In this week’s Research Tracker we focus on some recent papers about therapeutic treatments for Covid-19 symptoms (we looked at vaccines in our first Weekly highlights).
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre. As this is a new service, please don’t hesitate to provide feedback.
A large range of old and new drugs are being tested
SARS-CoV-2 can cause a variety of medical conditions, so treatment is not simple. No new drugs have yet been approved for general treatment of Covid-19.
As with vaccines, a variety of old and new drugs are being tested on Covid-19 patients. These fall into a range of types:
Antivirals - to reduce virus replication
Auto-immune - such as anti-inflammatory drugs
Antibodies - blood proteins produced to neutralise selected pathogens or foreign objects
Plasma - derived from blood and containing a mixture of antibodies, enzymes, and other proteins
Cell-based therapies - such as natural killer cells, and stem cells
RNA-based drugs that stimulate the immune response
Other - other treatments, such as anticoagulants and receptor blockers.
The Biorender site tracks clinical trials of drugs (as well as vaccines) being tested on Covid-19. At the time of writing over 200 drugs are being assessed, with 129 in human clinical trials.
Context - New drug development is usually slow and expensive
New drugs may take 15 years or more to develop, following testing of many thousands of initial compounds.
Just 19% of new drugs targeting infectious diseases that start Phase I clinical trials go on to be approved for use.
Median research and development costs for 63 drugs approved in the last 10 years was US$985 million (taking account of failed trials).
Consequently, pharmaceutical companies tend to look at how old drugs can be used for other conditions. According to one study, between 2005 and 2015 nearly 75% of drugs received patent extensions, enabling the companies to keep profiting from them.
However, the last item in this week’s list shows a different approach that avoids patenting.
The antiviral drug remdesivir shows some promise
A US National Institutes of Health randomised trial involving several hundred hospitalised Covid-19 patients with lower respiratory tract infections assessed the antiviral drug remdesivir (which has emergency use approval from the FDA). Initial results indicate that the drug helped reduce symptoms, and shortened hospital stays by several days. However, it did not eliminate deaths, so the researchers suggest that it may best be used alongside other treatments.
A summary of this study is available on Scimex.
The antimalarial drug hydroxychloroquine does not show promise
A large international study reviewed the outcomes of thousands of hospitalised Covid-19 patients treated with hydroxychloroquine or chloroquine. These drugs were associated with higher levels of mortality when compared with patients with similar symptoms who did not receive the drugs. In addition, hydroxychloroquine and chloroquine were associated with greater levels of heart problems.
As a consequence of this study, the WHO has suspended hydroxychloroquine from their SOLIDARITY clinical trial.
Expert reaction from Australia to this trial is available on Scimex.
Plasma from recovered Covid-19 patients may help others with severe symptoms
Transfusing plasma from recovered Covid-19 patients to a few with severe Covid-19 symptoms showed promising results. Improvements were seen within three days, and the virus was not found after seven days. Larger trials are advocated by the authors, and supported by two letters responding to the article.
Antibodies from previous SARS and Covid-19 patients can neutralise SARS-CoV-2 in lab experiments
A study just published in Nature indicates that a cocktail of antibodies from people who have recovered from the earlier SARS epidemic could help neutralise SARS-CoV-2. This requires further research.
Research from a Chinese research team published in Cell demonstrated that antibodies from Covid-19 patients can neutralise the virus in mice. They have started a clinical trial using one of the antibodies.
Anticoagulants may help some patients on ventilators
Anticoagulants were shown in an observational study to improve the survival of patients on ventilators. However, due to the greater risk of bleeding use of anticoagulants needs to be considered on a case by case basis.
Combinations of drugs, rather than a “silver bullet”, may be more effective
While a lot of focus is on trials of single drugs, a combination of drugs may be what works for many patients. A small randomised Phase II clinical trial found that treatment with three antivirals - interferon beta-1b, lopinavir–ritonavir and ribavirin - was safe and more effective at reducing the duration of viral shedding than lopinavir–ritonavir alone in patients with mild to moderate illness. Further research is planned. A summary of this study is available on Scimex.
The Biorender site shows which drugs are being used in combination trials.
A research roadmap for therapy development
A paper published in the British Journal of Pharmacology reviews a range of potential drug targets. It suggests that priorities for Covid-19 therapies should be to test proteinases that target specific viral proteins or infection processes, and inhibitors of viral replication.
Crowdsourcing drug designs
COVID Moonshot is a site that collects ideas for small molecule drug designs that target the virus’ proteins, and uses machine learning algorithms to determine how they can be made. It works with companies to synthesise these for free, or at reduced rates, so they can be tested. The designs of promising candidates will be made freely available so they will not be patentable. Several thousand designs have already been submitted to the site.