As soon as the SARS-CoV-2 virus, which causes Covid-19 was identified, researchers began investigating hundreds of drugs for their potential as a treatment, including those already marketed and ones in development for the treatment of other diseases.
The therapies under investigation generally fall into one of two categories: antivirals, which target virus replication, and immune modulators, which help the immune system to fight the virus or stop it from overreacting dangerously, but there are other drugs being investigated with multiple mechanisms or which act in another way.
UK large-scale RECOVERY trial
There are currently thousands of clinical trials ongoing worldwide. As part of these efforts in the UK, the University of Oxford, funded by multiple UK government and non-governmental organisations, is coordinating the large-scale RECOVERY trial. This ongoing trial is investigating a range of drugs that may be effective in the treatment of Covid-19 patients.
The RECOVERY Trial is currently testing some of these suggested treatments:
- Low-dose Dexamethasone
- Azithromycin, a commonly-used antibiotic
- Tocilizumab, an anti-inflammatory monoclonal antibody given by injection
- Convalescent plasma, which is collected from donors who have recovered from Covid-19 and contains antibodies against the SARS-CoV-2 virus
- REGN-COV2, a combination of monoclonal antibodies directed against coronavirus
- Aspirin, a commonly used drug to thin the blood.
Dexamethasone, the first treatment
Dexamethasone is a cheap and widely available steroid that has been used safely in humans for decades. To date, it is the only treatment proven to reduce mortality in patients with Covid-19 infection.
The drug is not an antiviral and does not target the Covid-19 virus, instead it acts on the body’s immune system to calm down its over-reaction to the virus infection. Infection with Covid-19 leads to inflammation in the body and the body’s anti-inflammatory response can lead to extensive damage and eventually death.
Dexamethasone is only effective in a small group of patients with Covid-19, however; patients in hospital who need oxygen or are ventilated. The drug does not work in those patients not on oxygen. Preliminary results from the RECOVERY trial released in July this year suggest that dexamethasone reduces deaths by 35% in ventilated patients and by 20% in other patients receiving oxygen only, but there was no benefit in patients who did not require respiratory support.
Remdesivir could speed recovery
The anti-viral remdesivir is the only other drug that has been shown to help speed recovery for severely ill patients. The drug developed by Gilead Therapeutics was originally developed to treat hepatitis C infection. The drug interferes with viral replication.
There is some evidence that the drug may shorten the time it takes to recover from SARS-CoV2 infection compared to placebo, but there are also a number of studies that have suggested it may have relatively little effect. It is definitely not a cure for Covid-19 infection. The drug continues to be investigated in clinical trials, including in combination with other drugs.
The drug is approved in several countries as a treatment. The UK drug regulatory authorities, the MHRA, okayed use of the drug in May 2020. It is approved for the treatment of adults and young people aged 12 years and over who are hospitalised with suspected or laboratory-confirmed Covid-19 infection with pneumonia and requiring supplemental oxygen.
Monoclonal antibodies in late-stage trials
One approach to the treatment of Covid-19 infection is the use of antibodies specific to blocking the virus.These monoclonal antibodies, as they are called, are designed to have a very precise target on the virus. The most advanced of these approaches is REGN-COV2 from Regeneron Pharmaceuticals.
REGN-COV2 is a combination of two monoclonal antibodies, being tested in four groups of people; people hospitalized with COVID-19; people with symptoms of the disease but not hospitalised; healthy people at high risk of getting sick with COVID-19; and healthy people who have had close contact with someone with COVID-19. REGN-COV2 is part of the RECOVERY trial in the UK.
In October, the company asked the FDA for emergency approval of its antibody cocktail. This is the antibody drug used to treat Donald Trump.
This approach is also being developed by other companies including AstraZeneca.
AstraZeneca’s antibody cocktail is being investigated in patients with weakened immune systems who can not be vaccinated. The trial, which will enroll 5,000 volunteers, will evaluate the safety and effectiveness of the combination of two monoclonal antibodies.The clinical trial will investigate whether the treatment will prevent Covid-19 for up to a year.
The UK government has an agreement with AstraZeneca to supply a neutralising antibody cocktail as a prophylactic treatment once clinical trials are completed and it is approved by regulators.
This treatment would be used for people who cannot receive a vaccine, such as those who are heavily immunosuppressed and cannot mount an immune response, or people who need immediate protection, such as healthcare workers.
The other monoclonal antibody of note is tocilizumab, this inhibits interleukin-6 (IL-6), which is released in the immune response to SAR-CoV-2, but could lead to damage in severely ill patients. It is already on the market for the treatment of rheumatoid arthritis.
It is thought that tocilizumab may act to control the inflammatory response in severely ill Covid-19 patients that can cause death. Numerous trials are ongoing worldwide and it is included in the UK’s RECOVERY trial.
It has been found in some trials that tocilizumab may reduce the need for mechanical and noninvasive ventilation. A study published in September 2020 found that patients who received tocilizumab were 44% less likely to progress to mechanical ventilation or death compared to patients who received placebo plus standard of care.
Convalescent antibodies
Convalescent antibodies refers to the antibody-rich plasma that can be donated by patients who have recovered from Covid-19 infection. Its use is currently being investigated in the RECOVERY trial. There is some evidence suggesting possible benefits of convalescent plasma in patients with Covid-19, but here is no confirmation from additional randomised controlled studies as yet. Despite this, the approach has been approved for use in critically ill patients in the UK.
Aspirin
Blood clots are now known to be a big problem in patients with Covid-19 and so Aspirin has now been included in the RECOVERY trial as it is a cheap and readily available drug that reduces blood clotting.
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