A COVID-19 antibody cocktail comprises of casirivimab and imdevimab which are monoclonal antibodies used for the treatment of mild to moderate COVID-19 (without high flow oxygen therapy required) in adults and pediatric patients (12 years of age or older) who are at high risk for progressing to severe COVID-19. However, the antibody cocktail may be associated with worse clinical outcomes when administered to COVID-19 patients who required high flow oxygen therapy or mechanical ventilation.
In COVID-19 clinical trials, casirivimab and imdevimab administered together as combination monoclonal antibodies were shown a significant reduction in viral load among hospitalized, seronegative COVID-19 patients (serum antibody-negative) who required low flow or no supplemental oxygen. In addition, giving casirivimab and imdevimab as co-formulated regimen can reduce the length of hospital stay while decreasing mortality rate in mild to moderate COVID-19 cases. Nevertheless, these monoclonal antibodies appear to offer a promising therapy outcome only if they are administered in the early course of COVID-19 infection. Casirivimab and imdevimab as antibody cocktail have been granted Emergency Use Authorization (EUA) by the US Food and Drug Administration and Thailand’s Food and Drug Administration for the treatment of COVID-19. Under the EUA, these medications are widely used in several countries, e.g. the US, the UK and Japan.
Mechanism of Action of Antibody Cocktail
The novel antibody cocktail consists of casirivimab and imdevimab which belong to monoclonal antibodies, known as Immunoglobulin G (IgG). Using advanced recombinant DNA technology, these medications are derived from fully-human antibodies identified from patients who have recovered from COVID-19 infection and antibodies produced by mice, which have been genetically modified to have a human immune system. The two potent, virus-neutralizing antibodies that form the cocktail bind non-competitively to the critical receptor binding domain of the virus spike proteins, which diminishes the ability of viruses to infect host cells in the body.
Indications of Antibody Cocktail
Under the EUA, casirivimab and imdevimab can be administered together for the treatment of mild to moderate COVID-19 in adults and pediatric patients (12 years of age or older) with positive results of direct SARS-CoV-2 viral testing who do not require high flow oxygen therapy. These medications can be used in patients who are at high risk for progressing to severe COVID-19. High-risk is defined as patients who meet at least one of the following criteria:
- Age ≥ 65 years old
- Obese (BMI ≥ 35 kg/m2)
- Cardiovascular diseases or hypertension
- Chronic Obstructive Pulmonary Disease, asthma or other chronic respiratory disease
- Type 1 or type 2 diabetes mellitus
- Chronic Kidney Disease (CKD) or undergo hemodialysis
- Chronic Liver Disease
- Immunosuppressive diseases or immunocompromized host diagnosed by the physician, e.g. patients receiving cancer treatment, bone marrow transplant or organ transplant, HIV patients, patients with certain hematologic diseases, e.g. sickle cell anemia and thalassemia as well as patients who are currently receiving immunosuppressive treatment.
Benefits of Antibody Cocktail in COVID-19 patients
In a clinical trial of COVID-19 patients aged 12 or older presented with mild to moderate symptoms, casirivimab and imdevimab administered together as combination monoclonal antibodies have shown a significant reduction in viral load among hospitalized COVID-19 patients who required low flow or no supplemental oxygen. A significant reduction in virus levels within days of receiving the combined monoclonal antibodies was associated with reduction of length of hospital stay or emergency room visits while decreasing mortality in hospitalized patients. Nevertheless, these monoclonal antibodies only offer a promising therapy outcome when they are administered in the early course of COVID-19 infection. Given as a co-formulated regimen, casirivimab and imdevimab help to diminish the ability of mutant viruses to escape treatment and they also help to protect against certain variants that have arisen in the human population.
Dosage Regimen and Administration
The authorized dosage is 600 mg of casirivimab with 600 mg of imdevimab administered together in 0.9% normal saline solution as a single intravenous (IV) infusion. Duration of infusion is 20-30 minutes. It is necessary to clinically monitor patients during infusion and observe any undesirable effects for at least 1 hour after infusion is completed.
Important Safety Information and Adverse Effects
Possible side effects caused by casirivimab and imdevimab include fever, chills, skin rash or urticaria, abdominal pain, nausea and hot flush. If signs or symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, administration will be immediately discontinued and appropriate medications and/or supportive therapy will be initiated by medical staff. However, the antibody cocktail is not recommended in COVID-19 patients who require high flow oxygen therapy or mechanical ventilation as they may be associated with worse clinical outcomes. More importantly, medical consideration whether the antibody cocktail is advised in each patient will be thoroughly made by the treating physician in which symptoms and patient’s conditions are taken into account.
Since monoclonal antibodies are novel laboratory-made proteins that mimic the ability of immune system to fight against SARS-CoV-2, there might be limited information known about the safety and effectiveness, especially in other special populations. Under the EUA, these medications are only authorized for treating COVID-19 in patients aged over 12 with mild to moderate symptoms in order to prevent disease progression under close supervision of healthcare providers.
Information compiled by (October 2021):
- Dr. Asawin Puwatanasan (Assistant Hospital Director, Bangkok International Hospital) and Pharmacy Department (Drug Information Service), Bangkok Hospital Headquarters.
