Drugs being tested in SOLIDARITY and Discovery Trials. [Credit: Nancy R. Gough, BioSerendipity, LLC]

WHO Testing 4 Possible Treatments for COVID-19

SOLIDARITY and Discovery Trials give medical staff quick and easy way to participate in finding treatments for COVID-19.

It is also important to remember that the majority (80%) of people who contract COVID-19 will recover without any treatment at all. For those who require hospitalization and respiratory support, treatment options are desperately needed. WHO has launched the SOLIDARITY Trial and the Discovery Trial to test the 4 most promising therapies for COVID-19.

The gold standard for clinical trials is a double-blind randomized study. The patient doesn’t know if he or she is receiving the drug or not and the physician does not know if the patient is receiving the drug or not. Then the data are analyzed. In some cases, the treatment group benefits so substantially that the trial is changed to include all of the patients, or the treatment group shows a serious adverse effect and all treatment is stopped.

In the rapidly escalating pandemic caused by SARS-CoV-2, this gold standard trial design will take too long and be too difficult to implement on the global scale needed. So, WHO has launched the SOLIDARITY Trial and the Discovery Trial, which are not double-blind randomized trials. They are randomized, but not blinded.

In these trials, doctors will test

Remdesivir, a drug that inhibits the enzyme necessary for the virus to replicate its genome

Chloroquine or hydroxychloroquine (anti-malarial drugs that showed early promise in a small trial)

Ritonavir and Lopinavir (brand name Kaletra), drugs that inhibit HIV

Ritonavir, Lopinavir, and interferon beta (IFN-β, an antiviral peptide)

Doctors will be able to enroll consenting patients with confirmed COVID-19 by entering information into a WHO database through a online interface. In addition to COVID-19 positivity, any other relevant conditions will also be recorded, such as chronic obstructive pulmonary disease, heart disease, diabetes, or HIV infection. Doctors will indicate which medications are available for testing at their facility. The WHO system will then randomly assign patients to receive one of the available medications plus standard of care or to only the local standard care for COVID-19. To simplify and speed data collection, the only follow up data required will be the day the patient died or left the hospital (recovered), the length of time in the hospital, and if the patient needed oxygen or artificial ventilation.

It is most likely that different treatments will be appropriate and needed at different stages of the disease. The early stages may be best treated by drugs that reduce viral load and boost the immune response; later stages associated with systemic hyperinflammation may require both drugs to reduce viral load and prevent a hyper-immune response that causes tissue damage and organ failure.

Additionally, each of the tested medications has limitations for use. Chloroquine and hydroxychloroquine cannot be used in patients with some types of heart disease or patients with G6PD deficiency (also known as Favism). Remsdivir is not an approved drug and so it’s safety within large populations is unknown. Kaletra is an approved drug for treating AIDS (HIV infection); however, this drug interacts with many other medications, so drug interactions could be a factor. IFN-β boosts antiviral immune response. This is a naturally produced cytokine that regulates many aspects of immune function. This drug could have complicated effects and may only be suitable in a subset of COVID-19 patients or at certain points in the disease process.

Thus, it is likely that no single treatment will work for all patients, and most people who contract COVID-19 will recover without any treatment at all. Hopefully, these trials will provide options for healthcare providers so that hospitals can stay ahead of the epidemic and minimize deaths.

Related Reading

K. Kupferschmidt, J. Cohen, WHO Launches global megatrial of the four most promising coronavirus treatments. Science (22 March 2020). https://www-sciencemag.org/news/2020/03/who-launches-global-megatrial-four-most-promising-coronavirus-treatments

B. Cao, et al. A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. The New England Journal of Medicine (18 March 2020) DOI: 10.1056/NEJMoa2001282

P. Gautret, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open label non-randomized clinical trial. International Journal of Antimicrobial Agents (20 March 2020) DOI : 10.1016/j.ijantimicag.2020.105949

COVID-1: Informal consultation on the potential role of chloroquine in the clinical management of COVID 19 infection. WHO R & D Blueprint (13 March 2020) https://www.who.int/blueprint/priority-diseases/key-action/RD-Blueprint-expert-group-on-CQ-call-Mar-13-2020.pdf

WHO Press Conference 18 March 2020: https://www.pscp.tv/w/1ypKdQPYELoGW

H. K. Siddiqi, M. R. Mehra, COVID-19 illness in native and immunosuppressed states. Journal of Heart and Lung Transplantation (20 March 2020) DOI https://doi.org/10.1016/j.healun.2020.03.012

N. R. Gough, Testing Treatments for COVID-19. Medium (21 March 2020)

Gough NR, A Combination Therapy that Eliminates the COVID-19 Virus. Medium (19 March 2020)