What is Seroconversion?

Antibodies may be important in diagnosing disease in several viral contexts, such as HIV. In many cases, an accurate diagnosis of COVID-19 is made by nucleic acid testing. However, there is dispute over this, with some research indicating that seroconversion detection can detect virus-specific antibodies despite negative nucleic acid tests.

Regardless, determining seroconversion can be important in understanding immune response, infection rates, and identifying potential serum donors.

Understanding the three aforementioned benefits of studying seroconversion is critical to understanding disease proliferation and spread. For example, information on the infection rate is needed to accurately determine the infection fatality rate.

Understanding seroconversion quantitatively can allow the detection of individuals who have strong antibody responses to viruses and therefore may be donors. Similarly, studying seroconversion can help understand which antibody responses are associated with protection against the virus in question.

Seroconversion is not limited to clear cases of infection. Asymptomatic patients can also undergo seroconversion. Similarly, the detection of a seroconversion does not mean that the antibodies are present for an indefinite period, nor that all individuals with a disease will undergo a seroconversion.

Seroconversion and infectivity

In most diseases, infectivity is at its peak before seroconversion. This is true for HIV, where most seroconversion research has focused, but there is also evidence that it occurs in severe acute respiratory syndrome coronavirus 2 SARS-CoV-2. Some cases also indicate that virus shedding may continue after seroconversion. When viral shedding continues after seroconversion, there are implications that the period of infectiousness is prolonged for up to a week after clinical recovery.

Similar results were found for asymptomatic patients. It has been confirmed that asymptomatic patients can transmit SARS-CoV-2. When a virus can spread through asymptomatic individuals, it can be very damaging to infectious spread and to the development of containment strategies.

Although seroconversion and the presence of antibodies can, in some diseases, confer immunity against reinfection, this is not always the case. Recent research in a pre-publication study* by Public Health England (PHE) suggests that seroconversion from COVID-19 does not lead to permanent protection against reinfection. Instead, it leads to protection for at least five months at an 83% level.

The basic reproduction number (R0) indicates how contagious a disease is. Seroconversion and cross-reactivity studies have shown that when tested for seroconversion, there is little or no cross-reactivity with other human coronaviruses.

This indicates that humans are "serologically naïve" to COVID-19, meaning it has never been encountered before (unlike other viral illnesses like influenza). This naivety about 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 immunoglobins G and M (IgG and IgM, respectively). Different combinations of seroconversion can also occur.

Usually, after infections, IgM antibody levels rise and fall, and then IgG levels rise and remain present. However, in COVID-19, IgM has been shown to increase before IgG, after IgG, simultaneously or even not at all.

One way to detect seroconversion is to use a self-replicating virus, but this process can take several days and requires strict biosafety regulations. Other methods, which have been developed more recently, include the use of traditional ELISAs in combination with entry tests based on pseudotyped virus particles. This type of method does not need to involve live virus particles, and therefore has less stringent regulations involved and can be performed more easily.