Antibody kinetics in recovered COVID-19 patients

The coronavirus disease 2019 (COVID-19) pandemic began nearly two years ago and rapidly spread across the globe, causing a worldwide health and economic disaster. While mass vaccination programs are beginning to allow restrictions to ease, concerns over the alternate strains such as the Delta variant remain.

Vaccination will also take much longer for some countries than others, as the most commonly used vaccines require strong logistic chains and constant refrigeration. As such, it is still very important to examine the persistence and level of antibody response. To this extent, researchers from Tel Aviv University have been examining the kinetics of antibodies in recovered COVID-19 patients.

Study: The longitudinal kinetics of antibodies in COVID-19 recovered patients over 14 months. Image Credit: Leonid Altman / Shutterstock

A preprint version of the group's study is available on the medRxiv* server, while the article undergoes peer review.

The most common antibodies that target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will target the spike protein – specifically the receptor binding domain (RBD) of the S1 subunit. The spike protein is responsible for a large element of the pathogenicity of SARS-CoV-2. The RBD binds to angiotensin-converting enzyme 2 (ACE2) in order to allow viral cell entry, while the N-terminal domain in the S2 subunit is required for membrane fusion. While antibodies can target multiple different areas of SARS-CoV-2, targeting the RBD tends to show the most effective response, and so RBD-specific antibodies tend to be evaluated in these studies.

The researchers examined samples gathered from over 200 patients who had recovered from COVID-19, with some gathered from those who had been infected over 400 days beforehand. Eighty-nine of these patients provided further samples periodically across 90 days. Patient ages ranged between 20 and 81 years old, from an equal number of men and women, and the severity of the COVID-19 infection was recorded, with the vast majority (82%) of participants suffering from mild symptoms.

In order to examine the difference between natural immunity and vaccine-induced immunity, another 17 individuals were sampled that had never been infected with SARS-CoV-2, but who had received both doses of the BNT162b2 mRNA vaccine. 24% of the examined individuals who had previously been convalescent had also been vaccinated. Anti-RBD IgG, IgM and IgA levels were measured by ELISA testing.

The scientists found that women tended to show higher levels of IgG, IgM and IgA. Interestingly, those over 50 showed significantly increased levels of IgG and IgM compared to those under 50. This same pattern showed with severity, with those displaying mild symptoms have lower levels of both IgG and IgA. By applying a regression model and determining the regression coefficient, the researchers examined the change in antibody concentration over time. For all three tested antibody isotypes, levels decayed over the 14 months, with IgA showing the fastest decrease in RBD binding. IgM followed, and then IgG. On the first round of testing, individuals who had previously been infected with COVID-19 mostly showed reasonably high antibody levels – only 14%, 49% and 40% for IgG, IgA and IgM, respectively, showed levels equivalent to the negative controls. By the final visit, 29%, 70% and 73% were equivalent to the negative control.

When comparing the antibodies in the recovered patients to those seen in vaccinees that had not been exposed to the disease, the authors saw significantly quicker antibody decay in vaccinated individuals. Similar to participants who had previously been infected with the disease, IgA decayed the quickest, followed by IgG and IgM. All non-exposed vaccinated individuals also showed lower overall antibody levels compared to the rest of the study. This data is supported by previous studies showing less binding to the RBD from antibodies taken from vaccinated individuals compared to previously convalescent individuals.

The authors highlight the difference between the immune response from natural infection and vaccination. They suggest that recently seen lower vaccination efficiency is likely due to the developing threat of the Delta strain. They also propose a potential mechanism by which the temporal difference in decay could be explained – as natural infection involves a full immune reaction, with inflammation and activation of the innate immune arm.

mRNA vaccination may avoid this, potentially due to an absence of cellular damage. This could lead to the reduced ability of the immune system to maintain the long-loved plasma cells that support the higher antibody counts seen in previously infected individuals. They also stress the importance of their own and similar studies' evidence in informing future vaccine plans. The information could also be useful in countries still looking at the possibility of reducing restrictions.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information

Written by

Sam Hancock

Sam completed his MSci in Genetics at the University of Nottingham in 2019, fuelled initially by an interest in genetic ageing. As part of his degree, he also investigated the role of rnh genes in originless replication in archaea.