What is the role of monoclonal antibodies (mAbs) in treating Covid-19?

From the Guidelines

Monoclonal antibodies (mAbs) are a crucial treatment option for COVID-19, particularly in high-risk patients, as they have been shown to reduce the rate of progression to severe COVID-19 or death, as evidenced by studies such as 1. The role of mAbs in treating COVID-19 is to target the SARS-CoV-2 virus and prevent it from entering human cells, thereby reducing viral replication and disease severity.

• The choice of mAb should be based on local availability, national approval, and the updated epidemiology of circulating SARS-CoV-2 viral variants, as their activity might be affected by specific mutations, with sotrovimab being the only anti-S MAb to retain activity against the recent Omicron variant, as noted in 1.
• mAbs like bamlanivimab/etesevimab, casirivimab/imdevimab, sotrovimab, or regdanvimab have been shown to be useful in reducing the rate of progression to severe COVID-19 or death in the general patient population with mild/moderate COVID-19, but at risk for severe COVID-19, as reported in 1.
• The use of mAbs in patients with severe COVID-19 has been controversial, but data from the RECOVERY trial documented the benefit of high-dose casirivimab/imdevimab in the subgroup of hospital-admitted seronegative patients, as mentioned in 1.
• A low rate of side effects, including infusion-related reactions, were reported in the pivotal trials, making mAbs a relatively safe treatment option, as stated in 1.
• The effectiveness of mAbs stems from their ability to bind to the spike protein of the virus, preventing it from attaching to and entering human cells, thereby reducing viral replication and disease severity, which is crucial in high-risk patients who may not develop a strong humoral response to the virus, as discussed in 1.

From the FDA Drug Label

Sotrovimab is not authorized for treatment of mild-to-moderate COVID-19 when infection is likely to have been caused by a non‑susceptible SARS-CoV-2 variant based on available information including variant susceptibility to these drugs and regional variant frequency The recommended dosage of sotrovimab in patients 12 years of age and older weighing at least 40 kg is 500 mg administered as a single intravenous infusion Clinical worsening of COVID-19 after administration of SARS-CoV-2 monoclonal antibody treatment has been reported and may include signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrhythmia (e.g., atrial fibrillation, tachycardia, bradycardia), fatigue, and altered mental status Benefit of treatment with sotrovimab has not been observed in patients hospitalized due to COVID-19. SARS-CoV-2 monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation

The role of monoclonal antibodies (mAbs), such as sotrovimab, in treating Covid-19 is to provide a single intravenous infusion for the treatment of mild-to-moderate Covid-19 in patients who are at high risk for progression to severe Covid-19, including hospitalization or death. However, sotrovimab is not authorized for treatment of Covid-19 when infection is likely to have been caused by a non-susceptible SARS-CoV-2 variant. Additionally, benefit of treatment with sotrovimab has not been observed in patients hospitalized due to Covid-19, and may be associated with worse clinical outcomes when administered to hospitalized patients with Covid-19 requiring high flow oxygen or mechanical ventilation 2. Key points to consider:

• Dosage and administration: 500 mg administered as a single intravenous infusion
• Contraindications: History of anaphylaxis to sotrovimab or to any of the excipients in the formulation
• Warnings and precautions: Hypersensitivity including anaphylaxis and infusion-related reactions, clinical worsening after SARS-CoV-2 monoclonal antibody administration, limitations of benefit and potential for risk in patients with severe Covid-19

From the Research

Role of Monoclonal Antibodies in Treating Covid-19

The use of monoclonal antibodies (mAbs) has been explored as a potential treatment for Covid-19. Studies have shown that mAbs can be effective in reducing hospitalization and death in patients with mild to moderate Covid-19.

• Efficacy of mAbs: A study published in JAMA network open 3 found that subcutaneously administered casirivimab and imdevimab was associated with reduced hospitalization and death in high-risk outpatients with mild to moderate Covid-19.
• Comparison of mAbs: Another study published in JAMA network open 4 compared the effectiveness of casirivimab-imdevimab and sotrovimab in patients with mild to moderate Covid-19 caused by the Delta variant. The study found that both mAb treatments were associated with a reduced risk of hospitalization or death.
• Cost-effectiveness of mAbs: A cost-effectiveness analysis published in PloS one 5 found that the administration of casirivimab and imdevimab in outpatients with Covid-19 can accelerate recovery from the disease, make hospital resource management more efficient, and significantly reduce costs for healthcare facilities.

Administration and Outcomes of mAbs

The administration of mAbs has been evaluated in various studies, including:

• Subcutaneous administration: A study published in JAMA network open 3 found that subcutaneous administration of casirivimab and imdevimab was associated with reduced hospitalization and death in high-risk outpatients with mild to moderate Covid-19.
• Intravenous administration: A study published in Lancet (London, England) 6 found that intravenous administration of casirivimab and imdevimab reduced 28-day mortality in patients admitted to hospital with Covid-19 who were seronegative at baseline.
• Outcomes: A study published in Health services insights 7 found that clinical symptoms of Covid-19 improved within 3 days of infusion in the majority of patients who received mAbs, and none of the patients who received mAbs showed progression of disease or required hospitalization at 30 days follow-up.

Patient Eligibility and Vaccination Status

The eligibility of patients for mAb treatment and the impact of vaccination status on treatment outcomes have been evaluated in various studies, including:

• Patient eligibility: A study published in JAMA network open 3 found that mAb treatment was effective in reducing hospitalization and death in high-risk outpatients with mild to moderate Covid-19.
• Vaccination status: A study published in Health services insights 7 found that mAbs were effective in reducing hospitalization and mortality in both vaccinated and unvaccinated patients with Covid-19.