From the Guidelines
The spike protein plays a crucial role in COVID-19 infection and treatment, as it is the primary target for vaccines and monoclonal antibody treatments, such as bamlanivimab/etesevimab, casirivimab/imdevimab, sotrovimab, or regdanvimab, which have been shown to reduce the rate of progression to severe COVID-19 or death in high-risk patients 1.
Role of Spike Protein in COVID-19 Infection
The spike protein is responsible for binding to ACE2 receptors on human cells, allowing the virus to enter and infect these cells. This protein undergoes structural changes that facilitate fusion of the viral and cell membranes, enabling the virus's genetic material to enter the cell and begin replication.
Treatment Targeting Spike Protein
Monoclonal antibody treatments, such as those mentioned earlier, work by binding to the spike protein and preventing it from attaching to human cells. The choice of anti-spike monoclonal antibodies 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 1.
- Key considerations for treatment include:
- Local availability of anti-spike monoclonal antibodies
- National approval of these treatments
- Updated epidemiology of circulating SARS-CoV-2 viral variants
- Potential side effects, including infusion-related reactions
Benefits and Limitations of Anti-Spike Monoclonal Antibodies
While anti-spike monoclonal antibodies have been shown to be beneficial in reducing the rate of progression to severe COVID-19 or death in high-risk patients, their use in patients with severe COVID-19 has been controversial, with initial trials halted due to lack of benefit 1. However, data from the RECOVERY trial documented the benefit of high-dose casirivimab/imdevimab in a subgroup of hospital-admitted seronegative patients 1.
- Benefits:
- Reduced rate of progression to severe COVID-19 or death in high-risk patients
- Benefit in hospital-admitted seronegative patients
- Limitations:
- Controversy surrounding use in patients with severe COVID-19
- Potential for side effects, including infusion-related reactions
From the Research
Role of Spike Protein in COVID-19 Infection
- The spike protein plays a key role in viral pathogenesis, evolutions, and transmission of SARS-CoV-2, the virus responsible for COVID-19 2.
- The spike glycoprotein is essential for SARS-CoV-2 entry into host cells, making it a key target for developing therapeutics capable of blocking virus invasion 3.
Spike Protein and Treatment
- Several vaccines utilizing the S protein have been developed, and neutralizing antibodies have been approved for emergency use 2.
- Targeting the spike protein is a promising strategy to neutralize virus infectivity, with various classes of molecules being explored, including antibodies, nanobodies, soluble ACE2 variants, miniproteins, peptides, and small molecules 4.
- A bivalent SARS-CoV-2 monoclonal antibody combination has been shown not to affect the immunogenicity of a vector-based COVID-19 vaccine in macaques, suggesting that monoclonal antibodies and vaccines can be administered together without loss of potency 5.
Immune Response to Spike Protein
- Three exposures to the spike protein of SARS-CoV-2, either through infection or vaccination, can elicit superior neutralizing immunity to all variants of concern, including omicron 6.
- The immune response to the spike protein can be enhanced through repeated exposures, resulting in increased neutralization capacity and antibody avidity 6.