The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, is characterized by the spike (S) protein covering its surface. This protein enables the virus to infect human cells by acting like a key for entry. Because the spike protein first interacts with the host, testing for its presence or the body’s reaction to it is central to managing the pandemic. Understanding these tests helps clarify whether a person has an active infection or has developed immunity.
Understanding the Spike Protein
The spike protein is a large, trimeric glycoprotein that protrudes from the viral envelope, giving coronaviruses their crown-like appearance. It is structured into two main functional parts: the S1 subunit and the S2 subunit.
The S1 subunit contains the Receptor Binding Domain (RBD), which attaches the virus to human cells. This occurs when the RBD binds specifically to the Angiotensin-Converting Enzyme 2 (ACE2) receptor found on the surface of human cells, particularly in the respiratory tract. The S2 subunit then facilitates the fusion of the viral membrane with the host cell membrane, allowing the viral genetic material to enter and begin the infection.
This mechanism of cell entry makes the spike protein the primary target for the body’s immune response and vaccine development. Vaccines, such as mRNA and vector types, instruct the body’s cells to produce a harmless version of the spike protein. This exposure safely primes the immune system to recognize and attack the virus if a real infection occurs.
Detecting the Presence of Active Spike Proteins
Detecting the spike protein itself indicates active or very recent viral replication within the body. These tests are primarily used to diagnose an ongoing infection. The most common type of assay for this purpose is the rapid antigen test, often performed at home or at point-of-care locations.
Rapid antigen tests, also known as lateral flow devices, detect viral proteins in samples like nasal swabs. They utilize monoclonal antibodies specific to viral antigens, including parts of the spike protein, to produce a visible color change. These tests offer quick results, often within 15 to 30 minutes, but require a higher concentration of the virus to register a positive result compared to genetic tests.
In laboratory settings, more sensitive methods can quantify the spike protein directly. Highly sensitive assays, such as specialized ELISA (Enzyme-Linked Immunosorbent Assay), measure the amount of spike protein present in bodily fluids like saliva. Detecting the spike protein this way confirms the presence of viral material, signaling an active infection or the persistence of viral remnants.
Measuring the Immune Response to Spike Proteins
Measuring the immune response involves looking for the biological reaction the body has mounted against the spike protein following exposure, either from infection or vaccination. Serological testing, or antibody tests, assesses the humoral immune response by looking for antibodies in the blood. These antibodies are proteins produced by B-cells that specifically recognize and bind to the spike protein.
Antibody tests look for two main types of immune response: binding antibodies and neutralizing antibodies. Binding antibodies attach to the spike protein, flagging the virus for destruction by other immune cells. Neutralizing antibodies are a specific subset that directly block the spike protein’s ability to bind to the ACE2 receptor, preventing the virus from entering the host cell.
Laboratories can differentiate between immunity from vaccination and immunity from natural infection by testing for antibodies against the nucleocapsid (N) protein. Since most vaccines only prompt the body to produce the spike protein, they result in anti-spike antibodies only. A natural infection exposes the body to the entire virus, generating antibodies against both the spike and nucleocapsid proteins. Therefore, a positive anti-spike result combined with a negative anti-nucleocapsid result suggests immunity from vaccination alone.
Besides antibodies, the body also mounts a cellular immune response involving T-cells. T-cell assays measure this response, which is crucial for long-term memory and clearing infected cells. The T-cell response is thought to be more durable and less affected by viral mutations than the antibody response, contributing significantly to protection against severe disease.
Interpreting Test Results in Clinical Context
Interpreting spike protein test results requires considering the timing of infection or vaccination. A positive rapid antigen test, which detects the protein itself, generally confirms an active infection, especially if the person is symptomatic. Conversely, a positive anti-spike antibody test indicates prior exposure, which could be due to either past infection or vaccination.
Clinicians use quantitative antibody test results, reported in units like Binding Antibody Units (BAU) per milliliter, to assess the magnitude of a person’s immune response. However, a specific antibody level that guarantees complete protection against future infection is not definitively established. The measured value represents the presence of a humoral response but does not guarantee immunity or protection against reinfection.
For immunocompromised patients, antibody testing is useful for assessing their response to vaccination and determining the need for additional doses. The results also help distinguish a breakthrough infection (infection after vaccination) from an infection in an unvaccinated person by comparing anti-spike and anti-nucleocapsid antibody levels. While high antibody levels correlate with a stronger neutralizing capacity, the overall clinical picture, including vaccination status and symptom presentation, remains paramount for medical decisions.