How Do COVID-19 Monoclonal Antibodies Work?

COVID-19 monoclonal antibodies are biological products used as single agents or in combination with other COVID-19 monoclonal antibodies to prevent or treat coronavirus disease (COVID-19). COVID-19 is an infectious disease caused by a type of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which resulted in a global pandemic that started in 2019.

SARS-CoV-2 is a virus with a single strand of RNA, and infection spreads through saliva droplets when an infected person talks, coughs, sneezes, or laughs. The virus has unique spike proteins on its surface membrane which help the virus attach to and penetrate the angiotensin converting enzyme 2 (ACE2) receptors on human cells. The virus then uses the host’s cell machinery to grow, replicate and infect other cells.

COVID-19 monoclonal antibodies are protein molecules produced in the laboratory using DNA recombinant technology. Most of the COVID-9 monoclonal antibodies used for prevention (prophylaxis) or treatment of COVID-19 are designed to specifically bind to the viral spike protein, and prevent viral attachment to the ACE2 receptors.

A COVID-19 monoclonal antibody, sotrovimab, does not prevent viral binding to ACE2 receptors, but inhibits an undefined step that occurs after binding and before fusion of the viral and host cell membranes, preventing viral entry into the host cell. Sotrovimab acts as a marker for the host’s immune system to destroy cells expressing the spike protein.

Another monoclonal antibody, tocilizumab, used for the treatment of severe COVID-19 in hospitalized patients, does not act on the virus, but controls severe inflammation (cytokine storm) that results from the infection. Tocilizumab blocks the activity of an inflammatory protein (cytokine) known as interleukin-6 (IL-6), which activates the immune system and the inflammatory process, by binding to IL-6 receptors.

All the COVID-19 monoclonal antibodies are investigational therapies that were authorized for use by the FDA under emergency use authorization (EUA) for prophylaxis or treatment of COVID-19. The FDA has revoked the EUA for most of the monoclonal antibodies because these treatments are unlikely to be effective for COVID-19 any more due to the high frequency of non-susceptible coronavirus variants.

Currently, tocilizumab is the only monoclonal antibody that is approved by the FDA for treatment of hospitalized adults with severe COVID-19 illness, and authorized under EUA to treat hospitalized children of age 2-17 years with severe COVID-19 disease. Pemivibart, which received EUA in March 2024, is the only COVID-19 monoclonal antibody still available for prophylaxis of COVID-19 under EUA.

Most of the COVID-19 monoclonal antibodies are solutions that are administered as slow intravenous (IV) infusions into a vein. Only tixagevimab and cilgavimab, a combination therapy, is administered into the muscle as an intramuscular (IM) injection.

COVID-19 monoclonal antibodies should be administered only in clinical settings which have the ability to activate the emergency medical system (EMS), and have immediate access to medications and qualified personnel to treat severe infusion reactions such as anaphylaxis, should they occur.

The uses of currently available COVID-19 monoclonal antibodies that are FDA-approved or have EUA:

• Treatment of COVID-19
  • Tocilizumab (Actemra): Treatment of hospitalized adult patients (FDA-approved) and children of age 2 to 17 years (EUA) with COVID-19 who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).
• Pre-exposure prophylaxis for COVID-19 (EUA)
  • Pemivibart (Pemgrada): Pre-exposure prophylaxis to help prevent COVID-19 in adults and children 12 years of age and older who weigh at least 88 pounds (40 kg) who:
  • Are not currently infected with SARS-CoV-2 and who have not been known to be exposed to someone who is infected with SARS-CoV-2 and
  • Have moderate-to-severe immune compromise because of a medical condition or because they receive medicines or treatments that suppress the immune system and they are unlikely to have an adequate response to COVID-19 vaccination.
  • Uses of COVID-19 monoclonal antibodies for which EUA has been revoked:
• Pre-exposure prophylaxis:
  • Tixagevimab and cilgavimab (Evusheld) for adults and children 12 years or older weighing 40 kg or more
  • Treatment and post-exposure prophylaxis of mild-to-moderate COVID-19
  • Bamlanivimab/etesevimab combination for adults and pediatric patients including neonates
  • Bebtelovimab for adults and children 12 years or older weighing 40 kg or more
  • Casirivimab/imdevimab combination for adults and children 12 years or older weighing 40 kg or more
  • Sotrovimab for adults and children 12 years or older weighing 40 kg or more
  • EUA allowed the use of COVID-19 monoclonal antibodies for treatment and post-exposure prophylaxis of mild-to-moderate COVID-19 only if the patient tested positive for SARS-CoV-2 and was in high risk for progression to severe illness, including hospitalization and death.

Common side effects of COVID-19 monoclonal antibodies, include the following:

• Tocilizumab
• Liver toxicity
• Increase in liver enzymes ALT and AST
• Constipation
• Urinary tract infection
• High blood pressure (hypertension)
• Low blood potassium (hypokalemia)
• Anxiety
• Diarrhea
• Nausea
• Gastrointestinal perforation
• Insomnia
• Infections, including serious infections
• Low count of neutrophil immune cells (neutropenia)
• Low platelet count (thrombocytopenia)
• Blood fat (lipid) abnormalities
• Immunosuppression
• Hypersensitivity reactions including anaphylaxis
• Pemivibart
• Administration site reactions including:
• Pain and soreness
• Redness
• Bleeding
• Bruising
• Swelling
• Infection
• Allergic and infusion-related reactions including:
• Fever
• Headache
• Chills
• Tiredness
• Weakness
• Throat tightness or irritation
• Trouble breathing or shortness of breath
• Swelling of face, lips, mouth, tongue, throat, hands or feet
• Chest pain or discomfort
• High or low blood pressure
• Rapid or slow heart rate
• Rash or hives
• Itching
• Dizziness or lightheadedness
• Nausea
• Confusion
• Sweating
• Common cold
• Viral infection
• Flu-like illness
• Tiredness
• Headache
• Nausea

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of COVID-19 monoclonal antibodies, include:

• bamlanivimab and etesevimab
• bebtelovimab
• casirivimab/imdevimab
• COVID-19 monoclonal antibody (VIR, GSK)
• etesevimab
• Evusheld
• GSK4182136
• Pemgarda
• pemivibart
• REGEN-COV
• sotrovimab
• tixagevimab and cilgavimab
• tocilizumab
• VIR-7831