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Islamabad, Jun 10: The World Health Organization has told Pakistan it should implement "intermittent" lockdowns to counter a surge in coronavirus infections that has come as the country loosens restrictions, officials said.

Since the start of Pakistan's outbreak in March, Prime Minister Imran Khan opposed a nationwide lockdown of the sort seen elsewhere, arguing the impoverished country could not afford it.

Instead, Pakistan's four provinces ordered a patchwork of closures, but last week Khan said most of these restrictions would be lifted.

Health officials on Wednesday declared a record number of new cases in the past 24 hours. The country has now confirmed a total of more than 113,000 cases and 2,200 deaths -- though with testing still limited, real rates are thought to be much higher.

"As of today, Pakistan does not meet any of the pre-requisite conditions for opening the lockdown", the WHO said in a letter confirmed by Pakistan officials on Tuesday.

Many people have not adopted behavioural changes such as social distancing and frequent hand-washing, meaning "difficult" decisions will be required including "intermittent lockdowns" in targeted areas, the letter states.

Some 25 percent of tests in Pakistan come back positive for COVID-19, the WHO said, indicating high levels of infection in the general population.

The health body recommended an intermittent lockdown cycle of two weeks on, two weeks off.

Responding to the WHO's letter, Zafar Mirza, the prime minister's special advisor for health, said the country had "consciously but gradually" eased lockdowns while enforcing guidelines in shops, mosques and public transport.

"We have to make tough policy choices to strike a balance between lives and livelihoods," Mirza said Wednesday.

Punjab's provincial health minister Yasmin Rashid, who received the WHO's letter, said the provincial government had already given "orders to take strict action against those violating" virus guidelines.

Hospitals across Pakistan say they are at or near capacity, and some are turning COVID-19 patients away.

WHO Director-General Tedros Adhanom Ghebreyesus said Monday that 136,000 cases had been reported in the previous 24 hours, "the most in a single day so far", with the majority of them in South Asia and the Americas.

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.