COVID-19 Treatments: What You Need to Know

Learn about the clinical evidence behind different treatment modalities

The novel coronavirus (COVID-19) 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 and new drugs and testing the viability of vaccines and blood products. This article outlines a list of high-profile treatments that have been tested against the virus, starting with those currently in clinical use and ending with those still undergoing investigation.

As of July 2022, the following treatments have full approval from the U.S. Food and Drug Administration (FDA), in order of approval:

  • Remdesivir (April 2022 for those 28 days of age and older)
  • The Pfizer-BioNTech mRNA vaccine (August 2021 for ages 16+, July 2022 for ages 12-15)
  • The Moderna mRNA vaccine (January 2022 for ages 18+)

Other treatments currently have an emergency use authorization, meaning that the FDA has allowed for their use but they are still under investigation. These include:

  • Convalescent plasma (August 2020)
  • Bamlanivimab and etesevimab (November 2020)
  • Baricitinib with remdesivir (November 2020)
  • Casirivimab with imdevimab (November 2020)
  • The Johnson & Johnson adenovirus-vectored vaccine (February 2021 for ages 18+)
  • The Pfizer-BioNTech mRNA vaccine (May 2021 for ages 12 to 15; October 2021 for ages 5 to 11; June 2022 for ages 6 months to 4 years)
  • Tocilizumab (June 2021)
  • Paxlovid (December 2021)
  • Molnupiravir (December 2021)
  • Evusheld (December 2021)
  • Bebtelovimab (February 2022)
  • Baricitinib alone (May 2022)
  • The Moderna mRNA vaccine (June 2022 for ages 6 months to 17 years)
  • The Novavax vaccine (July 2022)

Remdesivir

Remdesivir was initially developed as a treatment against Ebola. In vitro studies showed it may be effective against COVID-19. On May 2020, 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. In October 2020, remdesivir became the first drug approved by the FDA to treat COVID-19 without an emergency use authorization. In November, it was also authorized for a new EUA when used in combination with baricitinib (see "Biologics" below).

What the Research Says

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 four days sooner (31% faster) than those who were not treated. People with moderate infections, however, did not show significant improvement. Data released by the drug manufacturer Gilead Sciences found that people in the treatment group (remdesivir, n=541) recovered five days sooner than those in the control group (placebo, n=521), 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 time, WHO has formally advised against using the drug for hospitalized patients.

In October 2020, the FDA gave full approval for remdesivir, now named Veklury, for people hospitalized with severe COVID-19 infections if they were 12 years or older and weighed at least 40 kg. An emergency use authorization for people requiring oxygen without ventilator therapy continued for hospitalized adults and for pediatric patients if they weighed between 3.5 kg and 40 kg.

In January 2022, the FDA expanded remdesivir’s emergency use authorization to include people who were not hospitalized but who had mild-to-moderate symptoms and were considered at high risk for complications. A three-day course of treatment is recommended in these cases.

On April 25, 2022, the FDA expanded the approval of remdesivir treatment to include young children 28 days of age and older (weighing at least 3 Kg) who are either hospitalized or who have mild-to-moderate symptoms and are considered at high risk for complications. This is the first COVID-19 treatment to be approved for patients under 12 years of age.

The National Institutes of Health recommends remdesivir, dexamethasone, or a combination of remdesivir with dexamethasone for hospitalized COVID-19 patients who require conventional oxygen therapy.

Dexamethasone and Methylprednisolone

Dexamethasone and methylprednisolone are steroids that are often used to treat inflammation. They come 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 these common anti-inflammatory drugs.

What the Research Says

The RECOVERY (Randomised Evaluation of COVid-19 thERapY) trial found that people treated with 10 days of dexamethasone did better than those on placebo. Specifically, mortality rates decreased from 41% to 29% for people who needed ventilators and from 26% to 23% for people requiring oxygen without ventilator therapy.

A meta-analysis sponsored by the World Health Organization (WHO) reviewed seven randomized clinical trials including approximately 1,700 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 those treated with usual care or placebo (32% mortality rate for steroids vs. 40% for controls).

Steroids have shown benefits when used in combination with tocilizumab (see "Biologics" section below). A study in the Annals of the Rheumatic Diseases looked at people who had both COVID-19 and cytokine storm, a syndrome of overactive inflammation in the body. They were treated with five days of steroids, and if they did not improve within two days, they also received a dose of IV tocilizumab. This 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 in 5,776 patients hospitalized with COVID-19. Steroids decreased mortality by 34%, but the mortality rate decreased by 56% when combined with tocilizumab.

Children who develop multisystem inflammatory syndrome in children (MIS-C) may benefit from methylprednisolone, according to a study in JAMA. In the study, 111 children with the syndrome were treated with IV immunoglobulin with or without methylprednisolone. Children that received both treatments had improved outcomes, notably reduced fever within two days and decreased fever recurrence over seven days.

Casirivimab and Imdevimab (formerly REGEN-COV2)

Regeneron Pharmaceuticals Inc. developed a man-made antibody cocktail initially called REGEN-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 seven days of treatment. President Donald Trump, who reported positive COVID-19 test results on October 1, was treated with REGEN-COV2 on October 2, 2020.

Regeneron later released Phase 3 trial results, announcing in a press release that their casirivimab-imdevimab cocktail decreased COVID-19 infection in people with high-risk exposures. People who received the cocktail (n=186) did not develop symptomatic infections, although 10 developed asymptomatic infections. The placebo group (n=223), however, developed 8 symptomatic infections and 23 asymptomatic infections. Altogether, treatment decreased the rate of any COVID-19 infection by half (5% for treatment group vs. 10% for placebo) and fully protected against symptomatic infection.

In November 2020, 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.

In April 2021, Regeneron announced that the monoclonal antibody combination decreased the risk for symptomatic COVID-19 in contacts when household contacts were positive. The Phase 3 trial recruited 1505 people and treated them with either casirivimab-imdevimab or placebo within four days of a positive test in the household. The treatment was 81% effective in decreasing symptomatic infections. For those who became infected despite treatment, their symptoms resolved much faster than people who received placebo (one week vs. three weeks).

In July 2021, the FDA authorized the treatment for post-exposure prophylaxis. This allows it to be used for “people exposed to an infected individual, or who are at high risk of exposure to an infected individual in settings such as nursing homes or prisons.”

By January 2022, the majority of COVID-19 cases in the U.S. were attributable to the omicron variant. Unfortunately, REGEN-COV2 has not been as effective against this version of the virus. This is the reason the FDA limited emergency use authorization for the medication unless a patient was known to be infected with a different variant.

Other Synthetic Antibodies

The following COVID-targeted antibodies are listed in order of their development and use.

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. A Phase 3 trial treated 769 COVID-19 patients with the monoclonal antibody combination or placebo. All participants were 12 years or older, were considered high-risk, had mild-to-moderate symptoms, and were not hospitalized at the start of the study. Four people in the treatment group eventually required hospitalization (4/511) while 15 people in the placebo group were hospitalized (15/258), 4 of whom died. Altogether, the bamlanivimab-etesevimab combination decreased the risk for hospitalization or death by 87%.

In November 2020, 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 a January 2021 press release, Eli Lilly reported the effectiveness of bamlanivimab as a preventive therapy. In their BLAZE-2 trial, 965 nursing home residents who initially tested negative for COVID-19 were treated with the monoclonal antibody or placebo. Over eight weeks, those treated with bamlanivimab were 57% less likely to develop symptomatic COVID-19. Four people died from their infection, but none of them were in the treatment group.

In February 2021, the FDA granted an emergency use authorization for a combination of the monoclonal antibodies bamlanivimab and etesevimab. The treatment is intended for non-hospitalized patients with mild-to-moderate COVID-19 symptoms who do not require supplemental oxygen. Patients should be 12 years or older, weigh at least 40 kg, and be considered high risk (e.g., be 65 years or older, have certain chronic medical conditions, etc.). A randomized, double-blind, placebo-controlled clinical trial study of 1,035 people found that those who received this treatment were less likely to be hospitalized or die from COVID-19 (2% vs. 7%).

In April 2021, the emergency use authorization for bamlanivimab monotherapy was revoked due to decreased efficacy against virus variants. Combination therapy with bamlanivimab and etesevimab remains a treatment option.

Bamlanivimab and Virus Variants

Virus variants have had increasing resistance to bamlanivimab. For this reason, the Department of Health and Human Services no longer distributes this treatment on its own. It was authorized for combination treatment with etesevimab for a time. However, even combination treatment has been ineffective against the omicron variant, and the FDA has since limited its use.

Sotrovimab (formerly VIR-7831)

GlaxoSmithKline and Vir Biotechnology have come together to develop an investigational monoclonal antibody treatment called sotrovimab. Their Phase 3 trial included 583 people at high risk for hospitalization from COVID-19 infection. Emergency use authorization was granted by the FDA on May 26, 2021.

Due to increasing resistance to the BA.2 omicron variant, the FDA began restricting use of sotrovimab in March 2022. Then, in April 2022, the agency announced that sotrovimab was no longer authorized to treat COVID-19 in the U.S. due an increase in the proportion of COVID-19 cases caused by this omicron variant.

Evusheld (formerly AZD7442)

AstraZeneca developed investigation antibodies (tixagevimab and cilgavimab, formerly known as AZD7442) to treat and hopefully prevent COVID-19 infection in people exposed to the virus. Evusheld may be more effective as a preventive treatment than a post-exposure treatment.

A Phase 3 trial involved more than 5,000 adults at high risk for COVID-19 infection. Their risk was either due to underlying medical conditions or circumstances that increase their risk for exposure. People treated with these antibodies were 77% less likely to develop symptomatic COVID-19 infection. No cases of severe COVID-19 were detected in the treatment group. The placebo group, however, had three cases of severe COVID-19 and two deaths.

In December 2021, the FDA granted an emergency use authorization to Evusheld as a preventive treatment for people with weak immune systems or for those who had a serious reaction to a COVID vaccine or one of its components. It is intended to be used in people 12 years and older who weigh at least 40 kg, who do not currently have COVID infection, and who have not recently been exposed to someone with COVID.

Due to increasing resistance to some virus variants, the FDA has recommended that the dose of Evusheld be doubled.

BRII-196 and BRII-198

Brii Biosciences has developed a combination of monoclonal antibodies, BRII-196 and BRII-198. A Phase III trial, sponsored by the National Institute of Allergy and Infectious Diseases, included 837 participants that were diagnosed with COVID-19 within the past 10 days. Those that received the antibody treatment were 78% less likely to need hospitalization (12 in the treatment group and 45 in the placebo group). The treatment also decreased mortality by 10% (1 in the treatment group and 9 in the placebo group).

Bebtelovimab

Eli Lilly has continued to develop monoclonal antibodies against COVID-19, specifically the Omicron variant. Bebtelovimab is their latest treatment, and the FDA granted an emergency use authorization for it in February 2022. This monoclonal antibody is intended for use in anyone who is 12 years or older, who weighs at least 40 kg, who has tested positive for COVID-19, and who is at risk for complications from the infection. Details about the company’s Phase 2 BLAZE-4 trial have not been peer reviewed.

Vaccines Against COVID-19

The best hope for managing COVID-19 long-term: vaccines. Vaccines expose your body to an antigen—a substance that causes 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.

Pfizer Inc. — Comirnaty (formerly BNT162b2)

Efficacy: In November 2020, early data from a Phase 3 trial found an mRNA-vectored vaccine developed by Pfizer and BioNTech to be 90% effective in preventing COVID-19. The vaccine is administered in a two-dose series, three weeks apart. When looking at infection rates seven days after a second dose, 94 people developed symptomatic COVID-19 from a study population of 43,538 people. The company released additional data nine days later on November 18, noting that 170 cases of symptomatic 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, and a 94% efficacy rate in people over 65 years old.

Vaccination of nearly 600,00 people in Israel has shown results similar to those in the Pfizer clinical trials. After the second dose, it was noted to be 92% effective against COVID-19 at large—94% against symptomatic disease and 90% against asymptomatic disease.

A U.K. case control study also looked at the effectiveness of vaccination in the real world. Looking at approximately 157,000 seniors over 70 years old, a single dose of vaccine was 61% effective against symptomatic disease after 28 days. After a second dose, effectiveness increased to 85% to 90%. People who developed symptomatic COVID-19 after their first dose were 43% less likely to require hospitalization within 14 days of their diagnosis and were 51% less likely to die from their infection.

Similarly, the Centers for Disease Control and Prevention reported that partial vaccination in skilled nursing residents was 63% effective. Their analysis included 463 residents in Connecticut nursing homes where there was an outbreak of COVID-19. Residents were included in the analysis if they had received one dose of the vaccine (and were more than 14 days after their dose) or two doses (if they were less than seven days after their second dose).

Children:

  • Results from a Phase 3 trial of 2,260 adolescents 12 to 15 years old showed the vaccine to be 100% effective against COVID-19 one month after the second dose. There were 18 cases of COVID-19 in the placebo group and none in the treatment group. On May 10, 2021, the FDA granted an emergency use authorization for this age group.
  • In October 2021, the FDA authorized vaccination in children 5 to 11 years old, noting that the vaccine had no serious side effects and was 90.7% effective in preventing infection in this group.
  • In June 2022, the FDA expanded the emergency use authorization to include children as young as 6 months old.

Myocarditis

The CDC reports a small increase in myocarditis cases with use of the mRNA vaccines. The rates were higher for the Moderna vaccine than the Pfizer vaccine. Still, the risk for myocarditis remains very low, and most people tend to recover quickly. Noting that the risks of COVID-19 are greater than those for myocarditis, the CDC continues to recommend vaccination for everyone 5 years and older.

Approval: On December 11, 2020, the FDA granted emergency use authorization in the United States, and the first Americans were vaccinated on December 14. In August 2021, the vaccine, now referred to as Comirnaty, was given full approval by the FDA for anyone 16 years and older. In July 2022, full approval was granted for ages 12 to 15. The vaccine remains under an emergency use authorization for children and adolescents 6 months to 11 years old.

Booster Dose:

  • At least one booster dose for Pfizer is recommended for everyone age 5 and older (regardless of risk).
  • In December 2021, the FDA approved first booster doses for 16- and 17-year-olds and then for those 12 to 15 years old in January 2022.
  • In March 2022, the FDA approved a second mRNA booster dose for anyone 50 years or older and for anyone 12 or older who was immunocompromised.
  • In May 2022, the FDA approved Pfizer a first booster shot for children 5 to 11 years old.
  • In September 2022, the FDA approved an updated Pfizer booster that included additional coverage against omicron variants. This booster could be administered to anyone aged 12 and older at least two months after their last booster dose.

Booster Choice

The FDA has allowed a "mix and match" booster dosing regimen. This means that you can receive either a Pfizer, Moderna, or Johnson & Johnson vaccine after completing your initial vaccine series for any of these vaccines (although mRNA COVID-19 vaccines—Moderna and Pfizer—are recommended in most situations). Children and adolescents ages 6 months to 17 years who completed Pfizer's primary series are only eligible for the Pfizer booster.

Moderna Inc. — Spikevax (formerly mRNA-1273)

Efficacy: This mRNA-vectored vaccine was funded by the National Institute of Allergy and Infectious Diseases (NIAID) and the Biomedical Advanced Research and Development Authority (BARDA). In November 2020, data from their Phase 3 trial showed the Moderna vaccine to be 94.5% against COVID-19. When looking at infection rates two weeks after a second dose, 95 people developed symptomatic COVID-19 from a study population of more than 30,000 people. 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 symptomatic 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.

Children: Their Phase 2/3 study, referred to as teenCOVE, enrolled 3,723 adolescents between 12 and 17 years old. One dose was 93% effective against COVID-19 after 14 days. Effectiveness increased to 100% two weeks after the second dose. Four COVID-19 cases were detected in the placebo group. Based on these results, Moderna requested emergency use authorization for use in children 12 to 17 years old in June 2021. Due to concerns for myocarditis, there was a delay in FDA approval. Currently, there is an emergency use authorization in place for anyone 5 years and older.

Approval: The FDA granted the Moderna vaccine emergency use authorization on December 18, 2020. The FDA granted full approval for the two-dose mRNA vaccine series in January 2022. Now called Spikevax, the Moderna vaccine is approved for people 18 and older. The vaccine is also authorized under emergency use authorization for individuals ages 6 months to 17 years. Extra primary doses for people who are immunocompromised and booster doses remain under an emergency use authorization (see below).

Booster Dose:

  • A first Moderna booster dose is now recommended for all adults age 18 and older (regardless of age or risk).
  • In March 2022, the FDA approved a second booster dose for anyone older than 50 years old and for anyone 18 or older who is immunocompromised.
  • In September 2022, the FDA approved an updated Moderna booster that included additional coverage against omicron variants. This booster could be administered to anyone aged 18 and older at least two months after their last booster dose.

Johnson & Johnson — Vaccine Candidate Ad26.COV2.S

Efficacy: This vaccine was 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. Their Phase 3 trial included more than 43,000 people, and there were 468 cases of symptomatic COVID-19. The vaccine was most effective against severe infection, showing 85% effectiveness after 28 days with no cases detected after day 49. Effectiveness overall was 66%, (72% in the United States, 66% in Latin America, and 57% in South Africa). Of note, 95% of the cases in South Africa were from the B.1.351 variant. In September 2021, Johnson & Johnson released real-world data involving more than 390,000 people vaccinated with one dose. The vaccine was 75% effective against severe COVID-19 overall. When looking specifically at the United States, it was 74% effective against severe COVID-19, 89% against hospitalization, and 83% against COVID-19-related death.

Approval: The Johnson & Johnson vaccine was granted FDA emergency use authorization as a one-dose vaccine on February 27, 2021. WHO granted authorization on March 12, 2021. As of May 2022, however, the FDA advises against use of the Johnson and Johnson vaccine unless you are unable to get another kind of vaccine. The decision was made based on an increased risk for blood clots that can sometimes occur within one to two weeks of vaccination.

Booster Dose: Although the vaccine was initially released for one-time dosing, Johnson & Johnson reports that a booster dose may incur increased immunity. Their Phase III trial found that a second dose given two months after the first dose was 100% effective against severe COVID-19 infections. Globally, it was 75% effective against moderate infection, but the rate was even better in the United States at 94%. On October 15, 2021, an FDA panel unanimously recommended a booster shot two months from the first vaccine dose, and it granted an emergency use authorization for the dose on October 20. However, the CDC now recommends preferred use of the Pfizer and Moderna vaccines for primary and booster vaccination due to the risks of the Johnson & Johnson vaccine.

AstraZeneca — Vaccine Candidate AZD1222 (previously ChAdOx1)

Efficacy: 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.

In December 2020, 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 doses of the vaccine 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%.

In February 2021, they released more Phase 3 data, this time data on a larger population of more than 17,100 participants. Efficacy after a single dose was noted to be 76% after 22 to 90 days (59% for the full dose group, 86% for the half dose group). Efficacy 14 days after a two-dose regimen was 67% against symptomatic COVID-19 (57% for the full dose group, 74% for the half dose group). Interestingly, efficacy was also affected by the timing of the doses. It was as low as 55% when the doses were administered less than six weeks apart (33% for the full dose group, 67% for the half dose group) but increased to 82% when doses were separated by at least 12 weeks (63% for the full dose group, 92% for the half dose group). Of note, this efficacy is based on someone developing symptoms from COVID-19 and does not reflect asymptomatic COVID-19 infection.

In March 2021, a preprint case-control study from the United Kingdom looked at the effectiveness of single-dose vaccination in people over 70 years old. The researchers looked at approximately 157,000 people who were tested for COVID-19 in the real world. Vaccine effectiveness against symptomatic disease was 22% at 14 days, 45% at 21 days, 60% at 28 days, and 73% at 35 days. People who developed symptomatic COVID-19 despite vaccination were 37% less likely to require hospitalization within 14 days of their diagnosis.

In March 2021, an AstraZeneca press release announced results from a Phase 3 trial in the United States involving 32,449 participants, 60% who had pre-existing conditions that increased the risk for severe infection (e.g., diabetes, heart disease, obesity). Overall, there were 141 cases of symptomatic COVID-19. The company claimed that the vaccine was 79% effective against symptomatic COVID-19 (80% for people 65 and older) and 100% effective against severe infection and hospitalization. The National Institute of Allergy and Infectious Diseases later raised concern over the validity of the results, stating that the announcements focused on outdated information. AstraZeneca then released updated information, noting a 76% efficacy (85% for people 65 and older) and 100% effectiveness against severe disease.

Novavax Inc. — Vaccine Candidate NVX-CoV2373

Preliminary Results: 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 1/2 clinical trials have shown an antibody response that is greater than that seen in convalescent plasma from patients who were symptomatic with COVID-19.

Efficacy: In a press release, the company announced preliminary results from their Phase III trial in the U.K. (more than 15,000 participants) and their Phase 2 trial in South Africa (more than 4,400 participants). In the former study, 62 participants developed symptomatic COVID-19 (6 in the treatment group vs. 56 in the placebo group). Overall, effectiveness of the vaccine was 89.3%. This broke down to 95.6% against the original strain and 85.6% against the British variant. The latter study was less successful, noting 44 cases of symptomatic COVID-19 (15 in the treatment group vs. 29 cases in the placebo group), with an overall effectiveness of 60%. Sequencing was only done on 27 of the positive cases, but 25 of those were confirmed to be the South African variant. In May 2021, a study in the New England Journal of Medicine reported similar findings in South Africa with a 60% decrease risk for symptomatic infection in people without HIV and 49% for people with HIV.

Approval: The FDA granted an emergency use authorization to the two-dose vaccine in July 2022 for anyone 18 and older, noting that it was 90.4% effective in preventing COVD infection. Effeicacy decreased to 78.6% for people older than 65 years of age.

GlaxoSmithKline and Medicago – Vaccine Candidate CoVLP

GlaxoSmithKline and Medicago have come together to develop a novel vaccine based on a plant-based technology. A bacterial vector is used to infect a specific type of plant, N. benthamiana. The plants are then allowed to grow until enough vaccine material is grown. They are then harvested, and the vaccine material is extracted and isolated.

Efficacy: The companies released a press release in December 2021. A Phase 3 clinical trial included more than 24,000 adults across six countries and treated participants with a two-dose series 21 days apart. The overall efficacy rate of the vaccine was 71% but increased to 75.3% against the delta variant of COVID-19.

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 2/3 clinical trials on hold as it evaluates the safety of its delivery device, which injects DNA into cells.

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

Baricitinib is a JAK1/JAK2 inhibitor, a class of medications used to quell 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 3 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 authorized 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.

In May 2022, the FDA gave full approval for baracitinib as a treatment for people 18 and older hospitalized with COVID-19, who need to use oxygen, a ventilator, or extracorporeal membrane oxygenation (ECMO). It remains on an emergency use authorization for children 2 to 18.

Interferon Beta-1a

Interferons are a natural part of your immune system. These cytokines boost the immune response to viruses. Currently, interferons are currently an injected 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

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 also 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.

Unfortunately, not all studies have shown a benefit. A Brazilian study of 129 critically ill COVID-19 patients were treated with tocilizumab and standard care or standard care alone. At 15 days, mortality was actually higher for those treated with tocilizumab, 17% vs. 3%. At 29 days, mortality rates were not statistically significant between the two groups. Although other studies have shown a survival benefit, this study raises significant issues for safety. In fact, this study was terminated early for that reason.

The National Institutes of Health currently recommends tocilizumab plus dexamethasone for COVID-19 patients in the ICU who require mechanical ventilation or high-flow nasal cannula oxygen. Non-ICU patients who develop hypoxia and need noninvasive ventilation or high-flow oxygen can qualify for this regimen, too, if they also have elevated inflammatory markers. That said, tocilizumab should not be used for people who are significantly immunocompromised.

The FDA granted an emergency use authorization for tocilizumab as a treatment for COVID-19 on June 24, 2021. It is intended for hospitalized patients 2 years and older who have severe COVID-19. Specifically, these patients must also be receiving treatment with steroids and oxygen, ventilators, or extracorporeal membrane oxygenation (ECMO). Although tocilizumab has been FDA-approved for other medical conditions (e.g., rheumatoid arthritis), its use for COVID-19 is limited to the EUA at this time.

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.

What the Research Says

A study in Mayo Clinic Proceedings noted that convalescent plasma was generally safe when used to treat 20,000 hospitalized COVID-19 patients and decreased mortality, especially when administered earlier in the course of the illness. A trial of more than 35,000 hospitalized patients found that treatment with plasma that had high antibody levels lowered mortality if given within 3 days of the diagnosis. A 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. 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 noted that while convalescent plasma reduced viral loads within 7 days, there was no decrease in mortality rates. A randomized-controlled study including 228 adults with COVID-19 pneumonia found no clinical benefit for those treated with convalescent plasma over 30 days. The National Institutes of Health halted a clinical trial in March 2021 noting a lack of benefit for people with mild to moderate COVID symptoms. A subsequent study in the New England Journal of Medicine found that administration of convalescent plasma within seven days of COVID-19 symptoms did not slow down the disease when compared to placebo. All of the patients enrolled in the study were 50 years or older or otherwise considered to be high risk.

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 In February 2021, the EUA was updated. Only high-antibody-titer convalescent plasma was authorized for use. It has also been limited to hospitalized patients early in the course of their disease or in hospitalized patients who are immunocompromised.

A randomized, controlled trial in Nature Medicine was published in August 2021. It suggested that treatment with convalescent plasma may increase the risk for complications in people with severe COVID-19 infections, including intubation and death. This occurred 33.4% of the time in people treated with plasma vs. 26.4% in people who were not treated.

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.

Molnupiravir 

Molnupiravir is an oral antiviral medication that does not target the spike protein like the vaccines do. Instead, it is a drug that blocks the replication of some RNA viruses. Specifically, it is a prodrug, an inactive medication, that is metabolized to its active form (N4-hydroxycytidine) in the body. The drug has been developed by Merck and Ridgeback Biotherapeutics.

What the research says: Their Phase 3 trial, referred to as MOVe-OUT, included 775 adults who had mild to moderate COVID-19 and who were not hospitalized. Study participants were treated within 5 days of symptoms and they also had at least one factor (e.g., age 60 or older, diabetes, heart disease, obesity, etc.) that increased the risk for a bad outcome. When compared to people treated with placebo, those treated with molnupiravir were approximately 50% less likely to be hospitalized or to die within 29 days (7.3% in the treatment group vs. 14.1% in the placebo group). Of note, there were no deaths in the treatment group, but there were 8 deaths in the placebo group.

Updated data was presented to the FDA in November 2021 that included 1,433 adults. The effectiveness remained high but was lower than previously reported, 30% instead of 50%.

The FDA granted emergency use authorization for molnupiravir in December 2022. It is intended for use for people 18 years and older, who have a positive COVID test, who have mild to moderate symptoms, and who are at high risk for developing complications from the disease. Treatment should begin within five days of symptom onset.

Paxlovid (PF-07321332 and ritonavir)

Paxlovid is a new antiviral regimen developed by Pfizer. It is a combination of two medications, PF-07321332 and ritonavir. PF-07321332 prevents replication of the virus by blocking the SARS-CoV-2-3CL protease. The ritonavir does not attack the COVID virus directly. Instead, it is a cytochrome P450 inhibitor that helps to slow down the breakdown of PF-07321332 in the body so that it can act longer.

What the research says: Their Phase 2/3 trial, referred to as EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) decreased hospitalizations or deaths caused by COVID-19 when given within three days of symptoms to people who were considered to be high risk. After 28 days, only 3 out of 389 people treated with Paxlovid required hospitalization and none died. The placebo group had 27 hospitalizations out of 385 people and 7 died.

When treatment was given within five days of symptoms, results remained strong. Six out of 607 people receiving Paxlovid were hospitalized and none died, whereas 41 out of 612 people in the placebo group were hospitalized and 10 died. Altogether, the effectiveness of treatment is estimated to be 89%.

The FDA granted emergency use authorization for Paxlovid in December 2021. It is intended for use for people 12 years and older who weigh at least 40 kg, who have a positive COVID test, who have mild to moderate symptoms, and who at high risk for developing complications from the disease.

Although the medication was helpful in decreasing symptoms from COVID-19, it was not effective at preventing infection for people from catching the virus in the first place. who had been exposed to the virus.

Sabizabulin

Sabizabulin is a medication developed by Veru Inc. It works by impairing the ability of the SARS-CoV2 virus to move within cells. It does this by interfering with the formation of microtubules that transport the virus throughout your cells. It can also decrease inflammation by decreasing the number of cytokines and other inflammatory cells that get transported as well.  

Veru’s Phase 3 clinical trial included more than 200 people with COVID-19 who were hospitalized with moderate to severe symptoms. Everyone received standard treatments for COVID-19, but those who were also treated with sabizabulin were less likely to die within 60 days (20% with treatment vs. 45% with placebo). With a decrease in mortality by 55%, the study was stopped early and the company has sent data to the FDA to consider an emergency use authorization.

Influenza Medications

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.

Ivermectin

Ivermectin is a medication currently FDA-approved for treatment of certain parasitic infections. In humans, it has a pill form specifically used to treat intestinal strongyloidiasis, onchocerciasis, scabies, and pediculosis (e.g., lice). In animals, it is used to treat heartworm and other parasitic diseases. Researchers are looking to repurpose this medication as an antiviral medication.

What the Research Says:

Ivermectin as a treatment for COVID-19 remains controversial. In vitro studies (i.e., those that are not performed on animals or humans, but on cells) have shown that it may also prevent replication of some viruses, including SARS-CoV-2. In those cases, individual cells are infected with the virus and are treated with the medication.

This may sound promising, but there is concern about the dose needed to achieve this effect. Viral replication is not affected until a certain dose is reached. To achieve that dose in a live person, the theoretical dose required would be more than nine times the FDA-approved dose. Altogether, the high doses increase the risk for serious side effects from the medication, including hypotension, tachycardia, and seizures.

Decreased viral replication has been shown in animal studies with mice and pigs, but again, doses are administered at higher doses in those animals than in humans. Studies on humans have generally had a low number of patients treated with the drug but suggest that there may be a decreased risk for ICU stays, mechanical ventilation, and death in people who had severe COVID-19 disease. There has not been much benefit seen for people with mild to moderate disease or for preventing infection.

It is important to note that the quality of available studies is low. The doses of ivermectin are not readily comparable across studies, and there is a lot of bias in the studies. In many studies, other COVID-19 treatments that patients received are not taken into account. This makes it harder to tell which medication truly had the desired affect. Many of the available studies are also not registered as clinical trials.

At this time, the FDA does not recommend ivermectin for treatment of COVID-19.

Lopinavir-Ritonavir

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. People 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).

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.

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). 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 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.

Unfortunately, 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 2,500 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.

The FDA does not recommend treatment with hydroxychloroquine or chloroquine for treatment of COVID-19 at this time.

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. 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.

The information in this article is current as of the date listed, which means newer information may be available when you read this. For the most recent updates on COVID-19, visit our coronavirus news page.

98 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitroCell Res. 2020;30(3):269–271. doi:10.1038/s41422-020-0282-0

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

  3. U.S. Food & Drug Administration. FDA Approves First Treatment for COVID-19. October 22, 2020.

  4. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of COVID-19 — final report. N Engl J Med. 2020;383(19):1813-1826. 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. 2020;324(11):1048-1057. doi:10.1001/jama.2020.16349

  6. Agarwal A, Rochwerg B, Lamontagne F, et al. A living WHO guideline on drugs for COVID-19BMJ. 2020;370:m3379. doi:10.1136/bmj.m3379

  7. U.S. Food & Drug Administration. FDA’s approval of Veklury (remdesivir) for the treatment of COVID-19—the science of safety and effectiveness. October 22, 2020.

  8. Food and Drug Administration. Coronavirus (COVID-19) update: FDA approves first COVID-19 treatment for young children.

  9. The RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with COVID-19N Engl J Med. 2021;384(8):693-704. doi:10.1056/NEJMoa2021436

  10. WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: A meta-analysis. JAMA. 2020;324(13):1330-1341. 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. Ann Rheum Dis. 2020;79(9):1143-1151. 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. 2021;159(3):933-948. doi:10.1016/j.chest.2020.09.275

  13. Ouldali N, Toubiana J, Antona D, et al. Association of intravenous immunoglobulins plus methylprednisolone vs immunoglobulins alone with course of fever in multisystem inflammatory syndrome in childrenJAMA. 2021;325(9):855–864. doi:10.1001/jama.2021.0694

  14. Regeneron Pharmaceuticals. Regeneron's REGN-COV2 antibody cocktail reduced viral levels and improved symptoms in non-hospitalized COVID-19 patients.

  15. Regeneron Pharmaceuticals, Inc. Regeneron Reports Positive Interim Data with REGEN-COV™ Antibody Cocktail used as Passive Vaccine to Prevent COVID-19. January 26, 2021.

  16. U.S. Food & Drug Administration. Coronavirus (COVID-19) Update: FDA Authorizes Monoclonal Antibodies for Treatment of COVID-19. November 21, 2020.

  17. Regeneron Pharmaceuticals, Inc. PHASE 3 PREVENTION TRIAL SHOWED 81% REDUCED RISK OF SYMPTOMATIC SARS-COV-2 INFECTIONS WITH SUBCUTANEOUS ADMINISTRATION OF REGEN-COV™ (CASIRIVIMAB WITH IMDEVIMAB). April 12, 2021.

  18. Regeneron Pharmaceuticals, Inc. FDA EXPANDS AUTHORIZED USE OF REGEN-COV™ (CASIRIVIMAB AND IMDEVIMAB). July 30, 2021.

  19. U.S. Food & Drug Administration. Coronavirus (COVID-19) Update: FDA Limits Use of Certain Monoclonal Antibodies to Treat COVID-19 Due to the Omicron Variant. January 24, 2022.

  20. Lilly’s bamlanivimab and etesevimab together reduced hospitalizations and death in Phase 3 trial for early COVID-19. Eli Lilly and Company. March 10, 2021.

  21. Lilly’s neutralizing antibody bamlanivimab (LY-CoV555) prevented COVID-19 at nursing homes in the BLAZE-2 trial, reducing risk by up to 80 percent for residents. Eli Lilly and Company. January 21, 2021.

  22. Coronavirus (COVID-19) Update: FDA Authorizes Monoclonal Antibodies for Treatment of COVID-19. U.S. Food and Drug Administration. F‌ebruary 9, 2021.

  23. Coronavirus (COVID-19) Update: FDA Revokes Emergency Use Authorization for Monoclonal Antibody Bamlanivimab. U.S. Food and Drug Administration. April 16, 2021.

  24. Coronavirus (COVID-19) Update: FDA Limits Use of Certain Monoclonal Antibodies to Treat COVID-19 Due to the Omicron Variant. U.S. Food and Drug Administration. January 24, 2022.

  25. GSK and Vir Biotechnology announce submission of Emergency Use Authorization request to FDA for VIR-7831 for the early treatment of COVID-19. Gsk.com. March 26, 2021.

  26. Coronavirus (COVID-19) Update: FDA Authorizes Additional Monoclonal Antibody for Treatment of COVID-19. U.S. Food and Drug Administration. May 26, 2021.

  27. Food and Drug Administration. FDA updates sotrovimab emergency use authorization.

  28. AZD7442 PROVENT Phase III prophylaxis trial met primary endpoint in preventing COVID-19. Astra Zeneca. August 20, 2021.

  29. Coronavirus (COVID-19) Update: FDA Authorizes New Long-Acting Monoclonal Antibodies for Pre-exposure Prevention of COVID-19 in Certain Individuals. U.S. Food and Drug Administration. December 8, 2021.

  30. Update on FDA adjustment to Evusheld dosage regimen in US. Astra Zeneca. February 25, 2022.

  31. Brii Biosciences - Breakthrough innovation & insight. Briibio.com. August 25, 2021.

  32. Coronavirus (COVID-19) Update: FDA Authorizes New Monoclonal Antibody for Treatment of COVID-19 that Retains Activity Against Omicron Variant. U.S. Food and Drug Administration. February 11, 2022.

  33. Dagan N, Barda N, Kepten E, et al. BNT162b2 MRNA Covid-19 vaccine in a nationwide mass vaccination settingN Engl J Med. 2021 Apr 15;384(15):1412-1423. doi:10.1056/NEJMoa2101765

  34. Lopez Bernal J, Andrews N, Gower C, et al. Early effectiveness of COVID-19 vaccination with BNT162b2 mRNA vaccine and ChAdOx1 adenovirus vector vaccine on symptomatic disease, hospitalisations and mortality in older adults in England. medRxiv. Preprint posted online March 2, 2021. doi:10.1101/2021.03.01.21252652

  35. Britton A, Jacobs Slifka KM, Edens C, et al. Effectiveness of the Pfizer-BioNTech COVID-19 vaccine among residents of two skilled nursing facilities experiencing COVID-19 outbreaks — Connecticut, December 2020–February 2021. MMWR Morb Mortal Wkly Rep. 2021;70(11):396–401. doi:10.15585/mmwr.mm7011e3

  36. U.S. Food & Drug Administration. Coronavirus (COVID-19) Update: FDA Authorizes Moderna and Pfizer-BioNTech COVID-19 Vaccines for Children Down to 6 Months of Age. June 17, 2022.

  37. Food and Drug Administration. Coronavirus (COVID-19) update: FDA authorizes Moderna and Pfizer-BioNTech COVID-19 vaccines for children down to 6 months of age.

  38. Stay Up to Date with COVID-19 Vaccines Including Boosters. Centers for Disease Control and Prevention. August 23, 2022.

  39. Coronavirus (COVID-19) Update: FDA Expands Eligibility for Pfizer-BioNTech COVID-19 Booster Dose to 16- and 17-Year-Olds. U.S. Food and Drug Administration. December 9, 2021.

  40. Coronavirus (COVID-19) Update: FDA Takes Multiple Actions to Expand Use of Pfizer-BioNTech COVID-19 Vaccine. U.S. Food and Drug Administration. January 3, 2022.

  41. Food and Drug Administration. Coronavirus (COVID-19) update: FDA authorizes second booster dose of two COVID-19 vaccines for older and immunocompromised individuals.

  42. Food and Drug Administration. Coronavirus (COVID-19) update: FDA expands eligibility for Pfizer-BioNTech COVID-19 vaccine booster dose to children 5 through 11 years.

  43. Coronavirus (COVID-19) Update: FDA Authorizes Moderna, Pfizer-BioNTech Bivalent COVID-19 Vaccines for Use as a Booster Dose. U.S. Food and Drug Administration. August 31, 2022.

  44. Coronavirus (COVID-19) Update: FDA Authorizes Moderna, Pfizer-BioNTech Bivalent COVID-19 Vaccines for Use as a Booster Dose. U.S. Food and Drug Administration. August 31, 2022.

  45. Food and Drug Administration. Coronavirus (COVID-19) update: FDA limits use of Janssen COVID-19 vaccine to certain individuals.

  46. Voysey M, Costa Clemens SA, 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 UKLancet. 2021;397(10269):99-111. doi:10.1016/S0140-6736(20)32661-1

  47. Voysey M, Costa Clemens SA, Madhi SA, et al. Single-dose administration, and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine. Lancet. 2021;397(10277):881-891. doi:10.1016/S0140-6736(21)00432-3

  48. 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;383(24):2320-2332. doi:10.1056/NEJMoa2026920

  49. Shinde V, Bhikha S, Hoosain Z, et al. Efficacy of NVX-CoV2373 Covid-19 vaccine against the B.1.351 variant. N Engl J Med. 2021;384(20):1899-1909. doi:10.1056/NEJMoa2103055

  50. U.S. Food & Drug Administration. Coronavirus (COVID-19) Update: FDA Authorizes Emergency Use of Novavax COVID-19 Vaccine, Adjuvanted. July 13, 2022.

  51. INOVIO Pharmaceuticals. INOVIO reports FDA partial clinical hold for planned phase 2 / 3 trial of COVID-19 vaccine candidate INO-4800.

  52. Kalil AC, Patterson TF, Mehta AK, et al. Baricitinib plus remdesivir for hospitalized adults with Covid-19N Engl J Med. 2021;384(9):795-807. doi:10.1056/NEJMoa2031994

  53. Emergency Use Authorization (EUA) for emergency use of baricitinib (Olumiant). U.S. Food and Drug Administration. May 10, 2022.

  54. Kinase Inhibitors | COVID-19 Treatment Guidelines. National Institutes of Health. August 8, 2022.‌

  55. Food and Drug Administration. Eli Lilly and Company – authorization of baricitinib.

  56. 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 Respir Med. 2021 Feb;9(2):196-206. doi:10.1016/S2213-2600(20)30511-7

  57. Guaraldi G, Meschiari M, Cozzi-Lepri A, et al. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. Lancet Rheumatol. 2020 Aug;2(8):e474-e484. doi:10.1016/S2665-9913(20)30173-9

  58. Somers EC, Eschenauer GA, Troost JP, et al. Tocilizumab for treatment of mechanically ventilated patients with COVID-19. Clin Infect Dis. 2021;73(2):e445-e454. doi:10.1093/cid/ciaa954

  59. 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. 2021;181(1):41-51. doi:10.1001/jamainternmed.2020.6252

  60. 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 trialJAMA Intern Med. 2021;181(1):24-31. doi:10.1001/jamainternmed.2020.6615

  61. Salama C, Han J, Yau L, et al. Tocilizumab in patients hospitalized with Covid-19 pneumoniaN Engl J Med. 2021;384(1):20-30. doi:10.1056/NEJMoa2030340

  62. Veiga VC, Prats JAGG, Farias DLC, et al. Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trialBMJ. 2021;372:n84. doi:10.1136/bmj.n84

  63. Interleukin-6 Inhibitors | COVID-19 Treatment Guidelines. COVID-19 Treatment Guidelines. December 16, 2021.

  64. Coronavirus (COVID-19) Update: FDA Authorizes Drug for Treatment of COVID-19. U.S. Food and Drug Administration. June 24, 2021.‌

  65. Joyner MJ, Bruno KA, Klassen SA, et al. Safety update: COVID-19 convalescent plasma in 20,000 hospitalized patients. Mayo Clin Proc. 2020;95(9):1888-1897. doi:10.1016/j.mayocp.2020.06.028

  66. 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. Preprint posted online August 12, 2020. doi:10.1101/2020.08.12.20169359

  67. 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. 2021;384(7):610-618. doi:10.1056/NEJMoa2033700

  68. Agarwal A, Mukherjee A, 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. 2020;371:m3939. doi:10.1136/bmj.m3939

  69. Simonovich VA, Burgos Pratx LD, Scibona P, et al. A randomized trial of convalescent plasma in Covid-19 severe pneumoniaN Engl J Med. 2021;384(7):619-629. doi:10.1056/NEJMoa2031304

  70. NIH halts trial of COVID-19 convalescent plasma in emergency department patients with mild symptoms. National Institutes of Health (NIH). March 2, 2021.

  71. Korley FK, Durkalski-Mauldin V, Yeatts SD, et al. Early convalescent plasma for high-risk outpatients with Covid-19N Engl J Med. 2021;385(21):1951-1960. doi:10.1056/NEJMoa2103784

  72. FDA Issues Emergency Use Authorization for Convalescent Plasma as Potential Promising COVID–19 Treatment, Another Achievement in Administration’s Fight Against Pandemic. U.S. Food and Drug Administration. August 23, 2022.

  73. Emergency Use Authorization (EUA) for the emergency use of COVID-19 convalescent plasma. U.S. Food and Drug Administration. December 28, 2021.

  74. Bégin P, Callum J, Jamula E, et al. Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trialNat Med, 2021;27(11):2012-2024. doi:10.1038/s41591-021-01488-2

  75. Merck and Ridgeback’s Investigational Oral Antiviral Molnupiravir Reduced the Risk of Hospitalization or Death by Approximately 50 Percent Compared to Placebo for Patients with Mild or Moderate COVID-19 in Positive Interim Analysis of Phase 3 Study. Merck. October 1, 2021.

  76. Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients. N Engl J Med. 2022;386(6):509-520. doi:10.1056/NEJMoa2116044

  77. Coronavirus (COVID-19) Update: FDA Authorizes Additional Oral Antiviral for Treatment of COVID-19 in Certain Adults. U.S. Food and Drug Administration. December 23, 2021.‌

  78. Pfizer’s Novel COVID-19 Oral Antiviral Treatment Candidate Reduced Risk of Hospitalization or Death by 89% in Interim Analysis of Phase 2/3 EPIC-HR Study. Pfizer. November 5, 2021.

  79. Emergency Use Authorization 105 (Paxlovid). U.S. Food and Drug Administration. August 5, 2022.

  80. Pfizer. Pfizer Shares Top-Line Results from Phase 2/3 EPIC-PEP Study of PAXLOVID™ for Post-Exposure Prophylactic Use. April 29, 2022.

  81. Veru Inc. Veru’s Novel COVID-19 Drug Candidate Reduces Deaths by 55% in Hospitalized Patients in Interim Analysis of Phase 3 Study; Independent Data Monitoring Committee Halts Study Early for Overwhelming Efficacy. April 11, 2022.

  82. Chen C, Zhang Y, Huang J, et al. Favipiravir versus arbidol for clinical recovery rate in moderate and severe adult COVID-19 patients: a prospective, multicenter, open-label, randomized controlled clinical trial. Front Pharmacol. 2021;12:683296. doi:10.3389/fphar.2021.683296

  83. Kinobe RT, Owens L. A systematic review of experimental evidence for antiviral effects of ivermectin and an in silico analysis of ivermectin’s possible mode of action against SARS‐CoV‐2. Fundam Clin Pharmacol. 2021;35(2):260-276. doi:10.1111/fcp.12644

  84. Peña‐Silva R, Duffull SB, Steer AC, Jaramillo‐Rincon SX, Gwee A, Zhu X. Pharmacokinetic considerations on the repurposing of ivermectin for treatment of COVID‐19. Br J Clin Pharmacol. 2021;87(3):1589-1590. doi:10.1111/bcp.14476

  85. Cruciani M, Pati I, Masiello F, Malena M, Pupella S, De Angelis V. Ivermectin for prophylaxis and treatment of COVID-19: a systematic review and meta-analysis. Diagnostics. 2021;11(9):1645. doi:10.3390/diagnostics11091645

  86. Cao B, Wang Y, Wen D, et al. A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020;382(19):1787-1799. doi:10.1056/NEJMoa2001282

  87. Hung IF, Lung KC, Tso EY, 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. 2020;395(10238):1695-1704. doi:10.1016/S0140-6736(20)31042-4

  88. 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. Int J Antimicrob Agents. 2020;56(1):105949. doi:10.1016/j.ijantimicag.2020.105949

  89. Molina JM, Delaugerre C, Le Goff J, 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;50(4):384. doi:10.1016/j.medmal.2020.03.006

  90. RECOVERY Collaborative Group. Effect of hydroxychloroquine in hospitalized patients with Covid-19. N Engl J Med. 2020;383(21):2030-2040. doi:10.1056/NEJMoa2022926

  91. 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. 2021;73(1):36-47. doi:10.1002/art.41469

  92. Cavalcanti AB, Zampieri FG, Rosa RG, et al. Hydroxychloroquine with or without azithromycin in mild-to-moderate Covid-19. N Engl J Med. 2020;383(21):2041-2052. doi:10.1056/NEJMoa2019014

  93. Skipper CP, Pastick KA, Engen NW, et al. Hydroxychloroquine in nonhospitalized adults with early COVID-19: a randomized trial. Ann Intern Med. 2020;173(8):623-631. doi:10.7326/M20-4207

  94. Chen J, Liu D, Liu L, et al. A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19). Zhejiang Da Xue Xue Bao Yi Xue Ban. 2020;49(2):215-219. doi:10.3785/j.issn.1008-9292.2020.03.03

  95. 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. 2021;181(2):195-202. doi:10.1001/jamainternmed.2020.6319

  96. Borba MGS, Val FFA, Sampaio VS, et al. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial. JAMA Netw Open. 2020;3(4):e208857. doi:10.1001/jamanetworkopen.2020.8857

  97. Mercuro NJ, Yen CF, Shim DJ, 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. 2020;5(9):1036-1041. doi:10.1001/jamacardio.2020.1834

  98. Arshad S, Kilgore P, Chaudhry ZS, et al. Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19. Int J Infect Dis. 2020;97:396-403. doi:10.1016/j.ijid.2020.06.099

By Tanya Feke, MD
Tanya Feke, MD, is a board-certified family physician, patient advocate and best-selling author of "Medicare Essentials: A Physician Insider Explains the Fine Print."