Four months on from the fateful moment the first person likely fell ill with Covid-19, scientists still have some perplexing questions to answer.
Where – or what – did this explosive new coronavirus come from?
Why does it have the built-in capability to penetrate our cellular machinery and attack our immune system with such devastating effect?
Crucially, why can this virus spread so quickly and quietly? And why do we carry it for a week, passing it along to others, before knowing we're infected?
Professor David Hayman has spent most of his career working on Ebola.
In the public consciousness, few diseases are more feared.
But the Massey University infectious disease ecologist said he'd never been truly afraid of an Ebola pandemic, for the simple reason it could be contained.
"People who are infectious are often always sick, so you can see the signs and isolate them."
"The bigger fear was always something like this: not quite as lethal, but infectious well before the signs start.
"It has this asymptomatic phase that makes it much harder to control. You never see it coming."
Birth of a virus
When we think of viruses, we might picture individual, hidden nasties that silently sneak through our schools and offices.
Every so often, they catch us, invade our bodies and make us sick.
"The fact is, we are constantly bombarded with them," Hayman said.
"They're everywhere. Just a little bit of seawater holds millions of them."
They become a real problem for us when they're "novel" or new, and catch our incredibly sophisticated immune systems unprepared.
"If you think about it, every day in New Zealand, someone is getting infected with a bacteria - campylobacter - from a chicken, or a cow," Hayman said.
"They're basically getting hit by an organism that lives in another animal's poo.
"But for whatever reason, they're not adapted to be transmitted from one person to another."
The coronavirus that causes Covid-19 - severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) - has no such limitations.
Why?
While social media has been rife with conspiracy theories about secret laboratories, scientists have ruled out any notion the virus was engineered.
Rather, they've found it was the product of natural evolution, as were the two other infamous coronaviruses that came before it.
The first known severe illness caused by a coronavirus emerged with the Sars-CoV epidemic of 2002-2003.
The 8000 people it infected, and the 800 it killed, has been well and truly eclipsed by Sars-CoV-2, which has already caused more than 422,000 infections and nearly 19,000 deaths.
Epidemiologists expect it could go on to infect half the planet's population, which is why efforts to contain it, and produce a vaccine to stop it, are so crucial.
A second outbreak came in 2012 with Saudi Arabia's Middle East Respiratory Syndrome, or Mers-CoV, which spread across more than 1000 people in 24 countries, ultimately killing 400.
The animal origins of Sars-CoV and Mers-CoV have become clearer over time.
With the former, scientists found genetic links between civets – small nocturnal mammals found in tropical Asia and Africa – and humans, supporting claims it had managed to jump across species.
They also found a strain in horseshoe bats in China, which packed all of the genetic building blocks of the type of coronavirus which triggered that first global outbreak.
It's still unclear if Sars-CoV needed to go through civets to infect humans, or whether they just acted as an "amplifying host" and a pathway for transmission to people.
In Mers-CoV, the culprit, oddly, may have been camels.
Some DNA samples taken from a man who died of the virus, and from a sick camel he was tending to, proved to be virtually identical, suggesting it was able to jump from one to the other.
Hayman said the Mers virus almost certainly also had an ancestor in bats, but must have been circulating in camels over a prolonged period.
Bats, pangolins, or both?
So what happened with Sars-CoV-2?
"There is still a cloud of uncertainty over this, and so far, I haven't seen any new data that nails it down," Hayman said.
In one new study, scientists analysed its genetic template for spike proteins – or armatures on the outside of the virus that it used to grab and penetrate the outer walls of human and animal cells.
More specifically, they focused on two important features of the spike protein.
Those were its receptor-binding domain (RBD) - a kind of grappling hook that grips onto host cells - and what's called the cleavage site, a molecular can opener that allows the virus to crack open and enter host cells.
They found the RBD portion of the SARS-CoV-2 spike proteins had evolved to effectively target a molecular feature on the outside of human cells called ACE2 - a receptor involved in regulating blood pressure.
The SARS-CoV-2 spike protein was so effective at binding the human cells, in fact, that the scientists concluded it was the result of natural selection, and not the product of genetic engineering that theorists suspected.
The idea of natural evolution was given further credence by data on the virus' backbone - its overall molecular structure.
If someone were seeking to engineer a new coronavirus as a pathogen, they would have constructed it from the backbone of a virus known to cause illness.
But the scientists found that the backbone differed greatly from those of already known coronaviruses.
It turned out to mostly resemble related viruses found in bats and pangolins - scaly-skinned mammals that are prized delicacies in China.
That led scientists to suspect one of two possible scenarios.
In one scenario, the virus evolved to its current state through natural selection in an animal host and then jumped to humans, as happened with Sars-CoV and Mers-CoV.
They proposed bats were the most likely reservoir for SARS-CoV-2, as it was very similar to a bat coronavirus.
Yet there were no documented cases of direct bat-human transmission, suggesting that an intermediate host was likely involved between bats and humans.
In this scenario, both of the distinctive features of SARS-CoV-2's spike protein - the RBD portion that binds to cells and the cleavage site that opens the virus up - would have evolved to their current state before entering humans.
In this case, the current epidemic would probably have emerged rapidly as soon as humans were infected, as the virus would have already evolved the features that made it pathogenic, or able to spread between people.
In the other proposed scenario, a non-pathogenic version of the virus jumped from an animal host into humans and then evolved to its current state within the human population.
A coronavirus from a pangolin could possibly have been transmitted to a human, either directly or through an intermediary host such as civets or ferrets.
After that, the other distinct spike protein characteristic of SARS-CoV-2 - the cleavage site - could have evolved within a human host, or possibly among a group of people, before the outbreak kicked off.
The researchers found the cleavage site appeared similar to those of strains of bird flu that had been shown to cross easily between people.
Therefore, Sars-CoV-2 could have evolved such a virulent cleavage site in human cells and soon triggered the epidemic, as the coronavirus by then would've possibly become far more capable of spreading between people.
Hayman suspected bats were involved somewhere in the mix, and relatively recently.
"What's still unclear is whether it's ultimately come through some other species like pangolins," he said.
"They're so close, genetically, but still, the virus is the closest to the ones that we've got from bats."
Both happened to have been among those animals traded at a bustling and unsanitary market in the heart of Wuhan in central China, which became Covid-19's ground zero.
"So, this virus always had that built-in capability to replicate in human cells, without any mutations needed," Hayman said.
"It just needed the opportunity. Whether it was that market, or something else, it somehow got its chance to jump from wild animals to humans.
"One big question we have is why doesn't this happen more often? Why did it occur at this time and not at others? Finding that out helps to stop it happening next time around."
'It's just gone wild'
Hayman was just as curious – or perhaps horrified – at Covid-19's incredible power to spread.
"You get things like Ebola, then you get things like this, which is a nightmare. You have a virus very well adapted to human-to-human transmission, and, because it's begun in a high-density city like Wuhan, it's just gone wild."
One study, published last week by researchers at the University of Texas at Austin, found the time between cases in a chain of transmission was less than a week.
More than 10 per cent of patients happened to be infected by somebody who had the virus but didn't yet have symptoms – as happened when a 38-year-old man sparked northern Italy's outbreak.
To measure serial interval, scientists look at the time it takes for symptoms to appear in two people with the virus: the person who infects another, and the infected second person.
Researchers found the average serial interval for the novel coronavirus in China was approximately four days.
The speed of an epidemic depended on two things - how many people each case infected and how long it took for infection between people to spread.
The first quantity was called the reproduction number; the second was the serial interval.
The short serial interval of Covid-19 meant emerging outbreaks would grow quickly and be difficult to stop.
Ebola, for instance, had a serial interval of several weeks, and was much easier to contain than influenza, with a serial interval of only a few days.
The upshot was that Covid-19 could spread like the flu, but with potentially worse consequences for patients.
"The fact that it seems to bind to both our upper and lower respiratory tracts is perhaps also a reason why people are spreading it so easily," Hayman said.
More specifically, Sars-CoV-2 spread through droplets – of which a single cough could create 3000, and a sneeze could produce as many as 10,000.
But that didn't mean you had to be standing near a coughing, sneezing, infected person to catch it.
Scientists have shown Sars-CoV-2 could linger in aerosols for up to three hours, up to four hours on copper, up to 24 hours on cardboard and up to two to three days on plastic and stainless steel.
That led them to conclude that its rapid spread across the globe also may have been fuelled by people catching through the air or touching contaminated objects.
"The reason people get very sick with it is it also gets into that lower respiratory tract, and it basically strips your lungs."
In critical cases, Covid-19 has also been shown to cause acute respiratory distress syndrome, or ARDS, which brought on sudden breathlessness, rapid breathing, dizziness and rapid heart rate.
Those coronavirus patients who also developed ARDS tended to do so late in the infection, when their lungs had been severely damaged. It's now been cited as a common factor in Covid-19 deaths.
Breaking the chains
There were now 205 confirmed or probable cases of Covid-19 in New Zealand.
While it wasn't clear how Covid-19 might shake out here, models have suggested thousands – potentially tens of thousands – could die if bold measures aren't put in place.
But epidemiologists have expressed optimism that a four-week lockdown, beginning tonight, could help stamp out the disease before it properly takes root – or at least make it more manageable for the health system.
So far, there had only been a handful of cases classified as coming from community transmission.
Hayman expected there were likely more who had infected others.
"This is a concern because it is not now known how much transmission is happening and where it is," he said.
"With this coronavirus infection, that could lead to exponentially increasing numbers of cases. As we have seen, the Government has now increased the restrictions on people to prevent this happening further because of this."
Like others, he was confident the lockdown would greatly limit Covid-19's prospects here.
"Infectious diseases by definition must be transmitted from one person to another. The strict measures will limit human contact and so this quite simply means that those infected already cannot then go on to infected others in the community," he said.
"The infection chain ends there. No one else is infected. This means, if done properly, New Zealand can contain the infection present in the country."
• Covid19.govt.nz: The Government's official Covid-19 advisory website
