March 18, 2020

expert reaction to questions around potential treatments for COVID-19

There have been questions from journalists about potential treatments for COVID-19.

On the Synairgen trial:

Prof Ian Hall, Professor of Molecular Medicine, University of Nottingham, said:

“There are several clinical trials in the late stages of planning which aim to assess different drugs which could be used to treat COVID-19.  The Synairgen trial, which has been given expedited approval by the regulatory authorities, involves administering a drug called interferon beta, which is a molecule which forms part of the lung’s own defence mechanism to fight off viruses.  The idea behind the trial is that by giving more of this molecule to the lung this could help reduce the severity of infection with COVID-19, especially in those people who have reduced immune responses to the virus.

“Any new treatment for COVID-19 needs to be assessed properly to make sure it is safe and produces clinical benefit, and the intention of this trial is to evaluate both of these aspects when using interferon beta in patients with COVID-19 disease.  The best way to do this is to undertake what is known as a randomised controlled trial, where neither the patient nor the doctor knows whether or not the patient receives the active drug or an inactive ‘placebo’.  This allows an objective assessment of the drug’s effect to be analysed by the research team.  By using the infrastructure provided by NIHR (the National Institute for Health Research), this study can be initiated in multiple sites across the country to allow results to be obtained as quickly as possible.

“If the trial shows that interferon beta is a useful treatment for COVID-19 disease, this would provide a way to reduce the severity of disease and potentially reduce death rates.  At present, there are no proven treatments for COVID-19 other than supportive care, and so a positive result from the trial would represent a major step forward, especially as other approaches, such as using a vaccine to prevent disease, are likely to take much longer to develop.”

On chloroquine:

Dr Andrew Preston, Reader in Microbial Pathogenesis, University of Bath, said:

“The requirement for a vaccine to provide long-term protection against COVID-19 is clear. However, it is equally clear that a globally available vaccine is some way off. In the light of this, a number of anti-viral drugs are in tests as cures for COVID-19, and initial results are emerging.

“A key study tested a number of recognised anti-viral drugs in a laboratory assay of cell infection by a Wuhan strain of SARS-Cov-2 (1). Two showed potent inhibition of virus replication at levels of the drug thought to be safe in people, and levels that can be reached within the body. Remdesivir is a potent anti-viral in current development as an anti-Ebola virus treatment. It mimics one of the building blocks of the viral genome, but is non-functional, causing premature termination of virus genome replication.

“Chloroquine is better recognised as an anti-malarial drug. It is cheap, considered relatively safe in humans and has been used for over 70 years. However, for over 10 years there have been studies reporting the anti-viral effects of chloroquine, or its common derivative hydroxy-chloroquine, against ‘flu and SARS, raising hope of activity against the current pandemic virus (2).

“The anti-viral effects of chloroquine are thought to derive from two distinct functions. In one, chloroquine blocks the synthesis of parts of the virus receptors on cells, by inhibiting the addition of certain sugar groups to the cell surface that are recognised by the virus.

“In the second mechanism, following attachment of the virus to the cell surface, it is internalised within a membrane enclosed compartment. The virus escapes from this to reach the internal environment of the cell in a process that is triggered by a reduction in pH (making more acidic) of this compartment. Chloroquine can increase the intracellular pH (make it more alkaline) and this inhibits the escape of the virus into the cell where it replicates.

“A number of the studies of chloroquine’s anti-viral effects were demonstrated with the SARS virus, but received relatively little attention as the SARS outbreak died away. Recognising that the current COVID-19 virus is a close relative, several researchers have already tested whether chloroquine might be a therapeutic for the current pandemic. Early reports from China were promising. Creating particular interest, this week Prof. Didier Raoult in Marseille released the results of their initial trial of chloroquine treatment of hospitalised COVID-19 patients (3). Although numbers are small (20 patients treated with chloroquinine,16 control patients were not given the drug) there was a significant effect. After 6 days, 70% of the treated patients were considered cured, in that virus was no longer detected in samples taken from them, compared to 12.5% of the control group of patients. Remarkably, this study finished on March 16th, but the group have released their results publicly in the hope of stimulating other studies to establish larger data sets. This rapid and open release of data is typical of the response to the COVID-19 pandemic, and recognises the urgent and desperate need for any tool that might help treat patients and stem the tide of infection. The results have yet to be fully scrutinised, and of course, it is essential to conduct other, larger controlled trials to determine accurately the effectiveness of chloroquine as a treatment for COVID-19. But in among the oppressive darkness of the current situation, any glimmer of hope is very welcome.”

1. Wang, M., Cao, R., Zhang, L. et al. (2020). Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 30, 269–271. https://doi.org/10.1038/s41422-020-0282-0

2. Colson, P et al. (2020). Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int. J. Antimicrobial Agents. https://doi.org/10.1016/j.ijantimicag.2020.105932

3. https://drive.google.com/file/d/186Bel9RqfsmEx55FDum4xY_IlWSHnGbj/view

Prof Robin May, Professor of Infectious Disease, University of Birmingham, said:

“Chloroquine is a so-called ‘weak base’. In other words, it is a molecule that (broadly speaking) helps to neutralise acids.  It is a drug that has a long history of use against malaria, essentially because it diffuses into red blood cells, making the environment within the cell less suitable for the parasite to live in.

“Since it has a long history of clinical use, the safety profile of chloroquine is well-established and it is cheap and relatively easy to manufacture, so it would – theoretically – be fairly easy to accelerate into clinical trials and, if successful, eventually into treatment. 

“The mode of action against COVID19 is not established.  However, many viruses enter host cells through a process called endocytosis.  This means that the virus is initially taken up into an intracellular ‘compartment’ which is typically fairly acidic.  Chloroquine would alter the acidity of this compartment, which can interfere with the ability of viruses to escape into the host cell and start replicating.  Another possibility is that chloroquine may alter the ability of the virus to bind to the outside of a host cell in the first place (which is an essential first step for entry).  Lastly, chloroquine has subtle effects on a wide variety of immune cells (for this reason, the drug is sometimes used in autoimmune conditions like lupus or rheumatoid arthritis) and it may be that one of these effects helps stimulate the body’s ability to fight off COVID-19.”

All our previous output on this subject can be seen at this weblink: www.sciencemediacentre.org/tag/covid-19

Declared interests

None received.