Coronavirus treatments

With over 16 million confirmed cases of COVID-19, it is imperative we find a solution. Scientists are looking at a multi-pronged strategy from developing vaccines that prevent becoming infected, antivirals which tend to target the beginning of the illness (by preventing cell entry or replication of the virus) to post-infection therapies (including drugs that dampen down the immune system when it is in overdrive and antibodies taken from COVID-19 survivors). Other drugs are being tested to manage complications from COVID-19.

What kinds of research are being done to treat coronavirus?

Drugs are being tested alone and in combination therapies. Usually, this is against the standard of care which tends to be supportive treatments such as supplemental oxygen and fluids although comparisons between drugs also exist in trials. As of June 2020, there were approximately 300 potential therapies in all stages of research - pre-clinical or clinical.

How are drugs developed?

In brief, bringing a drug onto the market to treat diseases is a difficult process typically taking at least 5 years, usually a decade. There are several stages of regulatory approval, understanding the chemistry of the substance (solubility, formation, stability) to subsequent trials in animals and humans. Each stage has ongoing safety monitoring for example there is a focus on avoiding major organ toxicities before human trials can begin, to finding long term side effects during the final stages of research. Human tests typically consist of 4 phases:

Phase 1 - A small number of healthy volunteers take the drug. Side effects are identified and an appropriate dose is found. Only 21.5% of drugs reach marketing.

Phase 2 - A small number of patients with the disease receive the drug. Other side effects are screened for and the dose is fine-tuned.

Phase 3 - Large trials are conducted on patients to determine the efficacy of the drug. If this stage is passed the drug can be marketed

Phase 4 - Post-approval trials look at the long term use of the drug in a large number of patients.

During the pandemic, globally we have tried to streamline these processes and tried to facilitate co-operation between institutions (universities, governments, and pharmaceutical companies). Repurposing existing drugs should take less time than developing new drugs or vaccines. Despite this, it is estimated it will take 1-2 years to develop COVID treatments. Only around 20% of infectious diseases drugs make it onto the market which is why many avenues of research are being explored.

Which specific treatments are being tested against COVID-19?

Here we organize treatments that stand out. We have grouped them by class and summarise current findings. For information regarding a future vaccine please click here.

Antiviral medications

Hydroxychloroquine and Chloroquine

These drugs are used to treat malaria and some autoimmune conditions such as rheumatoid arthritis and lupus
Despite the original media hype surrounding these drugs, they are currently not thought to be an effective treatment as a result of large scale trials.
Side effects can include long QT syndrome. It may be contraindicated with heart conditions and diabetes.
These drugs may reduce the effectiveness of Remdesivir (another antiviral), so should not be taken together.
However, research is underway regarding the use of (hydroxy)chloroquine as a prophylactic medicine to prevent acquiring coronavirus infection.

Remdesivir

Remdesivir is a broad-spectrum antiviral originally developed to treat hepatitis C.
It is thought to be a promising drug to treat COVID-19 and works by mimicking a chemical needed to replicate virus genes.
The US bought nearly all supplies for this drug for the next 3 months in July.
The FDA has approved its use as emergency medicine.
Current guidelines state it can be used in those who require supplemental oxygen but not high flow oxygen, ventilation, or ECMO.
Most trials show improvement in time to recovery.
It is likely best used in earlier stages of the illness but it can only be given intravenously, complicating access to the medicine.
Side effects include infusion reactions and abnormal liver function.

Lopinavir-Ritonavir (Kaletra)

This is a combination medicine used to treat HIV and works by inhibiting the generation of new virus particles.
This medicine has been effective in the past against SARS and MERS which are other coronaviruses.
However unpublished results of large scale trials suggest that it is not effective in hospitalized patients for COVID-19. This may be because it is too late in the course of the illness to have a positive impact.
Furthermore, the combination can also be dangerous when taken with other medications such as certain statins.

Favipiravir

This is an antiviral used to treat influenza.
Results suggest that recovery from illness is faster with this medication.
However, the proportion of people who develop severe disease appears to be unchanged with this medication.
It is likely that it is less effective in severe cases where the virus has already made many copies.
It may not be safe for use in pregnant women or women trying to have a baby.

Drugs that dampen the immune system

Corticosteroids (including dexamethasone)

These drugs are used to reduce inflammation in a wide range of diseases such as asthma and arthritis.
They are likely to be useful in reducing mortality in severe cases of the disease. A large scale study showed it reduced risk of death by a third for patients on ventilators and by a fifth for those receiving oxygen.
They work to stop the immune system from going into overdrive. However in the case of milder disease without the need for oxygen support, it could be detrimental as some immune activity is also needed to fend against the virus. However, if you take steroids regularly you are advised to stay on them.
Steroids are cheap and easily accessible meaning they can be used worldwide.

Ibuprofen

This is a common painkiller used for many ailments causing pain/ fever.
Originally there were reports that it could cause more severe COVID-19 but it is now thought to be safe and trials are underway.
Paracetamol currently stands as a better choice to treat fevers by any infection.
NSAIDs like ibuprofen are best used with caution in those with heart problems for example.

Other:

Tocilizumab - This is an antibody drug that targets a specific inflammatory molecule called IL-6 involved in the immune response. It may improve survival.
Azithromycin - This is an antibiotic that could potentially improve recovery. However, caution must be taken as it can induce long QT syndrome, like chloroquine.
Barticinib - This is another antibody drug. It prevents the activation of inflammatory signalling pathways in our cells.
Interferon-beta1a - Early results suggest a dramatic reduction (79%) in numbers of patients deteriorating or dying due to COVID-19 when this signalling molecule produced by the body that helps to protect cells is used. While this may be promising small numbers of patients were involved in the study to draw reliable conclusions yet.

Drugs to manage COVID-19 complications

Drugs that affect blood clotting

In severe COVID-19 it is common for patients to develop blood clots for example in the lungs. This can lead to further breathing difficulties and respiratory failure. Different drug classes can be used to prevent blood clots:
Antiplatelet drugs- These are usually prescribed following a heart attack, for instance, aspirin.
Anticoagulant drugs - These can be used to treat and prevent stroke. Alteplase is an example being trialled in the US for COVID-19.
Thrombolytic drugs - These drugs can be used to break up clots already present for example in a heart attack or stroke.

ACE inhibitors and ARBs

Originally there were concerns that ACE inhibitors and angiotensin receptor blockers could increase ACE receptors in the body which the coronavirus needs to bind to enter cells, so individuals could get infected faster.
However, the evidence is not clear cut and may actually favor these medications. They may, in fact, be beneficial and actually improve survival. Ramipril is currently under investigation in the US.

Antibodies - Convalescent plasma

Trials are underway involving more than 1500 hospitals in the US to extract blood plasma (the fluid portion of blood containing antibodies against coronavirus) from those who have recovered from it.
This plasma is then given to a patient as a therapy.
The idea is that these borrowed antibodies will help to fight off the infection in the patient.

Novel Drugs

The main protease (3CLpro) needed for coronavirus replication was identified in March 2020 from the genetic code of the virus Chinese researchers published in January 2020.
Drugs specific to this protease are currently being researched in the lab (CLpro-1, GC376 and Rupintrivir).

Summary

Doctors are testing numerous therapies to see if they are effective against COVID-19. Multiple strategies being used due to difficulty in finding non-toxic, effective compounds. Combination therapies will also be helpful to provide adequate cover against the virus because viruses can mutate. Finding the right treatments against coronavirus will take time despite our best efforts. However it is a high priority so that the disease is at least milder, hospitals are not overwhelmed, and that restrictions impacting our everyday lives can eventually be lifted.