As everyone knows by now, the world as we know it has been completely flipped on its head by the Coronavirus outbreak. Schools have been closed, shelter in place orders have been issued, and social distancing has been touted as our best defense against this pandemic. But there may be a new hope emerging as we learn more about Coronavirus, its infectious course, and our immune response to infection. As new information becomes available as studies continue to be conducted, immunologists and virologists have been able to develop antibody tests that allow for much more rapid testing and results than the current PCR testing method which has serious limitations. The premise of PCR testing is to use manmade RNA primers to bind actual RNA from the virus if the individual has been infected. The issue, however, is that there has been reports of false negative PCR tests and that the test is uncomfortable due to how it must be performed. The antibody response can be tracked in the blood, making testing less invasive, and is greater in scale than viral RNA would be, making it easier to test for infection.
The antibody response is part of the adaptive immune response and involves production of antibodies that specifically target and bind to the antigen that activated the B cell from which they were produced and released. Therefore, antibodies are specific for a single antigen which fits perfectly in the binding site of the antibody. However, antibody production takes time following initial infection, which is why PCR testing is currently used for the purpose of diagnosing individuals. Antibody testing will be relevant to assessing the stage of viral infection, as well as whether or not an individual was previously infected despite being asymptomatic. Two antibody classes, IgM and IgG, are of particular interest to immunologists at this point, according to an article in the Journal of Medical Virology. IgM antibodies are among the first antibody classes produced in response to infection by novel antigens. IgG antibodies, in contrast, are more specific and are related to immunological memory of antigens. As such, antibody levels (aka titers) are useful for determining the stage of infection. Based on this information and that from the previously mentioned article, a high titer of IgM antibodies only would indicate that the individual is experiencing a primary infection and is in the relatively early stages since IgG antibodies have not been produced yet. Similarly, titers of both IgM and IgG in a patient would indicate a proper antibody response to primary infection as these antibodies worked to clear the viral infection. As reported by the study, titers of both IgM and IgG were seen in individuals who tested negative for CoVid-19 after previously testing positive. The study also demonstrated the delay in the adaptive immune response needed to produce antibodies as a cohort of individuals tested positive by PCR testing, yet were negative for both IgM and IgG antibodies.
But what about if you only have an IgG titer and no IgM antibodies are present? If this were the case, then the individual would have been previously infected by CoVid-19. This is because IgG antibodies serve as the immunological memory antibodies for the adaptive immune response while IgM antibody production falls off as the infection is dealt with. Therefore, if we were able to determine who was IgG positive then we would be able to determine the true level of exposure to Coronavirus. Furthermore, since a high titer of IgG and low to no titer of IgM has been shown to be related to negative PCR tests, those individuals with only IgG antibodies would NOT be able to spread CoVid-19. The negative PCR tests indicate there is no active infection by virus, meaning the virus cannot be spread by these individuals.
There is some information regarding individuals with high titers of both IgM and IgG that I found interesting and concerning. According to a review published in Nature, unusually high titers of combined IgM and IgG have been related to the worst prognoses. The review goes on to explain how these high titers could be causing what is referred to as antibody-dependent enhancement. The unusually high titers cause a vicious cycle of inflammation and has been linked to enhancing the virulence of the virus by promoting entry into body cells. The severe inflammation caused by the high titers of antibodies is related to the release of massive levels of pro-inflammatory cytokines that overwhelm body tissues and cause serious damage. While this pathology is certainly concerning, at least we now have some insight into how the virus works in its most severe cases, which could shed light on how to treat those severe cases and prevent further deaths in the future. Overall, the antibody tests that are being developed will be useful in a few different contexts: 1) determining stage of infection when used in conjunction with PCR tests and 2) determining prior exposure/infection in asymptomatic individuals to determine true statistics for this pandemic.
Keegan's Microbiology Blog 