Top 10 Most Studied Treatments for COVID 19 (updated November 2020)

As of November 2020, there are more than 4,000 studies that have been launched to investigate various treatments for COVID-19. You can review the details of these trials on ClinicalTrials.gov. New ones are being added every day. 

Below, we look at the top 10 most tested categories.

1. Hydroxychloroquine / Chloroquine


We have combined hydroxychloroquine and chloroquine under 1 category. This remains the no. 1 most tested treatment in the world for COVID-19. In June 2020, there were around 200 trials but has since increased to more than 400 trials as of November 2020.

Hydroxychloroquine, a less toxic form of Chloroquine is a widely used medication by people with lupus or arthritis. It was first approved in the 1950s. Chloroquine is used to treat and prevent malaria and amebiasis.

The drug stopped the coronavirus from replicating in test tubes. 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.

Although results have been mixed, some of the major ones have been published as covered below.

Check out c19study.com for real-time tracking of hydroxychloroquine publications and studies.

Most of the current trials are using this drug in combination with other treatments for patients with COVID-19 and there are also trials testing it as prevention for high risk individuals.

Henry Ford Health System: Treatment with hydroxychloroquine cut the death rate significantly in sick patients hospitalized with COVID-19 – and without heart-related side-effects, according to a study published by Henry Ford Health System.

WHO trial (Solidarity): The interim trial results reported that remdesivir, hydroxychloroquine, lopinavir/ritonavir and interferon regimens appeared to have little or no effect on 28-day mortality or the in-hospital course of COVID-19 among hospitalized patients.

UK's Recovery Trial (University of Oxford): It concluded that "there is no beneficial effect of hydroxychloroquine in patients hospitalised with Covid-19" and the drug has now been pulled from the trial.

Major studies to watch:
  • 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).
  • The “Will Hydroxychloroquine Impede or Prevent COVID-19,” or WHIP COVID-19, study is a 3,000-subject look at whether hydroxychloroquine prevents front-line workers from contracting the COVID-19 virus (link)

2. Antivirals

There are currently more than 200 trials involving various antivirals including lopinavir/ritonavir, remdesivir, favipiravir and umifenovir. This category is the 2nd largest treatment category that are being tested for COVID-19 in the world.

Related publications:
  • WHO trial (Solidarity): The interim trial results reported that remdesivir, hydroxychloroquine, lopinavir/ritonavir and interferon regimens appeared to have little or no effect on 28-day mortality or the in-hospital course of COVID-19 among hospitalized patients.
  • 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).

3. Convalescent Plasma

Convalescent plasma is a century-old treatment technique that has generated encouraging — yet early — results as a COVID-19 treatment. 

This remains the 3rd most tested treatment in the world for COVID-19 with more than 200 trials as of November 2020.

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)

4. Vaccine

This is the most watched and anticipated category. Technically, vaccine is not considered to be a treatment but rather a preventive strategy to reduce the risk of getting COVID-19.

As of November 2020, there are more than 170 on-going trials in various phases. The vaccine remains a promising agent for COVID-19 protection, and the preliminary reports of the candidate vaccines showcase some encouraging results.


5. Stem Cell Therapy

Just for 2020 alone, there are already more than 600 publications published on "stem cell and covid19" on the National Library of Medicine (PubMed).

As of November 2020, there are more than 90 studies that have been launched to investigate the benefits of stem cell therapy and COVID-19. You can review the status and details of these trials on Global COVID-19 Trial Tracker.

Mesenchymal stem cells are used as immuno-modulators for severe COVID-19 patients and some of the trial projects are launched in combination with other medications such as interleukin (IL) 6 inhibitors e.g. tocilizumab. IL-6 inhibitors have been studied mainly for their potential to calm down the 'cytokine storm' associated with ARDS (acute respiratory distress syndrome), a severe COVID-19 lung complication.

Mesoblast is an Austalian regenerative medicine company that is now applying an experimental stem cell treatment called remestemcel-L (a stem cell product based on allogeneic mesenchymal stem cells) 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. 


6. Azithromycin

Azithromycin is a widely prescribed generic antibiotic. While it's mainly used to fight bacteria, not viruses, there is some research suggesting the drug has antiviral properties.

As of November 2020, there are more than 120 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.

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)

7. Dietary Supplements (Vitamin D, C, Zinc and Melatonin)

There are more than 70 types of supplements that are being tested for COVID-19. You can review the details of these trials on clinicaltrials.gov. There are more than 120 trials testing the various nutrients and dietary supplements including vitamin D, vitamin C, zinc and melatonin. Vitamin D remains the most tested vitamin followed by vitamin C, for COVID-19.

The lung injury in COVID-19 patients is associated with ROS (reactive oxygen species) released by phagocytes, and thus the use of antioxidants is necessary for the management of COVID-19.

Do take note that for optimal effectiveness, each supplement should not be considered as a single intervention as most of the supplements are given as part of a combination protocol. Further, each nutrient will also have influence on another nutrient. For example, vitamin C and zinc need to be given together with copper. Also, vitamin D3 needs to be given with vitamin K2.



8. Steroids (Methylprednisolone, Dexamethasone)

As of November 2020, there are more than 60 on-going trials in this treatment category.

Do take note that most patients that suffered the COVID-19 disease will normally go through 2 overlapping but distinct phases i.e. viral phase and followed by inflammatory phase. Steroids remain a promising treatment category for COVID-19 especially for those with inflammatory organ injury.

Related publication:
  • UK's Recovery Trial (University of Oxford) - In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support.

9. Interleukin Receptor Blockers (Tocilizumab, Sarilumab)

Kevzara (trade name for sarilumab) 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)

10. Interferon beta-1a

Interferon beta-1a is used to treat multiple sclerosis.

Related publication:
  • WHO trial (Solidarity): The interim trial results reported that remdesivir, hydroxychloroquine, lopinavir/ritonavir and interferon regimens appeared to have little or no effect on 28-day mortality or the in-hospital course of COVID-19 among hospitalized patients.

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