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

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.

London/Milan, Jun 2: World Health Organization experts and a range of other scientists said on Monday there was no evidence to support an assertion by a high profile Italian doctor that the coronavirus causing the COVID-19 pandemic has been losing potency.

Professor Alberto Zangrillo, head of intensive care at Italy's San Raffaele Hospital in Lombardy, which bore the brunt of Italy's COVID-19 epidemic, on Sunday told state television that the new coronavirus "clinically no longer exists".

But WHO epidemiologist Maria Van Kerkhove, as well as several other experts on viruses and infectious diseases, said Zangrillo's comments were not supported by scientific evidence.

There is no data to show the new coronavirus is changing significantly, either in its form of transmission or in the severity of the disease it causes, they said.

"In terms of transmissibility, that has not changed, in terms of severity, that has not changed," Van Kerkhove told reporters.

It is not unusual for viruses to mutate and adapt as they spread, and the debate on Monday highlights how scientists are monitoring and tracking the new virus. The COVID-19 pandemic has so far killed more than 370,000 people and infected more than 6 million.

Martin Hibberd, a professor of emerging infectious disease at the London School of Hygiene & Tropical Medicine, said major studies looking at genetic changes in the SARS-CoV-2 virus that causes COVID-19 did not support the idea that it was becoming less potent, or weakening in any way.

"With data from more than 35,000 whole virus genomes, there is currently no evidence that there is any significant difference relating to severity," he said in an emailed comment.

Zangrillo, well known in Italy as the personal doctor of former Prime Minister Silvio Berlusconi, said his comments were backed up by a study conducted by a fellow scientist, Massimo Clementi, which Zangrillo said would be published next week.

Zangrillo told Reuters: "We have never said that the virus has changed, we said that the interaction between the virus and the host has definitely changed."

He said this could be due either to different characteristics of the virus, which he said they had not yet identified, or different characteristics in those infected.

The study by Clementi, who is director of the microbiology and virology laboratory of San Raffaele, compared virus samples from COVID-19 patients at the Milan-based hospital in March with samples from patients with the disease in May.

"The result was unambiguous: an extremely significant difference between the viral load of patients admitted in March compared to" those admitted last month, Zangrillo said.

Oscar MacLean, an expert at the University of Glasgow's Centre for Virus Research, said suggestions that the virus was weakening were "not supported by anything in the scientific literature and also seem fairly implausible on genetic grounds."

Jun 2: Pakistan's COVID-19 cases reached 76,398 on Tuesday after 3,938 new infections were reported across the country, while the death toll due to the coronavirus has gone up to 1,621, according to the health ministry.

The Ministry of National Health Services said that 78 COVID-19 deaths were recorded in the last 24 hours, taking the total number of fatalities in Pakistan to 1,621.

A total of 27, 110 people have recovered, it said.

Sindh has 29,647 patients, Punjab 27,850, Khyber-Pakhtunkhwa 10,485, Balochistan 4,514, Islamabad 2,893, Gilgit-Baltistan 738 and Pakistan-occupied Kashmir 271, it added.

The authorities have conducted 577,974 tests, including 16,548 in the last 24 hours.

The jump in the number of cases comes a day after Prime Minister Imran Khan said that people should learn to live with COVID-19 until a vaccine is developed.

Khan addressed the media after chairing the meeting of National Coordination Committee, the highest body to tackle the pandemic.

"Coronavirus will not go away until the vaccine is discovered. We need to learn to live with it and we can live with it if we follow precautions," he said.

He said the one million volunteers of the government's coronavirus force will raise awareness of the need to follow guidelines.

The government also said that all sectors will be opened slowly after deciding the negative list of businesses which will not be allowed.