Two tools are of crucial importance for the efficient fight against a pathogen: a vaccine to prevent people or animals from becoming infected in the first place and drugs to provide adequate treatment for those who are ill. Both of these are still lacking in the fight against COVID-19, but great research efforts are being made to change this as quickly as possible.
Vaccine development usually takes several years and has a relatively high failure rate [1]. This is partly due to the fact that in the development of vaccines that are ultimately administered to healthy people, the risk-benefit ratio must be viewed particularly critically, as Dr. Michael Mühlebach, researcher at the Paul-Ehrlich-Institute, explains in an interview with the Zoonoses Platform (see interview). However, in view of the pandemic, vaccine development has already been greatly accelerated, resulting in several candidates in clinical trials (for an overview of the status of vaccine studies against COVID-19, click here).
However, it will still take some time before a vaccine will be available. In addition, there is always the risk that the search for a vaccine against a pathogen will be unsuccessful, as HIV proves as an example. Drug approval is also a complex process that extends from the identification of a suitable drug candidate through numerous laboratory tests to the various phases of clinical trials on patients (see Fig. 1). This process can also fail at many stages. Nevertheless, many hope that it will be possible to find suitable drugs for the treatment of COVID-19 patients more quickly than a vaccine.
Figure 1: Individual stages of drug development
Two different approaches are being pursued in the search for drugs against COVID-19. On the one hand, there is the targeted new development of pharmaceutical agents specifically for the treatment of this disease. On the other hand, research is being carried out to determine the extent to which drugs that have already been approved for the treatment of another disease or have at least passed through part of the development stages are suitable for the therapy of COVID-19. This so-called "repurposing" of drugs has the advantage that it can be carried out more quickly than a completely new development, where one has to start from scratch, because results from preclinical investigations and phase I studies may already be available. Many projects are therefore focusing on the possible redesignation of already known active ingredients.
The escalating course of COVID-19 seems to be divided into different phases that manifest themselves in different symptoms and are based on different underlying processes. It is assumed that the first stage of the disease is primarily characterized by the virus itself, while in the further course of the disease the immune response of the patient becomes more important (Fig. 2). (summarized in [2])
Figure 2: proposed course of COVID-19 according to Siddiqi and Mehra (2000)
Depending on the phase of the disease, different effects of a drug are therefore required. The drugs that are now being considered for repurposing usually belong to one of the four groups:
- Antiviral drugs: these drugs are directed against the virus itself and prevent, for example, the virus from multiplying or from entering the host´s cell. Structures of the virus itself as well as the body's own structures that the virus needs for its replication can serve as drug targets.
- Attenuating immunomodulators: these drugs aim to ensure that the immune response of the infected person does not become too strong or is not directed against the wrong target, so that the body is not further damaged by its own immune system. According to the current state of knowledge, this plays a role particularly in the later course of the disease.
- Drugs for lung patients: these drugs are intended to ensure that patients are supplied with oxygen through the lungs, even if the virus already damaged the lung tissue.
- Cardiovascular drugs: these drugs are intended to prevent possible complications in patients, such as blood clots or cardiac rhythm disorders. This can happen when the body reaches its limit due to the defence against the virus or an excessive immune response.
Under the following links you will find an overview of ongoing drug studies against COVID-19:
- Overview by the World Health Organisation (WHO): https://www.who.int/publications/m/item/overview-of-the-types-classes-of-candidate-therapeutics
- Overview by the Verband Forschender Arzneimittelhersteller (vfa) e.V.: https://www.vfa.de/de/englische-inhalte/therapeutic-medicines-coronavirus-covid-19
- Overview by the Drug Commission of the German Physicians (Scientific Committee of the German Physicians Chamber), in German: https://www.akdae.de/Arzneimitteltherapie/AVP/COVID-19/index.html
First study results on the use of dexamethasone in severe courses of COVID-19 seem promising. In the RECOVERY clinical trial, which investigated different therapeutic approaches in hospitalized COVID-19 patients in the UK, dexamenthasone reportedly reduced mortality in ventilated patients by one third, according to a first press release. The study itself has not been published yet. Dexamethasone is a slow-acting artificial glucucorticoid that is already being used in various diseases. By binding to the glucocorticoid receptor of cells, it can influence certain genes, which can attenuate allergic and inflammatory processes [3]. This could explain why it seems to have an effect especially in the late severe courses. WHO Chief Tedros Adhanom Ghebreyesus has called the announced study results a "life-saving scientific breakthrough".
A drug candidate, that has been successfully tested in initial studies and will soon be tested on patients, comes from a research company in Tübingen, the Atriva Therapeutics GmbH. You can read more about this in an interview with Prof. Dr. Stephan Ludwig, chairman of the company's advisory board and head of the office site of the German Research Platform for Zoonoses in Münster. Go to the interview
Text: Dr. Dana Thal for the German Research Platform for Zoonoses
Literature:
- Vasilakis, N., et al., Risk in Vaccine Research and Development Quantified. PLoS ONE, 2013. 8(3).
- Siddiqi, H.K. and M.R. Mehra, COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. J Heart Lung Transplant, 2020. 39(5): p. 405-407.
- Newton, R., Molecular mechanisms of glucocorticoid action: what is important? Thorax, 2000. 55(7): p. 603-13.
