COVID changed the way we use drugs and alcohol — now it’s time to properly invest in treatment



Shutterstock

Nicole Lee, Curtin University

During crises and disasters, alcohol and other drug use often changes. But the changes are not straightforward and impacts may be different for different groups of people.

There doesn’t seem to have been significant overall increases or decreases in alcohol or other drug use during the COVID-19 pandemic, but some groups are at increased risk. And access to treatment is more limited for those who need it.

It’s a complex picture

There’s a bit of data around, but the picture is still not quite clear.
As researchers from the Centre for Alcohol Policy Research at La Trobe University have argued in an editorial published today, we need more research to understand the influence of the pandemic on use.

There were some early indicators of increases in Australians’ alcohol consumption as the pandemic hit, possibly related to increased stress. But that effect seemed to reduce as we settled into the new normal.

At the beginning of COVID-19 restrictions in March, Commonwealth Bank reported spending had increased on alcohol, but this was then reversed in April.

And in April, a study by the Foundation for Alcohol Research and Education found that most people who had stockpiled alcohol reported drinking more. Also around the same time, Australian Bureau of Statistics data showed more people had increased their drinking (14.4%) than had decreased it (9.5%).

By May, the Australian National University found more people had decreased their drinking (27%) than had increased it (20%). The Global Drug Survey between May and June found similar results among the mostly young people who responded.

However, alcohol use seemed to increase among some groups, possibly those who are more vulnerable to harms.




Read more:
Worried about your drinking during lockdown? These 8 signs might indicate a problem


In both the ABS and ANU studies, more women had increased their drinking than decreased it, which seemed to be related to higher stress linked to increased responsibilities at home.

In a survey of people who use illicit drugs, more people increased (41%) than decreased (33%) drinking. And among people who inject drugs around 11% reported increased drinking.

There have also been indicators that family violence has increased during this time. Alcohol and other drug use is a risk factor for family violence.

We need more data about heavy drug use

Since the onset of the pandemic, two studies found cannabis use had increased but other drug use had decreased or was stable. The respondents were mostly young, used for recreational purposes and were not dependent nor did they have serious problems.

Reductions in use of drugs like MDMA and cocaine, which are associated with festivals and parties, are not surprising since these large events have been restricted for months.

Two studies suggested cannabis use was on the rise, but we still need more and better data on how the pandemic has impacted heavy users.
Shutterstock

Most of the research hasn’t involved people who are heavy or dependent users, so we don’t know much about changes in use in these groups.

One study of people who inject drugs (who tend to use more regularly) reported some changes to availability and purity of some drugs, and small changes in use, but again some people increased and some decreased their use.

With physical distancing and lockdowns, it’s likely more people used alone or with fewer people. This means if anything goes wrong, help is further away.

Telehealth for drug treatment?

A survey of treatment services found that among services that reported changes in demand, most had an increase. Most services also reported that mental health problems, family violence and financial stress had all increased among people who use their services. These factors can make treatment more complex.

There is some evidence fewer people accessed medication treatment for opioids during the restrictions, like methadone.

COVID-19 restrictions have changed the way many services offer treatment. Most residential rehabilitation services have reduced the number of places available so they can ensure physical distancing.

Many treatment services are reporting increased demand.
Shutterstock

Before COVID-19 there were already long waiting lists for residential rehabilitation, so with more than 70% of services reporting reduced capacity, people may have found it harder to access residential treatment.

Non-residential services (like counselling or day programs) haven’t significantly reduced the number of people they see, and most have partially or fully moved to telehealth.

As a result, around 35% of services said fewer people missed appointments. This might be due to the easier access telehealth provides, including the reduced travel time.

However, around 25% of services said more people missed appointments. Anecdotal interviews suggest some of this might be due to difficulty transitioning to online appointments. One person said: “I know they are on Zoom but I don’t know how to use it”.

These adaptations are more complex than they appear. The time and effort required for services to make significant changes takes time away from providing treatment.

The move to telehealth is a significant one, requiring additional hardware and software, training of staff, and help for people who use the service to work out how to use the technology. Things like ensuring confidentiality can be more difficult when someone is receiving counselling at home with family around, for example.

Piecemeal funding for treatment services

The alcohol and other drug sector was already significantly under-resourced and struggling to meet existing demand before COVID-19.

In April, federal health minister Greg Hunt announced A$6 million in funding for alcohol and other drug services. Just over half of this was allocated to three organisations to increase online access to support services. The rest went to information and awareness campaigns. But no funds were set aside for existing treatment services to make COVID-19 related changes to their services.

Various state governments have allocated some funding to support alcohol and other drug services to adjust to COVID-19:

  • Tasmania released a total of A$450,000 to help services transition to telehealth

  • Western Australia allocated a total of A$350,000 for specialist alcohol and other drug services to maintain services amid the pandemic

  • Victoria and South Australia announced additional support to help people access medication treatment.

Further funding is needed to ensure services can continue to provide COVID-safe services.

It’s important for people who use alcohol and other drugs, and for the public, that alcohol and other drug treatment is well-supported to continue to operate during these changes. We know treatment is cost-effective, reduces crime and increases participation in the community. For every dollar invested in drug treatment, $7 is saved to the community.

Getting help

If you’re worried about your own or someone else’s alcohol or other drug use, you can get help by phoning the National Alcohol and Other Drug Hotline on 1800 250 015.

You can also access support online through CounsellingOnline, Hello Sunday Morning and SMART Recovery.

You may also be eligible to access one of the new telehealth services. Talk to your GP to find out more.The Conversation

Nicole Lee, Professor at the National Drug Research Institute (Melbourne), Curtin University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

The evidence is in. WHO says corticosteroids really do save lives of people critically ill with COVID-19



Shutterstock

Andrew McLachlan, University of Sydney

Readily available drugs, which dampen the runaway inflammatory response in patients severely ill with COVID-19, save lives, according to evidence released this week.

An analysis by the World Health Organisation (WHO), which drew together results from several studies, confirms the benefit of this group of anti-inflammatory steroid drugs, known as corticosteroids.

While earlier studies showed the apparent benefit of one of these drugs, dexamethasone, this latest evidence goes further.

It shows other cheap and readily available corticosteroid drugs, including hydrocortisone, could benefit patients at the life-threatening stages of coronavirus infection.

Remind me again, what are corticosteroids?

Corticosteroids have been used for decades to treat a variety of inflammatory conditions. These include severe forms of lung inflammation, such as pneumonia, shock due to infection, and severe respiratory syndromes. They are also used to treat more common conditions, including asthma and eczema.

These medicines are on the WHO list of essential medicines, meaning they are widely available (usually at low cost).




Read more:
What medicines would we pack for a trip to Mars?


What do we already know about corticosteroids for COVID-19?

In June, early release of results from the RECOVERY trial showed dexamethasone reduced the risk of death by up to a third in people hospitalised with COVID-19 who needed a ventilator to help them breathe.

Results of the dexamethasone trial were released early.

Despite the early release of the trial results, and limited details at the time, the findings were compelling and clinical practice changed.

Several other trials were stopped. All patients switched to receive active treatment with a corticosteroid.

The results of the RECOVERY trial have since been formally peer reviewed and published.




Read more:
Dexamethasone: the cheap, old and boring drug that’s a potential coronavirus treatment


What does the latest evidence say?

The WHO drew together results from seven randomised clinical trials, including data from 1,703 critically ill patients with COVID-19.

This is a powerful and compelling way to combine information and truly address the question of whether these medicines benefit people in hospital critically unwell with COVID-19.




Read more:
ICU ventilators: what they are, how they work and why it’s hard to make more


The study, which included patients from Australia and New Zealand, found almost 33% of people treated with corticosteroids died within 28 days of treatment. This was compared with 41% of patients who received supportive care (or placebo). Corticosteroid treatment helped patients whether or not they needed ventilation or oxygen.

Importantly, the analysis also concluded the benefits were not specific to one corticosteroid drug but were the same for dexamethasone and hydrocortisone.

Corticosteroids can also have an impact on the immune system. So the researchers looked at the risk of infection from other causes, for example bacterial pneumonia, and found it was not a major concern.

What does this mean for patients?

The weight of evidence has led WHO guidelines this week to strongly recommend using corticosteroids to treat people with severe or critical COVID-19.

This aligns with current Australian guidelines for treating hospitalised patients with COVID-19 needing oxygen support.

Corticosteroids are not for everyone and are not a cure

It is important to remember these findings only apply to using corticosteroids in critically ill people hospitalised with COVID-19. There is currently limited information to suggest these medicines are appropriate for people with mild COVID-19.

While corticosteroids help treat the body’s response to the coronavirus infection, they are not antiviral drugs. They do not inhibit the virus itself, so they are not a cure.




Read more:
In the fight against coronavirus, antivirals are as important as a vaccine. Here’s where the science is up to


A new way of doing research

Usually, several clinical trials on a common theme are published over a series of years. Then a meta-analysis draws together their results, publishing these combined results much later.

But the amazing thing about this latest evidence is the meta-analysis included data from clinical trials published at the same time. This shows a degree of co-operation and collaboration between researchers to share data to urgently address important research questions that guide clinical care.

Evidence to guide the best treatments and management for people with COVID-19 continues to emerge. You can follow the evidence and how it’s applied in Australia here.




Read more:
Ivermectin is still not a miracle cure for COVID-19, despite what you may have read


The Conversation


Andrew McLachlan, Head of School and Dean of Pharmacy, University of Sydney

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Multiple sclerosis drug may help treat COVID-19 and lead to faster recovery



Vadim Zakharishchev/Shutterstock

Nial Wheate, University of Sydney and Elise Schubert, University of Sydney

What do multiple sclerosis (MS) and the novel coronavirus have in common? Until this week, not much, but a recent clinical trial has shown a reformulation of a drug used to treat MS can potentially also be used to help patients infected with COVID-19.

SNG001 is an inhaled form of a drug called interferon-beta under development by the UK pharmaceutical company Synairgen. Interferon is normally prescribed for the treatment of symptoms relating to relapsing-remitting MS.

But the clinical trial, Synairgen found that when SNG001 was given to patients with COVID-19, it stopped the development of more severe symptoms, accelerated their recovery, and allowed them to leave hospital earlier.




Read more:
Vaccine progress report: the projects bidding to win the race for a COVID-19 vaccine


Like other clinical trials for COVID-19 treatments, the results still need to be thoroughly checked before SNG001 is included as a standard treatment for coronavirus. The drug’s key risks (potential for severe depression) also need to be weighed against the potential benefits.

How does it work?

MS is a condition of the central nervous system. The nerve impulses between the brain and spinal cord get blocked or mixed up. It happens because the body’s immune system attacks the protective layers around nerve fibres. The result is a loss of muscle control and balance.

In contrast, COVID-19 is a viral infection that affects a patient’s ability to breathe due to inflammation putting pressure on their lungs.

What both diseases have in common is the activation of the body’s immune response, so a drug that modulates the immune system for one can potentially work for the other.

Interferon-beta (interferon), a naturally occurring protein in the body, is used as an immunotherapy drug to combat relapsing-remitting MS by reducing inflammation and easing the symptoms of the disease.

Scientists at Synairgen hypothesised it could also treat COVID-19 through initiating the body’s antiviral response and potentially reducing inflammation on the lungs.

It is believed some at-risk patient groups cannot produce interferon as effectively as other people, reducing their ability to fight the virus and resulting in more severe symptoms.

So giving those patients interferon, in theory, should help them fight the virus, alleviate their symptoms, and improve survival rates.

Take a breath

For the treatment of MS, interferon is given as a weekly injection into muscle tissue.

The SNG001 drug developed by Synairgen contains the same interferon therapy used for MS, but formulated as an inhaled product.

Originally, the company was developing SNG001 as a treatment for a different type of lung condition called chronic obstructive pulomary diease (COPD), but it saw the direct potential for COVID-19 as well.

Instead of an injection, SNG001 is given to patients via a nebuliser, a machine that transforms a water solution of interferon into a fine mist that can be breathed in by patients through a face mask.

Promising results, so far

Between March and May this year, Synairgen sponsored a clinical trial at University Hospital Southampton to test SNG001 for COVID-19 patients. Those eligible for the trial only needed to have mild symptoms of COVID-19.

Other clinical trials conducted in the past for different drugs, such as remdesivir and dexamethasone, required patients to be hospitalised before they were eligible for drug treatment.

In total, 101 patients in a hospital setting were enrolled in the SNG001 trial and were given the drug daily for 14 days. Compared with a placebo, those given SNG001 had a 79% lower risk of developing severe disease.

Patients given the drug were also twice as likely to recover from their infection and were discharged earlier from hospital than those given the placebo.

Before SNG001 becomes standard care for COVID-19 treatment the results of the clinical trial need to be checked by independent scientists.

In the past, trial results for hydroxychloroquine did not stand up to scrutiny after they were announced and the results were subsequently retracted by the research team.

The risks and benefits

If the latest results are shown to be reliable, before doctors decide to make SNG001 a part of the standard treatment for hospitalised COVID-19 patients they will need to weigh its benefits against the potential risks.

One of the most important side effects of the drugs is that it can induce depression.

As a result, interferon is used with caution in patients with pre-existing depression or who have suicidal thoughts. These conditions may already be heightened by the pandemic if a potential patient for the drug has lost their job or they are not dealing well with the isolation of social distancing.

This means doctors would need to undertake a comprehensive mental health screen of all patients they consider for SNG001 treatment.




Read more:
Immunity to COVID-19 may not last. This threatens a vaccine and herd immunity


Other side effects relevant to interferon are that it can worsen seizure disorders or heart failures. So again, it needs to be used with caution in these patient groups.

The results of the SNG001 trial are very promising and potentially give us a treatment to prevent those people mildly infected with COVID-19 from developing more severe symptoms and needing hospitalisation.

But the results need to be checked by independent scientists first, and the drug’s benefits need to be weighed against its risk, as the ability to induce severe depression could cause a wave of mental health problems that make matters worse rather than better.The Conversation

Nial Wheate, Associate Professor | Program Director, Undergraduate Pharmacy, University of Sydney and Elise Schubert, Pharmacist and PhD Candidate, University of Sydney

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Alzheimer’s disease: protective gene uncovered in human cell model – bringing promise for new drug discoveries



Our method could someday potentially detect the disease before it starts developing in a person’s brain.
Robert Kneschke/ Shutterstock

Dean Nizetic, Queen Mary University of London

Every three seconds, someone in the world develops dementia. The most common form of dementia is Alzheimer’s disease. While researchers have identified a number of risk factors that are linked to dementia – including genetics, smoking, and high blood pressure – there is currently still no cure.

Part of the reason for this is because of how complicated it is to test potential Alzheimer’s drugs. In order to conduct clinical trials participants need to have symptoms. But by the time symptoms appear, it’s usually too late for treatments to have a large effect as many of their brain cells have already died.

But our latest research developed a new human cell model that is able to rapidly simulate the development of Alzheimer’s disease in the lab. This allowed us to identify a gene, called BACE2, that is naturally able to suppress the signs of Alzheimer’s disease in human brain cells. Our research is the result of around five years’ work, and was the collaborative effort of teams based in London, Singapore, Sweden and Croatia.

Researchers already know a lot about which genes cause Alzheimer’s disease or make someone more likely to develop it. These genes contribute to certain toxic proteins accumulating in the human brain. So our team thought that the opposite must also be true: our brain cells must also have proteins that can naturally slow down the development of Alzheimer’s.

One gene that can definitely cause Alzheimer’s disease is a gene found on the 21st pair of human chromosomes that is responsible for making the amyloid precursor protein (APP). Research shows that 100% of people born with just one extra copy of the APP gene (called “DupAPP”) will develop dementia by age 60.

People with Down’s syndrome are born with three copies of APP because they have a third 21st chromosome. But by age 60, only 60% of them will develop clinical dementia. We wanted to know why some people with Down’s syndrome have delayed development of – or never develop – Alzheimer’s dementia compared to those who have one extra DupAPP gene.

The simple answer for this is because they have an extra dose of all other genes located in chromosome 21. We believed that there could be some dose-sensitive genes on chromosome 21 that, when triplicated, protect against Alzheimer’s disease by counteracting the effects of the third APP gene.

These genes must then appear to delay the onset of clinical dementia in some people with Down’s syndrome by approximately 20 years. Studies have even shown that any future drug able to delay dementia onset by just five years would reduce the prevalence of Alzheimer’s in the general population by half.

We re-programmed cells, turning them into brain cells.
arrideo/ Shutterstock

To study the potential of the extra genes, we took hair follicle cells from people with Down’s syndrome and re-programmed the cells to become like stem cells. This allowed us to turn them into brain cells in a Petri dish.

We then grew them into 3D balls of cells that imitated the tissue of the grey matter (cortex) of the human brain. The 3D nature of the culturing allowed misfolded and toxic proteins to accumulate, which are crucial changes that lead to Alzheimer’s disease in the brain.

We found all three major signs of Alzheimer’s disease (plaque build-up in the brain, misfolded “tau” proteins and dying brain neurons) in cell cultures from 71% of people with Down’s syndrome who donated samples. This proportion was similar to the percentage of clinical dementia among adults with Down’s syndrome.

We were also able to use CRISPR – a technology that allows researchers to alter DNA sequences and modify a gene’s function – to reduce the number of BACE2 genes from three copies to two copies on chromosome 21. This was only done in cases where there were no indications of Alzheimer’s disease in our cellular model. Surprisingly, reducing the number of BACE2 genes on chromosome 21 provoked signs of the disease. This strongly suggest that having extra copies of a normal BACE2 gene could prevent Alzheimer’s.

The protective action of BACE2 reduces the levels of toxic amyloid proteins. This was verified in our cellular models, as well as in cerebrospinal fluid and post-mortem brain tissue from people with Down’s syndrome.

Our study provides proof that natural Alzheimer’s-preventing genes exist, and now we have a system to detect new potential protective genes. Importantly, recent research showed the protective action of BACE2 might also be relevant to people who don’t have Down’s syndrome.

Our results also show that all three signs of Alzheimer’s disease can be potentially detected in cells from live donors. Though this requires a lot more research, it means we may be able to develop tests that identify which people are at higher risk of Alzheimer’s disease by looking at their cells.

This would allow us to detect the disease before it starts developing in a person’s brain, and could make it possible to design personalised preventative treatments. However, we are still a long way from reaching this goal.

Most importantly, our work shows that all three signs of Alzheimer’s disease detected using our model could be prevented by drugs known to inhibit the production of the toxic amyloid protein – and this can be detected in as little as six weeks in the lab. We hope our discovery could lead to the development of new drugs aimed at delaying or preventing Alzheimer’s disease, before it causes brain cell death.The Conversation

Dean Nizetic, Professor of Cellular and Molecular Biology, Queen Mary University of London

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Dexamethasone: the cheap, old and boring drug that’s a potential coronavirus treatment




Nial Wheate, University of Sydney

First, we tried the antimalarial drug hydroxychloroquine. Then we tested the antiviral drug remdesivir. But new UK research gives the strongest indication yet we may have found a useful treatment for COVID-19.

This time it’s an old anti-inflammatory drug, dexamethasone, which has been described as cheap, old and boring.

Preliminary results from a clinical trial just released indicate the drug seems to reduce your chance of dying from COVID-19 if you’re in hospital and need oxygen or a machine to help you breathe.

The results were significant enough for the UK to recommend its use for severe COVID-19.

Before we roll it out in Australia, we need to balance the drug’s risks with its benefits after peer-review of the full trial data.

What is dexamethasone?

Dexamethasone has been used since the late 1950s, so doctors are familiar with it. It’s also inexpensive, with a packet of 30 tablets costing around A$22 (for general patients) under Australia’s Pharmaceutical Benefits Scheme.

So if it does work for COVID-19, this cheap and boring drug, already available in Australia with a prescription, would be easy to add to current treatments.

Dexamethasone belongs to a class of drugs known as corticosteroids and is used to treat a range of conditions related to inflammation. These include severe allergies, some types of nausea and vomiting, arthritis, swelling of the brain and spinal cord, severe asthma, and for breathing difficulties in newborn babies.

And it’s dexamethasone’s application to those latter two respiratory conditions that prompted doctors to think it may also help patients severely affected by COVID-19.




Read more:
ICU ventilators: what they are, how they work and why it’s hard to make more


What did the trial find?

The recently reported results come from the Randomised Evaluation of COVID-19 Therapy, or RECOVERY, trial.

The researchers put patients into one of three groups: those needing ventilation (a machine that helps them breath); those who just needed oxygen therapy; and those who needed no treatment to help them breathe.

Patients in each of those groups were given dexamethasone (6mg once a day, either as a tablet or via intravenous injection), for ten days. A fourth group (a control group) was not given the drug.

Dexamethasone was most useful for the ventilated patients; deaths for this group dropped by about one-third with drug treatment. In contrast, deaths only dropped by one-fifth for those patients who were only receiving oxygen therapy. There was no benefit to patients who could breathe normally.

Results of the dexamethasone trial have just been released.

The researchers calculated that giving dexamethasone to eight ventilated patients would prevent one from dying, on average. And giving it to around 25 patients needing oxygen alone would prevent one death.




Read more:
The fascinating history of clinical trials


How might dexamethasone work for COVID-19?

When a patient has severe COVID-19, their immune system ramps up to catch and control the virus in the lungs.

In doing this, their body produces more infection-fighting white blood cells. This results in inflammation and pressure on their lungs, making it very difficult for them to breath.

It’s therefore likely dexamethasone reduces this inflammation, and so reduces pressure on the lungs.




Read more:
How does coronavirus kill?


What are the downsides?

There are potential complications with using dexamethasone.

First, dexamethasone also suppresses the immune system when it reduces inflammation. So, it’s not usually recommended for people who are sick, or could be sick, from other infections. So doctors will need to make sure patients have no other infections before they are prescribed the drug.

If the results of this trial are correct though, the drug doesn’t appear to compromise the patient’s ability to fight COVID-19; it might just affect their ability to fight off other diseases.

Second, the drug is only useful for patients with difficulty breathing and needing some assistance either through ventilation in a hospital or from oxygen therapy.

There appears to be no benefit for patients who don’t need help breathing. So we shouldn’t be giving it to everyone who tests positive to the virus.




Read more:
In the fight against coronavirus, antivirals are as important as a vaccine. Here’s where the science is up to


Third, like all drugs, dexamethasone has side effects that need to be monitored. Serious, but rare ones include: severe stomach or intestinal pain, sudden changes with vision, fits, significant psychiatric or personality changes, severe dizziness, fainting, weakness and chest pain or irregular heartbeat, and swelling of the face, lips, mouth, tongue or throat, which may cause difficulty in swallowing or breathing.

What happens next?

The results of the clinical trial are preliminary. So we need to wait for the full study data and scientific peer-review before we can make a definitive decision as to whether dexamethasone treatment is a worthwhile, and safe, addition to COVID-19 therapy in Australia.




Read more:
What if the vaccine or drugs don’t save us? Plan B for coronavirus means research on alternatives is urgently needed


The Conversation


Nial Wheate, Associate Professor | Program Director, Undergraduate Pharmacy, University of Sydney

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Donald Trump is taking hydroxychloroquine to ward off COVID-19. Is that wise?


Teresa G. Carvalho, La Trobe University

The White House’s confirmation that US President Donald Trump has been taking hydroxychloroquine every day for the past two weeks, with his doctor’s blessing, has reignited the controversy over the drug. It has long been used against malaria but has not been approved for COVID-19.

Trump said he has “heard a lot of good stories” about hydroxychloroquine, and incorrectly claimed there is no evidence of harmful side-effects from taking it. His previous claims in March that the drug could be a “game changer” in the pandemic prompted many people, including Australian businessman and politician Clive Palmer, to suggest stockpiling and distribution of the drug to the public.

But the dangers of acting on false or incomplete health information were underlined by the death of an Arizona man in March after inappropriate consumption of the related drug chloroquine. It’s important to know the real science behind the touted health benefits.

How do these medicines work?

Hydroxychloroquine is an analogue of chloroquine, meaning both compounds have similar chemical structures and a similar mode of action against malaria. Both medications are administered orally and have common side-effects such as nausea, diarrhoea and muscle weakness. However, hydroxychloroquine is less toxic, probably because it is easier for the body to metabolise.

Chloroquine and hydroxychloroquine are listed by the World Health Organisation as an essential medicine. Both drugs have been used to treat malaria for more than 70 years, and hydroxychloroquine has also proved effective against auto-immune diseases such as systemic lupus erythematosus and rheumatoid arthritis. The US Food and Drug Administration has approved both chloroquine and hydroxychloroquine for treating malaria, but not for COVID-19.




Read more:
In the rush to innovate for COVID-19 drugs, sound science is still essential


We don’t know exactly how these drugs work to combat the malaria parasite. But we know chloroquine disrupts the parasite’s digestive enzymes by altering the pH inside the parasite cell, presumably effectively starving it to death.

Malaria parasites and coronaviruses are very different organisms. So how can the same drugs work against both? In lab studies, chloroquine hinders replication of the SARS coronavirus, apparently by changing the pH inside particular parts of human cells where the virus replicates.

This offers a glimmer of hope that these pH changes inside cells could hold the key to thwarting such different types of pathogens.

Is it OK to repurpose drugs like this?

Existing drugs can be extremely valuable in an emergency like a pandemic, because we already know the maximum dose and any potential toxic side-effects. This gives us a useful basis on which to consider using them for a new purpose. Chloroquine is also cheap to manufacture, and has already been widely used in humans.

But we shouldn’t be complacent. There are significant gaps in our understanding of the biology of SARS-CoV-2, which causes COVID-19, because it is a brand new virus. There is a 20% genetic difference between SARS-CoV-2 and the previous SARS coronavirus, meaning we should not assume a drug shown to act against SARS will automatically work for SARS-CoV-2.

Widely used, but with common side effects.
Gary L. Hider/Shutterstock

Even in its primary use against malaria, long-term chloroquine exposure can lead to increased risks such as vision impairment and cardiac arrest. Hydroxychloroquine offers a safer treatment plan with reduced tablet dosages and lessened side-effects. But considering their potentially lethal cardiovascular side-effects, these drugs are especially detrimental to those who are overweight or have pre-existing heart conditions. Despite the urgent need to confront COVID-19, we need to tread carefully when using existing medicines in new ways.

Any medication that has not been thoroughly tested for the disease in question can have seriously toxic side-effects. What’s more, different diseases may require different doses of the same drug. So we would need to ensure any dose that can protect against SARS-CoV-2 would actually be safe to take.

The evidence so far

Although many clinical trials are under way, there is still not enough evidence chloroquine and hydroxychloroquine will be useful against COVID-19. The few trials completed and published so far, despite claiming positive outcomes, have been either small and poorly controlled or lacking in detail.

A recent hydroxychloroquine trial in China showed no significant benefits for COVID-19 patients’ recovery rate. A French hydroxychloroquine trial was similarly discouraging, with eight patients prematurely discontinuing the treatment after heart complications.

The fascination with chloroquine and hydroxychloroquine has also adversely affected other drug trials. Clinical trials of other possible COVID-19 treatments, including HIV drugs and antidepressants, have seen reduced enrolments. Needless to say, in a pandemic we should not be putting all our eggs in one basket.

Then there is the issue of chloroquine hoarding, which not only encourages dangerous self-medication, but also puts malaria patients at greater risk. With malaria transmission season looming in some countries, the anticipated shortage of chloroquine and hydroxychloroquine will severely impact current malaria control efforts.




Read more:
Coronavirus: scientists promoting chloroquine and remdesivir are acting like sports rivals


Overall, despite their tantalising promise as antiviral drugs, there isn’t enough evidence chloroquine and hydroxychloroquine are safe and suitable to use against COVID-19. The current preliminary data need to be backed up by multiple properly designed clinical trials that monitor patients for prolonged periods.

During a pandemic there is immense pressure to find drugs that will work. But despite Trump’s desperation for a miracle cure, the risks of undue haste are severe.


This article was coauthored by Liana Theodoridis, an Honours student in Microbiology at La Trobe University.The Conversation

Teresa G. Carvalho, Senior Lecturer in Microbiology, La Trobe University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Could blood thinners be a lifesaving treatment for COVID-19? Here’s what the science says and what it means for you



Shutterstock

Karlheinz Peter, Baker Heart and Diabetes Institute; Hannah Stevens, Baker Heart and Diabetes Institute, and James McFadyen, Baker Heart and Diabetes Institute

A spate of recent media headlines have described blood thinning medications – which include aspirin and warfarin – as a “breakthrough treatment” for COVID-19 that could “save lives”.

It’s early days yet but a growing body of research evidence suggests COVID-19 causes abnormalities in blood clotting, which means blood thinning drugs may have a role to play in treatment.

Here’s what the research says on this question – and how it applies to you.

Mounting evidence

When COVID-19 first emerged, it was thought the illness was a typical respiratory disease causing symptoms such as fever, sore throat, dry cough, and potentially lung infection (pneumonia) and a build-up of fluid in the lungs making it difficult to breathe.

However, as we outlined in a previous article in The Conversation, 30-70% of COVID-19 patients admitted to intensive care units, developed blood clots.

These rates of blood clotting appear to be much higher than what is expected when compared with people who are hospitalised for reasons other than COVID-19.

Blood clots in the veins often present in the legs (deep vein thrombosis) and are dislodged into the lungs (called pulmonary embolism); approximately one in four COVID-19 patients admitted to intensive care will develop a pulmonary embolism (where an artery in the lungs gets blocked).

Arterial blood clots associated with COVID-19 can lead to strokes, including in younger patients, with potentially devastating outcomes.

In addition, COVID-19 appears to cause tiny blood clots that can block small vessels in the lungs. These “micro” blood clots may be a key reason why patients with COVID-19 often have very low oxygen levels.

Blood clots appear to be associated with a higher risk of dying from COVID-19. Likewise, elevated markers of blood clotting are associated with an increased risk of admission to the intensive care unit and a worse prognosis overall.

Should blood thinners be standard treatment for COVID-19 patients in hospital?

Because the rate of blood clotting is so high, all people admitted to hospital with COVID-19 should receive a low dose of blood thinner medication to prevent blood clots. This prophylactic dose of blood thinner is standard across most hospitals in Australia.

However, many blood clots in COVID-19 are occurring despite the use of low-dose blood thinners. As such, it is a question of intense discussion whether people admitted to hospital with severe COVID-19 should receive a higher-than-usual dose of blood thinners to prevent blood clots and improve clinical outcomes.

A recent study from the US suggests patients admitted to hospital and prescribed full dose blood thinners had a better chance of survival and lower chance of needing a ventilator.

However, this finding has to be confirmed before the higher dose can be generally recommended. Fortunately, several research studies are underway in Europe, the UK and elsewhere to test and answer this question definitively.

Several other blood thinner treatments are also being evaluated in people with COVID-19. Aspirin is commonly prescribed to people who are at high risk of strokes or heart attacks. There are now studies underway examining if aspirin can reduce risk of blood clotting in people with COVID-19. In the US, some stronger clot-busting medications are also being trialled in people with severe COVID-19.

It is important to note blood thinners are not without risk, as this treatment can increase the risk of bleeding. So without definite evidence to support the benefit of high dose blood thinners in all hospitalised patients with COVID-19, the decision to use higher doses of blood thinning medication outside of a clinical trial must be made on an individual basis.


The Conversation, CC BY-ND

Should I take an aspirin to prevent blood clots?

There is no evidence aspirin or other blood thinners should be taken to prevent blood clots in the general population. Also, there is no evidence blood thinners are required to prevent blood clots for people with mild COVID-19 who are isolating at home. Because blood thinners can cause bleeding, they should not be taken unless prescribed by a doctor.

It is important for people who are taking blood thinners for another reason to continue taking these medications as normal, particularly if they are diagnosed with COVID-19.

In summary, our understanding of COVID-19 and how the coronavirus attacks the body continues to rapidly evolve. Researchers from around the world are publishing data almost daily. However, not all of this research has been peer reviewed.

If you develop symptoms, the most important thing you can do is to get tested for COVID-19 and talk to your doctor about potential treatments, including hospital admission and then about blood thinning medication.

Similar to our colleagues in the UK and the US, we as doctors specialised in the field of blood clotting are indeed optimistic and hope clinical studies currently underway will show rigorous strategies for prevention and treatment of blood clotting will help to reduce severity and improve survival of patients with COVID-19.




Read more:
Coronavirus: how long does it take to get sick? How infectious is it? Will you always have a fever? COVID-19 basics explained


The Conversation


Karlheinz Peter, Lab Head, Atherothrombosis and Vascular Biology and Deputy Director, Baker Heart and Diabetes Institute; Interventional Cardiologist, Alfred Hospital; Professor of Medicine and Immunology, Monash University, Baker Heart and Diabetes Institute; Hannah Stevens, Haematologist and PhD student, Baker Heart and Diabetes Institute, and James McFadyen, Research Fellow, Baker Heart and Diabetes Institute, Haematologist, Alfred Hospital, Baker Heart and Diabetes Institute

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Is remdesivir a miracle drug to cure coronavirus? Don’t get your hopes up yet


Nial Wheate, University of Sydney and Andrew Bartlett, University of Sydney

The race is on to find a drug that is both effective and safe for treating COVID-19, which has spread to 3.1 million infections and caused 220,000 deaths worldwide.

This week, the US National Institute of Allergy and Infectious Diseases released findings of a clinical trial of the experimental antiviral drug remdesivir. This showed COVID-19 patients recovered more quickly and had an improved survival rate when taking the drug, compared with those given a placebo and standard care.

But these are just the preliminary results of one study. Other human trials have not shown similar results. Further trials are under way and will more definitively show whether remdesivir is a suitable and effective treatment for COVID-19.




Read more:
In the fight against coronavirus, antivirals are as important as a vaccine. Here’s where the science is up to


What is remdesivir?

Remdesivir is an experimental antiviral drug being developed by Gilead Sciences. Originally it was being developed as a treatment for Ebola, a viral infection that causes severe internal bleeding. But researchers are now interested in its potential to treat patients with COVID-19.

Remdesivir mimics a natural ingredient called adenosine of DNA and RNA, the latter being a molecule similar to DNA that is used to carry the genetic information of viruses. After the drug is activated in the body, it works by blocking a type of enzyme called a polymerase, which is needed to make DNA and RNA.

When you block the enzyme, the virus can’t make copies of itself, limiting the development of symptoms and spread of the disease.

It should be noted that no drug is perfectly safe, and remdesivir is no different. Studies undertaken so far suggest the drug may damage the liver and cause other short-term side effects such as nausea and vomiting.

These side effects need to be taken into consideration when treating COVID-19 patients who have other underlying conditions.

Clinical trials in US positive but only preliminary

This week the National Institute of Allergy and Infectious Diseases (NIAID) released the results of its trial using remdesivir for COVID-19 patients. They studied the effects of the drug on patients who were already infected with COVID-19 to see whether it helped them recover faster and improve their survival rate.

Adult patients hospitalised with COVID-19 were given daily injections of remdesivir. They were found to recover four days faster, an improvement of 31%, when compared with other patients who only received standard care and placebo.




Read more:
Coronavirus treatments: what drugs might work against COVID-19?


The results also indicated that more patients survived the infection with remdesivir treatment, with the death rate dropping from 11.6% to 8%.

The results are significant enough that director of NIAID Anthony Fauci said it was an “ethical responsibility” for the remaining trial patients who were taking the placebo to be switched to the active drug.

But we need to treat the results of this trial with caution; for the moment they are only preliminary.

A data and safety panel has looked at the initial results, but they haven’t been peer-reviewed. During peer review, independent experts from the scientific community scrutinise the study design, methods, data produced, and the conclusions before the study is published in a medical journal.

How does it compare with other studies?

The results of other trials, such as one undertaken in China, have not shown the same promising results.

The Chinese study was published in the Lancet, considered one of the most influential medical journals in the world. This trial was a randomised, double-blind, placebo-controlled study which means that neither the researchers nor the patients knew if they’d been given the active drug or a placebo.

These types of studies can reduce some biases that can influence studies, but also help quantify the effectiveness of the drug.

But the study also had limitations that need to be recognised. The patients were not as seriously ill as those in the NIAID trial, and the study was terminated early because the outbreak in China was easing.

In the end, the study only collected data on 237 patients, compared with 1,063 patients in the NIAID trial. The authors acknowledge further study is needed in more seriously ill patients and with a larger sample size.

Currently there are more than a dozen other clinical trials of remdesivir and COVID-19 being undertaken throughout the world. We need to await the data to know for sure whether the drug is as effective as we need it to be.




Read more:
Head lice drug Ivermectin is being tested as a possible coronavirus treatment, but that’s no reason to buy it


This article is supported by the Judith Neilson Institute for Journalism and Ideas.The Conversation

Nial Wheate, Associate Professor | Program Director, Undergraduate Pharmacy, University of Sydney and Andrew Bartlett, Associate Lecturer Pharmacy Practice, University of Sydney

This article is republished from The Conversation under a Creative Commons license. Read the original article.

In the fight against coronavirus, antivirals are as important as a vaccine. Here’s where the science is up to



Shutterstock

Lisa Sedger, University of Technology Sydney

While many scientists are working on developing a coronavirus vaccine, others are busy testing antiviral drugs.

Vaccines are generally only effective when administered prior to infection, but antiviral agents are important because they can treat people who already have COVID-19.

Here’s an overview of antiviral drugs scientists are investigating for coronavirus.




Read more:
How does coronavirus kill?


Targeting the copy cats

How do antiviral drugs work? First, it’s important to understand the genome of animals and plants is composed of deoxyribonucleic acid (DNA), but viral genomes can also be comprised of ribonucleic acid (RNA). This is the case for SARS-CoV-2 coronavirus – the virus that causes COVID-19.

In order to replicate, an RNA virus needs to make more copies of its RNA genome. This means antiviral drugs which block the copying of RNA genomes can potentially help treat COVID-19 patients. These drugs are known as RNA-polymerase inhibitors.




Read more:
Here’s why the WHO says a coronavirus vaccine is 18 months away


These types of drugs have successfully cured people of chronic hepatitis C – another RNA virus infection.

But not all viral RNA polymerases are the same, so the drugs that work for hepatitis C virus will not necessarily work for human coronaviruses.

Favilavir is an RNA polymerase inhibitor drug scientists are currently trialling against coronavirus.

Stopping the virus in its tracks

Another successful antiviral drug strategy is to use non-functional “analogues”, or inauthentic copies of the basic building blocks of the viral RNA genome. The presence of these analogues in the viral genome blocks the viral polymerase, meaning the virus cannot make another copy of its RNA. Acyclovir, ribavirin and azidothymidine (AZT) are examples of these drugs.

Unfortunately, this coronavirus is a bit tricky, because it “proofreads” the authenticity of its RNA genome. As such, it identifies the analogues as being inauthentic and removes them. This stops certain antiviral drugs like ribavirin from being effective.

Fortunately, the coronavirus’ proofreading powers don’t block a similar drug, remdesivir. So remdesivir potently halts coronavirus replication and represents a promising drug option for COVID-19 patients.

Remdesivir is also effective against other RNA viruses including Ebola virus and the coronaviruses SARS and Middle Eastern respiratory syndrome (MERS).

Scientists are currently assessing remdesivir in clinical trials in the United States and China. Time will tell if remdesivir is effective for COVID-19 patients. But doctors are already considering how the drug is best administered for optimal results and whether it should be used in combination with other drugs or as a single agent.




Read more:
COVID-19 treatment might already exist in old drugs – we’re using pieces of the coronavirus itself to find them


Other proven antiviral drugs

Many RNA viruses produce a single “multi-protein” that’s later broken down into individual proteins via enzymes called “proteases”. Any molecules that inhibit these proteases have potential as antiviral drugs. Viral protease inhibitor drugs have been highly effective in treating the human immunodeficiency virus (HIV) and hepatitis C virus.

Lopinavir and ritonavir are a combination protease-inhibitor drug (Kaletra) that can inhibit coronaviruses in human cells. Kaletra has already been used to treat a patient with COVID-19 in South Korea, but a larger trial found its effects were unconvincing. The reasons for these discrepancies are currently unclear and more research is obviously needed.

With any antiviral drug, the sooner it’s administered once a patient is infected, the better the outcome. This is because viruses replicate quickly, producing tens to hundreds of new infectious viruses.

Weathering the cytokine storm

In respiratory infections caused by influenza or SARS-CoV-2 viruses, clinically serious infection involves what’s called a “cytokine storm”. Here, a strong immune response results in the production of high levels of inflammatory mediators: cytokines and chemokines.

These molecules recruit inflammatory cells to the site of the virus infection, for example, the lungs of patients with COVID-19. These cytokines and cells then fight the virus infection, but their presence also partly obstructs the air sacs where oxygen exchange occurs.

Researchers are now considering add-on therapies that partly limit the inflammatory response by blocking the effects of certain cytokines and chemokines. These add-on therapies include antibody-based drugs, such as tocilizumab that blocks the interleukin-6 cytokine receptor or leronlimab that blocks the chemokine receptor CCR5. When cytokine receptors and chemokine receptors are blocked then it matters less that there are high levels of cytokines or chemokines, because their effects are significantly minimised.

The good news is antibody-based drugs have minimal side effects, and have proved effective for many human chronic inflammatory diseases. Expanding these drugs for use in COVID-19 patients is therefore an attractive possibility. Although this would require caution for careful dosing, and these drugs would need to be co-administered together with an antiviral drug.

Antivirals successfully treat other viral conditions, such as hepatitis C and HIV.
Shutterstock

Anti-malarial drugs

Chloroquine, a well-known anti-malarial drug, has also gained attention. One study tested it together with a broad-spectrum antibiotic azithromycin. While some COVID-19 patients in this small study recovered, other patients died (despite chloroquine treatment), and some patients ceased treatment for a variety of reasons – including the severity of their symptoms.

Nevertheless, people are interested in how chloroquine and azithromycin might work for coronavirus. Chloroquine exhibits antiviral activity and is currently used to treat autoimmune diseases because it also has anti-inflammatory properties. Azithromycin is an antibiotic used to treat bacterial infections, but it, too, exhibits antiviral activity, including against rhinovirus that causes the common cold. Chloroquine might need to be given early after infection to be most effective against coronavirus.




Read more:
Could chloroquine treat coronavirus? 5 questions answered about a promising, problematic and unproven use for an antimalarial drug


The World Health Organisation has announced a global clinical trial program testing possible COVID-19 treatments, including remdesivir, lopinavir/ritonavir, chloroquine, and certain antiviral cytokines.

The escalating number of coronavirus patients worldwide means alongside vaccine development, the focus must remain squarely on finding effective antiviral drugs that can treat those already seriously ill from SARS-CoV-2 infection.The Conversation

Lisa Sedger, Senior Lecturer, Head of the Viruses and Cytokine Biology group in the School of Life Science, University of Technology Sydney

This article is republished from The Conversation under a Creative Commons license. Read the original article.

How can I treat myself if I’ve got – or think I’ve got – coronavirus?



Kelly Sikkema/Unsplash

David King, The University of Queensland

New cases of the coronavirus are reported every day, and as yet there’s no vaccine. So what treatments are available if you’re one of the unlucky ones who gets infected?

If your symptoms are mild, you should treat them the same way you would a cold or flu.

A spectrum of severity

SARS-CoV-2, the virus that causes COVID-19, is one of hundreds of viruses that cause colds and flu symptoms in humans.

The infection ranges in severity from almost silent (asymptomatic), to a mild cold, all the way to lung and organ failure. The symptoms may be worse than a normal cold or flu because this coronavirus is new (or “novel”) to our species and we haven’t built up herd immunity to it yet.

But current estimates suggest about 80% of cases will have relatively mild to moderate illness.




Read more:
Coronavirus: how long does it take to get sick? How infectious is it? Will you always have a fever? COVID-19 basics explained


If you’re one of these, you might not know for sure whether you have COVID-19, as you may not be eligible for testing. It’s important you self-isolate if you’re unwell regardless.

But from the perspective of treatment, if your illness is reasonably mild, it doesn’t really matter whether you have a confirmed COVID-19 diagnosis or not.

So how do I treat the symptoms?

The World Health Organisation (WHO) says the most common symptoms of COVID-19 are fever, tiredness, and dry cough. Some patients may have aches and pains, nasal congestion, runny nose, a sore throat or diarrhoea.

The most bothersome symptoms tend to be fever and muscle pains. You can safely treat these with paracetamol.

The WHO initially recommended people with COVID-19 avoid taking ibuprofen to relieve symptoms. But it retracted that advice days later, so it seems reasonable to also consider using anti-inflammatory drugs.

You can treat nasal congestion with decongestants and nasal saline. Effective treatments for a sore throat include honey, salt water gargles, and sore throat sprays or gargles.




Read more:
Health Check: what’s the right way to blow your nose?


Cough is a more difficult symptom to control, but you may be able to improve it with honey, steam inhalations and saline nose sprays. Cough suppressants have only minimal benefit in reducing a dry cough.

It’s also important to support your immune system, particularly with rest and a healthy diet.

Look to the same kind of remedies you would if you were sick with a regular cold or flu.
Shutterstock

There’s some evidence zinc lozenges may shorten the duration of some colds and flus, including COVID-19. But this evidence is conflicting and not of high quality.

Meanwhile, there’s no convincing evidence beyond the placebo effect for a range of other common treatments, such a vitamin C and echinacea. But these are unlikely to cause harm.

Don’t try this at home

It’s important not to take medicines that haven’t been approved for the treatment of colds and flus.

Anecdotal reports and a small case series of patients in China have suggested a role for the antimalarial drug chloroquine in treating COVID-19.

Further clinical trials of this drug are currently underway, but at this stage it’s recommended as treatment only in COVID-19 cases complicated by viral or bacterial pneumonia, and under the guidance of medical professionals.

One HIV antiviral combination drug, lopinavir-ritonavir, seemed promising. But it failed to make a significant difference in 199 patients with COVID-19 in China.

So there are no effective curative treatments as yet, but clinical trials of different antiviral agents are continuing.




Read more:
To get on top of the coronavirus, we also need to test people without symptoms


While lots of information about prevention and treatments for coronavirus is circulating online, a good rule of thumb is if it sounds too good to be true, it probably is.

If you’re unsure about anything, look to reliable sources like the Australian government or the WHO, or consult a doctor.

What about people with more serious illness?

About five to seven days after the onset of symptoms, some patients develop shortness of breath and trouble breathing, which will require medical attention.

Shortness of breath occurs when pneumonia develops, causing a buildup of thick mucus in the lungs that blocks the transfer of oxygen into the blood vessels.

If your condition deteriorates, call ahead to a doctor or hospital and inform them of your COVID-19 status. If you’re experiencing severe symptoms, such as shortness of breath, call an ambulance.

If your symptoms are more severe, you might need treatment in hospital.
Shutterstock

How long before I’m not infectious anymore?

If you’re hospitalised with COVID-19, you will remain in isolation until you’re no longer experiencing symptoms and a test confirms you’re no longer infectious.

In a group of hospitalised patients in China, the average duration of virus still detected in the respiratory tract was 20 days.

Mild cases, however, have a shorter duration of illness, and the virus clears more quickly from their bodies.

Australian guidelines state that cases with a mild illness not requiring hospitalisation can end their self-isolation if they meet these two criteria:

  • at least ten days have passed since the onset of symptoms
  • all symptoms of acute illness have been resolved for the previous 72 hours.



Read more:
Can I take the dog for a walk? Can I put the kids to bed? What you should and shouldn’t do if you’re in coronavirus self-isolation


The Conversation


David King, Senior Lecturer, The University of Queensland

This article is republished from The Conversation under a Creative Commons license. Read the original article.