COVID-19 Treatments: What You Need to Know

Learn about the clinical evidence behind different 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.

Mature man taking a vaccine from his doctor
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There are hundreds of clinical trials underway evaluating the potential effectiveness of existing drugs, new drugs, and testing the viability of vaccines and blood products. The following outlines a list of high-profile treatments that have been tested against the virus, starting with those currently in clinical use to those still undergoing investigation.

As of December 2020, seven treatments have emergency use authorization from the U.S. Food and Drug Administration (FDA), in order of approval: remdesivir (May 2020), convalescent plasma (August 2020), bamlanivimab monoclonal antibody (November 2020), baricitinib combined with remdesivir (November 2020), combined casirivimab and imdevimab monoclonal antibodies (November 2020), the Pfizer-BioNTech mRNA vaccine (December 2020), and the Moderna mRNA vaccine (December 2020).

Remdesivir

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. 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. On October 22, remdesivir became the first drug approved by the FDA to treat COVID-19 without an emergency use authorization. On November 19, it was also approved for a new EUA when used in combination with baricitinib (see Biologics below).

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."

Data released by the drug manufacturer Gilead Sciences noted improved clinical outcomes in a randomized-control trial. People hospitalized with COVID-19 were treated with remdesivir (n=541) or placebo (n=521) for 10 days. People in the treatment group recovered five days sooner than those in the control group, needed fewer days of oxygen support, and were more likely to be discharged sooner.

In contrast, the World Health Organization (WHO) found no clinical benefit in their Solidarity trial. This study included nearly 11,300 hospitalized people with COVID-19 across 30 countries. Study participants received one of four treatments: hydroxychloroquine, interferon, lopinavir-ritanovir, or remdesivir. None of the treatments decreased the mortality rate over 28 days or the need to start ventilator therapy. Since that tine, WHO has formally advised against using the drug for hospitalized patients. Gilead Sciences has challenged these results, and a peer review is pending.

Dexamethasone

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. Another study, this one in Chest, confirmed the benefit of combined therapy finding in 5,776 patients hospitalized with COVID-19. Corticosteroids decreased mortality by 34% but the mortality rate decreased by 56% when they were combined with tocilizumab.

Convalescent Plasma

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 convalescent plasma for treating severe cases of infection. One case series included five patients with severe pneumonia requiring mechanical ventilation. A separate 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 went on to approve two randomized, placebo-controlled clinical trials at Johns Hopkins Medicine to see if blood plasma could help to prevent COVID-19 infection, not just treat those who are severely infected.

Results have been varied. On a positive note, a study in Mayo Clinic Proceedings noted that not only was convalescent plasma 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 high antibody levels lowered mortality if given within 3 days of the diagnosis. An Argentinian study of 160 COVID-19 patients found treating seniors 65 and older within 3 days of mild symptoms decreased their risk of progressing to severe respiratory disease by half (16% with treatment vs. 31% with placebo) over 15 days. While mortality was not assessed in the study, the researchers estimated only seven seniors would need to be treated to decrease severe illness in one adult.

Not all research has been as favorable. A study of nearly 500 adults in India noted that while convalescent plasma reduced viral loads within 7 days, there was no decrease in mortality rates. A randomized-controlled Argentinian study including 228 adults with COVID-19 pneumonia found no clinical benefit for those treated with convalescent plasma over 30 days.

Without more consistent or robust data, there has been controversy about the FDA’s emergency authorization for convalescent plasma as a treatment for COVID-19 in August 2020.

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.

Eli Lilly —Bamlanivimab

Sponsored in part by the National Institute of Allergy and Infectious Diseases, Eli Lilly and Company has developed a monoclonal antibody (initially known as LY-CoV555, since named bamlanivimab) intended to neutralize COVID-19. Phase 2 clinical trials treated 452 people with 3 doses each. Although viral loads were decreased after the second dose, the treatment and placebo groups had similar viral loads after the third dose. Treatment did, however, decrease the severity of symptoms from days 2 through 6 and decreased the number of people of people who remained in the hospital on day 29 (1.6% vs. 6.3%). Research progressed to Phase 3 clinical trials and combination treatment with remdesivir in the ACTIV-3- trial. On October 13, however, unspecified safety concerns were raised about the treatment and the trial was put on hold for hospitalized patients.

On November 9, the FDA issued an emergency use authorization for this treatment for high-risk people who have mild to moderate COVID-19, who are not hospitalized, and who are not requiring oxygen therapy because of their COVID-19 infection.

In December, a study of 314 people with mild-to-moderate COVID-19 was published in New England Journal of Medicine. All study participants were treated with remdesivir, and if appropriate, oxygen and/or dexamethasone. They were then randomized to received bamlanivimab or placebo. The researchers noted that people treated with the neutralizing antibody did not have improved respiratory symptoms by day 5. The study stopped recruiting due to a lack of effect.

Regeneron Pharmaceuticals —Casirivimab and Imdevimab (formerly REGN-COV2)

Regeneron Pharmaceuticals Inc. is reportedly in clinical trials with a man-made antibiotic cocktail initially called REGN-COV2, now known as casirivimab and imdevimab. 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. The company has since added 524 people to their trial, finding that REGN-COV2 also decreased the need for COVID-related medical visits by day 29 when compared to people who were treated with placebo (2.8% vs. 6.8%). The trials have since been put on hold for people who required high-flow oxygen or mechanical ventilation based on "an unfavorable risk/benefit profile" in these groups. President Donald Trump, who reported positive COVID-19 test results on October 1, was treated with REGN-COV2 on October 2, 2020.

On November 21, the FDA granted emergency use authorization for the antibody cocktail for people with COVID-19 with mild to moderate disease who are at high risk for complications, who are not hospitalized, and who do not require supplemental oxygen. The National Institutes of Health, however, states that this treatment should not be standard of care since there is "insufficient data to recommend either for or against the use of casirivimab plus imdevimab for the treatment of outpatients with mild to moderate COVID-19".

AstraZeneca —AZD7442

AstraZeneca will initiate Phase 3 clinical trials to find out if investigation antibodies (AZD7442) could treat and hopefully prevent COVID-19 infection. Preclinical studies showed effectiveness in mice. It is not yet being using clinically.

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, 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.

Six major vaccine candidates have undergone clinical trials in the United States.

Pfizer Inc. —Vaccine Candidate BNT162b2

In November 2020, early data from a Phase III trial suggested an mRNA-vectored vaccine developed by Pfizer and BioNTech may be 90% effective in preventing COVID-19. The vaccine is administered in a two dose series, three weeks apart. When looking at infection rates 7 days after a second dose, 94 people contracted COVID-19 from a study population of 43,538 people (30% were people of color). This put their vaccine at more than 90% efficacy. They released additional data 9 days later on November 18, noting that 170 cases of COVID-19 had occurred in trial participants, 8 cases in those who took the vaccine and 162 in people who took the placebo. This improved their data to show a 95% efficacy rate overall, a 94% efficacy rate in people over 65 years old. After reviewing that data, the FDA released a December briefing that noted a decrease in infection rates for vaccinated study participants as early as 10 to 14 days after their first dose. Peer-review data is pending for all of the above, and more long-term data may be needed to assure safety.

The results are promising but concerns are raised about the need to store the vaccine using cold chain technology, i.e., freezing it at -70 degrees Celsius (-94 degrees Fahrenheit). This could lead to logistical challenges in maintaining the viability of the vaccine before it is administered. Pfizer, however, reports that special temperature-controlled containers using dry ice were developed with GPS-thermal tracking to assure the vaccine is maintained at proper temperatures during shipping.

The vaccine was approved for use in the United Kingdom on December 2. On December 8, 90-year-old Margaret Keenan from the UK was the first non-study participant in the world to receive the vaccine. On December 11, the FDA granted emergency use authorization in the United States and the first Americans were vaccinated on December 14.

Controversy: With increasing spread of COVID-19, the United Kingdom announced plans to administer vaccine doses 12 weeks apart rather than the recommended 3 weeks. While this would increase the number of people to receive a first dose of the vaccine, Pfizer and BioNTech have stated that their clinical trials do not have the data to support the effectiveness of such a dosing schedule. At the present time, the United States will continue with the recommended three week dosing schedule.

Moderna Inc. — Vaccine Candidate mRNA-1273

Funded by the National Institute of Allergy and Infectious Diseases (NIAID) and the Biomedical Advanced Research and Development Authority (BARDA), Moderna published preliminary results from its Phase I vaccine trial in the New England Journal of Medicine in July 2020. 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 showed 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.

In November 2020, data from their Phase III trial showed the Moderna vaccine to be 94.5% against the COVID-10. When looking at infection rates 2 weeks after a second dose, 95 people contracted COVID-19 from a study population of more than 30,000 people that included more than 7,000 people over 65 years of age and more than 11,000 people of color. As much as 42% of the population had high-risk conditions such as diabetes, heart disease, or obesity. Of those who contracted the disease, 11 cases were listed as severe but none of those had received the vaccine. In December, they released additional data, noting that 196 cases of infection had occurred in trial participants, 11 cases in those who took the vaccine (none had severe COVID-19) and 185 in people who took the placebo. This suggested 94.1% efficacy for COVID-19 at large and 100% efficacy against severe disease. Peer review of the data is pending.

Importantly, Moderna has also published data about the expected duration of the vaccine response. A Phase I trial assessed 34 people who received 2 doses of the vaccine 28 days apart and compared their antibody response with 41 controls recovering from COVID-19. The researchers found that neutralizing antibodies persisted 90 days after the second dose of vaccine and at higher concentrations than those who actually had the disease. This offers hope that the vaccine may offer a reasonable period of immunity. More long-term data is needed to determine the true duration of the immune response.

Unlike the Pfizer vaccine which requires cold chain technology, the Moderna vaccine can be stored in standard freezers at -4 degrees Celsius (-20 degrees Fahrenheit) for six months, normal refrigerator temperatures for 30 days, and room temperature for 12 hours. Of note, Moderna is now planning trials for children as young as 12 years old.

The FDA granted the Moderna vaccine emergency use authorization on December 18, 2020. The first doses were administered on December 21. The UK approved this vaccine for use on January 8, 2021.

Controversy: The FDA is considering decreasing the dose of the Moderna vaccine to increase the available supply and the number of people who can be vaccinated with a first dose. Data from Phase II trials show that half doses of the vaccine offered the same level of immunity as full doses for people up to 55 years old. However, that data included hundreds of people and comes from trials aimed to determine if there was an immune response to the vaccine, i.e., did antibodies develop. The Phase III trials were the ones ones that actually assessed the effectiveness against COVID-19. The full vaccine dose was used in those latter studies.

AstraZeneca — Vaccine Candidate AZD1222 (previously ChAdOx1)

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. After determining that the illness was not associated with the vaccine, AstraZeneca resumed its trial after 6 weeks.

In November, more peer-reviewed Phase II/III data was published. With an increase to 560 study participants, 99% of people developed neutralizing antibodies within 2 weeks of the booster dose. In December, AstraZeneca published peer-reviewed data on more than 11,000 study participants across two different study trials. The vaccine efficacy rate was 62% after two full dose vaccines were administered a month apart (n=8,895) and 90% when given a half dose followed by a full dose a month later (n=2,741), for a combined efficacy rate of 70.4%. The company is looking into the latter regimen for obvious reasons. Not only is the efficacy rate higher but more people could be vaccinated given the use of half doses.

Unlike the mRNA vaccines, the vaccine does not need to be frozen and can be stored at normal refrigerated temperatures.

The vaccine was approved for use in the United Kingdom on December 30, 2020. The first doses were administered on January 4, 2021.

Controversy: Similar to the Pfizer vaccine, the United Kingdom has announced a change to the dosing schedule of the AstraZeneca vaccine from 4 weeks to 12 weeks between doses. Available data suggests that there is similar efficacy when administered at this frequency for people who received the full dose of the vaccine.

Johnson & 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-vectored 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%. The vaccine shows promise as it is the only current candidate that would require a single dose as opposed to two doses in series.

In October 2020, Johnson & Johnson reported an unexplained illness in one of their study participants. The company paused their clinical trial for 11 days until it was assured that the illness was not related to the vaccine. Their Phase III trial has since recruited approximately 45,000 people.

Since then, more Phase I/II data has been published, showing a neutralizing antibody response in two different age groups, ages 18 to 55 and ages 65 and older. They also compared different dosing regimens, e.g., high dose vs. low dose and single dose vs. two doses 56 days apart. Altogether, 805 participants were vaccinated. By day 29, an average of 90% of people had neutralizing antibodies (92-99% for the younger cohort, 88-96% for the older cohort depending on the dosing regimen). By day 57, seroconversion was 100% for everyone regardless of age or dosing regimen.

Novavax Inc. — Vaccine Candidate NVX-CoV2373

Sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) and the Biomedical Advanced Research and Development Authority (BARDA), this vaccine uses nanoparticle technology to develop an antibody response against the spike protein. Like many of the other vaccines, it is administered in two doses 21 days apart. Phase I/II clinical trials have shown an antibody response that is greater than that seen in convalescent plasma from patients who were symptomatic with COVID-19. A Phase III trial is actively enrolling with an aim for 30,000 study participants, two-thirds of whom will receive the vaccine, the rest placebo.

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. The company expects to resume trials in the second quarter of 2021.

Biologics

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. In November 2020, the FDA approved the drug combination (not baricitinib alone) for an emergency use authorization for treatment of hospitalized patients who required oxygen supplementation, ventilator treatment, or extracorporeal membrane oxygenation (ECMO). The National Institutes of Health, however, has stated that there is not enough evidence to support this regimen as a preferred treatment when dexamethasone is available.
  • Interferons are a natural part of your immune system. These cytokines boost the immune response to viruses. Currently, interferons are injected one treatment used for viral hepatitis.
  • What the research says: Since COVID-19 is a pulmonary condition in most cases, researchers looked to see if breathing interferon beta-1a into the lungs could help to boost the immune response against the virus. A Phase 2 randomized double-blinded clinical trial in The Lancet Respiratory Medicine looked at approximately 100 adults hospitalized with COVID-19. Participants were treated with inhaled interferon beta-1a via nebulizer or placebo for 14 days. The interferon group had twice the clinical improvement after 15 to 16 days and three times the improvement at day 28. While the length of a hospital stay did not decrease, there was a 79% decrease in the severity of disease or dying.
  • Tocilizumab is a monoclonal antibody 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 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. Three studies were published in JAMA Internal Medicine in October 2020 but the results were inconsistent. An American study treated 433 people with severe COVID-19 within two days of their admission into an intensive care unit. Their mortality rate was 29% compared to 41% for ICU patients who did not receive tocilizumab. French and Italian studies, however, did not find a clinical benefit in their randomized open-label trials for people with COVID-19 pneumonia. The former study looked at 130 people with moderate-to-severe disease and the latter at 126 people. They found no difference in the mortality rate at 28 days or symptom improvement with treatment after 14 days, respectively.  Another study in New England Journal of Medicine looked at nearly 400 people who had COVID-19 pneumonia.Those treated with tocilizumab were less likely to need mechanical ventilation by day 28 (12% vs. 19% when compared to standard care). Although clinical outcomes were improved, mortality rates did not significantly change.

Other Antivirals

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

  • 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.

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. The same holds true for people who regularly take hydroxychloroquine to treat rheumatologic diseases. Another study showed taking hydroxychloroquine did not decrease their risk for contracting COVID-19 when compared to people not taking the drug.

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.

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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  1. Wang, M., Cao, R., Zhang, L. et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitroCell Res 30, 269–271 (2020). doi:10.1038/s41422-020-0282-0

  2. U.S. Food and Drug Administration. Coronavirus (COVID-19) Update: FDA Issues Emergency Use Authorization for Potential COVID-19 Treatment. May 1, 2020.

  3. Grein J, Ohmagari N, Shin D, et al. Compassionate Use of Remdesivir for Patients with Severe Covid-19. NEJM. 2020 April 10. doi:10.1056/NEJMoa2007016

  4. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of Covid-19 — Preliminary Report. NEJM. Published online May 22, 2020. doi:10.1056/NEJMoa2007764

  5. Spinner CD, Gottlieb RL, Criner GJ, et al. Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19: A Randomized Clinical Trial. JAMA. Published online August 21, 2020. doi:10.1001/jama.2020.16349

  6. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of Covid-19 - Final Report. N Engl J Med. Published online October 8, 2020. doi:10.1056/NEJMoa2007764

  7. Rochwerg B, Agoritsas T, Lamontagne F, et al. A living WHO guideline on drugs for covid-19BMJ. Published online September 4, 2020. doi:10.1136/bmj.m3379

  8. Pan H, Peto R, et al. Repurposed antiviral drugs for COVID-19; interim WHO SOLIDARITY trial results. Published online October 15, 2020. medRxiv 2020.10.15.20209817; doi:10.1101/2020.10.15.20209817

  9. Horby P, Lim WS, Emberson JR, et al. Dexamethasone in Hospitalized Patients with COVID-19 - Preliminary Report. N Engl J Med. 2020 Jul. doi:10.1056/NEJMoa2021436

  10. Sterne JAC, Murthy S, Diaz JV, et al. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis. JAMA. Published online September 2, 2020. doi:10.1001/jama.2020.17023

  11. Ramiro S, Mostard RLM, Magro-Checa C, et al. Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study [published July 20, 2020]. Ann Rheum Dis. doi:10.1136/annrheumdis-2020-218479

  12. Narain S, Stefanov DG, Chau AS, et al. Comparative survival analysis of immunomodulatory therapy for coronavirus disease 2019 cytokine stormChest. Published online October 2020. doi:10.1016/j.chest.2020.09.275

  13. Roback JD, Guarner J. Convalescent Plasma to Treat COVID-19 Possibilities and Challenges. JAMA. Published online March 27, 2020. doi:10.1001/jama.2020.4940

  14. Shen C, Wang Z, Zhao F, et al. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. Published online March 27, 2020. doi:10.1001/jama.2020.4783

  15. Duan K, Liu B, Li C. The feasibility of convalescent plasma therapy in severe COVID-19 patients: a pilot study. Proceedings of the National Academy of Sciences Apr 2020, 202004168; doi:10.1073/pnas.2004168117

  16. Joyner MJ et al. Safety Update: COVID-19 Convalescent Plasma in 20,000 Hospitalized Patients. Mayo Clin Proc. 2020. 95(x):xx-xx.

  17. Joyner MJ, Senefeld JW, Klassen SA, et al. Effect of Convalescent Plasma on Mortality among Hospitalized Patients with COVID-19: Initial Three-Month Experience. medRxiv 2020.08.12.20169359; doi:10.1101/2020.08.12.20169359

  18. Libster R, Pérez Marc G, Wappner D, et al. Early high-titer plasma therapy to prevent severe covid-19 in older adultsN Engl J Med. Published online January 6, 2021. doi:10.1056/NEJMoa2033700

  19. Agarwal A, Mukherjee A, Gunjan Kumar G, et al. Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial). BMJ. Published online October 22, 2020. doi:10.1136/bmj.m3939

  20. Simonovich VA, Burgos Pratx LD, Scibona P, et al. A randomized trial of convalescent plasma in covid-19 severe pneumoniaN Engl J Med. Published online November 24, 2020. doi:10.1056/NEJMoa2031304

  21. Chen P, Nirula A, Heller B, et al. SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19. NEJM. Published online October 28, 2020. doi:10.1056/NEJMoa2029849

  22. ACTIV-3/TICO LY-CoV555 Study Group. A neutralizing monoclonal antibody for hospitalized patients with covid-19N Engl J Med. Published online December 22, 2020. doi:10.1056/NEJMoa2033130

  23. Regeneron Pharmaceuticals Inc. Regeneron's REGN-COV2 Antibody Cocktail Reduced Viral Levels and Improved Symptoms in Non-Hospitalized COVID-19 Patients. September 29, 2020.

  24. Regeneron. Regeneron’s COVID-19 Outpatient Trial Prospectively Demonstrates that REGN-COV2 Antibody Cocktail Significantly Reduced Virus Levels and Need for Further medical Attention. October 28, 2020.

  25. Zost SJ et al. Potently neutralizing human antibodies that block SARS-CoV-2 receptor binding and protect animalsNature. 2020. doi:10.1038/s41586-020-2548-6

  26. Jackson LA et al. An mRNA Vaccine against SARS-CoV-2 — Preliminary Report. N Engl J Med. 2020 Jul. doi:10.1056/NEJMoa2022483

  27. Corbett KS, Flynn B, Foulds KE, et al. Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates. NEJM. July 28, 2020. doi:10.1056/NEJMoa2024671

  28. Widge AT, Rouphael NG, Jackson LA, et al. Durability of Responses after SARS-CoV-2 mRNA-1273 VaccinationN Engl J Med. Published online December 3, 2020. doi:10.1056/NEJMc2032195

  29. Folegatti PM et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet. 2020 Jul. doi:10.1016/S0140-6736(20)31604-4

  30. Ramasamy MN, Minassian AM, Ewer KJ et al. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial. Lancet. Published online November 18, 2020. doi:10.1016/S0140-6736(20)32466-1

  31. Voysey M, Clemens SAC, Madhi SA, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (Azd1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UKThe Lancet. Published online December 2020. doi:10.1016/S0140-6736(20)32661-1

  32. Mercado, N.B., Zahn, R., Wegmann, F. et al. Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaquesNature (2020). Published online July 30, 2020. doi:10.1038/s41586-020-2607-z

  33. Sadoff J, LeGars M, Shukarev G, et. al. Safety and immunogenicity of the Ad26.COV2.S COVID-19 vaccine candidate: interim results of a phase 1/2a, double-blind, randomized, placebo-controlled trial. medRxiv 2020.09.23.20199604; Published online September 25, 2020. doi:10.1101/2020.09.23.20199604

  34. Sadoff J, Le Gars M, Shukarev G, et al. Interim Results of a Phase 1–2a Trial of Ad26.COV2.S
    Covid-19 Vaccine
    . N Engl J Med. Published online January 13, 2021. doi:10.1056/NEJMoa2034201

  35. Keech C, Albert G, Cho I, et al. Phase 1–2 trial of a sars-cov-2 recombinant spike protein nanoparticle vaccineN Engl J Med. 2020. doi:10.1056/NEJMoa2026920

  36. INOVIO Pharmaceuticals, Inc. INOVIO Reports FDA Partial Clinical Hold for Planned Phase 2 / 3 Trial of COVID-19 Vaccine Candidate INO-4800. September 28, 2020.

  37. Kalil AC, Patterson TF, Mehta AK, et al. Baricitinib plus remdesivir for hospitalized adults with covid-19N Engl J Med. Published online December 11, 2020. doi:10.1056/NEJMoa2031994

  38. Monk PD, Marsden RJ, Tear VJ, et al. Safety and efficacy of inhaled nebulised interferon beta-1a (Sng001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trialLancet Respiratory Medicine. Published online November 2020. doi:10.1016/S2213-2600(20)30511-7

  39. Guaraldi et al. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. Lancet Rheumatology. Published:June 24, 2020. doi:10.1016/S2665-9913(20)30173-9

  40. Somers EC et al. Tocilizumab for treatment of mechanically ventilated patients with COVID-19. Clin Infect Dis. 2020 Jul. doi:10.1093/cid/ciaa954

  41. Gupta S, Wang W, Hayek SS, et al. Association between early treatment with tocilizumab and mortality among critically ill patients with covid-19JAMA Intern Med. Published online October 20, 2020. doi:10.1001/jamainternmed.2020.6252

  42. Hermine O, Mariette X, Tharaux P-L, et al. Effect of tocilizumab vs usual care in adults hospitalized with covid-19 and moderate or severe pneumonia: a randomized clinical trialJAMA Intern Med. Published online October 20, 2020. doi:10.1001/jamainternmed.2020.6820

  43. Salvarani C, Dolci G, Massari M, et al. Effect of tocilizumab vs standard care on clinical worsening in patients hospitalized with covid-19 pneumonia: a randomized clinical trial. JAMA Intern Med. Published online October 20, 2020. doi:10.1001/jamainternmed.2020.6615

  44. Salama C, Han J, Yau L, et al. Tocilizumab in patients hospitalized with covid-19 pneumoniaN Engl J Med. Published online December 17, 2020. doi:10.1056/NEJMoa2030340

  45. Chen C, Huang J, Yin P, et al. Favipiravir versus Arbidol for COVID-19: A Randomized Clinical Trial. Published online April 8, 2020 (not yet peer reviewed). medRxiv 2020.03.17.20037432; doi:10.1101/2020.03.17.20037432

  46. Cao B, Wang Y, Wen D, et al. A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. NEJM. Published online March 18, 2020. doi:10.1056/NEJMoa2001282

  47. Hung et al. Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet. Published Online May 8, 2020. doi:10.1016/ S0140-6736(20)31042-4

  48. Liu, J., Cao, R., Xu, M. et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitroCell Discov 6, 16 (2020). https://doi.org/10.1038/s41421-020-0156-0

  49. Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International Journal of Antimicrobial Agents. Published online Mar 20, 2020. doi: 10.1016/j.ijantimicag.2020.105949

  50. Molina JM et al. No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection. Med Mal Infect. 2020 Mar. doi:10.1016/j.medmal.2020.03.006

  51. Horby P, Mafham M, Linsell L, et al. Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19. N Engl J Med. Published online October 8, 2020. doi:10.1056/NEJMoa2022926

  52. Putman M, Chock YPE, Tam H, et al. Antirheumatic Disease Therapies for the Treatment of COVID-19: A Systematic Review and Meta-analysis. Arthritis Rheumatol. Published online August 2, 2020. doi:10.1002/art.41469

  53. Cavalcanti AB et al. Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate COVID-19. N Eng J Med. 2020 Jul. doi:10.1056/NEJMoa2019014

  54. Skipper CP et al. Hydroxychloroquine in Nonhospitalized Adults with Early COVID-19: A Randomized Trial. Ann Intern Med. 2020 Jul; doi:10.7326/M20-4207

  55. Chen J. A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19). J Zhejiang Univ (Med Sci). 2020 Mar, 49(1). doi:10.3785/j.issn.1008-9292.2020.03.03

  56. Abella BS, Jolkovsky EL, Biney BT, et al. Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers: A Randomized Clinical Trial. JAMA Intern Med. Published online September 30, 2020. doi:10.1001/jamainternmed.2020.6319

  57. Gentry CA, Humphrey MB, Thind SK, et al. Long-term hydroxychloroquine use in patients with rheumatic conditions and development of SARS-CoV-2 infection: a retrospective cohort studyThe Lancet Rheumatology. 2020;2(11):e689-e697. doi:10.1016/S2665-9913(20)30305-2

  58. Borba MGS et al. Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study). 2020 April. medRxiv 2020.04.07.20056424; doi:10.1101/2020.04.07.20056424

  59. Mercuro NJ et al. Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. Published online May 1, 2020. doi:10.1001/jamacardio.2020.1834

  60. Arshad et al. Treatment with Hydroxychloroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19. Int J Infect Dis. Published July 1, 2020. doi:10.1016/j.ijid.2020.06.099