The COVID-19 pandemic is dominating the news as countries around the world work hard to control the spread of the disease. Social distancing can help “flatten the curve” and prevent the overload of healthcare systems; however, there is a large percentage of people who develop serious complications after getting the virus. The global community is fighting to develop effective treatments and vaccines as soon as possible, including therapies that can prevent and cure COVID-19 as well as therapies that can reduce and reverse pneumonia-associated damage to the lungs and other organs.
To help the community track the development of potentially lifesaving treatments, Lifespan.io is launching the COVID-19 Therapeutics Roadmap, a crowdsourced, curated database that visualizes the progress of candidate therapies through clinical trials.
We have already created and are maintaining the Rejuvenation Roadmap, a curated database that lists promising treatments for slowing down and reversing the damage associated with biological aging. Since its introduction in 2017, it has significantly expanded. We are glad to see that four of the nine root mechanisms of aging (mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered extracellular communication) are being gradually brought under medical control.
Once again, we have decided to use the power of visualization, this time to help the community track the trials of COVID-19 treatments. This will help the community navigate through the trials, get in touch with the researchers if necessary, and show the role that regenerative medicine plays in recovery from coronavirus infection.
The COVID-19 Therapeutics Roadmap is now up on our website. It presents the timeline of each potential therapy from its initial steps, such as testing a therapy in cell culture, to Phase 3 and 4 clinical trials in people. We will update the roadmap as studies are published, adhering to the phases indicated by the researchers. When the phase of a human trial is not indicated by its researchers, we will be considering it a Phase 1 trial. Trials with uncertain results will be frozen midway through the Phase and will contain a note indicating the uncertainty.
For now, the list of treatments under each category is short, but it is going to be gradually expanded over the next weeks.
First, the COVID-19 Therapeutics Roadmap includes antivirals. The best antiviral candidates are Remdesivir, which was initially developed for Ebola by the pharmaceutical company Gilead and shows promise against COVID-19, along with an inhibitor of viral RNA polymerase, Favipiravir (Avigan), which had been developed decades earlier by the Fujifilm subsidiary Toyama Chemical after screening a chemical library for antivirals against influenza.
Lopinavir and ritonavir, which are in the same section, are HIV protease inhibitors that act synergistically to decrease the amount of HIV in the blood. The combination is believed to be effective against COVID-19; however, an open-label clinical study in China found no benefit to adding lopinavir-ritonavir therapy to standard care.
In the section on vaccines, we are listing not only the ones that target SARS-CoV-2 directly but also those that are believed to increase immunity to it as a side effect.
BCG, or Bacillus Calmette-Guérin vaccine, is the live attenuated vaccine form of Mycobacterium bovis, used to prevent tuberculosis as well as other mycobacterial infections such as leprosy. In a preprint published on MedRxiv.org, a research group found that countries in which BCG vaccination is mandatory had lower COVID-19 mortality, suggesting that it may be effective in reducing the impact of the disease.
The next category is antibodies.
Tocilizumab is a humanized anti-interleukin-6 receptor monoclonal antibody for interleukin-6 (IL-6), an immune response molecule that is sometimes excessively produced, causing various complications and chronic immune-mediated disorders. Since COVID-19 involves a cytokine storm, it is hypothesized that tocilizumab may improve the outcomes of patients with this disease.
Next to antibodies, we will be listing therapies with convalescent plasma. Injection of plasma from a recovered person containing antibodies has been used to treat multiple infectious diseases for over a century. The FDA recently approved the use of convalescent plasma to treat critically ill COVID-19 patients, and many clinical trials of this treatment are currently on the way.
The section with antimalarials includes hydroxychloroquine and may also include more antimalarial drugs in the near future as information about their application is accumulated. It is still unclear how exactly they affect disease progression, but hypothesis is that their immunosuppressive effect helps to calm down the cytokine storm.
Another section with repurposed drugs includes anthelmintics, with the only representative of this class being Ivermectin. Little evidence is available regarding its potential to mitigate the symptoms of COVID-19, but the study in cell culture shows that it can significantly reduce the SARS-CoV-2 viral load. Taking into account that it is already registered for another indication for humans and domestic animals, it might be tested for COVID-19 relatively quickly to help people and their pets get free from the virus.
As the disease damages the lung tissue and reduces the vital capacity of the lungs by up to 25-30% in severe cases, it is crucial to track how the application of regenerative treatments can improve outcomes. Thus, we included the section with cell therapies that now lists several clinical trials of mesenchymal stem (stromal) cells (MSCs).
Mesenchymal stem cells (MSCs) are multipotent cells that can modulate the immune response by regulating the activity of other immune cell types. MSCs can decrease pro-inflammatory reactions and enhance lung tissue repair, and they have shown to improve outcomes of bacterial and viral pneumonia in animals and acute respiratory distress syndrome (ARDS) in humans. A pilot clinical study at Beijing YouAn Hospital in China demonstrated that the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia.
Apart from the categories listed above, the COVID-19 Therapeutics Roadmap will include a section on combination therapies and a section on diagnostic tests.
The map is still at the very beginning of its development and will be gradually updated over the coming weeks. We invite all interested parties to send suggestions for new entries to the project initiator, Elena Milova, or simply post them as a comment to this article.
If you are an active researcher and are willing to prepare and submit a full entry with sufficient information about a candidate therapy and references to relevant scientific papers and clinical trials, we will be happy to list you among the volunteer contributors of the COVID-19 Therapeutics Roadmap on the project page.