Therapeutics

Overview of COVID-19 Therapeutics 

At this time, there is no cure for COVID-19. Remdesivir (Veklury) is currently the only drug approved by the U.S. Food and Drug Administration (FDA) for the treatment of COVID-19, but several other therapeutics have received Emergency Use Authorizations (EUAs) from the FDA. Supply of these therapeutics may be limited, and the National Institutes of Health (NIH) COVID-19 Treatment Guidelines provide priorities for use. Other therapies, such as investigational antivirals, immunotherapy, and infusion of convalescent plasma are under study, or consideration of being studied, for pre-exposure prophylaxis, post-exposure prophylaxis, or treatment of COVID-19. 

Post-exposure prophylaxis therapies are not a substitute for vaccination against COVID-19. FDA currently has authorized three vaccines to prevent COVID-19 and serious clinical outcomes caused by COVID-19, including hospitalization and death. VDH urges you to get vaccinated, if you are eligible. Learn more about VDH’s COVID-19 vaccination efforts or find an appointment at vaccinate.virginia.gov.

The NIH COVID-19 Treatment Guidelines Panel (the Panel) continues to review the most recent clinical data to provide up-to-date treatment recommendations for clinicians who are caring for patients with COVID-19. A summary of selected COVID-19 therapeutics, including those currently approved and authorized by the FDA, is provided below. The Panel has created a figure to summarize their recommendations for managing hospitalized patients based on the severity of disease. The Panel has also created a figure to summarize their recommendations for managing non-hospitalized patients based on patient disposition. A summary of additional considerations in selected special populations is also provided below. Clinicians should check the NIH COVID-19 Treatment Guidelines regularly for information on the use of COVID-19 therapeutics and updates. Additionally, Yale School of Medicine provides an algorithm with treatment guidance for hospitalized adults with COVID-19 on their Internal Medicine homepage here. Emergency use authorization timelines about monoclonal antibodies as well as materials such as fact sheets for providers and patients can be found here

For patients without health insurance, healthcare providers can obtain compensation for all facets of COVID-19 care including testing, testing-related office visits, treatment (outpatient, inpatient, nursing home, etc.), rehabilitation care, emergency transport & more. The patient MUST have a primary diagnosis of COVID-19 to be eligible. Learn more about the HRSA COVID-19 Uninsured Program here.

For more on monoclonal antibodies, VDH’s COVID-19 Monoclonal Antibody Therapy Resource Center offers healthcare providers general information and FAQs, resources on specific products, and guidance on infusion and billing. 

Summary of Selected COVID-19 Therapeutics as of September 4, 2021

Drug Name Status with the FDA Summary of Recommendations*
Remdesivir (Veklury) Approved for use in hospitalized patients aged 12 years or older and weighing at least 40 kg for the treatment of COVID-19

Authorized for use in hospitalized children less than 12 years old and weighing at least 3.5 kg or pediatric patients weighing 3.5 kg to <40 kg

Remdesivir monotherapy is prioritized for hospitalized adult and pediatric patients (aged 12 years or older and weighing at least 40 kg) who require supplemental oxygen but who are not on high-flow oxygen, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

Hospitalized pediatric patients (less than 12 years old and at least 3.5 kg or weighing 3.5 kg to <40 kg) can also receive remdesivir through an EUA.

Dexamethasone plus Remdesivir Recommended for certain uses by the COVID-19 Treatment Guidelines Panel Recommended for hospitalized patients with COVID-19 who require supplemental oxygen (e.g., when increasing amounts of oxygen are needed), oxygen delivery through a high-flow device, or noninvasive ventilation.
Dexamethasone and other corticosteroids (prednisone, methylprednisolone, or hydrocortisone) Recommended for certain uses by the COVID-19 Treatment Guidelines Panel Dexamethasone is recommended for hospitalized patients with COVID-19 who require supplemental oxygen (e.g., when combination therapy with remdesivir is unavailable), oxygen delivery through a high-flow device, noninvasive ventilation, invasive mechanical ventilation, or ECMO. The Panel recommends against use in non-hospitalized patients and hospitalized patients who do not require supplemental oxygen. 

When dexamethasone is not available, alternative corticosteroids (e.g., prednisone, methylprednisolone, or hydrocortisone) can be used.

Tocilizumab (Actemra) Authorized by the FDA on June 24, 2021 for use in hospitalized patients aged 2 years of age and older Tocilizumab (Actemra) is recommended for hospitalized patients with COVID-19 who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or ECMO. It is not authorized for outpatients with COVID-19.
Tocilizumab plus dexamethasone Recommended for certain uses by the COVID-19 Treatment Guidelines Panel Certain hospitalized patients with rapid respiratory decompensation because of COVID-19. This population includes: 

  • Recently hospitalized patients admitted to the ICU in the past 24 hours who require invasive mechanical ventilation or ECMO.
  • Recently hospitalized patients (e.g., within 3 days of admission) with rapidly increasing oxygen needs  and significantly increased markers of inflammation who require oxygen delivery through a high-flow device or noninvasive ventilation. An alternative option for these patients is tocilizumab in combination with dexamethasone plus remdesivir. 

Use should be avoided in patients with significant immunosuppression. Additional exclusions and considerations are available here.

Baricitinib (Olumiant) Authorized by the FDA July 28, 2021 for use in hospitalized patients aged 2 years of age and older Baricitinib (Olumiant) is recommended for hospitalized patients requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). Under the revised EUA, baricitinib is no longer required to be administered with remdesivir (Veklury).
Baricitinib in combination with dexamethasone alone or dexamethasone plus remdesivir  Recommended for certain uses by the COVID-19 Treatment Guidelines Panel

 

Baricitinib in combination with remdesivir is authorized for use in certain hospitalized adult and pediatric patients (aged 2 years or older) requiring supplemental oxygen, invasive mechanical ventilation, or ECMO.

 

The Panel recommends using baricitinib in combination with dexamethasone alone or dexamethasone plus remdesivir for the treatment of COVID-19 in hospitalized patients on high-flow oxygen or noninvasive ventilation who have evidence of clinical progression or increased markers of inflammation. 

In rare circumstances when corticosteroids cannot be used, the Panel recommends the use of baricitinib with remdesivir for treating hospitalized, non-intubated patients who require oxygen supplementation. 

Clinical trials have been performed in hospitalized adults. Pediatric data are limited. There is not enough evidence for the Panel to recommend for or against use of baricitinib to treat children with COVID-19.

Casirivimab plus imdevimab (Regeneron) Authorized
EUA revised on July 30, 2021
Recommended for the treatment of adult and pediatric patients (aged 12 years or older and weighing at least 40 kg) with a positive SARS-CoV-2 viral test result and mild to moderate COVID-19 who are at high risk for progressing to severe disease and/or hospitalization as defined by the EUA criteria.* Administration is recommended as soon as possible after a positive SARS-CoV-2 viral test and within 10 days of symptom onset. Patients who are hospitalized because of COVID-19 should not receive anti-SARS-CoV-2 monoclonal antibodies, except in clinical trials.

Recommended as post-exposure prophylaxis (prevention) for COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kilograms) who are at high risk for progression to severe COVID-19, including hospitalization or death. Casirivimab plus imdevimab is not authorized for pre-exposure prophylaxis to prevent COVID-19 before being exposed to the SARS-CoV-2 virus -- only after exposure to the virus. Casirivimab plus imdevimab should only be used as post-exposure prophylaxis for specific patient populations as soon as possible following exposure to SARS-CoV-2.

Sotrovimab Authorized by the FDA on May 26, 2021 Recommended for the treatment of adult and pediatric patients (aged 12 years or older and weighing at least 40 kg) with a positive SARS-CoV-2 viral test result and mild to moderate COVID-19 who are at high risk for progressing to severe disease and/or hospitalization as defined by the EUA criteria.*

Administration is recommended as soon as possible after a positive SARS-CoV-2 viral test and within 10 days of symptom onset.

Patients who are hospitalized because of COVID-19 should not receive anti-SARS-CoV-2 monoclonal antibodies, except in clinical trials.

Bamlanivimab plus etesevimab Authorized
EUA revised on September 2, 2021
Recommended for the treatment of adult and pediatric patients (aged 12 years or older and weighing at least 40 kg) with a positive SARS-CoV-2 viral test result and mild to moderate COVID-19 who are at high risk for progressing to severe disease and/or hospitalization as defined by the EUA criteria.*

Administration is recommended as soon as possible after a positive SARS-CoV-2 viral test and within 10 days of symptom onset.

Patients who are hospitalized because of COVID-19 should not receive anti-SARS-CoV-2 monoclonal antibodies, except in clinical trials.

On April 16, 2021, the FDA revoked the EUA that allowed for bamlanivimab alone to be given to adult and certain pediatric patients with mild to moderate COVID-19. The spread of SARS-CoV-2 viral variants resistant to bamlanivimab monotherapy increases the risk of treatment failure. The FDA determined that the known and potential benefits of the treatment no longer outweigh the known and potential risks. Healthcare providers could consider the use of other monoclonal antibody therapies that remain available under EUA. More information is available here. The Panel also provides recommendations based on what is currently known about the susceptibility of SARS-CoV-2 viral variants to authorized monoclonal antibody therapies here

As of June 11, 2020, the Panel recommends against the use of chloroquine or hydroxychloroquine  for the treatment of COVID-19, except in a clinical trial. A summary of the FDA review of safety issues with the use of hydroxychloroquine and chloroquine to treat hospitalized patients with COVID-19 is available here. This includes reports of serious heart rhythm problems and other safety issues, including blood and lymph system disorders, kidney injuries, and liver problems and failure.

On August 26, 2021, CDC issued a Health Alert Network health advisory regarding the use of Ivermectin. “Ivermectin is not authorized or approved by FDA for prevention or treatment of COVID-19. The National Institutes of Health’s (NIH) COVID-19 Treatment Guidelines Panel has also determined that there are currently insufficient data to recommend ivermectin for treatment of COVID-19. ClinicalTrials.gov has listings of ongoing clinical trials that might provide more information about these hypothesized uses in the future."

As of September 2, 2021, based on FDA’s evaluation of the most recently available SARS-CoV-2 variant frequency data, bamlanivimab and etesevimab, administered together, can be used in all U.S. states, territories, and jurisdictions under the conditions of authorization for EUA 94. ASPR will resume the distribution of bamlanivimab and etesevimab together and etesevimab alone (to pair with existing supply of bamlanivimab at a facility for use under EUA 094) to all U.S. states, territories, and jurisdictions.

COVID-19 Therapeutics: Additional Considerations in Selected Special Populations

At this time, most available data on the epidemiology, clinical course, prevention, and treatment of COVID-19 have come from studies of nonpregnant adults. More information is needed regarding COVID-19 in other patient populations, such as children, pregnant individuals, and patients with immunocompromising conditions. Because of this, it is difficult to make evidence-based recommendations on the use of SARS-CoV-2 therapies in these patients and potentially limits their COVID-19 treatment options. When possible, these populations should not be excluded from clinical trials of therapeutic agents or vaccines for SARS-CoV-2 infection.

Children

  • COVID-19 Therapy Recommendations: 
    • Given the typically mild course of pediatric COVID-19, supportive care alone is suggested for the overwhelming majority of cases. Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. If an antiviral is used, remdesivir is the preferred agent.
    • Currently only remdesivir is approved for use in hospitalized patients with COVID-19 who are aged ≥12 years and weigh ≥40 kg and authorized for use for younger children (and those weighing <40 kg and >3.5 kg). The safety and effectiveness of remdesivir for treatment of COVID-19 has not yet been evaluated in children; however, the Panel does recommend using remdesivir for certain pediatric patients. Additionally, the Panel recommends using dexamethasone  for pediatric patients with COVID-19 respiratory disease who require high flow oxygen, noninvasive ventilation, or invasive mechanical ventilation. 
    • Guidance for the treatment of children with COVID-19 is mostly extrapolated from the recommendations for treatment of adults. 
  • Additional Considerations: 
    • There is limited information about risk factors, pathogenesis, clinical course, and treatment for Multisystem Inflammatory Syndrome in Children (MIS-C). At this time, only observational data are available to guide MIS-C treatment. Consultation with a multidisciplinary team is recommended when discussing treatment for patients with MIS-C. Summaries of current recommendations and findings are available here

People who are pregnant or breastfeeding

  • COVID-19 Therapy Recommendations:
    • Potentially effective treatments for COVID-19 should not be withheld from pregnant or lactating patients because of theoretical concerns related to the safety of these therapeutics in pregnancy. 
    • Decisions regarding the use of drugs approved for other indications or investigational agents for the treatment of COVID-19 in pregnant patients must be made with shared decision-making between the patient and the clinical team, considering the safety of the medication for the pregnant or lactating person and the fetus and the severity of disease. 
    • The decision to feed the infant breast milk while the lactating patient is receiving therapeutic agents for COVID-19 should be a collaborative effort. The patient and the clinical team should discuss the potential benefits of the therapeutic agent and evaluate the potential impact of pausing lactation on the future of breast milk delivery to the infant.
    • The American College of Obstetricians and Gynecologists (ACOG) has developed an algorithm to evaluate and manage pregnant outpatients with suspected or confirmed SARS-CoV-2 infection.
  • Additional Considerations:
    • Management of COVID-19 in the pregnant patient should include: Fetal and uterine contraction monitoring, when appropriate based on gestational age; individualized delivery planning; a team-based approach that may include consultation with obstetric, maternal-fetal medicine, infectious disease, pulmonary and critical care, and pediatric specialists, as appropriate.
    • In most cases, the timing of delivery should be dictated by obstetric indications rather than maternal diagnosis of COVID-19.
    • Breastfeeding is not contraindicated for people with laboratory-confirmed or suspected SARS-CoV-2 infection. Precautions should be taken to avoid transmission to the infant, including practicing good hand hygiene, wearing face coverings, and performing proper pump cleaning before and after breast milk expression. 

People with immunocompromising conditions

Other special population considerations including immunocompromising conditions, such as cancer, transplant, and HIV, are available from the NIH COVID-19 Treatment Guidelines. Clinicians should pay careful attention to potential drug-drug interactions and overlapping toxicities between drugs that are used to treat COVID-19 and other medications the individuals may be taking. Clinicians treating COVID-19 in immunocompromised individuals should consult with the appropriate specialists before adjusting or switching medications.

Additional Resources

Remdesivir (Veklury)

Dexamethasone and Other Corticosteroids 

Tocilizumab (Actemra) 

Baricitinib (Olumiant)

Baricitinib plus Remdesivir 

Casirivimab plus imedevimab (Regeneron) 

Sotrovimab

Bamlanivimab plus etesevimab

 

Page last updated: September 15, 2021