in human trials.

How a vaccine works

A vaccine gives our body a harmless flavour of the virus, alerting the immune response to generate antibodies and/or cellular immunity (T cells) ready to fight the infection. The idea is that we can then deploy a ready-made defence system next time we encounter the virus, and this spares us from severe symptoms. We know that most people who have recovered from COVID-19 have detectable antibodies in their blood.

We don't know if these antibodies are fully protective, but a vaccine still has the potential to elicit powerful neutralising antibodies and scientists will evaluate these following vaccination. Researchers will also look for potent T cell responses in the blood of vaccinated people. These measurements will help scientists predict the efficacy of the vaccine, and will be available before a vaccine is approved.

The best way to evaluate a vaccine, of course, is to judge how well it protects people from infection. But exposing vulnerable groups to the virus is far too risky, so most vaccines will be tested in younger people with no underlying health problems. There are ethical considerations for deliberately infecting a healthy person with a potentially dangerous virus for a vaccine trial, and these need to be considered carefully.

In the course of a pandemic, a vaccinated volunteer may become infected with the novel coronavirus, especially if they are a healthcare worker. It will take time to gather data on protection following infection and compare them to people that received a placebo vaccine.

Vaccine challenges

The ideal vaccine should protect everyone and cause lifelong defences with a single dose. It would be quick to produce, affordable, easy to administer (nasal or oral administration) and wouldn't need refrigeration, so non-specialists can distribute it to hard-to-reach parts of the world. In reality, we don't fully understand how to produce a vaccine that induces long-lived protective immunity for different viruses. For some infections, we need to administer booster vaccinations.

Ageing comes with a tired immune system that struggles to respond to vaccination, and this is also the case for people with weakened immune systems, so it is difficult to protect the most vulnerable. Therefore, vaccination programmes that protect over 80% of the population can reduce the incidence of virus spreading and protect the vulnerable by proxy, through herd immunity. Currently, the percentage of people who may have had COVID-19 in different parts of the world varies, but this is hard to estimate because of test availability.

Scientists test and confirm a vaccine's safety before it is approved. We appreciate that in some viral infections, existing antibodies from an earlier infection with the same type of virus can cause more severe disease. However, there is no strong evidence for any adverse effects of antibodies for SARS-CoV-2 infection.

Within reach

Here are some reasons to be optimistic. One, this virus can be cured. Unlike some viruses such as HIV that embed their genome in our own and make fresh copies of themselves after immune elimination, we know that SARS-CoV-2 is unable to persist in this way.

Two, most infected patients develop antibodies and there is evidence of virus-specific T cell responses. Although we don't know if these responses are protective yet, these are precisely the responses that can lead to immunological memory, the cornerstone of vaccination. Vaccine products will be refined and enriched to induce more potent immune responses than natural infection.

Three, coronaviruses mutate slower than viruses such as influenza, and we know from Sars and Mers that antibodies can persist for at least one to two years following recovery. This is good news for an effective vaccine that may not require updating for quite some time.

There are more reasons to be upbeat. Scientists are testing several approaches so there is a higher probability of success, and pharmaceutical companies have been engaged early, scaling up production and working out logistics for distribution even before there is evidence the vaccine will work. This is worth the investment because resources can be quickly repurposed for the most promising vaccines following the first clinical trials.

A coronavirus vaccine is within our reach, and it is our best hope to stem transmission and generate herd immunity to protect the most vulnerable. Taking away its hosts for replication, we can eradicate this virus from the human population just as vaccination previously eradicated smallpox.

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Coronavirus vaccine: reasons to be optimistic

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The first coronaviruses known to infect humans were discovered more than half a century ago - so why are there no vaccines against these viruses? Should we be optimistic that an effective vaccine will be developed now?

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As Australian authorities prepare for the coronavirus outbreak to be declared a global pandemic, health experts say there is already good evidence about who is most at risk from COVID-19.

Doctors have been quick to analyse who has been suffering serious complications of coronavirus

Children who contracted the virus overseas have only had mild symptoms

In China, those most at risk of dying were aged over 70

The good news is that children seem to be safe from severe symptoms.

Chief medical officer Dr Brendan Murphy said one of the surprising features about the virus was how few children seemed to have been identified as infected.

"It's very unusual compared to influenza," he said.

"We don't know whether children might be getting the disease but [their symptoms] are so mild they are not being picked up, or they're not becoming sick, or whether they are somehow less susceptible."

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Professor Robert Booy from the National Centre for Immunisation Research and Surveillance said for some reason children appeared to be getting a mild dose of COVID-19.

"Those children who did contract the virus overseas have only had mild symptoms such as fever and upper respiratory symptoms," he said.

So far, no children have been reported as having serious complications, but that is not the case for adults, particularly older ones.

"In adults, they are reacting quite violently because perhaps they have seen a previous coronavirus infection and that's set up the immune system to react inappropriately and excessively," Professor Booy said.

Who is most likely to get COVID-19?

Unlike previous disease outbreaks, doctors across the world have been quick to analyse just who has been suffering serious complications of coronavirus.

One of the largest studies looked at more than 72,000 patients with COVID-19 from China.

Researchers found most people only developed mild symptoms, and those with mild symptoms did not die.

The fatalities occurred in people who already had serious health conditions such as cardiovascular disease, diabetes, high blood pressure or cancer.

The most common symptoms are fever, fatigue, a dry cough and feeling unwell.(AP: Claudio Furlan/Lapresse)

No deaths occurred in children, and those most at risk of dying were aged over 70, with an even greater death rate in people aged over 80.

Another paper in the Journal of the American Medical Association analysed who was ending up in hospital in China with pneumonia from COVID-19.

Of the 138 patients, more than half were men with a median age of 56.

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The most common symptoms they suffered were fever, fatigue, a dry cough and feeling unwell.

Less common symptoms were headache, dizziness, abdominal pain and diarrhoea.

To treat COVID-19, patients were given a cocktail of antiviral and antibiotics treatments.

While one third of the patients were healthy enough to be discharged from hospital, six of them died from the illness.

The findings point Australian experts to where resources need to be deployed.

Professor Booy said Australia needed to focus on older people living in aged care and the elderly still living at home, as they were most at risk.

"People with chronic medical conditions of the lung or the heart also need to be closely monitored," he said.

So far, pregnant women do not appear to be at increased risk of contracting coronavirus and developing complications, unlike in the case of influenza.

How many Australians are likely to get COVID-19?

While some health experts have suggested the majority of Australians could become infected, Professor Booy said that was unlikely.

"I think with our containment approach, we can keep it down to well under 50 per cent of the population getting sick," he said.

"That's still a lot and I would like to see it down to 10 to 20 per cent of people."

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He said authorities needed to act promptly to prevent it spreading.

"This is a highly transmissible virus. It's surprising how transmissible it is. It is really quite worrying," Professor Booy said.

Professor Booy said countries with strong border controls like Australia now had the virus spreading in the community.

While several cases have been reported in Australia, he said COVID-19 would eventually affect a significant percentage of the population.

"It could be within a few weeks. it could be one to two months, [but] it's going to come here," he said.

"I don't think we can stop this."

Advice for everyone: keep your distance

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How coronavirus sparked a global emergency.

Even though research has shown that COVID-19 is more likely to be a severe illness in older people, experts say it is wise to treat everyone with "caution and respect".

"Anyone could transmit the infection to you," Professor Booy said.

"So smile, don't shake hands, keep a good distance away from other people."

Practice good hand hygiene with frequent hand washing, disposing of tissues and sneezing into the crook of your arm.

What the experts are saying about coronavirus:

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Who is vulnerable to coronavirus? So far children appear safe from COVID-19

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As Australian authorities prepare for the coronavirus outbreak to be declared a global pandemic, health experts say there is already good evidence about who is most at risk from COVID-19.

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History of Pandemics

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In the realm of infectious diseases, a pandemic is the worst case scenario. When an epidemic spreads beyond a country's borders, that's when the disease officially becomes a pandemic.

Communicable diseases existed during humankind's hunter-gatherer days, but the shift to agrarian life 10,000 years ago created communities that made epidemics more possible. Malaria, tuberculosis, leprosy, influenza, smallpox and others first appeared during this period.
READ MORE: See all pandemic coverage here.
The more civilized humans became, building cities and forging trade routes to connect with other cities, and waging wars with them, the more likely pandemics became. See a timeline below of pandemics that, in ravaging human populations, changed history.

430 B.C.: Athens

The earliest recorded pandemic happened during the Peloponnesian War. After the disease passed through Libya, Ethiopia and Egypt, it crossed the Athenian walls as the Spartans laid siege. As much as two-thirds of the population died.

The symptoms included fever, thirst, bloody throat and tongue, red skin and lesions. The disease, suspected to have been typhoid fever, weakened the Athenians significantly and was a significant factor in their defeat by the Spartans.

165 A.D.: Antonine Plague

The Antonine plague was possibly an early appearance of smallpox that began with the Huns. The Huns then infected the Germans, who passed it to the Romans and then returning troops spread it throughout the Roman empire. Symptoms included fever, sore throat, diarrhea and, if the patient lived long enough, pus-filled sores. This plague continued until about 180 A.D., claiming Emperor Marcus Aurelius as one of its victims.

250 A.D.: Cyprian Plague

Named after the first known victim, the Christian bishop of Carthage, the Cyprian plague entailed diarrhea, vomiting, throat ulcers, fever and gangrenous hands and feet.

City dwellers fled to the country to escape infection but instead spread the disease further. Possibly starting in Ethiopia, it passed through Northern Africa, into Rome, then onto Egypt and northward.

There were recurring outbreaks over the next three centuries. In 444 A.D., it hit Britain and obstructed defense efforts against the Picts and the Scots, causing the British to seek help from the Saxons, who would soon control the island.

541 A.D.: Justinian Plague

First appearing in Egypt, the Justinian plague spread through Palestine and the Byzantine Empire, and then throughout the Mediterranean.

The plague changed the course of the empire, squelching Emperor Justinian's plans to bring the Roman Empire back together and causing massive economic struggle. It is also credited with creating an apocalyptic atmosphere that spurred the rapid spread of Christianity.

Recurrences over the next two centuries eventually killed about 50 million people, 26 percent of the world population. It is believed to be the first significant appearance of the bubonic plague, which features enlarged lymphatic gland and is carried by rats and spread by fleas.

11th Century: Leprosy

Though it had been around for ages, leprosy grew into a pandemic in Europe in the Middle Ages, resulting in the building of numerous leprosy-focused hospitals to accommodate the vast number of victims.

A slow-developing bacterial disease that causes sores and deformities, leprosy was believed to be a punishment from God that ran in families. This belief led to moral judgments and ostracization of victims. Now known as Hansen's disease, it still afflicts tens of thousands of people a year and can be fatal if not treated with antibiotics.

1350: The Black Death

Responsible for the death of one-third of the world population, this second large outbreak of the bubonic plague possibly started in Asia and moved west in caravans. Entering through Sicily in 1347 A.D. when plague sufferers arrived in the port of Messina, it spread throughout Europe rapidly. Dead bodies became so prevalent that many remained rotting on the ground and created a constant stench in cities.

England and France were so incapacitated by the plague that the countries called a truce to their war. The British feudal system collapsed when the plague changed economic circumstances and demographics. Ravaging populations in Greenland, Vikings lost the strength to wage battle against native populations, and their exploration of North America halted.

1492: The Columbian Exchange

Following the arrival of the Spanish in the Caribbean, diseases such as smallpox, measles and bubonic plague were passed along to the native populations by the Europeans. With no previous exposure, these diseases devastated indigenous people, with as many as 90 percent dying throughout the north and south continents.

Upon arrival on the island of Hispaniola, Christopher Columbus encountered the Taino people, population 60,000. By 1548, the population stood at less than 500. This scenario repeated itself throughout the Americas.

In 1520, the Aztec Empire was destroyed by a smallpox infection. The disease killed many of its victims and incapacitated others. It weakened the population so they were unable to resist Spanish colonizers and left farmers unable to produce needed crops.

Research in 2019 even concluded that the deaths of some 56 million Native Americans in the 16th and 17th centuries, largely through disease, may have altered Earth's climate as vegetation growth on previously tilled land drew more CO2 from the atmosphere and caused a cooling event.
READ MORE: How Colonization's Death Toll May Have Affected Earth's Climate
1665: The Great Plague of London

In another devastating appearance, the bubonic plague led to the deaths of 20 percent of London's population. As human death tolls mounted and mass graves appeared, hundreds of thousands of cats and dogs were slaughtered as the possible cause and the disease spread through ports along the Thames. The worst of the outbreak tapered off in the fall of 1666, around the same time as another destructive event-the Great Fire of London.

1817: First Cholera Pandemic

The first of seven cholera pandemics over the next 150 years, this wave of the small intestine infection originated in Russia, where one million people died. Spreading through feces-infected water and food, the bacterium was passed along to British soldiers who brought it to India where millions more died. The reach of the British Empire and its navy spread cholera to Spain, Africa, Indonesia, China, Japan, Italy, Germany and America, where it killed 150,000 people. A vaccine was created in 1885, but pandemics continued.

1855: The Third Plague Pandemic

Starting in China and moving to India and Hong Kong, the bubonic plague claimed 15 million victims. Initially spread by fleas during a mining boom in Yunnan, the plague is considered a factor in the Parthay rebellion and the Taiping rebellion. India faced the most substantial casualties, and the epidemic was used as an excuse for repressive policies that sparked some revolt against the British. The pandemic was considered active until 1960 when cases dropped below a couple hundred.

1875: Fiji Measles Pandemic

After Fiji ceded to the British Empire, a royal party visited Australia as a gift from Queen Victoria. Arriving during a measles outbreak, the royal party brought the disease back to their island, and it was spread further by the tribal heads and police who met with them upon their return.

Spreading quickly, the island was littered with corpses that were scavenged by wild animals, and entire villages died and were burned down, sometimes with the sick trapped inside the fires. One-third of Fiji's population, a total of 40,000 people, died.

1889: Russian Flu

The first significant flu pandemic started in Siberia and Kazakhstan, traveled to Moscow, and made its way into Finland and then Poland, where it moved into the rest of Europe. By the following year, it had crossed the ocean into North America and Africa. By the end of 1890, 360,000 had died.

1918: Spanish Flu

The avian-borne flu that resulted in 50 million deaths worldwide, the 1918 flu was first observed in Europe, the United States and parts of Asia before swiftly spreading around the world (there is no universal consensus regarding where the virus originated). At the time, there were no effective drugs or vaccines to treat this killer flu strain. Wire service reports of a flu outbreak in Madrid in the spring of 1918 led to the pandemic being called the " Spanish flu."

By October, hundreds of thousands of Americans died and body storage scarcity hit crisis level. But the flu threat disappeared in the summer of 1919 when most of the infected had either developed immunities or died.
READ MORE: Why October 1918 Was America's Deadliest Month Ever
1957: Asian flu

Starting in Hong Kong and spreading throughout China and then into the United States, the Asian flu became widespread in England where, over six months, 14,000 people died. A second wave followed in early 1958, causing an estimated total of about 1.1 million deaths globally, with 116,000 deaths in the United States alone. A vaccine was developed, effectively containing the pandemic.

1981: HIV/AIDS

First identified in 1981, AIDS destroys a person's immune system, resulting in eventual death by diseases that the body would usually fight off. Those infected by the HIV virus encounter fever, headache, and enlarged lymph nodes upon infection. When symptoms subside, carriers become highly infectious through blood and genital fluid, and the disease destroys t-cells.

AIDS was first observed in American gay communities but is believed to have developed from a chimpanzee virus from West Africa in the 1920s. The disease, which spreads through certain body fluids, moved to Haiti in the 1960s, and then New York and San Francisco in the 1970s.

Treatments have been developed to slow the progress of the disease, but 35 million people worldwide have died of AIDS since its discovery, and a cure is yet to be found.

2003: SARS

First identified in 2003 after several months of cases, Severe Acute Respiratory Syndrome is believed to have possibly started with bats, spread to cats and then to humans in China, followed by 26 other countries, infecting 8,096 people, with 774 deaths.

SARS is characterized by respiratory problems, dry cough, fever and head and body aches and is spread through respiratory droplets from coughs and sneezes.

Quarantine efforts proved effective and by July, the virus was contained and hasn't reappeared since. China was criticized for trying to suppress information about the virus at the beginning of the outbreak.

SARS was seen by global health professionals as a wake-up call to improve outbreak responses, and lessons from the pandemic were used to keep diseases like H1N1, Ebola and Zika under control.

2019: COVID-19

On March 11, 2020, the World Health Organization announced that the COVID-19 virus was officially a pandemic after barreling through 114 countries in three months and infecting over 118,000 people. And the spread wasn't anywhere near finished.

COVID-19 is caused by SARS-CoV-2, a novel coronavirus strain that had not been previously found in people. Symptoms include respiratory problems, fever and cough, and can lead to pneumonia and death. Like SARS, it's spread through droplets in the air produced when an infected person coughs or sneezes.

The first reported case in China appeared November 17, 2019, in the Hubei Province, but went unrecognized. Eight more cases appeared in December with researchers pointing to an unknown virus.

Many learned about COVID-19 when ophthalmologist Dr. Li Wenliang defied government orders and released safety information to other doctors. The following day, China informed WHO and charged Li with a crime. Li died from COVID-19 just over a month later.

The virus spread beyond Chinese borders to nearly every country in the world. By December 2020, it had infected more than 75 million people and led to more than 1.6 million deaths worldwide.

Funding and political will in the United States and around the world accelerated the development of vaccines to fight the virus and by December 11, 2020, the FDA issued an Emergency Use Authorization for the use of the first COVID-19 vaccine. A week later the government agency approved a second, and by February 2021, Americans had access to three FDA-approved vaccines. By December 2021, 71 percent of the U.S. population had received at least one dose of a COVID-19 vaccine.

Despite the new vaccines (which all eventually gained full FDA approval), COVID-19 cases and deaths continued to rise as new variants of the virus emerged and some Americans remained reluctant to become vaccinated. As of December, 2021, the confirmed U.S. COVID-19 death toll had surpassed 800,000.

SOURCES

Disease and History by Frederick C. Cartwright, published by Sutton Publishing, 2014.

Disease: The Story of Disease and Mankind's Continuing Struggle Against It by Mary Dobson, published by Quercus, 2007.

Encyclopedia of Pestilence, Pandemics, and Plagues by Ed, Joseph P. Byrne, published by Greenwood Press, 2008.

Influenza, The American Experience.

Source Book of Medical History, Logan Clendening, published by Dover Publications, 1960.

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Pandemics That Changed History: Timeline

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As human civilizations rose, these pandemic diseases, from the bubonic plague to smallpox to influenza, struck them down.