Prediction of antibody responses in recovered COVID-19 patients remains unclear

By Dr. Liji Thomas, MDMar 22 2021

It is crucial to gain a better understanding of how an antibody response is developed against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and how long it lasts. This will determine the antibody titers and duration that protect against reinfection by the virus. A new preprint on the medRxiv* server shows this to be still a distant goal.

Study: Can we predict antibody responses in SARS-CoV-2? A cohort analysis. Image Credit: Juan Gaertner / Shutterstock

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Seroconversion depends on severity of disease

It is known that among hospitalized COVID-19 patients, two out of three seroconvert within two weeks from infection, showing IgG antibodies. This figure approaches 90% still later on in the course of the disease.

In mild infection, only about half the patients seroconvert. There is a correlation between the strength of the disease and the antibody response, and the IgG titer changes over time.

Neutralizing antibodies (nAbs) are essential to clear the virus and inhibit its replication during ongoing infection, and probably also in preventing reinfection. The virus can produce a nAb response, but earlier research shows that nAbs also wane after six to eight months from infection, but their titers are higher after symptomatic infection.

Study aim

In order to understand the utility of convalescent plasma (CP) in COVID-19 patient management, the predictors of such a response need to be identified. This was the focus of the current study.

What are the results?

The researchers examined nAb IgG responses in a cohort of 200 participants, of which 55% were male, with a median age of 39 years. The vast majority had an ambulatory infection.

The median cycle threshold at the time of the diagnostic polymerase chain reaction (PCR) was 25, while IgG titers were high in only half of the population (including 80 participants who did not participate in the accompanying survey).

Of the cohort of 281 subjects, only 12.5% had repeated serologic testing at the time of CP donation. CP was tested in all subjects, however, irrespective of whether they donated CP or not.

IgG and neutralizing antibody responses

At the time of CP screening, the median IgG OD ratio was 3.1 among all 281 subjects. The median time of donation was 29 days from the resolution of symptoms and 34 days from the first positive PCR.

Almost 60% of them had a highly positive response, and a quarter had a positive response. However, 15% showed a failure to seroconvert or borderline IgG responses.

High nAb titers (above 1:80) were found in only a quarter of all seropositive subjects.

Age and severity associate with IgG titer

The highest IgG titer was in adults aged 18-29 years, falling in those aged 30-44 years, but then rising again in those between 45-60 years of age. This was not found in nAb titers. However, rising IgG and nAb titers were correlated.

The cycle threshold value of the diagnostic swab or the convalescent swab was not found to predict the IgG OD value of the screening CP sample.

Higher IgG titers were observed in people aged 45-60 years, and with people who reported that their activity was moderately or severely restricted by the illness.  Again, high nAbs were found to be more common among males and a cycle threshold of 25-30.

Nucleoprotein assays for the virus showed a 73% correlation with the spike assay, but only 17% with the nAb assays.

Persistence of IgG titers

Among the 35 subjects who were tested again at 46 days after the convalescent test, the median IgG OD ratio was 3.7, and about three-quarters had high positive titers. The median increase over this period was 0.5, but nAb titers were uniformly low.

What are the implications?

Older patients with more severe disease had higher IgG titers, detected at 1.5 months after infection. The clinical characteristics failed to correlate with the neutralizing antibody response.

The nAb response also showed a waning in strength, which needs to be confirmed in future research. About 15% failed to seroconvert, agreeing with an earlier New Zealand study.

The earlier correlation of both advancing age and male sex with higher antibody responses was borne out in this study only in respect of neutralizing activity. The IgG titers did not reflect such an association.

Waning antibody responses may be most closely associated with asymptomatic infection, of which there were few in the current study. This may account for the fact that IgG titers were maintained in those with initially high levels even after 46 days.

The findings also emphasize the need to use CP from those who have recovered from a severe illness in order to provide plasma with high neutralizing activity. The collection date should also be as soon as feasible to exploit the high nAb titers in early convalescence.

*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.