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Scientists have been playing a lethal game of cat and mouse with the novel coronavirus. Each time we learn a little more about COVID-19, it adapts and mutates into a new strain, affecting transmission, diagnosis, treatment and vaccination development.

Studies have found hundreds of mutated versions of the novel coronavirus in infected patients, with some more severe and more contagious than the original one.

In fact, there’s a lot we don’t know about COVID-19 — arguably, what we don’t know outweighs what we do. Some of the biggest questions overshadowing the virus concern origin and spread, symptoms and immunity. 

Where did it come from?

Conspiracy theories, perpetuated by protesters, far-right commentators and oh, the US government, have dominated headlines, with believers spruiking 5G, Bill Gates, Chinese operatives, and the US army as potential sources of COVID-19.

What would do well to silence these theories is an evidence-based, surefire explanation on how it emerged — something we simply don’t have yet, physician and professor of medicine at Monash University Paul Komesaroff told Crikey. 

“It’s complicated. The biggest thing is that there are many factors involved here. It’s a conjunction of different factors coming together at the wrong moment,” he said. 

While we know COVID-19 wasn’t constructed synthetically in a lab, he said, we also know it didn’t originate in the Wuhan wet market. In fact, it didn’t really originate anywhere at all.

“The term originated is a problematic term. It didn’t come into existence at the point of discovery,” he said. While a cluster developed in Wuhan, cases were discovered weeks before in other areas.

We don’t know for sure whether the virus jumped from bat to human, but it’s likely another animal — or multiple animals — were intermediate hosts, though we don’t know for sure which animal this was.  

The rate at which zoonotic diseases — diseases passed from animals to humans — are increasing is alarming. While previously the world had to worry about bacterial infections, now roughly 70% of emerging infectious diseases in humans are zoonotic. 

Komesaroff said deforestation, climate change and population density all had an impact on how animals interacted with one another and with humans, making it easier for the virus to jump from animal to animal and human, mutating each time.

Knowing how the virus started is important to prevent future pandemics, Dr Abrar Chughtai, an epidemiologist at the University of UNSW, told Crikey. 

“We see coronavirus in hundreds of different species, from bats to camels to birds. There are lots circulating, but very few jumping into humans in what we call a ‘spillover event’,” he said. 

“The transmission chain is still ongoing … We don’t know the exact reason as to why it jumps to humans, but we want to know the origin to stop future pandemics.” 

How does it spread?

Transmission is one of the other great unknowns in COVID-19, especially when it comes to asymptomatic carriers, Chughtai said. 

“25% of people are asymptomatic carriers. We don’t know how much these people transmit infections, and if they are major drivers.”

To predict transmission, parameters and data are fed into mathematical models, Professor Adrian Esterman, an epidemiologist and biostatistician at the University of South Australia, told Crikey. 

“Without exception, these parameters are guesses — educated guesses, but guesses,” he said. 

For example, he said, cases per day are completely dependent on the rate of testing. “Even the simplest thing we measure is a guess,” he said.

We don’t know how far the virus can spread through the droplets; whether the virus could be airborne; or how long different strains can survive on different surfaces.

“A lot of the tests are experimental,” Esterman said.

How do we diagnose it? 

Frostbitten toes to kidney failure, a spike in blood clots, loss of taste and smell, heart muscle degeneration, low oxygen levels in the blood, Kawasaki disease in children — the list of potential symptoms and comorbidities go on and on, with new discoveries every day.  

“The characteristics of the virus is that symptoms are nondescript,” Komesaroff said. “Like the flu, it’s a range of symptoms … a lot of the early symptoms are common and unremarkable.”

The only real way to know if someone has COVID-19 is to test for it. Yet tests are also problematic, thanks to the constant mutations, Stuart Tangye, an immunologist from the Garvan Institute of Medical Research, told Crikey. 

“One of the wonders of viruses is their ability to mutate — you have to admire their chameleon lifestyle and ability to change the way they look to predator and prey,” he said. 

This evolutionary adaptation is a response to the host’s immune system. As viruses are small, Tangye said, it’s easy to change something small in the genetic material to trick the immune system into not recognising it. 

Knowing how the immune system will respond is also unknown, with COVID-19 patients either having a good immune response, or a damaging one. 

“It can trigger a Cytokine storm, which is hyperinflammation. In some cases, the immune system goes out of control and overreacts, causing collateral damage to the body’s own tissue, particularly in the lungs,” Tangye said. 

Knowing who will be affected by this — or even who will be severely affected by the coronavirus — is difficult. 

“Demographic representation is one of the great unknowns,” he said. 

How do we treat it? 

Experts agree COVID-19 isn’t likely to go anywhere: like the flu, scientists may every year have to predict what strains are likely to spread, and develop a vaccine. 

“With the flu, every year there’s a tiny change,” Esterman said. “While the vaccine from the year before will give you minor immunity, every four to five years there’s a major variation.”

No COVID-19 treatments have been found to be effective. Remdesivir was an emerging treatment, though there have been issues with efficacy and trials

“Understanding where the virus itself is going will be a key piece of the puzzle to ensure vaccines are being designed appropriately and has the effect we want,” Tangye said. 

Despite all the unknowns, one thing that has emerged is the sharing of information. 

“One thing that has been very impressive with this pandemic is how open and collegial the scientific and medical communities have been,” he said.

“For this reason, we know as much as we do already, in a relatively short period of time.”