COVID-19 Treatments in the Pipeline

Learn about the clinical evidence behind treatment modalities

The novel coronavirus (COVID-19) has evolved into a pandemic that has infected millions of people worldwide. Scientists and researchers are actively working to find treatments for the disease, and ideally, find a way to prevent infection in the first place.

There are hundreds of clinical trials underway evaluating the potential effectiveness of existing drugs and testing the viability of vaccines and blood products. A February 2020 study published in the journal Cell Research showed seven different drugs had some effect against the virus, but many require concentrations too high to be safely administered. The following outlines a list of high-profile treatments that have also been tested against the virus.

As of October 2020, only two treatments have emergency use authorization from the U.S. Food and Drug Administration (FDA): remdesivir and convalescent plasma.

Hydroxychloroquine and Chloroquine

Hydroxychloroquine and chloroquine are medications currently FDA-approved to treat malaria and autoimmune diseases such as lupus and rheumatoid arthritis. By interfering with protein glycosylation and other enzymatic processes, it is believed these medications could prevent COVID-19 from binding to, entering, and replicating in human cells.

A study comparing hydroxychloroquine to chloroquine found that hydroxychloroquine is slightly less potent, but still potentially effective against COVID-19 in vitro.

What the Research Says

A French study led the way in hydroxychloroquine and chloroquine research. It initially included 26 COVID-19 patients treated with a hydroxychloroquine regimen and 16 untreated control patients. Six of the patients treated with hydroxychloroquine were also treated with azithromycin (also known as a Z-Pack, which is prescribed for several infections). On paper, the results looked promising. By day six, the study authors noted that people treated with hydroxychloroquine decreased their viral load—the amount of virus in their blood—by 57%, and those also treated with azithromycin had cleared the virus altogether.

While this was encouraging, the study did not address how the patients fared clinically, meaning whether or not their symptoms started getting better. Also, it was unclear if the treatment led to the medical issues that prevented study participants from following up with researchers (one died, three transferred to the intensive care unit, one stopped treatment due to medication side effects, one left the hospital).

While the FDA granted emergency use authorization for both chloroquine phosphate and hydroxychloroquine sulfate products for COVID-19 in March, on June 15, it revoked the authorization, citing ineffectiveness and serious side effects.

While there is anecdotal evidence to support the use of these medications, subsequent studies have not shown the same benefits. A second French study followed the same protocol as the original study but found that hydroxychloroquine did not significantly improve symptoms or decrease the clearance of the virus from the body. Multiple other studies have shown hydroxychloroquine not to be more effective than placebo when treating people who had COVID-19.    In September 2020, a double-blind placebo-controlled randomized clinical trial in JAMA Internal Medicine concluded that hydroxychloroquine was ineffective in preventing infection in 132 healthcare workers.

More concerning are the potential side effects from these medications. A Brazilian study had to be discontinued early due to complications from high-doses of chloroquine. A JAMA study showed that treatment with hydroxychloroquine prolonged the QT interval in more than 20% of COVID-19 patients, a finding on an electrocardiogram (ECG) that can be associated with the development of life-threatening cardiac arrhythmias.

Not all reports are bad. A study has been released that shows potential benefits for hydroxychloroquine in the treatment of COVID-19. Researchers studied over 2500 adults and found that people treated with the drug had a mortality of 14% compared to 26% without it. When hydroxychloroquine was combined with azithromycin, mortality was 20%. There is controversy over the study, however, because the number of people treated with the steroid dexamethasone was considerably higher in the treatment groups, suggesting that the benefit may derive from the steroid rather than hydroxychloroquine or azithromycin. While 68% of all study participants were treated with steroids, only 35% in the non-treatment group received dexamethasone. Approximately 79% in the hydroxychloroquine group and 74% in the combined hydroxychloroquine with azithromycin group had also received steroids.


Dexamethasone is a steroid that is often used to treat inflammation. It comes in both oral and IV formulations. COVID-19 has been associated with a severe inflammatory reaction in many cases, and researchers looked to investigate the benefits of using this common anti-inflammatory drug.

What the Research Says

The RECOVERY trial (Randomised Evaluation of COVid-19 thERapY) trial) has found that treatment with once-daily dexamethasone over 10 days improved clinical outcomes when compared to placebo. Specifically, mortality rates decreased from 41% to 29% for patients who were placed on ventilators and from 26% to 23% for people requiring oxygen without ventilator therapy. Patients who did not require oxygen or ventilator therapy did not see a clinical benefit from dexamethasone.

A meta-analysis sponsored by the World Health organization (WHO) reviewed 7 randomized clinical trials including approximately 1700 critically-ill COVID-19 patients. Published in JAMA, the study found that the 28-day mortality rate was significantly lower for people treated with steroids (dexamethasone, hydrocortisone, or methylprednisolone) than for those treated with usual care or placebo (32% absolute mortality for steroids vs. 40% for controls).

Glucocorticoids have shown benefits when used in combination with tocilizumab (see Biologics section below). A study in the Annals of the Rheumatic Diseases assessed patients with COVID-19 who also had cytokine storm, a syndrome of overactive inflammation in the body. Patients who had COVID-19 and cytokine storm were treated with a high-dose glucocorticoid, methylprednisolone, for five days. If they did not start to have clinical improvement within two days, they also received a dose of IV tocilizumab. When compared to people treated with supportive care, the treatment group was 79% more likely to have clinical improvement in respiratory symptoms over 7 days, 65% less likely to die in the hospital, and 71% less likely to need mechanical ventilation.


There are a number of antiviral treatments—medications that prevent a virus's ability to reproduce—being investigated for COVID-19 at this time.

  • Remdesivir was initially developed as a treatment against Ebola. After in vitro studies showed it may be effective against COVID-19, compassionate use requests allowed hospitals to access the drug for the treatment of severely ill patients. Gilead Sciences, who produces the drug, began looking into expanding use to allow more people access to the medication. On May 1, it became the first treatment option for COVID-19 to receive emergency use authorization from the FDA. The FDA has permitted it to be used in adults and children hospitalized with severe cases of the disease.
  • What the research says: A study published in the New England Journal of Medicine looked at 61 compassionate use cases of remdesivir treatment among hospitalized COVID-19 patients. These patients were severely ill; at the start of the study, 30 were on mechanical ventilation and four were on extracorporeal membrane oxygenation (ECMO). Over an average of 18 days, 68% of patients had improved oxygenation and 57% of the people on ventilators were able to be extubated. However, as many as 60% had side effects, and 23% of people (all in the mechanical ventilation group) developed severe complications, including multiple-organ-dysfunction syndrome, septic shock, acute kidney injury, and hypotension. A clinical trial—the Adaptive COVID-19 Treatment Trial (ACTT)—by the National Institutes of Health (NIH)—showed that people with severe COVID-19 infections treated with the drug had improvement in symptoms 4 days sooner (31% faster) than those who were not treated. Although there appeared to be an improvement in the overall survival rate, this was not statistically significant. People with moderate infections, however, did not show significant improvement when treated with 10 days of remdesivir vs. standard care. Although there were improvements for people treated with 5 days of remdesivir treatment, the researchers noted that "the difference was of uncertain clinical importance." Additional remdesivir studies are currently underway to assess effectiveness and clinical safety.
  • Favipiravir and arbidol are antiviral medications used to treat influenza. In high concentrations, they may be effective against COVID-19.
  • What the research says: In a study of 240 COVID-19 patients, researchers compared favipiravir effectiveness to arbidol. Symptoms of cough and fever improved much quicker with favipiravir than with arbidol, but there was no significant difference in the recovery rate by day seven. Both medications were well-tolerated with only mild side effects. Favipiravir continues to be investigated in other studies.
  • Lopinavir-ritonavir is a pair of antiviral medications used to treat HIV that may be effective against COVID-19.
  • What the research says: In a study of 199 people with pneumonia from COVID-19 and low oxygen levels, 94 were given lopinavir-ritonavir and the rest were given a placebo. Although more people treated with lopinavir-ritonavir had improved symptoms by day 14, (45.5% vs. 30%), there was no significant difference between the two groups when it came to the duration of oxygen therapy, the need for mechanical ventilation, the length of hospitalization, or mortality rate. Another study randomized 127 hospitalized adults with COVID-19 to either triple therapy with lopinavir-ritonavir, ribavirin, and interferon β-1b or to lopinavir-ritonavir alone. Patients in the triple therapy group stopped shedding the virus sooner (7 days vs. 12 days), had earlier improvement in symptoms (4 days vs. 8 days), and left the hospital sooner (9 days vs. 15 days). Other studies continue to explore the potential of this therapy.


Severe cases of COVID-19 have been associated with what is called a cytokine storm. As part of the normal immune response, the body recruits cytokines—proteins secreted by immune system cells—to the site of infection. In some cases, however, that process becomes hyperresponsive and excess cytokines are released. Some of these cytokines are inflammatory in nature and can lead to worsening of respiratory symptoms or organ failure. Biologic agents—pharmaceutical treatments created from biological sources—are now being considered to address this.

  • Baricitinib is a JAK1/JAK2 inhibitor, a class of medications used to inflammation by decreasing the effect of certain cytokines.
  • What the research says: As part of the Adaptive COVID-19 Treatment Trial (ACTT-2), a Phase III randomized double-blind placebo-controlled trial has shown early promise for the drug. Approximately 1,000 patients hospitalized with COVID-19 were randomized to receive remdesivir alone or remdesivir with baricitinib. On average, patients clinically improved one day earlier with the combination treatment. The results were announced in a press release by Ely Lilly and Company but have not yet been peer-reviewed in a medical journal.
  • Tocilizumab is a medication that blocks cell receptors from binding to interleukin-6 (IL-6), one of the pro-inflammatory cytokines. This, in theory, would help to decrease the severity of the cytokine storm and help people to recover faster.
  • What the research says: A case study of a patient with COVID-19 and underlying multiple myeloma noted high serum levels of IL-6. The patient was treated with conventional therapies (antivirals and steroids) and then received tocilizumab on day nine of his hospitalization. He had symptom improvement by day 12 and his IL-6 levels improved before he was discharged home. A study in Lancet Rheumatology found 39% decreased risk for ventilator use or death in COVID-19 pneumonia patients who were treated with tocilizumab when compared to those treated with standard therapy. However, tocilizumab acts as an immunosuppressant and the researchers found that those treated with the drug also had a 3-fold increase in developing other new infections like invasive aspergillosis. According to a study of 154 patients in Clinical Infectious Diseases, tocilizumab decreased the mortality rate in COVID-19 patients who required a ventilator by 45% when compared to those not treated with the drug. Although those treated with tociluzumab were more likely to develop superinfections (54% vs. 26%) over a follow-up of 47 days, they did not have increased death as a result of those superinfections.

Convalescent Plasma and Plasma Exchange

Medications are one way to target COVID-19, but our own bodies may offer a way to combat the disease too. When we are exposed to a foreign substance like COVID-19, our immune system can develop antibodies against it. Blood that contains these antibodies is referred to as convalescent plasma.

Removing blood plasma from someone who is ill and replacing it with convalescent plasma from someone who has recovered from COVID-19 may help them fight the infection. This process is known as plasma exchange.

Convalescent plasma can be collected like a blood donation, and techniques are performed to assure the plasma is free of infection. It is currently recommended that someone be symptom-free for at least two weeks before donating plasma.

What the Research Says

Two small Chinese studies showed the potential benefit of using plasma exchange for treating severe cases of infection.

  1. One case series included five patients with severe pneumonia requiring mechanical ventilation
  2. A pilot study included 10 patients with severe COVID-19 infections

All patients underwent transfusion with convalescent plasma. Both studies noted improved symptoms within three days and decreased viral load within two weeks (12 days for the case series, seven days for the pilot study). The ability to wean off a ventilator was slow, however, and was not achieved for all patients. Most importantly, there seemed to be no harm caused by the treatment.

In April 2020, the FDA approved two randomized, placebo-controlled clinical trials at Johns Hopkins Medicine to see if blood plasma can help to prevent COVID-19 infection, not just treat those who are severely infected. A study in Mayo Clinic Proceedings noted that not only was convalescent generally safe when used to treat 20,000 hospitalized COVID-19 patients, it may be associated with decreased mortality, especially when administered earlier in the course of the illness.

The largest trial to date treated more than 35,000 hospitalized patients with convalescent plasma. The findings suggested that treatment with plasma that had higher antibody levels lowered mortality if given within 3 days of the diagnosis. Without more robust data (there was no placebo and the study has not yet been peer reviewed), there has been controversy about the FDA’s emergency authorization for convalescent plasma as a treatment for COVID-19.

The studies are complicated by the fact that patients in these studies also received other therapies, like antiviral medications and steroids. Without standardized controls, it can be hard to know if the convalescent plasma or one of those other therapies led to the actual clinical improvements. More robust trials need to be performed to determine the optimal concentration of the convalescent plasma and timing of the plasma exchange to see if this can be a viable treatment for patients.

Dozens of U.S. hospitals are now a part of the National COVID-19 Convalescent Plasma Project, working together to investigate therapeutic plasma exchange.

Synthetic Antibodies

Our bodies make antibodies but pharmaceutical companies are also looking to explore the effectiveness of synthetic antibodies made in the laboratory. It is proposed that giving these antibodies early in the disease course may help to jump start the immune response.

Regeneron Pharmaceuticals, Inc. is reportedly in clinical trials with a man-made antibiotic cocktail called REGN-COV2. The investigational treatment includes two antibodies targeted against COVID-19. The company announced preliminary data suggesting that viral loads and COVID-19 symptoms were reduced within 7 days of treatment. However, they did not release the actual data and it is unclear how the much the treatment improved clinical outcomes, if it decreased mortality, or if it is even safe to use. This data has yet to be published in a medical journal and has not been peer reviewed.

President Donald Trump, who reported positive COVID-19 test results on October 1, was treated with REGN-COV2 on October 2, 2020.

Vaccines for COVID-19

The best hope for managing COVID-19 long-term is to develop a vaccine. Vaccines expose your body to an antigen—a substance that cause an immune response, in this case from a virus—and trigger antibody production from your immune system. The goal is to make antibodies against the virus without causing an infection. That way, if you are exposed to that antigen again (if, say, COVID-19 resurges in the fall), your body will remember how to make those antibodies against it. Hopefully, your immune response will be so strong you won't get sick at all. But if you do get sick, your symptoms will be milder than if you did not get the vaccine.

What the Research Says

An initial study looked to develop a vaccine by targeting the coronavirus spike (S) protein, a structural component of the virus. Researchers were able to generate an immune response to COVID-19 in rodents, and antibodies were produced within two weeks. This is promising as we turn to clinical trials in humans.

To date, there are four major vaccine candidates undergoing clinical trials in the United States.

AstraZeneca — Vaccine Candidate AZD1222

Partnered with AstraZeneca, Oxford University's Jenner Institute has surged ahead in vaccine research. Because its vaccine for a different type of coronavirus showed promise in smaller human trials last year, the Jenner Institute was able to move forward quickly. After a first injection of their adenovirus-vectored vaccine, neutralizing antibodies developed in 91% of the 35 study participants who received the vaccine, peaked at 28 days, and remained high over 56 days. With a booster vaccine at 4 weeks, neutralizing antibodies were found in all participants. Their vaccine also had a T-cell response noted after 7 days, peaking at 14 days, and lasting up to 56 days. The vaccine temporarily halted its Phase III trial in September 2020 after a participant developed transverse myelitis, a neurologic condition that can be triggered by viruses. An investigation is underway to see if this was an incidental finding or a complication from the vaccine itself. That individual has since recovered from the condition. British regulators have resumed the trial but a decision to continue the trial in the United States remains under review by the FDA.

INOVIO Pharmaceuticals, Inc. — Vaccine Candidate INO-4800

The Coalition for Epidemic Preparedness Innovations and the Bill and Melinda Gates Foundation are among the multiple funding sources for this vaccine candidate. The first injections of this DNA vaccine developed by INOVIO Pharmaceuticals, Inc. were administered to healthy subjects on April 6, 2020. In September 2020, the FDA put Phase II/III clinical trials on hold as it evaluates the safety of its delivery device which injects DNA into cells. A decision on whether to continue clinical trials will be made by November.

Johnson and Johnson — Vaccine Candidate Ad26.COV2.S

This vaccine is being developed by Janssen Pharmaceutical Companies, a division of Johnson and Johnson. It is an adenovirus-vector vaccine that attacks the spike protein expressed by SARS-CoV-2. A study in 52 rhesus macaque monkeys found that a single injection triggered a neutralizing antibody response with protection against the virus. A Phase I/II trial of 56 adults assessed for safety using a single dose or two-dose schedule. Common side effects included fever, headache, muscle aches, and injection site pain. After one dose, seroconversion (development of antibodies against the spike protein) was 99% and the T-cell response against the spike protein reached 83%. With encouraging results to date, the FDA has approved the Janssen vaccine for Phase III clinical trials. The vaccine shows promise as it is the only current candidate that would require a single dose as opposed to two doses in series.

Moderna, Inc. — Vaccine Candidate mRNA-1273

The National Institute of Allergy and Infectious Diseases (NIAID) is funding a trial. It is based on a RNA vaccine co-developed by the NIAID and the biotechnology company Moderna Inc. In July 2020, Moderna published preliminary results from its Phase I vaccine trial in the New England Journal of Medicine. After two doses of the mRNA vaccine, administered 4 weeks apart, the 45 study participants developed neutralizing antibodies in concentrations comparable to those seen in convalescent plasma. A subsequent Phase II trial in has shown promising results in monkeys. Twenty-four rhesus macaques were treated with vaccine or placebo and received two injections 4 weeks apart. They were then directly exposed to high doses of COVID-19. After 2 days, only 1 in 8 of the vaccinated monkeys had detectable virus while all monkeys treated with placebo had the infection. Again, neutralizing activity was significantly higher than that seen with convalescent serum. They also detected a CD4 T-cell response against the spike protein.

A Word from Verywell

It is important to offer hope in this time of uncertainty, but it is also imperative that we find objective, scientifically-proven ways to protect ourselves. With hundreds of clinical trials in the works, we must stay vigilant when it comes to vetting what works and what does not. Treatments need to be proven safe and effective before we use them to treat large parts of the population.

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