Seroconversion is the transition from the point of viral infection to when antibodies of the virus become present in the blood. Given that many diagnostic tests use the presence of antibodies to infer illness, understanding seroconversion becomes a very important part of immunology and virology.
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Antibodies attacking SARS-CoV-2 virus. Image Credit: Kateryna Kon/Shutterstock.com
Why is determining seroconversion important?
Antibodies can be important for diagnosing disease in several viral contexts, such as with HIV. In many cases, an accurate diagnosis of COVID-19 is done by nucleic acid tests. However, there is some dispute over this, with some research indicating that detection of seroconversion can detect virus-specific antibodies despite negative nucleic acid tests.
Either way, determining seroconversion can be important for understanding the immune response, infection rates, and identification of potential serum donors.
Understanding all three aforementioned benefits of studying seroconversion is critical for understanding disease proliferation and spread. For example, information on the rate of infection is needed to determine the infection fatality rate with any accuracy.
Understanding the seroconversion in a quantitative manner can allow for the detection of individuals who have strong antibody responses to viruses, and can, therefore, be donors. Similarly, studying seroconversion can aid in understanding which antibody responses are associated with protection from the virus in question.
Seroconversion is not limited to clear cases of infection. Asymptomatic patients can also undergo seroconversion. Similarly, detection of seroconversion does not mean antibodies are present for an indefinite amount of time, nor that all individuals with a disease will undergo seroconversion.
Seroconversion and infectiousness
In most diseases, infectiousness is at its highest before seroconversion. This is true for HIV, where most seroconversion research has focused, but there is also some evidence that this is occurring in severe acute respiratory syndrome coronavirus 2 SARS-CoV-2. Certain cases also indicate that virus shedding can continue after seroconversion. Where viral shedding continues past seroconversion, there are implications that the contagious period is extended by as much as a week after clinical recovery.
Similar results have been found for asymptomatic patients. It has been confirmed that asymptomatic patients may transmit SARS-CoV-2. When a virus can be spread through asymptomatic individuals, it can be very damaging for infectious spread and for developing containment strategies.
While seroconversion and the presence of antibodies can, in some diseases, confer immunity from reinfection, this may not always be the case. Recent research in a study in preprint* by the Public Health England (PHE) suggests that seroconversion of COVID-19 does not lead to permanent protection from reinfection. Instead, it leads to protection for at least five months at a level of 83%.
The basic reproduction number (R0) indicates how contagious a disease is. Studies on seroconversion and cross-reactivity have shown that when testing for seroconversion, there is little or no cross-reactivity from other human coronaviruses.
This indicates that humans are ‘serologically naïve’ to COVID-19, meaning it has not been encountered before (unlike other viral diseases like influenza). This naivety to COVID-19 could be a contributing factor to the disease’s relatively high R0 number.
How is seroconversion detected?
Seroconversion is detected based on the presence of antibodies. However, different diseases can trigger different types of antibodies. For example, for COVID-19, there have been documented cases of seroconversion of immunoglobin G and M (IgG and IgM, respectively). There can also be different combinations of seroconversion occurring.
Usually, after infections, IgM antibody levels rise and fall, then IgG levels increase and stay present. However, in COVID-19, IgM has been shown to increase before IgG, after IgG, simultaneously or even not at all.
One way in which seroconversion can be detected is via a replication-competent virus, but this process can take several days and requires strict biosafety regulations. Other methods, which are more recently developed, include the use of traditional ELISAs in combination with pseudotyped viral particle-based entry assays. This type of method does not need to involve live viral particles, and therefore has fewer strict regulations involved and can be carried out easier.
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Viral load and seroconversion in COVID-19
In a recent study published by the Centers for Disease Control and Prevention (CDC), the authors recognized that much of the initial research into antibodies and COVID-19 was undertaken on Chinese populations and that many variables such as race can influence antibody dynamics.
In their recent research on a cohort of diverse populations, published in January 2021, the authors found that a significant proportion of COVID-19 patients took three to six weeks for antibodies to be generated, and 2-8% of patients did not have detectable antibodies 60 days post-infection. They also found that certain variables affected seroconversion, such as older individuals being more likely to seroconvert and non-white individuals showing higher antibody concentrations.
Jiang et al. carried out a study on antibody seroconversion in asymptomatic and symptomatic COVID-19 patients, obtaining results that suggested IgG and IgM levels post-infection were lower in those who had experience asymptomatic disease.
A recent study by Masía et al. in January 2021 found a correlation between viral load and time taken for seroconversion. A higher peak viral load (SARS-CoV-2 RNA levels) was linked to earlier antibody detection, and low viral load in the initial stages of infection was observed in patients who lacked certain antibodies post-infection. These findings suggest that adaptive humoral immune response could be dependent on viral replication intensity.
The same study found that some patients did not develop antibodies against SARS-CoV-2 and that most of these showed a very low virological profile, suggesting that a low viral load of SARS-CoV-2 may not be enough to stimulate adaptive humoral immunity.
The link between COVID-19 and seroconversion is still not fully understood. Research into immune responses and SARS-CoV-2 infection is ongoing and new research on diverse and large cohorts is in demand to provide more knowledge. With the increasing number of significant SARS-CoV-2 variants, it should be noted that seroconversion could be affected different strains of the disease.
*Important Notice
This article contains information from a preliminary scientific report that is not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or be treated as established information.
References
- Liu, W.D, et al. (2020). Prolonged virus shedding even after seroconversion in a patient with COVID-19. Journal of Infection, 81(2), 318-356. 10.1016/j.jinf.2020.03.063
- Amanat, F. et al. (2020). A serological assay to detect SARS-CoV-2 seroconversion in humans. Nature Medicine, 26, 1033-1036. https://doi.org/10.1038/s41591-020-0913-5
- Long, Q. et al., 2020. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nature Medicine, 26, 845-848. https://doi.org/10.1038/s41591-020-0897-1
- Hall, V. et al. (2021). Do antibody positive healthcare workers have lower SARS-CoV-2 infection rates than antibody negative healthcare workers? Large multi-centre prospective cohort study (the SIREN study), England: June to November 2020. medRxiv. https://doi.org/10.1101/2021.01.13.21249642 * This article is a preprint and has not been peer-reviewed. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.
- Jiang, C., et al. (2020). Antibody seroconversion in asymptomatic and symptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical & translational immunology, 9(9), e1182. https://doi.org/10.1002/cti2.1182
- Masía, M., et al. (2021). SARS-CoV-2 Seroconversion and viral clearance in patients hospitalized with covid-19: viral load predicts antibody response. Open Forum Infectious Diseases, 8(2). https://doi.org/10.1093/ofid/ofab005
- Staines, H. M., et al. (2021). IgG Seroconversion and Pathophysiology in Severe Acute Respiratory Syndrome Coronavirus 2 Infection. Emerging Infectious Diseases, 27(1), 85-91. https://dx.doi.org/10.3201/eid2701.203074.
- Wajnberg, A., et al. (2020). Humoral response and PCR positivity in patients with COVID-19 in the New York City region, USA: an observational study. The Lancet Microbe, 1(7), E283-E289. https://doi.org/10.1016/S2666-5247(20)30120-8
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