Monday, April 13, 2020

Cure for coronavirus? The antimalarial drug hydroxychloroquine (HCQ)

Worried Medicaid patients in an urban emergency room are reportedly asking doctors for “dat Klorokine pill.” Meanwhile, highly educated persons are quoting media reports that HCQ is very dangerous because it can trigger fatal heart rhythms.

Governors and state medical and pharmacy boards are threatening physicians who prescribe and pharmacists who dispense HCQ for COVID-19. One rationale is that lupus and rheumatoid arthritis patients might not be able to get their prescriptions filled from the millions of doses drug manufacturers are now cranking out. Apparently, HCQ is not too dangerous for them.

Evidence is pouring in from around the world, including Los Angeles, where very ill patients were symptom-free within 12 hours after receiving HCQ combined with zinc.

In Brazil, HCQ plus azithromycin is being sent to patients’ homes based on a telemedicine consultation, and patients are reportedly cured at home. Virologist Paolo Zanotto of the University of São Paulo states that the drug should be given before day 5 to prevent lung damage. He believes opposition to the drug is political: President Trump and Brazilian President Bolsonaro have recommended it.

“If the people were not saying that this is ‘Bolsonaro’s remedy’ or ‘Trump's remedy,’ it would be different. If it were ‘Doria’s drug’ or ‘Lula’s drug,’ I guarantee it would be a success. There is a lot of ideology involved in the problem. For some, if the death of millions is needed to take Trump and Bolsonaro out, so be it.”

Can HCQ cause heart rhythm disturbances? Yes, but rarely. These have occurred in ICU patients who had heart damage from the coronavirus. Can it kill you? Very rarely—everybody has heard about the man who drank aquarium cleaner containing ten times the recommended dose of chloroquine.

Are there controlled, peer-reviewed studies? No. These take years; this novel coronavirus has been known for about 4 months.

Are Americans willing to learn from patients and Brazilians? Will American doctors be allowed to try promising drugs before millions are denied “unproved” remedies?



Haywire Immune Reaction Linked to Most Severe Cases

An immune system gone haywire may be doing more damage than the coronavirus itself in patients with the severest forms of Covid-19, doctors and scientists say, a growing theory that could point the way to potential treatments.

Much remains unknown about the path the virus takes in the sickest patients, but an increasing number of experts believe a hyperactive immune response, rather than the virus, is what ultimately kills many Covid-19 patients.

The out-of-control immune response eventually causes the patients’ lungs to stop delivering oxygen to the rest of organs, leading to respiratory failure and in some cases death, the experts said. The malfunctioning immune system might be driving the rapid decline in lung function experienced by some patients, including younger and relatively healthy ones, after the initial onset of symptoms, doctors said.

As scientists race to better understand the phenomena, pharmaceutical companies including Roche Holding AG are partnering with hospitals to explore whether drugs proven to tamp down an out-of-control immune response could help the sickest Covid-19 patients.

Some doctors are already administering the drugs to patients who are unable to breathe without the support of ventilators, or to prevent deterioration of patients who appear ready to slip into respiratory failure.

“You remove one piece of the storm, and it can quiet the whole thing,” said Kevin Tracey, president of the Feinstein Institutes for Medical Research at Northwell Health, which is testing Kevzara, an anti-inflammatory drug from Regeneron Pharmaceuticals Inc.

Doctors have used the term “cytokine storm” to describe an overactive immune response triggered by external pathogens such as bacterial and viral infections. Proteins called cytokines are part of the immune system’s arsenal for fighting disease.

When too many are released into the bloodstream too quickly, however, it can have disastrous results, including organ failure and death.

As with other diseases, it is a mystery why cytokine storms are experienced by some but not all Covid-19 patients, doctors said. Genetics may be a factor.

In the most severe coronavirus patients, the disease appears to have two stages, doctors and researchers said. First the immune system fails to respond quickly or effectively enough to the virus. Then the immune response becomes too aggressive and floods the body with cytokines.

The surge of cytokines damages blood vessels and allows fluids to seep into the lungs, filling them up like water balloons, doctors say.

“The virus initiated it,” said Ya-Chi Ho, an assistant professor at the Yale School of Medicine who studies infectious diseases. “The second problem is our immune system handled it wrongly, and induces this cytokine storm and clogs our lungs. That’s why patients die.”

Drugs called corticosteroids can be used to treat patients with cytokine storms, but studies are mixed on their effectiveness, with some studies indicating that Covid-19 patients might be at a higher risk of death when treated with steroids. Some doctors are reluctant to use steroids because they broadly damp the immune response, which is risky in patients fighting infections.

Drugs targeting specific cytokines rather than the entire immune system may be more effective, doctors said.

Among the most promising targeted treatments, doctors said, is Roche’s rheumatoid-arthritis drug tocilizumab, which is marketed under the brand name Actemra. The drug was approved in 2017 to treat cytokine storms caused by cancer treatments known as CART cell therapies.

On Tuesday, a federal agency that supports health research said it is committing $25 million to accelerate a late-stage study of Actemra in Covid-19 patients.

Last month, doctors from Seattle’s Swedish Health Services used Actemra to treat a 45-year-old emergency-room physician who was infected while caring for patients from a nursing home in Kirkland, Wash.

The man was transferred to Swedish and put on life support after his lungs and kidneys began to fail, said Samuel J. Youssef, a cardiothoracic surgeon at Swedish. Lab tests showed the man’s inflammation levels were 200 times greater than the normal range, indicating he might be suffering from a cytokine storm.

The doctors at Swedish decided to administer Actemra after discussing a small Chinese study that had shown that 21 Covid-19 patients with high levels of inflammation had been successfully treated with the drug. Over the next two days, the patient’s inflammation levels began to decline and his blood-oxygen levels increased, Dr. Youssef said. After a week, he was well enough to be taken off life support on March 23, and was released from the hospital on Sunday.

“All we did was quiet the storm and support his body— his kidneys, his lungs, his heart—to give him the time to fight the virus,” said Dr. Youssef, who attributes the recovery both to Actemra as well as other interventions like being put on life support.



Are we all authoritarians now?

‘China bans 23million from buying travel tickets as part of “social credit” system’, said one outraged headline in the Guardian, just one year ago. The Chinese social-credit scheme set out to penalise citizens for their errant behaviour while rewarding others for good behaviour. The State Council, China’s chief administrative authority, said the scheme’s purpose is to ‘allow the trustworthy to roam everywhere under heaven while making it hard for the discredited to take a single step’.

Such an insidious assault on civil liberties by the Chinese state, under the guise of protecting social stability, was roundly and rightly condemned in the UK as authoritarian, illiberal and staunchly un-British. Britain firmly believes in the autonomy of the individual and the right to free movement, it was said. The Chinese Communist Party’s dictatorial actions were held up as exemplary evidence of the differences between our two countries and our two systems.

One year later, the Sun newspaper reports that British Transport Police have been ‘deployed… to enforce a ban on unnecessary travel’. The Guardian dutifully announces that ‘Dominic Raab advises UK public to avoid all non-essential travel’. The BBC unquestioningly reports the London mayor proclaiming that key workers and ‘nobody else’ should be using public transport. The freedom of movement ideal was ditched rather quickly. Suddenly, the British government has restricted travel for almost 60million citizens – the same number of people quarantined in China’s Hubei province – but this was hardly questioned in the media.

The West has also long criticised the covert monitoring of citizens carried out by China’s ruling Communist Party. The government stalks the public’s social-media activities to find details of illicit online behaviour. It films people secretly using CCTV and drones. Ordinary people are encouraged to send in their own footage to the authorities to ensure that the state doesn’t miss anyone in its official trawl. Last year, the Wall Street Journal compared China’s attempts to enrol the public to snitch on miscreants to the East German Stasi. Fast forward six months and the same paper reports casually on Western internet users ‘naming and shaming people they believe have flouted lockdown orders, travelled or socialised recklessly’, without making any moral judgement on the shamers.

How have we lost our moral compass in such a short space of time? The medical basis for state-enforced isolation is still debatable. But even if it is a fundamental necessity to protect lives, should we be welcoming confinement so eagerly? Should we really be asking for ever-more state powers to enforce lockdowns? Shouldn’t we be defending liberty, free movement and assembly rather than accepting restraint at the behest of the political and medical establishment?

I am not suggesting that we all rush out and hug each other, but it seems that Western values can be usurped and abandoned much more easily than we ever imagined. That ought to be a cause for concern, and maybe something worthy of national debate. Instead, those advocating for the liberal rights that have upheld the cause of Western societies for centuries are frequently shouted down and branded ‘irresponsible’ or ‘dangerous’. In the words of the Chinese state, penalties will be enforced in order to ensure a harmonious society. Responsible citizens and trustworthy actions are rewarded; dissenters are blacklisted.

One Chinese dissident warned that China’s social-credit system would give ‘officials unparalleled scrutiny over every minute of everyone’s life’. So what are we to make of Google’s announcement last week – made without permission from any of us – that it will release all of our location data to the authorities? It seems that the footnote ‘in order to prevent the spread of coronavirus’ is all that is needed to justify such a monstrous breach of privacy. Facebook is also in talks with the US government about the possibility of sharing our location data. After months of alarmist criticism of Huawei’s potential to reveal users’ data to the Chinese state, few in the media or Twittersphere are raising critical concerns about the same thing happening in the West. Some are raising their glasses. After all, it might save lives, so it’s all right, apparently.

The media seem to have forgotten the maxim of ‘holding truth to power’ and are perhaps intent on simply holding power. During China’s Cultural Revolution, intellectuals were forced to participate in ‘struggle sessions’ – a vicious form of public humiliation. There were echoes of this at the weekend when Scotland’s Chief Medical Officer, Catherine Calderwood, was forced to make a grovelling televised appearance to beg for the nation’s forgiveness. She had ‘made a mistake and let people down’. ‘I cannot justify it’, she said. ‘I did not follow the advice I am giving to others, and I am truly sorry for that… What I did was wrong.’ The media were delighted with the scalp. Her crime? She had driven to her second home in a car.

Actually, there is one good lesson to learn from China, and that is the proud – and often unsung – tradition of rebellion. China has had a couple of revolutions, after all. In recent weeks, thousands of migrant workers and working-class protesters from Hubei province have revolted, overturning police cars and fighting with state forces who refused to allow them to cross over into the neighbouring Jianxi province. These desperate people have been locked down for months. They have no work and no money, even though they are healthy. But the neighbouring provincial authorities were worried about the risk of the second wave of the virus.

In these topsy-turvy times, the best lesson to take from China is how, even in the most dire circumstances, ordinary people can still keep the spirit of free movement, critical engagement and non-complicity alive.



For more blog postings from me, see  TONGUE-TIED, EDUCATION WATCH INTERNATIONAL, GREENIE WATCHPOLITICAL CORRECTNESS WATCH, AUSTRALIAN POLITICS, and Paralipomena (Occasionally updated), A Coral reef compendium and an IQ compendium. (Both updated as news items come in).  GUN WATCH is now mainly put together by Dean Weingarten. I also put up occasional updates on my Personal blog and each day I gather together my most substantial current writings on THE PSYCHOLOGIST.

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