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Beijing:  Around 5,000 people have signed up for the phase I clinical trial of recombinant novel coronavirus vaccine in Chinese city Wuhan where the virus first emerged late last year.

The recruitment for participants ended this week with nearly 5,000 volunteers signing up for the trial, state-run Beijing News reported on Wednesday.

A single-centre, open and dose-escalation phase I clinical trial for recombinant novel coronavirus vaccine (adenoviral vector) will be tested in healthy adults aged between 18 and 60 years, according to the ChiCTR (China Clinical Trial Register).

The trial, led by experts from the Academy of Military Medical Sciences, gained its approval on March 16 and the research is expected to last half a year.

Requiring at least 108 participants, the trial will be conducted in Wuhan, capital of Hubei province, the region worst-affected by the virus in the country, state-run China Daily reported.

Participants will experience 14-day quarantine restrictions after being vaccinated and their health condition will be recorded every day.

Chinese scientists are hastening the development of COVID-19 vaccines through five approaches --- inactivated vaccines, genetic engineering subunit vaccines, adenovirus vector vaccines, nucleic acid vaccines and vaccines using attenuated influenza virus as vectors.

So far, most teams are expected to complete preclinical research in April and some are moving forward faster, Wang Junzhi, an academician with the Chinese Academy of Engineering said.

Wang noted that research and development of COVID-19 vaccines in China is not slower than foreign counterparts and has been carried out in a scientific, standardised and orderly way.

China has stepped up the process to finalise vaccines to counter COVID-19 after Kaiser Permanente research facility in Seattle and Washington stole the march and began human trials.

China lifted tough restrictions on the Hubei province on Wednesday after a months-long lockdown as the country reported no new domestic cases.

But there were another 47 imported infections from overseas, the National Health Commission said. In total, 474 imported infections have been diagnosed in China -- mostly Chinese nationals returning home.

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."