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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."

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.

Madrid, Mar 26: More than three billion people around the world were living under lockdown on Wednesday as governments stepped up their efforts against the coronavirus pandemic which has left more than 20,000 people dead.

As the number of confirmed cases worldwide soared past 450,000, UN Secretary General Antonio Guterres warned that only a concerted global effort could stop the spread of the virus.

In Spain, the number of fatalities surpassed those of China, where the novel coronavirus first emerged three months ago, making it the hardest-hit nation after Italy.

A total of more than 20,800 deaths have now been reported in 182 countries and territories, according to an AFP tally.

Stock markets rebounded after the US Congress moved closer to passing a $2.2 trillion relief package to prop up a teetering US economy.

In Washington, President Donald Trump said New York, the epicenter of the US outbreak with over 30,000 cases, likely has a few "tough weeks" ahead but he would decide soon whether unaffected parts of the country can get back to work.

"We want to get our country going again," Trump said. "I'm not going to do anything rash or hastily.

"By Easter we'll have a recommendation and maybe before Easter," said Trump, who had been touting a strong US economy as he faces an election in November.

UN chief Guterres said the world needs to ban together to stem the pandemic.

"COVID-19 is threatening the whole of humanity -- and the whole of humanity must fight back," Guterres said, launching an appeal for $2 billion to help the world's poor.

"Global action and solidarity are crucial," he said. "Individual country responses are not going to be enough."

India's stay-at-home order for its 1.3 billion people is now the biggest, taking the total number of individuals facing restrictions on their daily lives to more than three billion.

Anxious Indians raced for supplies after the world's second-biggest population was ordered not to leave their houses for three weeks.

Russia, which announced the death of two patients who tested positive for coronavirus on Wednesday, is expected to follow suit.

President Vladimir Putin declared next week a public holiday and postponed a public vote on controversial constitutional reforms, urging people to follow instructions given by authorities.

In Britain, heir to the throne Prince Charles became the latest high-profile figure to be infected, though he has suffered only mild symptoms.

The G20 major economies will hold an emergency videoconference on Thursday to discuss a global response to the crisis, as will the 27 leaders of the European Union, the outbreak's new epicenter.

China has begun to relax its own draconian restrictions on free movement in the province of Hubei -- where the outbreak began in December -- after the country reported no new cases.

Crowds jammed trains and buses in the province as people took their first opportunity to travel.

But Spain saw the number of deaths surge to more than 3,400 after 738 people died in the past 24 hours and the government announced a 432-million-euro ($467 million) deal to buy medical supplies from Beijing.

The death toll in Italy jumped in 24 hours by 683 to 7,503 -- by far the highest of any country.

The number of French deaths was up by 231 on Wednesday to more than 1,330, and metro and rail services in Paris were cut to a minimum.

Spain and Italy were joined by France and six more EU countries in urging Germany and the Netherlands to allow the issue of joint European bonds to cut borrowing costs and stabilise the eurozone economy.

The call is likely to fall on deaf ears when EU leaders talk on Thursday -- with northern members wary of pooling debt with big spenders -- but they will sign off on an "unprecedented" recovery plan.

At La Paz University Hospital in Madrid, nurse Guillen del Barrio sounded bereft as he related what happened overnight.

"It is really hard, we had feverish people for many hours in the waiting room," the 30-year-old told AFP.

"Many of my colleagues were crying because there were people who are dying alone, without seeing their family for the last time."

Coronavirus cases are also spreading in the Middle East, where Iran's death toll topped 2,000, and in Africa, where Mali declared its first case and several nations announced states of emergency.

In Japan, which has postponed this year's Olympic Games, Tokyo's governor urged residents to stay home this weekend, warning of a possible "explosion" of the coronavirus.

Jerusalem's Church of the Holy Sepulchre, believed by Christians to house Christ's tomb, was shut as Israel tightened movement restrictions.

The impact of the pandemic is also hitting European football, with leagues and tournaments cancelled, while the fate of the Wimbledon tennis tournament could be decided next week.

The economic damage of the virus -- and the lockdowns -- could also be devastating, with fears of a worldwide recession worse than the financial meltdown more than a decade ago.

But financial markets rose after US leaders reached agreement on a stimulus package worth roughly 10 percent of the US economy, an injection Senate Majority Leader Mitch McConnell said represented a "wartime level of investment."

Meanwhile, more than half of all Americans have been told to stay at home, including residents of the largest state, California.

The United States has at least 65,700 cases and 942 people have died.