The process of finding a cure for any disease is long, arduous and uneasy. As was discussed in The CoviD-19 Saga: Finding a Cure part 1, we are very much looking at years of development before finding a definite cure for CoviD-19.
But hope is not lost, as the globe has pooled in to fast track all researches on a treatment and with it the Repurposing of various drugs, we may very well see definitive treatment options soon.
The Solidarity Trial
WHO together with their partners made a multinational initiative to compare untested treatments for hospitalized people with severe COVID-19 illness. It is participated by Argentina, Bahrain, Canada, France, Iran, Malaysia, Norway, South Africa, Spain, Switzerland and Thailand. The Trials aim to provide rapid insights on key clinical questions: Do any of the drugs reduce mortality? Do any of the drugs reduce the time a patient is hospitalized? Do the treatments affect the need for people with COVID-19-induced pneumonia to be ventilated or maintained in intensive care? And could such drugs be used to minimize the illness of COVID-19 infection in healthcare staff and people at high risk of developing severe illness?
The solidarity trial hopes to “dramatically cut down the time needed to generate robust evidence about what drugs work”. The drugs in question are remdesivir, lopinavir + ritonavir combination, lopinavir + ritonavir + interferon-beta combination, and Hydroxychloriquine / Chloriquine which was discussed In part 1.
Remdesivir
Remdesivir was created and developed by Gilead Sciences as a treatment for Ebola virus disease and Marburg virus infections. Gilead Sciences subsequently discovered that remdesivir had antiviral activity in vitro against multiple virus families including the coronavirus.
In late January 2020, remdesivir was given to a U.S. patient confirmed to be infected by SARS-CoV-2, in Snohomish County, Washington, for “compassionate use” after he progressed to pneumonia. While no broad conclusions can be made based on the single treatment, the patient’s condition improved, and he was eventually discharged. Around the same time, Chinese medical researchers reported that remdesivir seemed to have “fairly good inhibitory effects” on SARS-CoV-2, after which requests to begin clinical testing were submitted.
While a cohort study published in April 2020 saw possible improvement in patients, determining whether or not the medication is effective is going to require a randomized controlled trial. In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). The study was limited that it did not provide any conclusive evidences – like how much the remdesivir acted as an antiviral as viral loads were not measured and the durations were not uniform.
As of April 2020, remdesivir is viewed as the most promising treatment for COVID-19 by Johns Hopkins University and there are at least seven separate clinical trials planned or underway.
Lopinavir/ritonavir
Sold under the brand name Kaletra among others, is a fixed dose combination medication for the treatment and prevention of HIV/AIDS. It combines lopinavir with a low dose of ritonavir. It may be used for prevention after a needlestick injury or other potential exposure. The drugs were designed to inhibit HIV from replicating by binding to the HIV protease.
While data for using this drug against SARS-CoV-1 looked promising, the benefit in COVID-19 is unclear as of March 2020. A non-blinded, randomized trial in China found lopinavir/ritonavir was not useful to treat severe COVID-19. In this study the medication was started typically around 13 days after the start of symptoms. It wasn’t too surprising that the drugs did not work well because they are designed to inhibit HIV, not the new coronavirus. This is why a team of researchers at the University of Colorado is hoping to modify those drugs to find a compound that will bind with the protease of SARS-CoV-2.
Lopinavir/ritonavir + Interferon Beta
Interferon Beta are a part of mammalian type I interferons designated alpha, beta and so on. The IFN-β proteins are produced in large quantities by fibroblasts. They have antiviral activity that is involved mainly in innate immune response, and is currently in development to become an inhaled drug for chronic obstructive pulmonary disorder, a severe lung disease. This has been paused to conduct testing on 100 patients who have been diagnosed with Covid-19.
The combination Lopinavir/ritonavir + Interferon Beta was recently tested in January as an inhibitor of MERS-CoV thus it made sense to also investigate it’s possible inhibitory effects to SARS-CoV-2. These 4 Drugs / Drug Combinations together with Hydroxychloriquine / Chloriquine form the Solidarity Trials.
This April, the British “Recovery Trial” was launched initially in 132 hospitals across the UK, expanding to become the world’s largest COVID-19 clinical study involving 5400 infected people under treatment. It is now at 165 UK hospitals, as of April 17. The trial is examining different potential therapies for severe COVID-19 infection: lopinavir/ritonavir, low-dose dexamethasone (an anti-inflammatory steroid), hydroxychloroquine, and azithromycin (a common antibiotic) – we will discuss this and other drugs on the subsequent The CoviD-19 Saga: Finding a Cure part 3 (link) and part 4 (link)
A friendly reminder that we must stick to facts and evidence in the midst of tackling this pandemic, a single spread of misinformation could be detrimental to the society’s efforts in finding a cure. An accidental overdose due to carelessness and false information is another hospital bed and dozens of healthcare workers exerting extra effort instead of focusing on urgent cases, especially CoviD-19 patients that could be on clinical trials. Continue to be informed and stay safe.
REFERENCE:
Remdesivir
- Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys
- GS-5734 and Its Parent Nucleoside Analog Inhibit Filo-, Pneumo-, and Paramyxoviruses
- Compassionate Use of Remdesivir for Patients with Severe Covid-19
- Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro
Lopinavir/ritonavir
- Lopinavir and Ritonavir
- Coronavirus Disease 2019 Treatment: A Review of Early and Emerging Options
- A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19
- Colorado researchers are racing to find an antiviral drug that could save people with the new coronavirus
Lopinavir/ritonavir + Interferon Beta
- Experimental lung drug to be tested on UK coronavirus patients
- Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV
- RECOVERY trial rolled out across the UK
