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Tokyo, April 6: Japan Prime Minister Shinzo Abe is planning to declare a state of emergency in view of the surging cases of coronavirus in the country, especially in Tokyo and other large cities, government sources said on Monday.

Pressure had been mounting on Abe to make the declaration amid a spurt in COVID-19 cases recently, with calls for the move from Tokyo Governor Yuriko Koike and the Japan Medical Association intensifying, Xinhua news agency reported.

The Tokyo metropolitan government, along with healthcare specialists, said that the number of hospital beds available for coronavirus patients will soon reach capacity, with the health ministry rapidly trying to secure more beds.

Adding to pressure on the government to demonstrably bolster its preventive and countermeasures to the spread of the virus, a panel of government experts warned recently that the country's healthcare system could collapse if coronavirus cases continue to spike.

The healthcare system in Tokyo and four other prefectures are under increased strain and "drastic countermeasures need to be taken as quickly as possible," the experts said.

As of Sunday, 143 new cases of COVID-19 were recorded in Tokyo, a record daily high for the capital, bringing the total to 1,034, with Japan's health ministry and local governments adding that nationwide cases rose to 3,531 as of Sunday afternoon.

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."

Canadian researchers are developing a DNA vaccine for SARS-CoV-2, the coronavirus that causes COVID-19 and has currently infected nearly 5,00,000 people worldwide and crippled the global economy.

Entos Pharmaceuticals, a health-care biotechnology company headed by a University of Alberta researchers, develop new therapeutic compounds using the company's proprietary drug-delivery platform and has begun manufacturing vaccine candidates against the novel coronavirus.

"Given the urgency of the situation, we can have a lead candidate vaccine within two months. Once we have that it's a race to get it into clinical trials," said John Lewis, CEO of Entos and a Professor at the University of Alberta in Canada.

Lewis said in comparison to a traditional vaccine, DNA-based vaccines hold several advantages.

Nucleic acids are introduced directly into the patient's own cells, causing them to make pieces of the virus--tricking the immune system into mounting a response without the full virus actually being present, the researcher said.

According to the company, the approach is recognised as being easier to move into large-scale manufacturing, offers improved vaccine stability and works without needing an infectious agent.

In the current absence of a vaccine for COVID-19, several companies around the world are mounting efforts to begin similar work.

The first clinical trial using a DNA-based vaccine developed by Moderna Inc.in the US on March 13.

Their approach allows for antibodies to be made in the human trial volunteers against a specific protein on the surface of the coronavirus that lets the virus enter human cells.

The hope is that the antibodies will stop the interaction.

Though this approach is designed to be effective against COVID-19 specifically, Lewis said Entos is taking a different tack.

The company plans to use plasmid DNA to amplify the production of key coronavirus surface and structural proteins with each injection, with an eye to the bigger picture.

"Many of the structural proteins in the virus are pretty well conserved across all the coronaviruses, including SARS and MERS," said Lewis.

"We're hoping that if we express more of the structural proteins that are common to most coronaviruses, we can inhibit the current COVID-19, and also potentially protect against all coronaviruses both past and future," Lewis added.

To move the project forward quickly, the company is seeking financial support from both provincial and federal levels of government.

"We have the opportunity to save a lot of lives, and I think it's really upon us and governments to find solutions for that," Lewis said.