SARS-CoV-2, also known as COVID-19, is the novel coronavirus that has been wreaking havoc worldwide. The virus is a zoonotic, enveloped RNA virus from the Betacoronavirus family. In order to understand the antibody response to the virus, we first need to understand the structure of the pathogen because that highly influences the way in which it affects the body’s immune response. The virus has a S spike protein that contains the receptor binding domain which binds to ACE2 – the virus receptor. The virus has a nucleocapsid protein N which helps to attach the virus’s RNA to a replicase-transcriptase complex and then package the resulting genome. The envelope protein on the membrane helps with assembly and release of the virus as well as ion transport. The membrane protein allows for the virus to have two different conformations and bind to nucleocapsid. The hemagglutinin-esterase dimer protein helps the virus with protein-mediated cell entry which allows the virus spread through the respiratory mucosa.
When the body recognizes a foreign pathogen, the body responds by activating the innate immune system. Naive B cells bind to the antigen using their B cell receptor, then bring the antigen into the cell and break it down into its peptide fragments. These fragments are then presented on MHC class II molecules on the membrane of the B cell. If these fragments are recognized by the T helper cells the T cell receptor binds to the antigen fragment and activates the B cell. Once the B cell is activated, it can begin proliferating and some can differentiate into antibody-secreting plasma cells. Initially, all of these plasma cells will be secreting IgM but when the T helper cells induce activation in the B cells, they release cytokines that allow the B cells to class switch, meaning that their genetic codes change in order to produce different types of antibodies. Thus, at the onset of a disease, we expect to see mostly IgM antibodies, but as the disease progresses, we expect to see other classes such as IgG or IgA. In one study, we saw that COVID-19 patients seemed to peak with IgM production at day 9 but by week 2, they switched to mostly IgG production. IgG typically is known to control infection of body tissues and activates the classical pathway of the complement system. Thus we can see that clinically, when the IgG levels are measured in an individual they can show the immune status of that person.
Based on the way the virus proliferates there are currently a few different tests to see if a person is positive for SARS-CoV-2, including gene tests and immunoglobulin detection based tests. The gene based tests use a swab kit to take a sample of secretions from the nose and then use specific reagents to lyse the virus and test it for the RNA sequence of COVID-19. Yet with this test, we can’t tell if the person is immune from past infections or is still in danger. The immunoglobulin detection based tests work based on the idea that the IgG antibody will replace the IgM antibody as the predominant serum antibody to fight the disease. Serum (the liquid part of clotted blood) is taken from a patient and the serum is put into contact with SARS-CoV-2 antigen. The IgM and IgG antibodies in the serum will form complexes with the antigen in the test if they are the ones made in response to the virus in the body. This test will show 4 possible results, negative if the antibodies in the serum are not responsive to the COVID-19 antigen, and 3 possible positive cases – IgM only positive, IgG only positive and IgM and IgG positive. These tests though do not confirm whether the virus is currently infecting you, only if you have had past exposure.
Microbiology Blog 