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Washington, Apr 28: After nearly three weeks in an intensive care unit in Los Angeles, doctors treating 41-year-old Broadway actor Nick Cordero for COVID-19 were forced to amputate his right leg.

The flow of blood had been impeded by a blood clot: yet another dangerous complication of the disease that has been bubbling up in frontline reports from China, Europe and the United States.

To be sure, so-called "thrombotic events" occur for a variety of reasons among intensive care patients, but the rates among COVID-19 patients are far higher than would be otherwise expected.

"I have had 40-year-olds in my ICU who have clots in their fingers that look like they'll lose the finger, but there's no other reason to lose the finger than the virus," Shari Brosnahan, a critical care doctor at NYU Langone said.

One of these patients is suffering from a lack of blood flow to both feet and both hands, and she predicts an amputation may be necessary, or the blood vessels may get so damaged that an extremity could drop off by itself.

Blood clots aren't just dangerous for our limbs, but can make their way to the lungs, heart or brain, where they may cause lethal pulmonary embolisms, heart attacks, and strokes.

A recent paper from the Netherlands in the journal Thrombosis Research found that 31 percent of 184 patients suffered thrombotic complications, a figure that the researchers called "remarkably high" -- even if extreme consequences like amputation are rare.

Behnood Bikdeli, a doctor at New York-Presbyterian Hospital, assembled an international consortium of experts to study the issue. Their findings were published in the Journal of The American College of Cardiology.

The experts found the risks were so great that COVID-19 patients "may need to receive blood thinners, preventively, prophylactically," even before imaging tests are ordered, said Bikdeli.

What exactly is causing it? The reasons aren't fully understood, but he offered several possible explanations.

People with severe forms of COVID-19 often have underlying medical conditions like heart or lung disease -- which are themselves linked to higher rates of clotting.

Next, being in intensive care makes a person likelier to develop a clot because they are staying still for so long. That's why for example people are encouraged to stretch and move around on long haul flights.

It's also now clear the COVID-19 illness is associated with an abnormal immune reaction called "cytokine storm" -- and some research has indicated this too is linked to higher rates of clotting.

There could also be something about the virus itself that is causing coagulation, which has some precedent in other viral illnesses.

A paper in the journal The Lancet last week showed that the virus can infect the inner cell layer of organs and of blood vessels, called the endothelium. This, in theory, could interfere with the clotting process.

According to Brosnahan, while thinners like Heparin are effective in some patients, they don't work for all patients because the clots are at times too small.

"There are too many microclots," she said. "We're not sure exactly where they are."

Autopsies have in fact shown some people's lungs filled with hundreds of microclots.

The arrival of a new mystery however helps solve a slightly older one.

Cecilia Mirant-Borde, an intensive care doctor at a military veterans hospital in Manhattan, told AFP that lungs filled with microclots helped explain why ventilators work poorly for patients with low blood oxygen.

Earlier in the pandemic doctors were treating these patients according to protocols developed for acute respiratory distress syndrome, sometimes known as "wet lung."

But in some cases, "it's not because the lungs are occupied with water" -- rather, it's that the microclotting is blocking circulation and blood is leaving the lungs with less oxygen than it should.

It has just been a little under five months since the virus emerged in Wuhan, China, and researchers are learning more about its impact every day.

"While we react surprised, we shouldn't be as surprised as we were. Viruses tend to do weird things," said Brosnahan.

While the dizzying array of complications may seem daunting, "it's possible there'll be one or a couple of unifying mechanisms that describe how this damage happens," she said.

"It's possible it's all the same thing, and that there'll be the same solution."

The head of the World Health Organisation on Tuesday warned the novel coronavirus was a "very grave threat" for the world as he opened a conference to combat the epidemic.

"With 99% of cases in China, this remains very much an emergency for that country, but one that holds a very grave threat for the rest of the world," Tedros Adhanom Ghebreyesus said in Geneva.

Some 400 scientists will review how the virus is transmitted and possible vaccines at the two-day forum.

"What matters most is stopping the outbreak and saving lives. With your support, that's what we can do together," Tedros said.

The virus, first identified in China on December 31, has killed more than 1,000 people, infected over 42,000 and reached some 25 countries.

Participants will also discuss the source of the virus, which is thought to have originated in bats and reached humans via another animal such as snakes or pangolins.

There is no specific treatment or vaccine against the virus, which can cause respiratory failure.

Tedros, who has repeatedly urged countries affected to share their data, called for global "solidarity".

"That is especially true in relation to the sharing of samples and sequences. To defeat this outbreak, we need open and equitable sharing, according to the principles of fairness and equity," he said.

"We hope that one of the outcomes of this meeting will be an agreed roadmap for research around which researchers and donors will align," Tedros said.

Several companies and institutes in Australia, China, France, Germany and the United States are racing to develop a vaccine -- a process that normally takes years.

Asked whether scientists from Taiwan would be allowed to take part in this week's Geneva conference, WHO officials said that they would do so but only online -- along with colleagues from other parts of China.

While the WHO does not deal with Taiwan directly and only recognises Beijing, Taiwan was often allowed to attend annual assemblies and sideline meetings as an observer.

But in recent years it has been frozen out as Beijing takes an increasingly combative stance towards democratic Taiwan, which it considers its own territory.

Melbourne, Apr 10: Scientists have identified six drug candidates from more than 10,000 compounds that may help treat COVID-19.

The research, published in the journal Nature, tested the efficacy of approved drugs, drug candidates in clinical trials and other compounds.

"Currently there are no targeted therapeutics or effective treatment options for COVID-19," said Professor Luke Guddat from the University of Queensland in Australia.

"In order to rapidly discover lead compounds for clinical use, we initiated a programme of high-throughput drug screening, both in laboratories and also using the latest computer software to predict how different drugs bind to the virus," Guddat said.

The project targeted the main COVID-19 virus enzyme, known as the main protease or Mpro, which plays a pivotal role in mediating viral replication, the researchers said.

This makes it an attractive drug target for this virus, and as people don't naturally have this enzyme, compounds that target it are likely to have low toxicity, they said.

"We add the drugs directly to the enzyme or to cell cultures growing the virus and assess how much of each compound is required to stop the enzyme from working or to kill the virus. If the amount is small, then we have a promising compound for further studies," said Guddat.

After assaying thousands of drugs, researchers found of the six that appear to be effective in inhibiting the enzyme, one is of particular interest.

"We're particularly looking at several leads that have been subjected to clinical trials including for the prevention and treatment of various disorders such as cardiovascular diseases, arthritis, stroke, atherosclerosis and cancer," Guddat said.

Researchers said compounds that are already along the pipeline to drug discovery are preferred, as they can be further tested as antivirals at an accelerated rate compared to new drug leads that would have to go through this process from scratch.

"With continued and up-scaled efforts we are optimistic that new candidates can enter the COVID-19 drug discovery pipeline in the near future," Guddat said.