by Catherine Colquitt, MD
Tarrant County Public Health Medical Director
This article was originally published in the November/December issue of the Tarrant County Physician. You can read find the full magazine here.
With local hospitals and emergency responders struggling to meet the space and staffing challenges brought on by the COVID-19 Delta variant, monoclonal antibody infusions (and subcutaneous injections when applicable for REGEN-COV) are being used to treat early COVID-19 infections. These are effective options in persons who don’t require hospitalization for COVID-19, aren’t hypoxic (or, if chronically O2-dependent, aren’t needing to augment their percentage of supplemental O2), or even as postexposure prophylaxis for persons at high risk for severe disease and poor outcome if they contract COVID-19 after an exposure.
The science underlying the development of the three monoclonal products granted Emergency Use Authorization (EUA) by the FDA capitalizes on the importance of the COVID-19 spike protein as a means of host cell entry. When viral particles are tagged by SARS-CoV-2 monoclonal antibody therapies, the monoclonal antibody-tagged viruses can’t enter host cells and replicate.
The mRNA vaccines, encoded for the COVID-19 spike protein and currently in wide usage, target the same essential viral spike protein by stimulating the host to transcribe the spike protein mRNA. They mount an immune response to that transcribed viral spike protein which the host’s immune system will then remember and repeat (anamnestic response) when COVID-19 viral particles present the spike protein to the now-vaccinated host’s primed immune system.1
Three SARS-CoV-2 monoclonal antibody formulations have been granted EUA by the FDA, though the first monoclonal SARS-CoV2 product (the coformulation bamlanivimab and etesevimab) is no longer authorized in the U.S. because of the decreased susceptibility of Beta and Gamma COVID-19 variants to it.2 Two combinations remain in use— the coformulation monoclonal casirivimab and imdevimab (REGEN-COV), which binds to nonoverlapping epitopes of the spike protein, and sotrovimab (XeVudy). Both are given under EUA’s for mild to moderate COVID-19 infections in persons 12 years or older weighing at least 40 kg and at high risk for severe COVID-19 infection. REGEN-COV use in postexposure prophylaxis is also granted under its EUA for COVID-19-exposed persons not yet fully vaccinated and for persons who are vaccinated but regarded as unlikely to respond well to COVID-19 vaccinations.3 Locally, only REGEN-COV is in use at present.
Comorbidities to consider in deciding who to refer for SARS-CoV-2 monoclonal therapy after onset of mild to moderate illness (early is best but both products are approved through day 10 after symptom onset) include:
- Age 65 and older
- BMI over 25kg/meter squared
- For 12 to 17 years old, BMI over 85th percentile for height and age
- Chronic kidney disease
- Diabetes mellitus
- Immunosuppressive disorder or treatment
- Cardiovascular disease, including hypertension and congenital heart disease
- Chronic lung disease, including COPD
- Moderate to severe asthma
- Interstitial lung disease
- Cystic fibrosis
- Pulmonary hypertension
- Sickle cell disease
- Neurodevelopmental disorders such as cerebral palsy or other conditions “conferring medical complexity such as congenital abnormalities and genetic or metabolic syndromes, and medical-related technology dependence such as tracheostomy, gastrostomy or feeding jejunostomy, mechanical ventilation, etc.”4
Data supporting the use of both SARS-CoV-2 monoclonal products currently in use is persuasive if primary outcomes of all deaths and hospitalizations through day 29 after administration of the products is the measure. For REGEN-COV there was an absolute reduction in death and hospitalization of 2.2 percent and a relative reduction of 70 percent in the treatment group versus placebo. For XeVudy, using the same primary outcome measures of all-cause mortality and hospitalization through day 29, the treatment group experienced a 6 percent absolute reduction and an 85 percent relative risk reduction compared with the placebo group.5
Some special considerations for the use of SAR-CoV-2 monoclonal products:
Variants: So far both products are rated as efficacious against variants available to test, including Delta and Mu, though this is a rapidly changing field of study.
Vaccinations Against COVID-19: Contraindicated in the 90 days following monoclonal administration due to theoretical concerns regarding a blunted immune response to COVID-19 vaccination.
Monitoring After Infusion: For one hour in a health care setting.
Drug Interactions: None so far identified.
Pregnancy: Monoclonals can be used in pregnancy and should certainly be considered when a pregnant woman has additional risk factors (beyond pregnancy alone) for severe COVID-19 disease.
Reactions to SARS-CoV-2 Monoclonal Products: Injection site reactions (pain, redness, swelling, pruritus, injection site ecchymosis) in approximately 1 percent and infusion related reactions such as urticaria, pruritus, flushing, pyrexia, shortness of breath, chest tightness, nausea, vomiting, and, rarely, anaphylaxis. In general, the REGEN-COV current dose of 600mg of casirivimab and 600mg of imdevimab is significantly better tolerated than the previously higher dosed formulations.
Lactation: No data yet available.
Hepatic impairment: No dose adjustment needed.
And please remember – COVID-19 monoclonal therapeutics are not a substitute for COVID-19 vaccination!
Locations of Tarrant County Infusion Centers:
JPS Urgent Care Center
1500 S. Main Street, Fort Worth , Texas 76104
Call 817-702 1451 for appt.
North Central Texas COVID-19 Regional Infusion Center
815 8th Avenue, Fort Worth, Texas 76104
Call 800-742-5990 for appt
Medical City Healthcare
Additional Infusion Center resources are available at www.tarrantcounty.com or by phone at HHS Protect Public Data Hub
(1-877-332-6585 in English and 1-877-366-0310 in Spanish).
1. http://email@example.com, updated 8/4/2021
2. Fact Sheet for Health Care Providers and Emergency USE Authorization (EUA) of Bamlanivmab and Etesevimab (REVOKED)
4. Fact Sheet for Health Care Providers and Emergency Use Authorization (EUA) of REGEN-COV
5. Fact Sheet for Health Care Providers and Emergency Use Authorization (EUA) of Sotrolivumab