Evusheld is a combination of drugs designed to prevent COVID-19 infection in vulnerable and immunocompromised people. It is the first pre-exposure prophylaxis approved for COVID-19. That means that it is taken before a COVID-19 exposure, to prevent infection.

Evusheld has emergency use authorization (EUA) in a number of countries, including Canada, the U.S., and six countries in Europe. It has a similar classification in Great Britain.

Evusheld is available for immunocompromised people over 12 years old and over 40 kilograms (88 pounds). It's not an appropriate substitute for COVID-19 vaccination in those for whom vaccination is recommended. 

There are two antibodies that make up Evusheld – tixagevimab and cilgavimab. They are administered as two separate, consecutive injections in a muscle (preferably, one in each gluteal muscle). 

The antibodies neutralize the virus is neutralized and protect the human host from COVID-19 infection.

Evusheld works differently than other antiviral drugs. For instance, molnupiravir works by stopping the virus from replicating within cells. Evusheld also stays longer in the body, because it's made of natural human antibodies that are modified to last longer.

The emergency authorizations of Evusheld were based on results from two main types of studies: 1) cell and animal studies, and 2) the PROVENT study – which is a randomized, double-blinded human trial, meaning it was rigorously conducted among human participants for both safety and efficacy.

PROVENT participants were 5,172 adults who were not vaccinated against COVID-19 and had a higher risk of infection than others for some reason (for instance, due being older than 60 years, having a comorbidity, or based on risks where they live). Half of the participants randomly received a placebo, and half received Evusheld (150mg of tixagevimab and 150 mg of cilgavimab). After 6 months, the treatment group (the group that received Evusheld) had a reduced risk of developing symptomatic COVID-19 by 83% compared to the placebo group who did not get the drug combination. It also made severe cases and death significantly less likely.

Multiple research studies (including one preprint) show that Evusheld is able to reduce the viral burden of all three Omicron subvariants in the lungs, making the drug combination promising in working against Omicron and/or future variants. 

Currently, those eligible to receive Evusheld are:

• Over 12 years of age and weigh at least 40 kilograms (88 pounds)
• Not previously nor currently infected with COVID-19
• Have not had a known recent exposure to someone with COVID-19
• Moderately to severely immunocompromised and may not have an effective immune response to COVID-19 vaccination 
• Not recommended to receive COVID-19 vaccination due to a history of severe adverse reactions, such as anaphylaxis

There is limited research about the use of Evusheld in the following groups:

1. Kids (under 12 years)
2. People lactating
3. Pregnant people

Administering Evusheld to a pregnant or lactating person is recommended only if the potential benefits outweigh the potential risks to the mother and fetus or nursing child. Evusheld is contraindicated (i.e., not recommended) for individuals who have a history of severe hypersensitivities to any of its ingredients. 

The COVID-19 pandemic is ongoing. This infection is life-threatening and lacks adequate, approved, and available treatments. Under these circumstances, the U.S. FDA and Health Canada have issued emergency use of an unapproved product, Evusheld. 

This decision was based on vigorous scientific research in both animals and humans indicating that it is safe, of high quality, and may be effective in preventing COVID-19 in immunocompromised patients over 12 years old and 40 kilograms. EUA in both countries remains contingent upon results from ongoing testing for safety, quality, and efficacy.

The U.S. FDA first issued EUA in December 2021 for treatment with 150mg of tixagevimab and 150 mg of cilgavimab in combination. In February 2022, the dosage was raised to 300mg of each antibody when data indicated that a higher dose may be more effective at preventing COVID-19. Evusheld was granted EUA by Health Canada in April 2022 at a recommended dose of 150mg of each antibody. 

Until recently, two other monoclonal antibody drugs: 1) casirivimab-imdevimab and 2) bamlanivimab-etesevimab, were used to prevent COVID-19 infection in people who were recently exposed to COVID-19. Unfortunately, however, both drugs have been shown to be ineffective against the omicron variant which is now the dominant variant globally. As a result, they are no longer currently approved for use.