Seroconversion

In immunology, seroconversion is the time period during which a specific antibody develops and becomes detectable in the blood. After seroconversion has occurred, the antibodies can be detected in blood tests for the disease. During an infection or immunization, antigens enter the blood, and the immune system begins to produce antibodies in response. Before seroconversion, the antigen itself may or may not be detectable, but the antibody is, by definition, absent. During seroconversion, the antibody is present but not yet detectable.

Mechanism

The physical structure of an antibody allows it to bind to a specific antigen to form a complex. Because of this binding, if the amounts of antigen and antibody in the blood are equal, each molecule will be in a complex and be undetectable by standard techniques. The antibody or antigen is only detectable in the blood when there is more of one than the other.

Early in an infection, the antigen molecules outnumber the antibody molecules, and there will be unbound antigen that may be detectable, while all the antibody molecules are bound. After seroconversion, there is more antibody than antigen, so there is a detectable amount of free antibody, while all the antigen is bound and undetectable.

Terminology

During seroconversion, when the amounts of antibody and antigen are very similar, it may not be possible to detect free antigen or free antibody. This may give a false negative result when testing for the infection.[1] This time is referred to as the window period.

Serology (testing for antibodies) is used to determine if specific antibodies are in an organism's blood. Serostatus is a term denoting the presence or absence of particular antibodies in an individual's blood. Before seroconversion, the blood test is seronegative for the antibody; after seroconversion, the blood test is seropositive for the antibody.[1]

The word 'seroconversion' is often used in reference to blood testing for anti-HIV antibodies. In particular, "seroconverted" has been used to refer to the process of having "become HIV positive".[2]

In epidemiology, seroconversion is often used in reference to observing the evolution of a virus from a host or reservoir host to the human population, based on the analysis of archived human blood specimens taken from infected hosts before an epidemic, and comparison with later specimens from infected hosts at later stages of the epidemic.[3]

Seroreversion is the opposite of seroconversion. This is when the tests can no longer detect antibodies in a patient's serum.[1]

Background

The immune system maintains an immunological memory of infectious pathogens to facilitate early detection and to confer protective immunity against a rechallenge. This explains why many childhood diseases never recur in adulthood (and when they do, it generally indicates immunosuppression).

It generally takes several days for B cells to begin producing antibodies. In the initial (primary infection) phase of the infection, immunoglobulin M (IgM) antibodies are produced and as these levels drop (and become undetectable) immunoglobulin G (IgG) levels rise and remain detectable.[4] Immunoglobulin class switching often results in IgM-generating B-cells switching to IgG-generating B-cells.[5]

Upon reinfection, IgM antibodies usually do not rise again but IgG levels will increase. Thus an elevated IgM titre indicates recent primary infection, while the presence of IgG suggests past infection or immunization.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus causing COVID-19) sometimes does not follow the usual pattern, with IgM sometimes occurring after IgG, together with IgG, or not occurring at all.[5] Generally however, median IgM detection occurs 5 days after symptom onset, and IgG is detected a median 14 days after symptom onset.[6]

See also

References
  1. Nauta, Jozef (2010). Statistics in Clinical Vaccine Trials. Springer. pp. 28–29. ISBN 978-3-642-14690-9.
  2. "What is Acute HIV Infection?". Johns Hopkins School of Bloomberg School of Public Health.
  3. 🖉"COVID-19 Seroconversion Among Medical and Paramedical Staff in Emergency, ICU and Infectious Disease Services During the 2020 Epidemic". 30 November 2020 – via clinicaltrials.gov.
  4. Shi J, Han D, Zhang R, Li J, Zhang R (2020). "Molecular and Serological Assays for SARS-CoV-2: Insights from Genome and Clinical Characteristics". Clinical Chemistry. 66 (8): 1030–1046. doi:10.1093/clinchem/hvaa122. PMC 7314174. PMID 32437513.
  5. Bauer G (2020). "The variability of the serological response to SARS-corona virus-2: Potential resolution of ambiguity through determination of avidity (functional affinity)". Journal of Medical Virology. doi:10.1002/jmv.26262. PMC 7361859. PMID 32633840.
  6. Ravi N, Cortade DL, Ng E, Wang SX (2020). "Diagnostics for SARS-CoV-2 detection: A comprehensive review of the FDA-EUA COVID-19 testing landscape". Biosensors and Bioelectronics. 165: 112454. doi:10.1016/j.bios.2020.112454. PMC 7368663. PMID 32729549.
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