COVID-19: 10 leading coronavirus treatments and the major trials now underway to see if they work
Repurposed drugs are the most promising options for finding a treatment quickly for COVID-19, the disease caused by the novel coronavirus.
Dozens of clinical trials are enrolling patients and testing drugs originally designed for other ailments, such as Ebola, HIV, malaria, and arthritis. Results will trickle in over the coming weeks and months.
These potential treatments have already been tested in humans for other diseases, and some are already approved to treat other conditions. That means we already know how safe they are for people to take, and what side effects to expect. Therefore, researchers can skip some of the early steps of drug development, and instead move them quickly into human trials testing their efficacy in COVID-19.
While repurposed drugs can be tested now, they aren't expected to be anything close to a panacea for the virus. The gold standard for halting infectious diseases remains vaccines, which can protect healthy people from getting infected in the first place.
Vaccine research typically takes years. Even under the urgency of this pandemic, US health officials have said it will take at least a year to know if any vaccine is safe and effective.
Other biotech and pharma companies are scrambling to craft new therapeutics. These will be tailored specifically to fighting this novel coronavirus. Even under the most aggressive timetables for clinical testing, those won't be widely available to patients until at least the fall.
That leaves repurposed drugs as the near-term hope. Here are the top candidates and how they are being tested against COVID-19. These treatments have already been tested in people and are now in late-stage trials to find out whether they work against the coronavirus.
1. Hydroxychloroquine
Hydroxychloroquine is a widely used medication by people with lupus or arthritis. It was first approved in the 1950s.
Update: As of June 2020, there are more than 200 studies that have been launched to investigate the benefits of hydroxychloroquine against COVID-19. You can review the status of these trials on clinicaltrials.gov.
The drug stopped the coronavirus from replicating in test tubes. Some very small studies in COVID-19 patients have shown promising results, but experts have questioned the quality of that data.
US physicians are free to write prescriptions for hydroxychloroquine to treat COVID-19, since it is an approved drug. This is called off-label use, and data shows demand has skyrocketed for the pills.
But we still don't know if it works against this coronavirus. Multiple trials are now enrolling hundreds or thousands of people, often randomizing them with a placebo group to generate reliable data.
Major studies to watch:
Editor's Note (May 15, 2020): Do take note that the study above was designed to assess 'hydroxychloroquine alone' and not 'hydroxychloroquine in combination' with other treatments.
Updated April 16, 2020: Hydroxychloroquine does NOT speed up coronavirus recovery, Chinese study finds in another blow for drug hopeful after Brazilian trial was called off because of heart problems
2. Azithromycin
Azithromycin is a widely prescribed generic antibiotic, sometimes provided in a Z-Pak. While it's used to fight bacteria, not viruses, there is some research suggesting the drug has antiviral properties.
Update: As of June 2020, there are 95 studies that have been launched to investigate the benefits of Azithromycin against COVID-19. You can review the status of these trials on clinicaltrials.gov.
The big pharma Pfizer said it will soon publish a review of these antiviral characteristics seen in laboratory research and clinical tests.
Several trials are testing azithromycin in combination with hydroxychloroquine.
One potential concern is serious heart side effects. Both drugs can cause abnormal changes in the rhythm of the heart. These can be fatal, particularly for susceptible patients who already have heart problems. Many studies are using EKG tests to closely monitors patients receiving this treatment combination.
While QT-prolonging medication use has been associated with increased risk of death, this risk may be smaller than the potential benefit from treatment of COVID-19 for some patients (American College of Cardiology).
3. Remdesivir
Remdesivir is an antiviral drug developed by Gilead Sciences in 2009. It was previously tested in more than 100 Ebola patients during that outbreak.
Some test tube research showed the drug can stop the coronavirus from copying itself. Through clinical trials and expanded access programs, more than 1,700 COVID-19 patients have been treated with remdesivir.
We are now on the brink of having the first results from randomized clinical trials. Two studies in China are expected to provide results in mid-April, and two more studies run by Gilead should provide additional data in May.
Major studies to watch:
4. Interferon beta-1a
Interferon beta-1a is used to treat multiple sclerosis.
5. Kaletra
Kaletra is an HIV therapy combining two antiviral medicines: lopinavir and ritonavir. It was approved by the FDA in 2000.
Preliminary results from one randomized controlled study from China comparing the drug against standard care found Lopinavir–Ritonavir (Kaletra) did not improve COVID-19 outcomes (NEJM. 2020).
Major trial to watch:
Convalescent plasma is a century-old treatment technique that has generated encouraging — yet early — results as a COVID-19 treatment.
The treatment requires recovered COVID-19 patients to donate blood that is rich in the antibodies that fight the virus. These are then infused into hospitalized patients with severe disease.
If further studies validate this approach, a critical challenge will be scaling up this treatment to address a pandemic. That requires having widespread and reliable antibody testing as well as the medical workers to collect blood and get plasma to patients in need.
Major study to watch:
Kevzara was approved in the US in 2017 to treat rheumatoid arthritis. The biologic injection is an anti-inflammatory medication. Regeneron and Sanofi co-promote the drug.
It may help the most severe COVID-19 patients who are suffering from an overactive immune response. This condition, known as a cytokine storm, may be the reason some patients crash. Kevzara inhibits a key cytokine called IL-6.
Major studies to watch:
8. Remestemcel-L (Stem Cell)
9. Avigan
Fujifilm Toyama Chemical's Avigan (also known as favipiravir), is an influenza treatment and a broad-spectrum antiviral drug. It's not approved in the US, but is used in Japan and China.
Avigan outperformed another antiviral drug called arbidol in a trial conducted in China, according to a recent report of those findings. The flu drug helped COVID-19 patients recover seven days faster than the patients on arbidol and reduced the frequency of symptoms like coughing and fever.
A couple ongoing studies in China are projected to finish in late April or May.
Major trial to watch:
10. Vitamin C
Dozens of clinical trials are enrolling patients and testing drugs originally designed for other ailments, such as Ebola, HIV, malaria, and arthritis. Results will trickle in over the coming weeks and months.
These potential treatments have already been tested in humans for other diseases, and some are already approved to treat other conditions. That means we already know how safe they are for people to take, and what side effects to expect. Therefore, researchers can skip some of the early steps of drug development, and instead move them quickly into human trials testing their efficacy in COVID-19.
While repurposed drugs can be tested now, they aren't expected to be anything close to a panacea for the virus. The gold standard for halting infectious diseases remains vaccines, which can protect healthy people from getting infected in the first place.
Vaccine research typically takes years. Even under the urgency of this pandemic, US health officials have said it will take at least a year to know if any vaccine is safe and effective.
Other biotech and pharma companies are scrambling to craft new therapeutics. These will be tailored specifically to fighting this novel coronavirus. Even under the most aggressive timetables for clinical testing, those won't be widely available to patients until at least the fall.
That leaves repurposed drugs as the near-term hope. Here are the top candidates and how they are being tested against COVID-19. These treatments have already been tested in people and are now in late-stage trials to find out whether they work against the coronavirus.
1. Hydroxychloroquine
Hydroxychloroquine is a widely used medication by people with lupus or arthritis. It was first approved in the 1950s.
Update: As of June 2020, there are more than 200 studies that have been launched to investigate the benefits of hydroxychloroquine against COVID-19. You can review the status of these trials on clinicaltrials.gov.
The drug stopped the coronavirus from replicating in test tubes. Some very small studies in COVID-19 patients have shown promising results, but experts have questioned the quality of that data.
US physicians are free to write prescriptions for hydroxychloroquine to treat COVID-19, since it is an approved drug. This is called off-label use, and data shows demand has skyrocketed for the pills.
But we still don't know if it works against this coronavirus. Multiple trials are now enrolling hundreds or thousands of people, often randomizing them with a placebo group to generate reliable data.
Major studies to watch:
- A WHO trial (Solidarity) involving over 90 countries will test remdesivir, hydroxychloroquine, Kaletra, and inteferon-beta-1a in COVID-19 patients (link)
- NIH trial for 510 hospitalized COVID-19 patients randomized to either hydroxychloroquine or placebo (link)
- University of Minnesota study testing hydroxychloroquine as prophylaxis and preemptive treatment. Focused on people who have been recently exposed to the virus or have a positive COVID-19 test and within four days of showing symptoms (link)
- The Bill and Melinda Gates Foundation is working with the University of Washington and other partners to test 2,000 asymptomatic people who are in close contact with a COVID-19 patient. The trial randomly assigns either hydroxychloroquine or vitamin C pills as a placebo comparison (link)
- The University of Oxford is recruiting 40,000 participants to test the malaria drug as preventive treatment for frontline healthcare workers. Volunteers will receive either hydroxychlorouqine in Europe or chloroquine in Asia and be compared against a placebo arm (link)
Editor's Note (May 15, 2020): Do take note that the study above was designed to assess 'hydroxychloroquine alone' and not 'hydroxychloroquine in combination' with other treatments.
Updated April 16, 2020: Hydroxychloroquine does NOT speed up coronavirus recovery, Chinese study finds in another blow for drug hopeful after Brazilian trial was called off because of heart problems
Azithromycin is a widely prescribed generic antibiotic, sometimes provided in a Z-Pak. While it's used to fight bacteria, not viruses, there is some research suggesting the drug has antiviral properties.
Update: As of June 2020, there are 95 studies that have been launched to investigate the benefits of Azithromycin against COVID-19. You can review the status of these trials on clinicaltrials.gov.
The big pharma Pfizer said it will soon publish a review of these antiviral characteristics seen in laboratory research and clinical tests.
Several trials are testing azithromycin in combination with hydroxychloroquine.
One potential concern is serious heart side effects. Both drugs can cause abnormal changes in the rhythm of the heart. These can be fatal, particularly for susceptible patients who already have heart problems. Many studies are using EKG tests to closely monitors patients receiving this treatment combination.
While QT-prolonging medication use has been associated with increased risk of death, this risk may be smaller than the potential benefit from treatment of COVID-19 for some patients (American College of Cardiology).
Major studies to watch:
- Intermountain Health Care and the University of Utah will treat 300 COVID-19 patients with either azithromycin or hydroxychloroquine. (link) They are also testing 1,550 COVID-19 patients in an outpatient setting with either hydroxychloroquine or azithromycin (link)
- Rutgers University is planning to test 160 COVID-19 patients with either hydroxychloroquine or hydroxychloroquine and azithromycin (link)
- Duke University will test 500 hospitalized COVID-19 patients randomly with either standard of care or hydroxychloroquine. Those selected for hydroxychloroquine will also be randomized to either receive azithromycin in addition or just hydroxychloroquine (link)
3. Remdesivir
Remdesivir is an antiviral drug developed by Gilead Sciences in 2009. It was previously tested in more than 100 Ebola patients during that outbreak.
Some test tube research showed the drug can stop the coronavirus from copying itself. Through clinical trials and expanded access programs, more than 1,700 COVID-19 patients have been treated with remdesivir.
We are now on the brink of having the first results from randomized clinical trials. Two studies in China are expected to provide results in mid-April, and two more studies run by Gilead should provide additional data in May.
Major studies to watch:
- A WHO trial (Solidarity) involving over 90 countries will test remdesivir, hydroxychloroquine, Kaletra (Lopinavir/Ritonavir) and interferon-beta-1a in COVID-19 patients (link)
- China-Japan Friendship Hospital randomizing 308 mild and moderate COVID-19 patients to remdesivir or placebo (link)China-Japan Friendship Hospital randomizing 453 severe COVID-19 patients to remdesivir or placebo (link)
- Gilead study enrolling 1,600 moderate COVID-19 patients randomized to either 5-day IV infusion of remdesivir, 10-day infusion of remdesivir, or standard of care (link)
- Gilead study enrolling 2,400 severe COVID-19 patients all receiving either 5-day or 10-day administration of remdesivir (link)
- National Institutes of Health randomizing 440 hospitalized COVID-19 patients between remdesivir and placebo (link)
4. Interferon beta-1a
Interferon beta-1a is used to treat multiple sclerosis.
Major study to watch:
- A WHO trial (Solidarity) involving over 90 countries will test remdesivir, hydroxychloroquine, Kaletra (Lopinavir/Ritonavir) and interferon-beta-1a in COVID-19 patients (link)
Kaletra is an HIV therapy combining two antiviral medicines: lopinavir and ritonavir. It was approved by the FDA in 2000.
Preliminary results from one randomized controlled study from China comparing the drug against standard care found Lopinavir–Ritonavir (Kaletra) did not improve COVID-19 outcomes (NEJM. 2020).
Major trial to watch:
- A WHO trial (Solidarity) involving over 90 countries will test remdesivir, hydroxychloroquine, Kaletra (Lopinavir/Ritonavir) and interferon-beta-1a in COVID-19 patients (link)
6. Convalescent Plasma
Convalescent plasma is a century-old treatment technique that has generated encouraging — yet early — results as a COVID-19 treatment.
The treatment requires recovered COVID-19 patients to donate blood that is rich in the antibodies that fight the virus. These are then infused into hospitalized patients with severe disease.
If further studies validate this approach, a critical challenge will be scaling up this treatment to address a pandemic. That requires having widespread and reliable antibody testing as well as the medical workers to collect blood and get plasma to patients in need.
Major study to watch:
- Netherlands researchers are now recruiting 426 severe COVID-19 patients to randomly receive either convalescent plasma or just standard of care (link)
7. Kevzara
Kevzara was approved in the US in 2017 to treat rheumatoid arthritis. The biologic injection is an anti-inflammatory medication. Regeneron and Sanofi co-promote the drug.
It may help the most severe COVID-19 patients who are suffering from an overactive immune response. This condition, known as a cytokine storm, may be the reason some patients crash. Kevzara inhibits a key cytokine called IL-6.
Major studies to watch:
- Regeneron is running a US trial of 400 hospitalized COVID-19 patients with severe cases. It randomizes patients to a low dose, high dose, or placebo arm (link)
- Sanofi is running a trial outside the US of 300 severe COVID-19 patients, also testing a low dose and high dose against a placebo comparison (link)
8. Remestemcel-L (Stem Cell)
Can a stem cell therapy help some COVID-19 patients recover? Mesoblast is an Austalian regenerative medicine company that is now applying an experimental stem cell treatment called remestemcel-L to the pandemic.
The company is working with NIH researchers to run a large randomized trial for patients with respiratory distress due to COVID-19. Like other medicines being tested, the treatment is aiming to quiet an overactive immune response in certain patients.
This intravenous stem cell infusion has been given to more than 1,100 patients in other settings, although it is not yet FDA-approved. (The FDA is expected to make an approval decision by October on remestemcel-L as a treatment for graft versus host disease in children.)
Major study to watch:
- A placebo-controlled randomized study in 240 patients in acute respiratory distress caused by COVID-19 (link)
Fujifilm Toyama Chemical's Avigan (also known as favipiravir), is an influenza treatment and a broad-spectrum antiviral drug. It's not approved in the US, but is used in Japan and China.
Avigan outperformed another antiviral drug called arbidol in a trial conducted in China, according to a recent report of those findings. The flu drug helped COVID-19 patients recover seven days faster than the patients on arbidol and reduced the frequency of symptoms like coughing and fever.
A couple ongoing studies in China are projected to finish in late April or May.
Major trial to watch:
- Three Massachusetts hospitals will run the first US trials of Avigan, enrolling about 50 COVID-19 patients (link)
10. Vitamin C
A commentary article published in The Lancet Respiratory Medicine (March 20, 2020) has recommended rescue therapy with high-dose vitamin C to be considered.
The CITRIS-ALI randomised trial published in Oct 2019 in JAMA showed a 30% absolute mortality reduction. However, there was no statistical difference in primary outcomes (based on the clinical trial design) among patients with sepsis treated with vitamin C versus placebo. The difference was in a secondary outcome - overall mortality.
Dr Perry Wilson reviewed the above study and provided a commentary on Medscape:
But basically, this is a pretty low-risk intervention. It's easy for me to sit here and say, "Unless the patient has scurvy, wait for more data." But if a loved one was in the ICU with sepsis, would you ask for vitamin C? After reviewing the literature to prepare for this commentary, I'd be hard-pressed to dismiss it out of hand.
Major study to watch:
The CITRIS-ALI randomised trial published in Oct 2019 in JAMA showed a 30% absolute mortality reduction. However, there was no statistical difference in primary outcomes (based on the clinical trial design) among patients with sepsis treated with vitamin C versus placebo. The difference was in a secondary outcome - overall mortality.
Dr Perry Wilson reviewed the above study and provided a commentary on Medscape:
But basically, this is a pretty low-risk intervention. It's easy for me to sit here and say, "Unless the patient has scurvy, wait for more data." But if a loved one was in the ICU with sepsis, would you ask for vitamin C? After reviewing the literature to prepare for this commentary, I'd be hard-pressed to dismiss it out of hand.
Major study to watch:
- Vitamin C Infusion for the Treatment of Severe 2019-nCoV Infected Pneumonia: a Prospective Randomized Clinical Trial, enrolling about 140 patients in China.
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