Malaria drug Hydroxychloroquine fails to prevent COVID-19 in a rigorous study

News Network
June 4, 2020

Jun 4: A malaria drug President Donald Trump took to try to prevent COVID-19 proved ineffective for that in the first large, high-quality study to test it in people in close contact with someone with the disease.

Results published Wednesday by the New England Journal of Medicine show that hydroxychloroquine was no better than placebo pills at preventing illness from the coronavirus.

The drug did not seem to cause serious harm, though -- about 40% on it had side effects, mostly mild stomach problems.

 “We were disappointed. We would have liked for this to work,” said the study leader, Dr. David Boulware, an infectious disease specialist at the University of Minnesota.

“But our objective was to answer the question and to conduct a high-quality study,” because the evidence on the drug so far has been inconclusive, he said.

Hydroxychloroquine and a similar drug, chloroquine, have been the subject of much debate since Trump started promoting them in March.

Hydroxychloroquine has long been used for malaria, lupus, and rheumatoid arthritis, but no large studies have shown it or chloroquine to be safe or effective for much sicker patients with coronavirus, and some studies have suggested the drugs may do harm.

Trump took a two-week course of hydroxychloroquine, along with zinc and Vitamin D, after two staffers tested positive for COVID-19, and had no ill effects, according to results of his latest physical released by his doctor Wednesday.

Federal regulators have warned against hydroxychloroquine's use except in hospitals and formal studies because of the risk of side effects, especially heart rhythm problems.

Boulware's study involved 821 people in the United States and Canada living with someone diagnosed with COVID-19 or at high risk of getting it because of their job -- doctors, nurses, ambulance workers who had significant exposure to a sick patient while not wearing full protective gear.

They were randomly assigned to get either the nutrient folate as a placebo or hydroxychloroquine for five days, starting within four days of their exposure. Neither they nor others involved in the research knew who was getting which pills.

After 14 days in the study, 12 per cent on the drug developed COVID-19 symptoms versus 14 per cent in the placebo group, but the difference is so small it could have occurred by chance, Boulware said.

“There's basically no effect. It does not prevent infection,” he said of the drug. Even if it were to give some slim advantage, “we'd want a much larger effect” to justify its use and risk of side effects for preventing illness, he said.

Results were no different among a subgroup of participants who were taking zinc or vitamin C, which some people believe might help make hydroxychloroquine more effective or fight the coronavirus.

There are some big caveats: The study enrolled people through the Internet and social media, relying on them to report their own symptoms rather than having them tracked in a formal way by doctors.

Participants were not all tested for the coronavirus but were diagnosed as COVID-19 cases based on symptoms in many cases. And not all took their medicines as directed.

The results “are more provocative than definitive,” and the drug may yet have prevention benefits if tried sooner or in a different way, Dr. Myron Cohen of the University of North Carolina at Chapel Hill wrote in a commentary in the journal.

Others were glad to see a study that had a comparison group and good scientific methods after so many weaker reports on hydroxychloroquine.

“This fits with everything else we've seen so far which suggests that it's not beneficial," said Dr. Peter Bach, director of a health policy center at Memorial Sloan Kettering Cancer Center in New York.

This study was in younger relatively healthy people, but the results “would make me very discouraged about trying to use this in older people” who are most vulnerable to serious illness from the coronavirus, Bach said.

“If it does work, it doesn't work very well.” Dr. Dan Culver, a lung specialist at the Cleveland Clinic, said there's still a chance that giving the drug sooner than four days after someone's exposure to the virus may help prevent illness.

But the study “takes 'home run' off the table” as far as hopes for the drug, he said.

The study was mostly funded by David Baszucki, founder of Roblox, a California-based game software company, and other private donors and the Minnesota university.

Boulware also is leading a study testing hydroxychloroquine for treating COVID-19. The study is finished and results are being analyzed now.

On Tuesday, the journal Lancet posted an “expression of concern” about a study it published earlier this month of nearly 15,000 COVID-19 patients on the malaria drugs that tied their use to a higher risk of dying in the hospital or developing a heartbeat problem.

Scientists have raised serious questions about the database used for that study, and its authors have launched an independent audit.

That work had a big impact: the World Health Organization suspended use of hydroxychloroquine in a study it is leading, and French officials stopped the drug's use in hospitals. On Wednesday, the WHO said experts who reviewed safety information decided that its study could resume.

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News Network
June 9,2020

Jun 9: The World Health Organization says it still believes the spread of the coronavirus from people without symptoms is “rare,” despite warnings from numerous experts worldwide that such transmission is more frequent and likely explains why the pandemic has been so hard to contain.

Maria Van Kerkhove, WHO''s technical lead on COVID-19 said at a press briefing on Monday that many countries are reporting cases of spread from people who are asymptomatic, or those with no clinical symptoms.

But when questioned in more detail about these cases, Van Kerkhove said many of them turn out to have mild disease, or unusual symptoms.

Although health officials in countries including Britain, the U.S. and elsewhere have warned that COVID-19 is spreading from people without symptoms, WHO has maintained that this type of spread is not a driver of the pandemic and is probably accounts for about 6 per cent of spread, at most.

Numerous studies have suggested that the virus is spreading from people without symptoms, but many of those are either anecdotal reports or based on modeling.

Van Kerkhove said that based on data from countries, when people with no symptoms of COVID-19 are tracked over a long period to see if they spread the disease, there are very few cases of spread.

“We are constantly looking at this data and we''re trying to get more information from countries to truly answer this question,” she said. “It still appears to be rare that asymptomatic individuals actually transmit onward.”

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News Network
April 28,2020

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."

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Agencies
May 19,2020

Washington DC, May 19: US President Donald Trump has threatened to permanently halt funding for the World Health Organisation (WHO) if it did not commit to improvements within 30 days, and to reconsider the membership of the United States in the global health body.

On Monday, Trump wrote a letter to WHO Director-General Tedros Ghebreyesus that read, "If WHO doesn't commit to major substantive improvements within the next 30 days, I will make my temporary freeze of US funding to WHO permanent and reconsider our membership in the organisation."

Trump had temporarily suspended US' contribution to the WHO last month, accusing it of promoting China's "disinformation" about the coronavirus outbreak, although WHO officials denied the accusation and Beijing said that it was transparent and open.

"The only way forward for the WHO is if it can actually demonstrate independence from China. My administration has already started discussions with you on how to reform the organisation. But action is needed quickly. 

We do not have time to waste," Trump said in the letter.

"I cannot allow American taxpayer dollars to continue to finance an organisation that, in its present state, is so clearly not serving America's interests," he added.

On Monday, the WHO said that an independent review of the global coronavirus response would begin at the earliest and it received backing from China, where the virus was first discovered.

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