Treatment Research

Therapeutic drug development

(up to March 2021)

Below, I provide information on some of the medications and other treatments that were investigated or developed for the treatment of COVID-19.

STAT Covid-19 Drugs and Vaccines Tracker has an excellent chart explaining current research on Treatments and Vaccines.

Access Clinical Studies (on Stanford University’s Coronavirus Antiviral Research Database).
All COVID-19 clinical trials at a glance | ClinicalTrials.gov
NYT: Coronavirus Drug and Treatment Tracker
The Pharmaceutical Journal: Everything you need to know about the COVID-19 therapy trials

A therapeutic drug is a medication that helps heal a disease.

Remdesivir (manufactured by Gilead) was the first therapeutic drug that, based on rigorous clinical trials, demonstrated some effect in treating COVID-19 (reported on April 29, 2020). It is an antiviral drug medication administered intravenously, designed to slow viral replication in the human body. Clinical trials have shown that remdesivir can reduce the length of hospitalization, but it has not been shown to decrease mortality

Dexamethasone, a common and inexpensive corticosteroid, was the first drug proven to significantly reduce mortality in COVID-19 patients receiving oxygen therapy by mitigating the effects of an overactive immune response. (See the Timeline for June 16, 2020.)

Numerous other treatments have been tested in laboratories and hospitals. These include blood thinners to reduce clotting, anti-inflammatory drugs to mitigate inflammation and other effects of the cytokine storm (with the caveat that immune-suppressing drugs must be administered at the appropriate stage to avoid weakening early defenses), and antibody-based treatments—both drugs containing COVID-19 antibodies and synthetic antibodies. Antibody-based therapies now appear more promising than convalescent plasma (transfusions of plasma containing antibodies from recovered patients). Additionally, interferon has been evaluated for treating severely ill patients to counteract the virus’s inhibition of its production, although its use can lead to serious side effects. A review of the Treatment Research (Timeline) section shows that researchers are exploring nearly every possible approach to effectively treat COVID-19.

Considerably fewer COVID-19 patients are dying in hospitals because medical treatments have advanced rapidly—not only through drug research but also by deepening our understanding of how the virus attacks the body. Although there is essentially no scientific evidence supporting the existence of a “wonder drug” that could cure all COVID-19 patients, numerous therapies are currently in use for hospitalized individuals. These treatments are designed to be administered at the appropriate stage of the disease.

For a comprehensive overview of COVID-19 therapy trials, see Everything you need to know about the COVID-19 therapy trials in The Pharmaceutical Journal

Skip to the detailed sections on this page for:

For more general information on potential Covid-19 treatments on this site, scroll down to Other sources of information.



dexamethasone

Dexamethasone is an inexpensive, widely used corticosteroid that reduces inflammation and is the first drug shown to lower COVID-19 mortality. Researchers at the University of Oxford in the UK announced on June 16, 2020, that a randomized, controlled clinical trial involving 6,000 patients demonstrated that dexamethasone can save the lives of patients with severe COVID-19—approximately one in three patients on ventilators.

WHO: Q&A: Dexamethasone and COVID-19

STAT: Watch: Understanding dexamethasone, the steroid used to treat Trump’s Covid-19
(October 12, 2020)

BMJ: Dexamethasone in the management of Covid-19 (July 3, 2020)

  • “Unresolved questions remain, however. RECOVERY investigators did not explore optimal type of corticosteroid nor timing, dose, or duration of giving this drug class.”

Science: Drug recently shown to reduce coronavirus death risk could run out, experts warn
(June 21, 2020)

  • “Hoarding and speculative procurement [of dexamethasone] appear to have already started.”

nature: Coronavirus breakthrough: dexamethasone is first drug shown to save lives
(June 16, 2020)

  • Dexamethasone, “an inexpensive and commonly used steroid can save the lives of people seriously ill with COVID-19, a randomized, controlled clinical trial in the United Kingdom has found.”
  • “In the trial, it cut deaths by about one-third in patients who were on ventilators because of coronavirus infection.”
  • This drug is far more accessible than remdesivir (which is in short supply) and is much easier to administer.
  • “For less than £50 [63 USD], you can treat 8 patients and save one life.”

STAT: Major study finds common steroid reduces deaths among patients with severe Covid-19 (June 16, 2020)

  • In clinical trials, dexamethasone reduced mortality by 35% in patients on ventilators and by 20% in patients receiving oxygen but not on ventilators. These reductions are significant; however, no benefit was observed in patients who did not require supplemental oxygen.

NYT: Coronavirus Live Updates: Drug Proven to Reduce Virus Deaths, Scientists Say
(June 16, 2020)

  • “Scientists at the University of Oxford said on Tuesday that they have identified what they called the first drug proven to reduce coronavirus-related deaths, after a 6,000-patient trial of the drug in Britain showed that a low-cost steroid could reduce deaths significantly for hospitalized patients.”



remdesivir

remdesivir

Manufacturer: Gilead
Type of Drug: Antiviral
Mode of Administration: Intravenous
Testing: Clinical trials were conducted during April and May 2020 (with news of success reported on April 29, 2020).

Remdesivir is the first therapeutic drug conclusively shown to have a significant effect in treating COVID-19. Essentially, this means that remdesivir is expected to benefit certain COVID-19 patients by reducing the overall duration of illness. However, it has not been demonstrated—based on scientific evidence—to reduce mortality. As an antiviral, remdesivir is designed to slow the replication of viruses in the human body. Originally developed to treat Ebola, it ultimately proved unsuccessful for that disease. Remdesivir is one of many drugs developed either to combat viral infections in general or to target specific diseases, with researchers hoping it would also be effective against COVID-19.

One obvious benefit of these findings is the potential to reduce hospitalization times, which could help free up hospital beds and alleviate strain on healthcare capacity. However, there is an even more important reason for the scientific community to be excited about these results. As Dr. Anthony Fauci described it, this represents a “proof of concept.” It is the first drug that shows that the virus can be treated with a drug, and it paves the way for researchers to learn not only from its use but also from the mechanisms through which it works, enabling them to develop more effective treatments in the future.

Mechanism: delayed chain termination
  • Remdesivir slows viral replication by interfering with the copying of RNA in host cells through a process called “delayed chain termination.” Once the virus hijacks a host cell—and its RNA assembly line—an enzyme called polymerase begins synthesizing new RNA strands by linking together four types of nucleotide bases. One of these bases is adenine.. When a patient receives remdesivir, the active compound enters host cells and is similar enough to adenine that polymerase can mistakenly incorporate it into the new RNA strand. However, once it is inserted, only about five additional nucleotide bases can be added before RNA synthesis stops. Because each new virus requires a complete RNA strand, this premature termination results in fewer viruses being produced. The fact that a few extra bases are added before synthesis halts is why the mechanism is known as delayed chain termination.

STAT: WHO group recommends against using remdesivir to treat hospitalized Covid-19 patients (November 19, 2020)

  • The WHO’s Guideline Development Group bases this recommendation on:
    • Lack of evidence of improving “patient-important outcomes”
      (reducing mortality, ventilation…)
      • This does not imply “proof” of its ineffectiveness.
    • Price, expense of delivering it intravenously, “potential harm”.

AP: FDA approves first COVID-19 drug: antiviral remdesivir (October 22, 2020)

FDA: FDA Approves First Treatment for COVID-19 (October 22, 2020)

  • “Today, the U.S. Food and Drug Administration approved the antiviral drug Veklury (remdesivir)…”

Science: Remdesivir and interferon fall flat in WHO’s megastudy of COVID-19 treatments
(October 16, 2020)

STAT: From Houston to Miami, hospitals running short of remdesivir for Covid-19 patients
(July 10, 2020)

STAT: Gilead announces long-awaited price for Covid-19 drug remdesivir (June 29, 2020)

  • “For all governments in the developed world, including the U.S. government’s Medicaid program and the Department of Veterans Affairs, Gilead will charge $2,340 for a five-day course. U.S. insurers will pay 33% more, or $3,120. Countries in the developing world will get the drug at greatly reduced prices through generic manufacturers to which Gilead has licensed production.”

STAT: To allocate remdesivir fairly, give it to communities that bear a disproportionate burden of Covid-19 (June 9, 2020)

STAT: Gilead’s remdesivir shows some benefit in patients with moderate Covid-19, new data show (June 1, 2020)

  • This study adds to the growing evidence that remdesivir is effective in treating moderately ill COVID-19 patients (those hospitalized but not on ventilators). It is now widely accepted that remdesivir significantly reduces the length of hospital stays for seriously ill patients.

NYT: Federal Scientists Finally Publish Remdesivir Data (May 23, 2020)

STAT: Gilead should ditch remdesivir and focus on its simpler and safer ancestor
(May 14, 2020)

  • Remdesivir is a pro-drug (the patient’s body needs first to process it chemically) requiring five steps in the body before it becomes GS-441524 triphosphate, the active compound.
  • Gilead has also developed GS-441524, also a pro-drug, but GS-441524 triphosphate is produced in the body in only three steps. GS-441524 also can be manufactured in three steps instead of the seven steps for remdesivir.

STAT: Inside the NIH’s controversial decision to stop its big remdesivir study
(May 11, 2020)

  • “The National Institute of Allergy and Infectious Diseases has described to STAT in new detail how it made its fateful decision: to start giving remdesivir to patients who had been assigned to receive a placebo in the study, essentially limiting researchers’ ability to collect more data about whether the drug saves lives — something the study, called ACTT-1, suggests but does not prove. In the trial, 8% of the participants given remdesivir died, compared with 11.6% of the placebo group, a difference that was not statistically significant.”

STAT: Watch: How does Gilead’s experimental drug remdesivir work against the coronavirus? (VIDEO) (May 4, 2020)

  • The polymerase enzyme that copies the virus’s RNA inside the host cell may confuse nearby remdesivir molecules with the adenine unit of the RNA and add it instead to the new strand. This molecule then blocks any more units from being added (after about five more are added), thus sabotaging the process.

CNN: FDA issues emergency-use authorization for remdesivir to treat hospitalized patients with severe Covid-19 (May 1, 2020)

  • “The experimental drug remdesivir has been approved to treat hospitalized patients with severe Covid-19, the US Food and Drug Administration said in a letter on Friday. Remdesivir is the first authorized therapy drug for Covid-19 in the United States.”

CNN: Remdesivir drug shows promise — but it is far from a coronavirus cure
(April 30, 2020)

  • “It improved recovery time for coronavirus patients from 15 to 11 days. That’s similar to the effect that the influenza drug Tamiflu has on flu.”
  • “The study also showed that 8% of patients who took remdesivir died compared to 11% of patients who received the placebo. However, there were not enough deaths to make those numbers statistically significant.”
  • “The value, instead, is more in what the study’s results represent — that a drug can indeed have an impact on Covid-19.”

STAT: Gilead says critical study of Covid-19 drug shows patients are responding to treatment (April 29, 2020)

  • This is “the first treatment shown to improve outcomes in patients infected with” Covid-19.
  • “[T]he NIAID study, which was not expected to be released so soon, was by far the most important and rigorously designed test of remdesivir in Covid-19. The study compared remdesivir to placebo in 800 patients…”

nature: Hopes rise on coronavirus drug remdesivir (April 29, 2020)

  • The NIAID results put a new sheen on remdesivir. “It may not be the wonder drug that everyone’s looking for, but if you can stop some patients from becoming critically ill, that’s good enough”
  • Remdesivir works by gumming up an enzyme that some viruses, including SARS-CoV-2, use to replicate. In February, researchers showed that the drug reduces viral infection in human cells grown in a laboratory.

NIH: Antiviral remdesivir prevents disease progression in monkeys with COVID-19
(April 17, 2020)

  • “Early treatment with the experimental antiviral drug remdesivir significantly reduced clinical disease and damage to the lungs of rhesus macaques infected with SARS-CoV-2, the coronavirus that causes COVID-19, according to National Institutes of Health scientists.”

For more information on remdesivir on this site, visit The search for treatments page to access news summaries and comments.



hydroxychloroquine and chloroquine

hydroxychloroquine

Hydroxychloroquine (HCQ) and chloroquine (CQ) have been extensively studied for the treatment of COVID-19. Many researchers and clinicians now agree that these drugs offer little or no significant benefit in treating the disease, despite early in vitro studies that showed strong antiviral effects. Nevertheless, some doctors during this first year of the pandemic believe that administering hydroxychloroquine at home during the early stages of infection—before the disease becomes severe enough to require hospitalization—might still provide some benefit.

These two drugs are antimalarial (AM) drugs, though they are no longer recommended for malaria treatment due to the availability of more effective alternatives. However, they remain in use for other medical conditions.

Clinical trials were conducted to evaluate their potential benefits in treating or preventing COVID-19. As of early 2021, no conclusive evidence supported their effectiveness for this purpose.

The history of these drugs traces back to the bark of the cinchona tree in the Andes, which Jesuits were already using to treat malaria in the 17th century. Quinine, the active ingredient effective against malaria, was extracted from this “Peruvian bark” in France in 1820.

Throughout the early 20th century, German scientists attempted to synthesize a non-toxic, effective antimalarial drug based on quinine’s chemical structure. Their efforts led to the development of quinacrine in 1930 and chloroquine in 1934. However, Germany deemed chloroquine too toxic and did not adopt it for medical use. Instead, the drug was patented in the United States.

Hydroxychloroquine (HCQ), a safer derivative of chloroquine, was first synthesized in New York in 1946. It received FDA approval in the U.S. in 1955 for the treatment of malaria, lupus, and rheumatoid arthritis. Today, HCQ remains an essential medication for for managing lupus, a chronic autoimmune disease affecting the skin and other organs.

Hydroxychloroquine and chloroquine have been used in China and other countries to treat COVID-19, but one year into the pandemic there is practically no evidence supporting their effectiveness for this purpose. In some places, particularly in the U.S., their use has become a highly controversial issue.

Initially, there was hope within the scientific community, as HCQ was found to slow down the virus in vitro (in the laboratory). However, many drugs that show promise in lab studies failed to be effective in humans for various reasons. While some small studies suggested potential benefits, others have found none, leading to conflicting results.

These contradictions have fueled controversy, with some arguing that scientific research on the drug was not being conducted properly. However, based on my readings, I have not seen any red flags suggesting that the scientific process was being compromised.

There were valid scientific reasons to be cautious about small trials, which is why it was crucial to plan larger trials with proper controls. Several trials had already been conducted on hydroxychloroquine (HCQ). As of May 26, 2020, the COVID-evidence Database listed 22 completed trials, and according to ClinicalTrials.gov, 192 trials involving HCQ were either planned or in progress globally.

There was still a chance of finding evidence of some benefit. While many researchers had already lost optimism that any potential benefit would outweigh the known dangers of its side effects, others remained hopeful and continued looking forward to the results of larger, double-blind trials.

By early 2021, many trials on hydroxychloroquine (HCQ) had concluded, with results consistently showing that it was ineffective for treating COVID-19 and that its potential risks outweighed any benefits. While earlier research had left room for some optimism, larger, more rigorous double-blind trials provided definitive evidence against its use. As a result, major global health agencies like the NIH and WHO officially recommended against HCQ for COVID-19 treatment, and most large-scale research on the drug had been discontinued. Despite this, some smaller studies and advocacy for its use persisted in certain circles.

If science were to find conclusive evidence that hydroxychloroquine (HCQ) helps, even to a small degree, it could open up another avenue for drug research, much like what happened with remdesivir. The excitement in the scientific community over remdesivir seemed, above all, to be about the drug providing proof of concept (according to Dr. Anthony Fauci). This essentially means that there is likely a molecular mechanism by which the drug works, which could be better understood and used to develop more effective treatments for COVID-19.

This would have been a win-win situation, both for saving lives and for generating monetary profit. Perhaps many who continued to believe in the effectiveness of hydroxychloroquine (HCQ) were unaware of this important aspect.

The fact that both hydroxychloroquine (HCQ) and remdesivir have been in use for over six decades and are listed in the WHO Model List of Essential Medicines does not imply that they are without risks. All drugs have side effects, and powerful drugs, in particular, can have dangerous ones. However, due to their long history of use, the risks associated with these drugs are now well understood.

Although rare, the side effects of hydroxychloroquine (HCQ) can be serious. The American Academy of Ophthalmology warns of Hydroxychloroquine-Induced Retinal Toxicity which can lead to irreversible vision loss. They recommend that a complete ophthalmic examination be performed before starting treatment to establish a baseline for maculopathy. However, this may not be practical in an emergency setting, and it might not be as much of a concern for COVID-19 patients given the limited duration of HCQ use (though further investigation into this is warranted).

What health experts have been highlighting more recently is the risk of life-threatening heart rhythm disturbances, particularly “QT prolongation and subsequent arrhythmias”. QT prolongation refers to a lengthening of the heart muscle’s “recharge” time between heartbeats, as the QT interval is the phase where the heart reverses its electrical polarity. This can lead to arrhythmias, such as tachycardia (a pulse rate over 100 beats per minute), which could result in heart failure, stroke, cardiac arrest (where the heart stops beating), or even death.

Dr. Peter McCullough, a professor at Texas A&M, considered hydroxychloroquine (HCQ) to be effective in the early stages of COVID-19 when used at home. Here is a link to A Guide to Home-Based COVID Treatment:

A Guide to Home-Based COVID Treatment edited by Dr. Peter McCullough et al.
(updated February 1, 2021) Download

Wired: The Strange and Twisted Tale of Hydroxychloroquine (November 11, 2020)

SWI: Basel study: hydroxychloroquine not effective (July 10, 2020)

STAT: WHO drops hydroxychloroquine from Covid-19 clinical trial (June 17, 2020)

  • “Patients who were already enrolled and were in the midst of their hydroxychloroquine regimen can complete their course or stop, the WHO said.”
  • “The Solidarity trial is continuing to compare other potential Covid-19 drugs. More than 400 hospitals in 35 countries are participating in the study.”

STAT: FDA revokes emergency use ruling for hydroxychloroquine (June 15, 2020)

  • The US FDA considers HCQ to be ineffective for treating Covid-19, but doctors may still use the drug off-label.

Science: Three big studies dim hopes that hydroxychloroquine can treat or prevent COVID-19 (June 9, 2020)

  • After three large studies on HCQ, scientists are losing hope for any significant benefit from the drug, although some still want to see all the data before deciding.

Science: Who’s to blame? These three scientists are at the heart of the Surgisphere COVID-19 scandal (June 8, 2020)

STAT: Study: Hydroxychloroquine had no benefit for hospitalized Covid-19 patients, possibly closing door to use of drug (June 5, 2020)

nature: High-profile coronavirus retractions raise concerns about data oversight
(June 5, 2020)

  • Articles in question during the past three days were retracted because the little-known company Surgisphere that supplied the researchers data from hospitals worldwide did not allow its raw data to be verified.
  • “This whole event is catastrophic — it is problematic for the journals involved, it is problematic for the integrity of science, it is problematic for medicine, and it is problematic for the notion of clinical trials and evidence generation.”

This is far from the ideal way for science to advance. While science will eventually progress, even if those involved in research are not fully honest, such practices slow down the process, which is unfortunate, especially during a time when rapid scientific advancement is critical. Even if the company supplying the data made honest mistakes, researchers have a responsibility to verify that data. Given that top journals were involved, this situation must be very embarrassing for them.

PopSci: A major study just found hydroxychloroquine doesn’t prevent COVID-19
(June 4, 2020)

STAT: WHO resumes hydroxychloroquine study for Covid-19, after reviewing safety concerns (June 3, 2020)

  • The WHO resumed its trials after another HCQ study was called into question. (See yesterday’s news sources.)

PopSci: Hydroxychloroquine is getting another shot as a COVID-19 treatment
(June 3, 2020)

  • A simpler article explaining the issues surrounding the retraction of an HCQ study discussed in other news articles yesterday and today.

Science: A mysterious company’s coronavirus papers in top medical journals may be unraveling (June 2, 2020)

  • An investigation is now underway on Surgisphere, a relatively unknown company that provided seemingly implausible data on deaths of Covid-19 patients for a hydroxychloroquine study that concluded that the drug was associated with a high risk of death. (These results made the WHO decide to suspend its trials of the drug.)
  • Two other studies that used Surgisphere’s data also produced controversial results.

STAT news also wrote about this same issue.

nature: Safety fears over hyped drug hydroxychloroquine spark global confusion
(May 29, 2020)

  • “Early laboratory studies suggested that the drug, as well as a similar medicine named chloroquine, might interfere with replication of the coronavirus, but trials in humans have been inconclusive so far.”
  • “Researchers have been waiting for results from a number of randomized, controlled clinical trials testing hydroxychloroquine as a COVID-19 treatment.” Because of negative publicity many trials have now been halted. Yet many scientists find it is very important to continue with these trials.

NYT: Scientists Question Validity of Major Hydroxychloroquine Study (May 29, 2020)

Reuters: Beyond politics, gold-standard COVID-19 trials test malaria drug taken by Trump
(May 22, 2020)

STAT: What a big new study on malaria drugs as Covid-19 treatments tells us — and what it doesn’t (May 22, 2020)

  • A recent study on choroquine and hydroxychloroquine failed to give significant evidence that these drugs are effective against Covid-19. Moreover, it showed that these drugs have a dangerous side effect of causing irregular heart rhythms.

To obtain conclusive results, a drug trial must account for the placebo effect, where the belief of either the patient or the doctor that a medication will have a specific effect can bias the results. It is an accepted scientific fact that belief alone can influence the outcome of taking a drug. Currently, there are ongoing double-blind trials in which neither the patient nor the doctor knows whether the patient is taking the drug being tested or a placebo. While many scientists may not be expecting positive results from these trials, it will be interesting to see what they reveal. – MH

STAT: Life with lupus: Trump’s hydroxychloroquine hype puts my treatment — and himself — at risk (May 20, 2020)

  • The author suffers from lupus (a disease that inflames the skin) and needs hydroxychloroquine, a drug that works for her condition. She fears that the hype (the exaggerated publicity) of this drug, for which there is too little evidence that it can treat Covid-19, will keep her and others from obtaining it for a disease it is known to treat effectively.
hydroxychloroquine tablet

BBC: Coronavirus and chloroquine: Is there evidence it works? (April 28, 2020)

  • There are “risks of serious side effects, including renal and liver damage.”
  • “More than 20 trials carried out, including in the US, UK, Spain and China.”
  • France has authorised its use but has warned of side effects.
  • India has recommended it as a preventative treatment for healthcare workers but warns it is “experimental” and only for emergency situations.
  • “Several Middle Eastern countries have authorised its use or are conducting trials. This includes Bahrain, Morocco, Algeria and Tunisia.”
  • There are reports of people poisoned from chloroquine overdoses.

nature: Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology

IJAA: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial

NYT: 7 Answers to Questions About the Malaria Drug Trump Keeps Pushing (April 9, 2020)

  • There are still many unanswered questions about hydroxychloroquine and it is possible that it is dangerous to use when certain conditions develop that Covid-19 causes.

Chloroquine, Ibuprofen and Beyond: Doctors Discuss Latest Treatments, and Treatment Rumors, For COVID-19 (April 2, 2020)

BBC: Coronavirus and chloroquine: Is there evidence it works? (April 28, 2020)

  • There are “risks of serious side effects, including renal and liver damage.”
  • “More than 20 trials carried out, including in the US, UK, Spain and China.”
  • France has authorised its use but has warned of side effects.
  • India has recommended it as a preventative treatment for healthcare workers but warns it is “experimental” and only for emergency situations.
  • “Several Middle Eastern countries have authorised its use or are conducting trials. This includes Bahrain, Morocco, Algeria and Tunisia.”
  • There are reports of “people poisoned from overdoses of chloroquine”.

CNN: Study finds no benefit, higher death rate in patients taking hydroxychloroquine for Covid-19 (April 22, 2020)

  • This report describes the research article pre-print (not yet peer reviewed or published) found on medRxiv.com.



ivermectin

ivermectin

This is a popular and inexpensive anti-parasite drug used around the world. Although used extensively in some countries against Covid-19, the FDA has warned: Why You Should Not Use Ivermectin to Treat or Prevent COVID-19 (March 5, 2021)

The Lancet: The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19 (January 19, 2021)

  • In this study, some benefits have been found for treating Covid-19 (“marked reduction of self-reported anosmia/hyposmia, a reduction of cough and a tendency to lower viral loads and lower IgG titers“) which would warrant further testing in larger clinical trials.

FDA: FAQ: COVID-19 and Ivermectin Intended for Animals (December 16, 2020)

nature: Latin America’s embrace of an unproven COVID treatment is hindering drug trials
(October 20, 2020)



fluvoxamine

fluvoxamine

CBS: Finding a possible early treatment for COVID-19 in a 40-year-old antidepressant
(60 Minutes video) (March 7, 2021)

STAT: Pill used to treat OCD and anxiety may prevent Covid-19 from worsening, a preliminary study suggests (November 12, 2020)



molnupiravir

Medical Dialogues: COVID-19: Antiviral drug Molnupiravir blocks virus transmission within 24 hours, claims Study (December 7, 2020)



tocilizumab

Science: World’s largest COVID-19 drug trial identifies second compound that cuts risk of death (February 11, 2021)

nature: COVID research updates: Two anti-inflammatory drugs prevent COVID deaths
(January 15, 2021)

  • Tocilizumab and sarilumab have been tested at Imperial College London.

SN: The arthritis drug tocilizumab doesn’t appear to help fight COVID-19
(October 23, 2020)

NYT: A Promising Treatment for Coronavirus Fails (March 18, 2020)

  • “There is no solid evidence yet that anything works, but the epidemic is moving so fast that doctors are trying approaches where even preliminary data suggests there may be a benefit. Many feel they are on their own to develop treatment protocols. Federal health authorities like the Centers for Disease Control and Prevention recommend supportive care, but have said there is no evidence yet to support antiviral drugs or treatments for inflammation…For critically ill patients suffering from intense inflammatory reactions, called a cytokine storm, some centers are trying a drug called tocilizumab.”



sarilumab

nature: COVID research updates: Two anti-inflammatory drugs prevent COVID deaths
(January 15, 2021)

  • Tocilizumab and sarilumab have been tested at Imperial College London.



colchicine

MedScape: Colchicine Promising in COVID-19 Treatment? (July 30, 2020)

  • Clinical results show that colchicine might help in the treatment of serious Covid-19 by reducing inflammation.



interferon

Science: Remdesivir and interferon fall flat in WHO’s megastudy of COVID-19 treatments
(October 16, 2020)

SciAm: An Immune Protein Could Prevent Severe COVID-19—if It Is Given at the Right Time
(September 2020 issue) (September 7, 2020)

SciAm: An Immune Protein Could Prevent Severe COVID-19—if It Is Given at the Right Time
(July 28, 2020)

  • Interferon could help prevent severe Covid-19 if given early, but make the disease more severe if given later.

Science: Can boosting interferons, the body’s frontline virus fighters, beat COVID-19?
(July 8, 2020)



EIDD-2801

NPR: Promising Drug On The Horizon For COVID-19 (April 6, 2010)

  • EIDD-2801 is a pill that will hopefully keep the virus from making copies of itself.



monoclonal antibodies

Science: Monoclonal antibodies protect against COVID-19 in a second study
(January 26, 2021)

STAT: Eli Lilly says its monoclonal antibody prevented Covid-19 infections in clinical trial
(January 21, 2021)

STAT: Eli Lilly says its monoclonal antibody cocktail is effective in treating Covid-19
(October 7, 2020)

Science: ‘Provocative results’ boost hopes of antibody treatment for COVID-19
(September 30, 2020)

Science: Eli Lilly reports first, promising results for an antibody against COVID-19
(September 16, 2020)



synthetic antibodies

SciAm: Lab-Made ‘Miniproteins’ Could Block the Coronavirus from Infecting Cells
(October 12, 2020)



other antibody therapies

SciAm: COVID Antibody Treatments Show Promise for Preventing Severe Disease
(March 16, 2021)

SciAm: To Beat COVID, We May Need a Good Shot in the Nose (March 1, 2021)

Science: Can a nose-full of chicken antibodies ward off coronavirus infections?
(November 10, 2020)

  • “A clinical trial has begun in Australia to find out whether nasal drops that contain chicken antibodies to SARS-CoV-2 can offer temporary protection.”

STAT: Antibody drugs seem to work. But the virus is moving faster than we can make them
(October 29, 2020)

nature: The race to make COVID antibody therapies cheaper and more potent
(October 23, 2020)

SciAm: Costa Rica Readies Horse Antibodies for Trials as an Inexpensive COVID-19 Therapy
(August 17, 2020)

nature: Antibody therapies could be a bridge to a coronavirus vaccine — but will the world benefit? (August 11, 2020)

STAT: Inspired by llamas’ unique antibodies, scientists create a potent anti-coronavirus molecule (August 11, 2020)

Science: This cow’s antibodies could be the newest weapon against COVID-19
(June 5, 2020)

  • A biotech company in South Dakota, USA, has inserted genes into the DNA of cows so that certain immune cells will produce antibodies in the same way it happens in the human body. Antigens introduced into the cows such as the SARS-CoV-2 spike will then produce human antibodies.
  • One advantage of this method is that different kinds of antibodies could be produced that attach to different parts of the virus.
  • In clinical trials these antibodies appear to be four times better than convalescent plasma in preventing the virus from entering cells.
  • One cow could produce enough antibodies for hundreds of people per month.
  • “Essentially, the cows are used as a giant bioreactor.”
  • Clinical trials will begin to see if these antibodies can prevent infections.
  • There has never yet been any approval for treatment of any antibodies produced in animals.
  • “The whole approach is based on sound science and on past experience going back more than a century.”

Science: Designer antibodies could battle COVID-19 before vaccines arrive (August 4, 2020)

STAT: GlaxoSmithKline and Vir aim to take on Covid-19 with antibodies and CRISPR (April 6, 2020)

  • “Antibody drugs could be used in three possible ways: to prevent people at high risk, such as healthcare workers, from ever becoming infected; to prevent those infected from developing severe respiratory problems that can make Covid-19 … deadly; and to treat people who are already in respiratory distress.”

Tsinghua and partners to develop neutralising antibodies against COVID-19 (April 1, 2020)

  • “Researchers … have identified various diverse and potent neutralising monoclonal antibodies that are claimed to have therapeutic potential against SARS CoV-2. These antibodies have been characterised from coronavirus patients in China who have recovered from their infection …”

Hungary Today: Coronavirus: Blood Plasma Therapy Promising, Recovered Patients Asked to Donate Blood (April 29, 2020)

  • “In a scientific collaboration, two patients from Semmelweis University [Budapest] who tested positive for coronavirus, have received the already licensed serum infused with the blood plasma of healed COVID-19 patients. The serum was developed by a group of Hungarian research physicians, together with Semmelweis University and the Virology Center of the University of Pécs.”



blood thinners

STAT: Giving blood thinners to severely ill Covid-19 patients is gaining ground
(May 6, 2020)

  • “Treating Covid-19 patients with medicines to prevent blood clots might help reduce deaths in patients on ventilators, based on new observational data.”
  • “A team from Mount Sinai Health System in New York on Wednesday reported better results for hospitalized Covid-19 patients who received anticoagulant drugs compared to patients who didn’t.”



convalescent plasma

SciAm: Can My Blood Really Help COVID Patients? (November 3, 2020)

PopSci: Evidence for Convalescent Plasma Coronavirus Treatment Lags Behind Excitement
(August 24, 2020)

STAT: Is convalescent plasma safe and effective? We answer the major questions about the Covid-19 treatment (August 23, 2020)

nature: Evidence lags behind excitement over blood plasma as a coronavirus treatment
(August 19, 2020)

NYT: F.D.A.’s Emergency Approval of Blood Plasma Is Now on Hold (August 19, 2020)

STAT: Large study suggests convalescent plasma can help treat Covid-19, but experts have doubts (August 13, 2020)

Science: Can plasma from COVID-19 survivors help save others? (May 27, 2020)

  • Convalescent plasma has been known to help in recovery with other illnesses, such as the Spanish Flu of 1918. Some reports are promising with regards to Covid-19, but more trials are needed.
  • “The difference in mortality—12.8% in the plasma group and 24.4% in the control group—was not statistically significant, but when the team compared the patients’ supplemental oxygen needs after transfusion, those on plasma did significantly better.”

MNT: Using convalescent blood to treat COVID-19: The whys and hows (May 22, 2020)



radiation

STAT: Once a relic of medical history, radiation emerges as an intriguing — and divisive — treatment for Covid-19 (July 16, 2020)

Forbes: How Low-Dose Radiation Could Be The Trick For Treating COVID-19
(June 13, 2020)

  • “It’s the anti-inflammatory effects of radiation, not its antiviral action, that could be invaluable to helping patients with COVID-19.”



Other sources of information

Science: How do you treat coronavirus? Here are physicians’ best strategies
(March 16, 2021)

PJ: Everything you need to know about the COVID-19 therapy trials (March 15, 2021)

  • An excellent overview of Covid-19 therapy trials.

nature: COVID antibody treatments show promise for preventing severe disease
(March 12, 2021)

Science: Researchers race to develop antiviral weapons to fight the pandemic coronavirus
(March 11, 2021)

Science: International megatrial of coronavirus treatments is at a standstill
(March 3, 2021)

SciAm: Why It’s So Hard to Make Antiviral Drugs for COVID and Other Diseases
(February 11, 2021)

SciAm: These Drugs Might Prevent Severe COVID (December 14, 2020)

  • These are Regeneron’s monoclonal antibody combination, remdesivir, molnupiravir, fluvoxamine and mini binders (synthetic antibodies).

Science: First-of-its-kind African trial tests common drugs to prevent severe COVID-19
(December 3, 2020)

STAT: As a new Covid-19 treatment arrives, hospitals scramble to solve logistical and ethical challenges (November 20, 2020)

SciAm: For COVID Drugs, Months of Frantic Development Lead to Few Outright Successes
(November 13, 2020)

PopSci: These are the best COVID-19 treatments right now (October 5, 2020)

NYT: Steroids Can Be Lifesaving for Sickest Patients, Studies Show (September 2, 2020)

STAT: Yes, we need a vaccine to control Covid-19. But we need new treatments, too
(August 5, 2020)

  • “In addition to saving lives and boosting hospital capacity, an effective treatment could also increase people’s willingness to return to more normal levels of economic activity.”
  • “If an effective treatment could be found that prevents severe disease — or, even better, provides a cure — the urgent need to vaccinate millions of healthy people would diminish.”
  • “More realistically, we will need to manage Covid-19, and possibly other novel viruses, for years to come. A vital tool will be effective treatments.”

STAT: NIH to start ‘flurry’ of large studies of potential Covid-19 treatments
(July 23, 2020)

STAT: Using a global network of adaptive clinical trials to fight Covid-19 (Opinion)
(July 23, 2020)

BBC: Coronavirus cure: What progress are we making on treatments? (July 8, 2020)

Pharmaceutical Journal: Everything you need to know about the COVID-19 therapy trials
(July 8, 2020)

Science: One U.K. trial is transforming COVID-19 treatment. Why haven’t others delivered more results? (June 30, 2020)

SciAm: Hospitals Experiment with COVID-19 Treatments, Balancing Hope and Evidence
(June 29, 2020)

  • “With little data on what works and what doesn’t, doctors trade tips and argue about risks.”

nature: Coronavirus research updates: Modified mice could aid the quest for vaccines and drugs (June 12, 2020)

  • A team in the US and one in China have successfully used an adenovirus to introduce the gene that expresses the human ACE2 receptor into mice, which normally cannot catch Covid-19. This allows them to become infected so they can be used for laboratory experiments.

nature: The coronavirus outbreak could make it quicker and easier to trial drugs
(June 4, 2020)

  • “Remote clinical trials and other changes could permanently alter pharmaceutical development.”

STAT: Covid-19 has exposed cracks in the global medicines supply chain. We need to fix them (June 2, 2020)

  • “Now is the time to address these vulnerabilities and enhance our ability to respond to pandemics and other public health crises.”:
    • “Increase geographic diversity in manufacturing”
    • “Ensure supply of critical medicines”
    • “Increase transparency and enhance global cooperation”
    • “Strengthen regulatory systems and quality assurance”

SciAm: Three Ways to Make Coronavirus Drugs in a Hurry (June 1, 2020)

  • Researchers are searching through 20,000 FDA approved drugs for other conditions to see if any are effective against Covid-19. 133 of these became experimental drugs by mid-April and 49 are entering clinical trials.
  • 12 potential treatments are described on a chart.
  • The goal is to have a pill that can work early to prevent severe illness.
  • “By limiting symptoms, drugs may be able to keep some patients out of the hospital and keep hospitalized patients off of ventilators. They can serve as a bridge to survival as other scientists rush to develop the real virus slayer: a vaccine.”

nature: Dozens of coronavirus drugs are in development — what happens next?
(May 14, 2020)

  • One major challenge is the supply-chain (series of steps in obtaining materials, producing, transporting, etc.) negatively affected by the pandemic.
  • Another major challenge is manufacturing up to hundreds of millions of doses.
  • Remdesivir depends on a complex chemical synthesis [production] that takes several weeks and would be badly hurt by shortages of required ingredients.
  • Demand will surely be much greater than the supply of the first drugs available.

TBIJ: Stretched, secret supply chains hold Covid-19 patients’ lives in the balance
(May 12, 2020)

nature: Portraits of a viral enzyme could aid hunt for drugs (May 4, 2020)

  • A research team in Germany used “cryo-electron microscopy” to determine the shape of the polymerase enzyme that copies SARS-CoV-2 RNA in a host cell (see STAT article summary above). A better understanding of this enzyme could lead to the development of antiviral drugs that affect its function.

CR: Doctors on the Front Lines Are Testing New Therapies to Treat COVID-19 (April 15, 2020)

  • An excellent summary by Consumer Reports, simply explained, of the current state of drug development.

JAMA: Pharmacologic treatments for Coronavirus Disease 2019 (COVID-19) A Review (April 13, 2020)

  • “The speed and volume of clinical trials launched to investigate potential therapies for COVID-19 highlight both the need and capability to produce high-quality evidence even in the middle of a pandemic. No therapies have been shown effective to date.”

WHO: “Solidarity” clinical trial for COVID-19 treatments (April 2020)

CNN: How a 100-year-old vaccine for tuberculosis could help fight the novel coronavirus (April 10, 2020)

Every Vaccine and Treatment in Development for COVID-19, So Far (April 1, 2020)

FDA-approved drugs could help fight COVID-19 (March 19, 2020)

Science: Some Clinical Trial Data (March 19, 2020)

BBC: Coronavirus cure: When will we have a drug to treat it? (April 30, 2020)

STAT: WHO launches ambitious global project to develop Covid-19 medical products
(April 24, 2020)

  • “[A] key goal is to level the global playing field so that any products will be available to rich and poor populations alike.”

Reuters: Blood-pressure drugs are in the crosshairs of COVID-19 research (April 23, 2020)

  • A clue is the “disproportionate number” of Covid-19 patients with high blood pressure.
  • Blood-pressure drugs might increase the number of ACE2 enzymes on a cell’s surface in order to raise levels of a hormone that dilates blood vessels, but the ACE2 enzymes are the sites where the virus strikes and where its RNA enters the cell.
  • “Other evidence, however, suggests the infection’s interference with ACE2 may lead to higher levels of a hormone that causes inflammation, which can result in acute respiratory distress syndrome (ARDS), a dangerous build-up of fluid in the lungs.”

BBC: Coronavirus cure: When will we have a drug to treat it? (April 22, 2020)

  • “There are three broad approaches being investigated:
    • Antiviral drugs that directly affect the coronavirus’s ability to thrive inside the body
    • [Immunosuppressant drugs] that can calm the immune system – patients become seriously ill when their immune system overreacts and starts causing collateral damage to the body [in a cytokine storm]
    • Antibodies, either from survivors’ blood or made in a lab, that can attack the virus”

WSJ: When to Reopen: What We Know About Coronavirus Tests, Treatment and Vaccines
(April 17, 2020)

Visit the Treatment Development (Timeline) page to view the links on this page in chronological order.

©2020, 2021 Dr. Michael Herrera