Monoclonal antibodies for COVID-19 are lab-made proteins designed to mimic the immune system’s natural defense against SARS-CoV-2. They work by binding to the virus’s spike protein, blocking it from entering your cells. During the pandemic, several of these treatments received emergency authorization for treating or preventing COVID-19, though most have since lost effectiveness as the virus mutated. Today, only one monoclonal antibody product remains authorized in the U.S., and it’s reserved for a narrow group of patients.
How Monoclonal Antibodies Neutralize the Virus
SARS-CoV-2 infects cells by latching onto a receptor called ACE2 on the surface of human cells. It does this through a specific area on its spike protein called the receptor-binding domain, or RBD. Monoclonal antibodies are engineered to attach to this same region, essentially covering the part of the virus that would normally dock with your cells. Once the antibody is bound, the virus can no longer make contact and is effectively neutralized.
Different monoclonal antibodies target the spike protein in slightly different ways. Some only bind when the spike protein is in an “open” position, mimicking the way ACE2 itself connects. Others can attach whether the spike is open or closed, giving them a broader window to intercept the virus. In addition to physically blocking infection, these antibodies flag the virus for destruction by other parts of the immune system, helping clear it from the body faster.
Why Most Treatments Stopped Working
The biggest challenge with monoclonal antibodies is that they target a very specific shape on the spike protein. When that shape changes through mutation, the antibody can no longer bind effectively. This is exactly what happened as Omicron subvariants emerged. Research published in Cell found that the BQ and XBB subvariants rendered all previously authorized monoclonal antibodies inactive. Out of 23 antibodies tested that had worked against the original Omicron variant, none maintained meaningful activity against these newer subvariants.
This is a fundamental limitation of monoclonal antibody therapy compared to other COVID treatments. Oral antivirals like nirmatrelvir/ritonavir (Paxlovid) target the virus’s internal replication machinery, which mutates far less than the spike protein. A systematic review comparing treatments during the Omicron wave confirmed that antiviral drugs generally maintained their effectiveness while monoclonal antibodies experienced significant drops in neutralizing ability. That review found nirmatrelvir/ritonavir reduced both death and hospitalization risk by roughly 50 to 70 percent compared to no treatment, and those numbers held across multiple Omicron sublineages.
Who Can Still Get Monoclonal Antibodies
The only monoclonal antibody currently authorized in the U.S. is pemivibart, marketed as Pemgarda. It is not a treatment for active COVID-19 infection. Instead, it’s authorized strictly for pre-exposure prophylaxis, meaning it’s given to prevent infection before it happens. The FDA limits its use to adults and adolescents (12 and older, weighing at least 40 kg) who meet two criteria: they have moderate to severe immune compromise from a medical condition or immunosuppressive treatment, and they are unlikely to mount an adequate immune response to COVID-19 vaccination.
This covers people like organ transplant recipients on anti-rejection drugs, patients undergoing chemotherapy, and those with certain immune deficiencies. If you’ve already been exposed to someone with COVID or are currently infected, Pemgarda is not authorized for you.
There’s an important caveat. The FDA built a variant-surveillance trigger into the authorization. Pemgarda can only be used when the combined national frequency of variants with substantially reduced susceptibility to it is 90 percent or less. If circulating variants shift enough to make the antibody largely ineffective, the authorization essentially pauses. This means availability can change as the virus evolves.
What the Infusion Looks Like
Pemgarda is given as a single intravenous infusion at a healthcare facility. The infusion itself takes a minimum of 60 minutes, and you’ll be monitored afterward for potential reactions. The initial dose is 4,500 mg. If ongoing protection is needed, you return every three months for a repeat dose at the same amount.
Possible side effects include allergic reactions ranging from mild (hives, itching, flushing) to severe (anaphylaxis), along with fever and chills. Serious reactions are uncommon but are the reason the infusion takes place in a clinical setting with observation time built in.
Cost and Access
Monoclonal antibody treatment for COVID is not cheap. According to CMS pricing data, a single dose of pemivibart is listed at $7,239, with an additional $450 infusion and monitoring fee. Because this is an emergency-authorized product, coverage varies. During the early pandemic, the federal government purchased doses and distributed them for free, but that program has wound down for most products. If your provider received doses through remaining government-purchased inventory, you should not be billed for the product itself. Otherwise, coverage depends on your insurance plan, and you may want to verify costs before scheduling.
How Monoclonal Antibodies Compare to Antivirals
For most people who get COVID today, oral antivirals are the frontline outpatient treatment. Nirmatrelvir/ritonavir is a pill taken at home for five days, which is far more practical than an IV infusion at a clinic. A network meta-analysis found that nirmatrelvir/ritonavir reduced the risk of death by about 68 percent and hospitalization by about 52 percent compared to no treatment during the Omicron period. It also outperformed molnupiravir, the other available oral antiviral, on both measures.
Monoclonal antibodies fill a different niche. They’re not competing with Paxlovid for treating active infections in most patients. Their current role is specifically preventive, for immunocompromised people whose bodies can’t build adequate protection from vaccines alone. For this group, a quarterly infusion offers a layer of passive immunity that their own immune system cannot reliably produce. Think of it as borrowing antibodies rather than making your own.
The CDC’s current clinical guidance reflects this division: oral antivirals for treatment of active infection in high-risk patients, and pemivibart for ongoing prevention in the immunocompromised. Convalescent plasma, which contains antibodies from people who have recovered from COVID, also remains authorized for immunosuppressed patients as a treatment option, though it’s used less frequently.