Health Care: COVID-19

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Infectious Disease Epidemiology, Prevention and Control Division
651-201-5414
IDEPC Comment Form

Contact Info

Infectious Disease Epidemiology, Prevention and Control Division
651-201-5414
IDEPC Comment Form

Therapeutic Options for COVID-19 Patients

Information about investigational medication treatments (therapeutics), to be updated as new information is available.

FDA Announcement, Nov. 30, 2022

The FDA announced bebtelovimab is no longer authorized for use in the U.S. as it is not expected to neutralize Omicron subvariants BQ.1 and BQ.1.1. Refer to FDA Announces Bebtelovimab is Not currently Authorized in Any US Region for more information. Patients currently scheduled for bebtelovimab should be referred for alternative therapeutic options.

COVID-19 Therapeutics Webinar: Dec. 7, 2022

The Minnesota Department of Health invites prescribers to the webinar “Antiviral Therapies for COVID-19: A Review of Current Therapeutic Options.”
Wednesday, Dec. 7, 2022 | 12 - 1 p.m. CST

This 1-hour presentation will provide an overview of currently authorized outpatient therapeutic options for the prevention and treatment of COVID-19 and a case-based discussion on the indications and use of various treatment options. It is intended for all health care providers who may assess patients who are at risk for COVID-19 or present with acute COVID-19 infection, including physician and non-physician prescribers in primary care, specialty care, urgent care settings, pharmacies, or in congregate settings such as long-term care facilities. This webinar is free and registration is required.
Register

Webinar presenter, moderator, and objectives
The webinar will be recorded for those who are unable to join and will be posted when available.
Featured speaker
Raymund Razonable, MD
Professor of Medicine and Vice Chair of Infectious Diseases
Mayo Clinic, Rochester, MN
Moderator
Sarah Lim, MD, MPH
Medical Specialist and Clinical Lead of COVID-19 Therapeutics Distribution Program
Minnesota Department of Health, St. Paul, MN
Learning objectives
Appreciate strategies for preventing severe COVID-19 in high-risk persons.
Explore different options for treatment of COVID-19 in high-risk patients as variants evolve.
Understand reasons for choosing among the various drugs for the management of COVID-19.

MMA Disclosure: COVID Therapeutics (PDF)
Continuing education
This activity has been approved for 1.0 AMA PRA Category 1 Credit™
Minnesota Medical AssociationThis activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the Minnesota Medical Association and the Minnesota Department of Health. The Minnesota Medical Association (MMA) is accredited by the ACCME to provide continuing medical education for physicians.
  • An application has been submitted to the Minnesota Board of Pharmacy for continuing education approval.
  • Other participants are responsible for determining if this training meets CE criteria for their professional organization.

 

Antiviral Therapy Resources for Providers
Includes eligibility, treatment options, management of drug interactions, and pharmacy locations for prescribing outpatient antiviral therapy for acute COVID-19.		 Antiviral Resources: medication bottle and IV bag icons

Oral antivirals

New oral antivirals for the treatment of COVID-19 include molnupiravir and nirmatrelvir/ritonavir (Paxlovid). These have received emergency use authorization from the FDA, and are being distributed to states by the federal government. These therapies are for the treatment of mild to moderate COVID-19 in outpatients and are not authorized for the treatment of patients hospitalized due to COVID-19 or for pre- or post-exposure prophylaxis.

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Nirmatrelvir/ritonavir (Paxlovid)
  • Nirmatrelvir/ritonavir is an oral antiviral treatment that combines a SARS-CoV-2 protease inhibitor (nirmatrelvir) with ritonavir, an HIV-1 protease inhibitor and CYP3A inhibitor. Ritonavir acts as a pharmacological booster to increase the levels of nirmatrelvir. It is authorized for the treatment of mild-to-moderate COVID-19 in patients at high risk for severe illness from COVID-19. Treatment must be started within five days of symptom onset and is given as a five-day treatment course. In the EPIC-HR trial, ritonavir-boosted nirmatrelvir (Paxlovid) reduced the risk of hospitalization or death by 88% compared to placebo in nonhospitalized adults with laboratory-confirmed SARS-CoV-2 infection.

NOTE: The following are limitations to the use of Paxlovid:

  • Paxlovid is not authorized for use in patients younger than 12 years.
  • Paxlovid is not recommended for use in patients with severe renal impairment (GFR<30ml/min) or hepatic impairment (Child-Pugh Class C).
  • For patients with moderate renal impairment (GFR 30-60ml/min), the dose of nirmatrelvir should be reduced from 300mg to 150mg (refer to FDA: Fact Sheet for Providers below).

Due to the co-administration with ritonavir, it is critical to evaluate the patient medication regimen for potentially serious drug-drug interactions prior to prescribing Paxlovid. Please refer to guidance on Antiviral Therapy Resources for Providers.

There have been recent case reports of COVID-19 rebound following treatment with Paxlovid. These cases of COVID-19 rebound had negative test results after Paxlovid treatment and resolution of symptoms, followed by recurrence of symptoms and positive viral antigen and/or PCR testing. The limited information currently available suggests that these patients typically have mild illness that resolves within days without additional COVID-19 treatment, but patients should still be counseled to follow isolation guidance. More information for providers is available at CDC Health Alert Network: COVID-19 Rebound After Paxlovid Treatment. Health care providers are encouraged to report cases of COVID-19 rebound to Pfizer using Pfizer's COVID-19 Treatment Adverse Event Reporting online tool and to the FDA using MedWatch: The FDA Safety Information and Adverse Event Reporting Program.

Molnupiravir
  • Molnupiravir is an oral nucleoside analogue that inhibits SARS-CoV-2 replication by inducing viral mutagenesis. It is authorized for the treatment of mild to moderate COVID-19 in patients at high risk for severe illness from COVID-19. Treatment must be started within five days of symptom onset and is given as a five-day treatment course. In the MOVe-OUT trial, molnupiravir reduced the rate of hospitalization or death by 30% compared to placebo.

NOTE: the following are limitations to the use of molnupiravir.

  • Molnupiravir is not authorized for use in patients younger than 18 years.
  • Molnupiravir is not recommended for use in pregnancy. Patients of childbearing potential should be advised to use effective contraception correctly and consistently, as applicable, for the duration of treatment and for four days after the last dose of molnupiravir.
  • Molnupiravir is not recommended for use while breastfeeding. Breastfeeding is not recommended during treatment and for four days after the last dose of molnupiravir. A lactating individual may consider interrupting breastfeeding and may consider pumping and discarding breast milk during treatment and for four days after the last dose of molnupiravir.

More information can be found at Antiviral Therapy Resources for Providers.

Remdesivir

Remdesivir is approved by the FDA under the name Veklury for the treatment of COVID-19 in adult and pediatric patients (ages 28 days and older and weighing at least 3 kg) who are either hospitalized or who are not hospitalized but have mild to moderate COVID-19 and are at high risk for progression to severe illness.

Authorization, guidelines, and resources

It was previously approved only in hospitalized patients, but approval was expanded by the FDA on Jan. 21, 2022, to include use in non-hospitalized patients: FDA Takes Actions to Expand Use of Treatment for Outpatients with Mild-to-Moderate COVID-19. The approval was expanded again on April 25, 2022, to include pediatric patients ages 28 days and older and weighing at least 3 kg: Coronavirus (COVID-19) Update: FDA Approves First COVID-19 Treatment for Young Children.

Remdesivir has been studied in non-hospitalized patients with mild to moderate illness who are at high risk of progressing to more severe illness. A clinical trial (PINETREE) showed that three consecutive days of IV remdesivir resulted in an 87% reduction in the risk of hospitalization or death compared to placebo.

  • Dosing is 200mg IV on day 1, followed by 100mg IV once daily on days two and three
  • Treatment should be initiated as soon as possible and within seven days of symptom onset

More information:

More information can be found at Antiviral Therapy Resources for Providers.

Monoclonal antibody (mAb) treatment

Monoclonal antibody treatments are available through Food and Drug Administration (FDA) emergency use authorizations (EUA) for the prevention of illness due to COVID-19 in nonhospitalized people.

Note: As of Nov. 30, 2022, the only mAb authorized for use for COVID-19 in the U.S. is Evusheld (tixagevimab/cilgavimab), which is used for pre-exposure prophylaxis. Bebtelovimab is no longer authorized for use due to lack of activity against circulating variants. There are currently no authorized mAbs for the treatment of acute infection.

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General resources for health care providers on monoclonal antibody administration and billing
Variants

Certain circulating SARS-CoV-2 viral variants may be associated with resistance to monoclonal antibodies. Health care providers should review the viral neutralization data in the authorized fact sheets for each mAb available under EUA for details regarding specific variants and resistance (see below). Information on the proportion of SARS-CoV-2 variants circulating in the U.S. is available on CDC COVID Data Tracker: Variant Proportions and will be updated regularly.

Please note that although sequencing information is helpful on a population level, individual patient results will not be reported back to the provider or submitting laboratory. Whole genome sequencing is not currently approved for use as a diagnostic test to make individual patient treatment decisions. In addition, the lengthy turnaround time for this type of testing means it is unsuitable for treatment decisions involving mAbs, which should be given as soon as possible once a patient has developed symptoms and tests positive.

Evusheld (Tixagevimab/Cilgavimab)

Tixagevimab/cilgavimab is available for use through HHS allocation and distribution.

NIH: special considerations in people who are immunocompromised

National Institutes of Health (NIH) recommendations on eligibility for use of tixagevimab/cilgavimab for pre-exposure prophylaxis for patients with moderate or severe immunocompromise, including but not limited to:

  • Active treatment for solid tumor and hematologic malignancies
  • Hematologic malignancies that are associated with poor responses to COVID-19 vaccines or an increased risk of severe COVID-19 (e.g., acute leukemia, chronic lymphocytic lymphoma, non-Hodgkin lymphoma, plasma cell dyscrasias), regardless of the treatment status for the hematologic malignancy.
  • Solid-organ transplant or an islet transplant and are receiving immunosuppressive therapy.
  • Chimeric antigen receptor T cell (CAR T-cell) therapy or a hematopoietic stem cell transplant (HCT) and are within 2 years of transplantation or are receiving immunosuppressive therapy.
  • Moderate or severe primary immunodeficiency (e.g., common variable immunodeficiency disease, severe combined immunodeficiency, DiGeorge syndrome, Wiskott-Aldrich syndrome).
  • Advanced or untreated HIV infection (defined as people with HIV and CD4 T lymphocyte [CD4] cell counts <200 cells/mm3, a history of an AIDS-defining illness without immune reconstitution, or clinical manifestations of symptomatic HIV).
  • Active treatment with high-dose corticosteroids (i.e., ≥20 mg prednisone or equivalent per day when administered for ≥2 weeks), alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive, and biologic agents that are immunosuppressive or immunomodulatory.

Patients with other medications or conditions that result in moderate to severe immune compromise may also be eligible. Please refer to the FDA's Fact Sheet for Healthcare Providers on tixagevimab/cilgavimab for updates to eligibility and dosing.

Providers with questions about the availability of tixagevimab/cilgavimab should contact the patient's specialist provider for information. Providers who are not currently receiving distributions of Evusheld, but are interested in small volume ordering (1-3 patient courses), may now place those orders directly with the federal government at EVUSHELD Small Volume Order Form. AstraZeneca has established a helpline for providers with questions about prescribing and ordering: 1-833-EVUSHLD (833-388-7453).

On Oct. 3, 2022, FDA updated the provider fact sheet to include information on the increased risk for developing COVID-19 when exposed to variants of SARS-CoV-2 that are not neutralized by Evusheld. Details are available in the FDA: Fact Sheet for Healthcare Providers for Evusheld. Patients receiving tixagevimab/cilgavimab should be counseled about this potential risk and should be advised about continuing all other COVID-19 mitigation efforts including vaccination of family and caregivers; diligent, high-quality mask wearing when recommended; and avoidance of large gatherings. Patients should also be advised to test for SARS-CoV-2 infection if they develop signs or symptoms of COVID-19 and should seek medical attention immediately if positive for consideration of antiviral treatment.

Other monoclonal antibodies
  • As of Jan. 24, 2022, REGEN-COV (casirivimab/imdevimab) and bamlanivimab/etesevimab are no longer authorized for use due to lack of activity against circulating variants.
  • As of March 30, 2022, sotrovimab is no longer authorized for use due to lack of activity against circulating variants.
  • As of Nov. 30, 2022, bebtelovimab is no longer authorized for use due to lack of activity against circulating variants.

Other treatments

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Convalescent plasma

COVID-19 convalescent plasma (CCP) is human plasma obtained from donors who have recovered from COVID-19. It may contain antibodies to SARS-CoV-2 that suppress viral replication. As of Dec. 28, 2021, CCP with high titers of anti-SARS-CoV-2 antibodies is currently authorized for the treatment of COVID-19 in patients with immunosuppressive disease or who are receiving immunosuppressive treatment. It is authorized for use in either the outpatient or the inpatient setting. This authorization is based on the totality of the scientific evidence available that suggests the potential benefits of CCP outweigh the potential risks when used for this indication. However, additional data from randomized controlled clinical trials are needed.

Plasma donations must be tested by registered or licensed blood establishments for high titers of anti-SARS-CoV-2 antibodies as a manufacturing step to determine suitability before release, using one of the tests and qualifying results listed in the FDA EUA.

Clinical dosing may first consider starting with one high titer CCP unit (about 200mL), with administration of additional high titer CCP units based on the prescribing physician’s judgment and the patient's clinical response.

Tocilizumab

Tocilizumab is an interleukin (IL)-6 inhibitor that can be used in hospitalized patients with progressive severe or critical COVID-19 illness that demonstrate elevated markers of inflammation. For a more complete review of the evidence, benefits/harms and treatment criteria, refer to the National Institutes of Health (NIH) and Infectious Disease Society of America (IDSA) COVID-19 treatment guidelines below:

Baricitinib

Baricitinib is a Janus kinase (JAK) inhibitor that can be used in hospitalized patients with severe COVID-19 disease and elevated inflammatory markers, but not requiring mechanical ventilation. It can also be given in conjunction with remdesivir to hospitalized patients with severe disease who are unable to receive corticosteroids due to a contraindication. For a more complete review of the evidence, benefits/harms and treatment criteria, refer to the NIH and IDSA COVID-19 treatment guidelines below:

Other COVID-19 response guidance

For other health care related COVID-19 response guidance documents, including ethical frameworks for allocation of ventilators and cardiopulmonary resuscitation as well as previous operational guidance for therapeutics, please visit Crisis Standards of Care.

Thank you for your continued partnership. For health care questions, please contact the MDH provider hotline at 651-201-5414.

 

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Last Updated: 12/06/2022