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, ten treatments have been granted 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, revoked in April 2021), baricitinib combined with remdesivir (November 2020), combined casirivimab and imdevimab monoclonal antibodies (November 2020), the Pfizer-BioNTech mRNA vaccine (December 2020 for ages 16+, May 2021 for ages 12 to 15), the Moderna mRNA vaccine (December 2020), combined bamlanivimab and etesevimab monoclonal antibodies (February 2021), the Johnson & Johnson adenovirus-vectored vaccine (February 2021), and sotrovimab monoclonal antibody (May 2021).

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 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. People with moderate infections, however, did not show significant improvement when treated with 10 days of remdesivir vs. standard care.

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 time, WHO has formally advised against using the drug for hospitalized patients. Gilead Sciences has challenged these results, and a peer review is pending.

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 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% 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 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 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.

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 2 days and decreased fever recurrence over 7 days.

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.

What the Research Says

Two small 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.

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. 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. 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 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.

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 2020, the EUA was updated. Only high-antibody-titer convalescent plasma is now approved for use. It has also been limited to hospitalized patients early in the course of their disease or in hospitalized patients who are immunocompromised.

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

Regeneron Pharmaceuticals Inc. developed 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. After adding an additional 524 people to their trial, REGN-COV2 was found to decrease 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 were 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.

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. 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".

Regeneron released Phase 3 trial results in a press release, announcing that their casirivimab-imdevimab cocktail decreased COVID-19 infection in people with high-risk exposures. The study randomized 400 people to treatment or placebo. 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 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 who and treated them with either casirivimab-imdevimab or placebo within 4 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 (1 week vs. 3 weeks).

Other Synthetic Antibodies

Regeneron Pharmaceuticals Inc. is not the only company looking to explore the effectiveness of synthetic antibodies made in the laboratory.

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.

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 December 2020, 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.

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 8 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%).

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 April 2021, the emergency use authorization for bamlanivimab monotherapy was revoked due 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 U.S. Department of Health and Human Services will no longer distribute this treatment on its own. It will continue to be made available in combination with etesevimab.

GlaxoSmithKline — 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. The treatment decreased the risk for hospitalization or death by 85% when compared to placebo. In vitro studies have also shown VIR-7831 to be effective against the Indian, UK, South African, and Brazilian virus variants. Emergency use authorization was granted by the FDA on May 26, 2021.

AstraZeneca — AZD7442

AstraZeneca developed investigation antibodies (AZD7442) to treat and hopefully prevent COVID-19 infection in people exposed to the virus. Preclinical studies showed effectiveness in mice. Their Phase III study included 1,121 people from the United States and United Kingdom who had been exposed to someone with the virus within the past 8 days. Although there was a 33% reduction in infections in the treatment group, AstraZeneca stated this was not statistically significant and more likely related to chance based on the study design (2 people treated for every 1 person given a placebo).

Vaccines for COVID-19

The best hope for managing COVID-19 long-term are 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. —Vaccine Candidate BNT162b2

Efficacy: In November 2020, early data from a Phase III 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 7 days after a second dose, 94 people developed symptomatic COVID-19 from a study population of 43,538 people (30% were people of color). They released additional data 9 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, 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.

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 7 days after their second dose).

Virus Variants

Some strains of the virus, also known as variants, have developed mutations in the spike protein that could change the effectiveness of some vaccines. Many variants have been discovered to date. Here are four of the most researched.

  • British variant: Also known as B.1.1.7, this variant includes 8 mutations in the spike protein) and was first detected in September 2020.
  • South African variant: Also known as B.1.351, this variant includes 10 mutations in the spike protein and was first detected in October 2020.
  • Delta variant: Also known as B.1.617.2, this variant includes 10 mutations in the spike protein and was first detected in December 2020.
  • Brazilian variant: Also known as B.1.28.1, this variant includes 3 mutations in the spike protein and was first detected in January 2021.

Virus Variants: Pfizer assessed the serum of 40 people who had received both doses of the vaccine and tested it against a virus similar to the original virus detected in Wuhan, China (as a control) and then to a virus with the spike protein mutations found in the British variant. The goal was to see how effective the serum was in neutralizing those viruses. Serum from younger study participants (23-55 years old, n=26) neutralized the British variant at a 78% rate and those from older participants (57-73 years old, n=14) at an 83% rate. They then went on to test against other variants. Neutralizing antibody assays were performed on the serum of 20 vaccinated people using a control virus and viruses with mutations found in the British and South African variants. In 6 of the sera, titers were only half as effective against the South African variant. That said, in 10 of the sera, titers were twice as high against the British variant. A preliminary report of serum from 15 vaccinated recipients in the New England Journal of Medicine found a two-thirds decreased ability to neutralize the B.1.351 variant. In June 2021, the U.K. reported that 2-dose vaccination was 96% effective against hospitalizations due to the delta variant. In July 2021, Canadian research showed 2 doses to be 87% effective against symptomatic infection from the delta variant. Israeli, however, tweeted it to be less effective at 64%. The data for that has not yet been formally released. Pfizer is looking into a third vaccine dose as a way to boost the antibody response against COVID-19 variants.

Children: Early results from a Phase III trial of 2,260 adolescents from 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. They were granted an emergency use authorization for this age group on May 10, 2021. Trials are underway to assess the effectiveness of vaccination in younger children.

Complications: The CDC reports a small increase in myocarditis cases with vaccination. Based on data through May 31, 2021, people 16 to 24 years old accounted for 52.5% of vaccine-related cases even though they only represented 8.7% of the people vaccinated. These cases were reported within 21 days of a vaccine dose. Looking at people 16 to 39 years old, the second dose was associated with the greatest risk, more so for boys and young men. Rates were at 10.4 cases per million people for the Pfizer vaccine. Israel reported 148 cases of myocarditis in young men, out of 5 million doses, that were associated in time with the vaccine. That said, the risk remains very low and most people tend to recover from myocarditis quickly. Noting that the risks of COVID-19 are greater than those for myocarditis, the CDC continues to recommend vaccination for everyone 12 years and older.

Storage: Concerns have been raised about the need to store the vaccine using cold chain technology, i.e., freezing it at -70 degrees Celsius (-94 degrees Fahrenheit). Pfizer developed special temperature-controlled containers using dry ice with GPS-thermal tracking to assure the vaccine was maintain at proper temperatures during shipping. Data provided to the FDA has since shown that the vaccine remains stable at standard freezer temperatures up to 2 weeks.

Approval: The vaccine was approved for use in the United Kingdom on December 2, 2020. 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.

Moderna Inc. — Vaccine Candidate mRNA-1273

Preliminary Results: 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.

Efficacy: 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 developed symptomatic 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 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.

Virus Variants: Moderna performed an in vitro analysis, testing the serum from 8 vaccinated people from their Phase I trial against the B.1.1.7 and B.1.351 variants. The company claims there was no significant decrease in neutralizing titers against the British variant but noted a 6-fold decrease in titers to the South African variant. A preliminary report of serum from vaccinated recipients in the New England Journal of Medicine found a marginal 1.2-fold decrease in the ability to neutralize the B.1.17 variant but a 6.4-fold decrease against the B.1.351 variant. Moderna has since developed a new vaccine targeted against the B.1.351 variant. A Phase II trial of this new vaccine was tested in 40 people who had previously received the 2-dose vaccination series but who had low antibody titers to variants B.1.351 and P.1. The booster dose was administered 6 to 8 months after the initial series and showed a boost in immunity against these two variants. A Canadian study reported that one dose of the vaccine protected against symptomatic infection (72%) but did not provide information regarding two dose effectiveness.

Children: Their Phase II/III 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.

Complications: Similar to the mRNA-based Pfizer vaccine, there has been an increase in myocarditis for people shortly after mRNA-based Moderna vaccination (see above). Within 21 days of a Moderna vaccine dose, rates for myocarditis were reported by the CDC to be at 24.7 cases per million people, more so in younger males. Since the CDC reports that the risks of COVID-19 far outweigh the risks of myocarditis, vaccination continues to be recommended.

Approval: 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.

AstraZeneca — Vaccine Candidate AZD1222 (previously ChAdOx1)

Preliminary Results: 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.

Efficacy:

  • 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 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%.
  • In February 2021, they released more Phase III 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 6 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.

Virus Variants: To check efficacy against the B.1.1.7 variant, researchers sequenced the viral genome from 499 Phase II/III participants who contracted COVID-19. There was a 9-fold decrease in neutralizing antibodies against B.1.1.7 when compared to the original virus. For people exposed to the B.1.1.7 variant, efficacy was 75% against symptomatic COVID-19 infection but only 27% against asymptomatic infection. This was in contrast to 84% and 75% respectively for the original strain. Effectiveness against the B.1.351 variant was considerably lower. A study in the New England Journal of Medicine looked at more than 2,000 people who had received at last one dose of the vaccine in South Africa. The vaccine prevented mild-to-moderate COVID-19 only 22% of the time. Of the people who were infected, 93% were infected with the B.1.35 variant. Altogether, efficacy against that variant was only 10%. The U.K. reported that this vaccine was 92% effective against hospitalization from the delta variant.

Complications: Several European countries temporarily halted administration of the vaccine in March 2021 due to concerns for associated blood clots with low platelets (7 cases of disseminated intravascular coagulation and 18 cases of cerebral venous sinus thrombosis out of 20 million vaccinated people). Later that month, the European Medicines Agency concluded that the benefits of the AstraZeneca vaccine outweigh the potential risks. Since then, two studies confirmed thrombosis or bleeding problems after vaccination, including the development of anti-platelet antibodies. The first identified 11 cases (9 women, 2 men) in Germany and Norway between 5 and 16 days after vaccination. The second found 5 cases (4 women, 1 man) in Norway between 7 and 10 days of vaccination. Another study in Scotland reviewed the risk for blood clots, low platelet counts, or bleeding in the brain in 1.71 million people vaccinated with AstraZeneca vaccine. Nineteen cases of cerebral venous sinus thrombosis (CSVT) were identified but only six of them occurred after vaccination. ITP was also very rare, affecting only 1.13 in 100,000 vaccinated people. 

Approval: The vaccine was approved for use in the United Kingdom on December 30, 2020. The first doses were administered on January 4, 2021. The World Health Organization recommended use of the vaccine in February 2021.

Johnson & Johnson — Vaccine Candidate Ad26.COV2.S

Preliminary Results: 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. 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. 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.

Efficacy: Their Phase 3 trial has included more than 43,000 people and there have been 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.

Virus Variants: A small study of 20 vaccinated people showed that immunity remained strong against the South African and Brazilian variants. The amount of neutralizing antibodies produced was not as high as it was with other strains of COVID-19 but the T cell response remained strong. A July 2021 press release announced that the vaccine was protective against the delta variant (n=8), generating neutralizing antibodies at levels higher than it did against the South African variant.

Complications: The CDC and FDA recommended a temporary pause in using the vaccine due to concerns for possible blood clots. Of the more than 6.8 million doses administered by early April 2021, 6 women developed cerebral venous sinus thrombosis and low platelet levels. Symptoms occurred 6 to 13 days after vaccination. After careful review, the pause on the vaccine was lifted on April 23. Updated data showed 15 cases of thrombosis and thrombocytopenia syndrome in 7.98 million vaccine doses. Overall, the rate for these complications was 1.9 per 1 million doses overall but 7 per 1 million doses in women 18 to 49 years old. In July 2021, the FDA added warning and precautions to the EUA, this time for an increased risk for Guillain -Barre syndrome. They noted that risk for the condition increased within 42 days of vaccination. There were approximately 100 cases reported over 12.8 million vaccinations.

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.

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 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.

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.

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.

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 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.

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. Some have shown potential harm. A Brazilian study of 129 critically ill COVID-19 patients were treated with tocilizumab with 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.

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 a drug that blocks the replication of some RNA viruses. 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: A phase 2 clinical trial included 78 non-hospitalized people with symptomatic COVID-19 and detectable levels of virus on their baseline nasopharyngeal swab. Treatment with molnupiravir decreased their viral load to 0 by day 5 (0/47) but virus remained detectable in 24% of the placebo group (6/25). No serious side effects were attributed to the treatment.

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.

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. 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).

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.

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.

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