How do SARS-CoV-2 antibodies change over time in recovered patients?

Researchers studied convalescent plasma from recovered coronavirus disease 2019 (COVID-19) patients, with samples collected up to 34 weeks after recovery. They found IgG antibodies gradually declined with a median half-life of about 60 days.

Study: Dynamics of antibodies to SARS-CoV-2 in convalescent plasma donors. Image Credit: KTSdesign / Shutterstock
Study: Dynamics of antibodies to SARS-CoV-2 in convalescent plasma donors. Image Credit: KTSdesign / Shutterstock

One of the methods to combat COVID-19, the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is by the transfusion of convalescent plasma, collected from people who have recovered from the infection. However, its effect in severely ill patients seems to be limited. The most potent convalescent plasma is considered to be that which has the most neutralizing antibodies to SARS-CoV-2.

Almost all COVID-19 patients develop IgG, IgM, and IgA antibodies to the virus spike protein and nucleocapsid protein. Antibody levels vary depending on disease severity and duration.

Studies have reported the antibodies can be detected up to eight months after recovery. Other studies have reported antibodies can be detected within a week to three weeks after symptoms are seen. However, there is little information on how the antibody levels change over a longer time. Some longer-term studies have reported a small decline in IgG antibody levels over eight months, while others have seen a rapid decline in IgM and IgA levels after a month of symptom onset.

Antibody levels change with time

In a new study, researchers studied antibody trends over 34 weeks from plasma collected from 151 adults who had recovered from the disease. They published their results in the medRxiv* preprint server.

The authors measured the total antibody levels, IgM and IgA antibodies to the spike protein receptor-binding domain (RBD) and IgG antibodies to the RBD and nucleocapsid protein. They assessed the neutralization capacity of the antibodies using a competition assay. The study included a total of 676 samples for the period up to 22 weeks after symptom onset and an additional 148 samples up to 34 weeks after symptom onset.

They found that all the samples collected before five weeks of symptom onset had IgG antibodies to the RBD and decreased only a little with time. IgA and IgM antibodies were seen only in about 70 to 75% of the samples and gradually decreased over time.

Antibody levels varied more than 100-fold among the plasma donors, with greater levels seen in hospitalized patients and males compared to females. Up to 22 weeks, the IgG levels decreased steadily and they had a median half-life of 62 and 50 days for anti-RBD anti-nucleocapsid protein, respectively. The decrease in IgG levels over time and their variation among individuals is important to take into consideration in assessing seroprevalence immunity in populations and selecting convalescent plasma donors.  

The half-life of the IgG antibody subclass IgG3, about seven days, was lower than that of the subclass IgG1, which had a half-life of about 21 days.

To understand the neutralizing capacity of the antibodies, the authors carried out a competition ELISA. They found a strong correlation between anti-RBD IgG levels and the level of competition, and a weak correlation between anti-RBD IgM and IgA and the competition. This suggests IgG is important in neutralizing SARS-CoV-2.

Correlation between IgG levels and virus neutralization Plasma samples were tested in the in-house developed competition ELISA (676 samples from 151 individual donors), and in the classic plaque reduction assay (147 samples from 129 individual donors). The correlation between anti-RBD IgG and virus neutralization in the (A, B) competition assay and (C) plaque reduction assay was assessed by Spearman (r = 0.85, r = 0.75, resp., p < 0.001). (D) A correlation between the two viral neutralization assays was also observed (Spearman r = 0.65, p < 0.001).
Correlation between IgG levels and virus neutralization Plasma samples were tested in the in-house developed competition ELISA (676 samples from 151 individual donors), and in the classic plaque reduction assay (147 samples from 129 individual donors). The correlation between anti-RBD IgG and virus neutralization in the (A, B) competition assay and (C) plaque reduction assay was assessed by Spearman (r = 0.85, r = 0.75, resp., p < 0.001). (D) A correlation between the two viral neutralization assays was also observed (Spearman r = 0.65, p < 0.001).

The study included a median number of five samples per patient, which allowed a more detailed analysis. The data collected indicated that the decrease in antibody levels in not uniform but slows down with time.

The authors also determined the amounts of IgG antibody subclasses. In contrast to previous studies that found IgG3 to be more in numbers, the authors found the IgG1 subclass to be dominant. This could be because in previous studies of plasma collected samples soon after recovery, while in this study plasma was collected up to 22 weeks after recovery.

The study found higher IgG levels in patients who were seriously ill compared to those who had only mild symptoms. Thus, severely ill patients may be more suited for donating convalescent plasma. But, other studies have shown that severely ill patients have autoantibodies against a.o. type I IFN-a2 and IFN-w, which may negatively impact convalescent plasma treatment. So, it may be safer to obtain plasma from mild or moderately ill patients despite their lower antibody levels.          

Antibodies are produced over a long time by long-lived plasma cells and memory B cells, which can last the entire lifetime. With continued study, it can be determined if antibodies to SARS-CoV-2 are long-lived, similar to those of SARS-CoV, which can be detected even after three years.

*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.

Journal reference:
Lakshmi Supriya

Written by

Lakshmi Supriya

Lakshmi Supriya got her BSc in Industrial Chemistry from IIT Kharagpur (India) and a Ph.D. in Polymer Science and Engineering from Virginia Tech (USA).

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