News Flash

September 14, 2021

Clinician Update--COVID-19: 

Use of Monoclonal Anti-SARS-CoV2 Antibodies for Prevention of Severe Disease

Requested Actions

• Consider using monoclonal antibodies to treat eligible, high-risk patients with mild-to-moderate COVID-19 illness, regardless of vaccination status. 
• Consider using monoclonal antibodies for post-exposure prophylaxis of not fully vaccinated high-risk patients as soon as possible and preferably within 7 days of high-risk exposure (note: fully vaccinated patients with moderate-to-severe immunosuppression are also eligible).
• If you do not have an infusion center at your clinic, consider keeping subcutaneous dosing options on hand. Some monoclonal antibodies can now be administered subcutaneously in a provider's office, so patients no longer need to go to a special site for an IV infusion.
• If you can do neither infusion nor subcutaneous injection, know where monoclonal antibody treatment centers are located so you can refer eligible patients. 

Background

• Monoclonal antibodies prevent viral attachment by binding to a non-overlapping epitope on the surface spike protein receptor binding domain (RBD) of SARS-CoV-2 with high affinity, thereby blocking the binding of the virus to the human ACE2 receptor.
• Their timely use in eligible high-risk patients can reduce the risk of hospitalization among by up to 70%.
• Their use in eligible contacts can reduce the risk of developing symptomatic infection by up to 80%.
• Patients are eligible if they meet the following criteria:
  • are 12 years of age or older, 
  • weigh at least 40 kg,
  • symptom duration of 10 days or less, 
  • are at high risk of serious COVID-19 illness that may lead to hospitalization or death, and 
  • are not hospitalized, and
  • are not requiring supplemental oxygen due to COVID-19.
• Patients with moderate-to-severe immunosuppression are eligible for post-exposure prophylaxis even if they are fully vaccinated.
• Some monoclonal antibodies can now be administered subcutaneously in a provider's office, so patients no longer need to go to a special site for an IV infusion.
• Casirivimab-plus-imdevimab (REGEN-COV) is an antibody preparation containing two noncompeting IgG1 antibodies. The rationale behind combining two antibodies in a single product is to minimize mutational viral escape. Preliminary data from a Phase 3 trial of REGN-COV (casirivimab/imdevimab) revealed a 70% reduction in hospitalization or death in non-hospitalized patients with COVID-19. It may be infused intravenously or administered subcutaneously (2.5mL volume SQ q5min x 4 doses) to deliver 600mg of each antibody in total.  
• Recent laboratory studies suggest that the monoclonal antibodies bamlanivimab-plus-etesevimab may be less effective for treating cases of COVID-19 caused by variants with certain substitutions or combinations of substitutions in the spike protein associated with the alpha and beta variants. Use of this product was consequently paused in June 2021. However, the Food and Drug Administration restored the authorization for the product’s use on September 2.  Based on in vitro assays that are used to assess the susceptibility of viral variants to monoclonal antibodies, bamlanivimab and etesevimab, administered together, are expected to retain activity against the Delta variant (B.1.617.2), which is now the dominant variant in the United States. The increase in prevalence of Delta has been associated with a decrease at the same time in the frequency of identified variants that are expected to be resistant to bamlanivimab-and-etesevimab. The National Institutes of Health (NIH) has not yet updated its treatment guidelines to address this development.
• Sotrovimab, another RBD-binding monoclonal antibody, and tocilizumab, an IL-6 blocking monoclonal antibody, also have EUAs as COVID-19 therapeutics. Neither has been purchased and distributed by the federal government. You may purchase these products through typical purchasing channels if and where available.  
• Although monoclonal antibodies are generally well-tolerated, administration of monoclonal antibodies, in general, is associated with the risk of immune-mediated reactions that include anaphylaxis, serum sickness, and antibody generation. Besides these reactions, the adverse effects of monoclonal antibodies are also related to their specific targets. 
• These monoclonal antibodies should only be administered in settings in which healthcare providers have immediate access to medications to treat a severe infusion reaction, such as anaphylaxis, and the ability to activate the emergency medical system (EMS), as necessary.
• For assistance in  ordering and reporting monoclonal antibody use in Washington, contact Ezra.Stark@doh.wa.gov. 

Additional Resources 

• Washington State Department of Health 
  • Use of monoclonal antibody products to treat COVID-19
  • Overview of Direct Order Process for COVID-19 Therapeutics
  • Monoclonal Antibody Therapeutic Treatment Locations.
• National Infusion Center Association.  Monoclonal Antibody Locator
• Department of Health & Human Services 
  • Distribution of COVID-19 Monoclonal Antibody Therapeutics
  • REGEN-COV: Subcutaneous Injection Instructions for Healthcare Providers
  • Administering Monoclonal Antibody Treatments for COVID-19 in Your Facility
  • Coverage of Monoclonal Antibody Products to Treat COVID-19.
  • Federal Response to COVID-19: Monoclonal Antibody Playbook (Updated July 30, 2021)
• Food & Drug Administration.  Fact Sheet for Healthcare Providers-- Emergency Use Authorization of RegenCOV.
• National Institutes of Health. COVID-19 Treatment Guidelines
• Infectious Disease Society of America Guidelines on the Treatment and Management of Patients with COVID-19.
• Aleem A, Slenker AK.  Monoclonal Antibody Therapy for High-Risk COVID-19 Patients with Mild to Moderate Disease Presentation.