Researchers at Tel Aviv University in Israel have gained valuable insights into the serological and B cell response to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
While symptomatic infected patients mounted a robust antibody response to SARS-CoV-2, serological memory declined over the course of six months in recovered individuals.
By contrast, the B cell response was stable, with virus-specific memory B cells persisting over the six-month period.
These findings point to the persistence of humoral memory in patients who have recovered from coronavirus disease 2019 (COVID-19), say Yariv Wine and team.
However, the researchers say whether or not the persistence of SARS-CoV-2-specific memory B cells is correlated with future protection in the absence of serological memory still needs to be determined.
The authors suggest that this question should be investigated once samples from patients who have been convalescent for one year become available.
A pre-print version of the paper is available on the server medRxiv*, while the article undergoes peer review.
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Understanding the breadth of humoral memory
Since the first cases of SARS-CoV-2 were identified in Wuhan, China, late last year, researchers have established that a viral surface structure called the spike protein is highly immunogenic. The receptor-binding domain (RBD) of this viral protein has been shown to elicit neutralizing antibodies as early as 3 days following the onset of symptoms.
“Still, the question remains if serological memory persists over time,” writes the team.
Recent studies reporting on the isolation of RBD-specific B cells tried to elucidate the composition of neutralizing antibodies. Still, information regarding the dynamics of antibodies and their association with RBD-specific B cells in recovered COVID-19 patients is lacking.
The authors say this information would help researchers assess the breadth of humoral memory and whether this contributes to long-lasting serological and cellular memory.
There are two components to adaptive memory, explain the authors. Long-lived antibody-secreting plasma cells (LLPC) contribute to serological memory, and long-lived memory B cells react quickly to repeated antigenic challenge (cellular memory).
“It is imperative to determine the persistence of humoral memory in COVID-19 recovered patients as it will help to evaluate the susceptibility of recovered patients to re-infection,” says the team.
What did the researchers do?
Now, Wine and colleagues have investigated the dynamics of the serological and cellular response in recovered COVID-19 patients using blood serum collected from 54 symptomatic patients with active disease, 57 recovered patients (6 of whom provided follow-up samples) and 26 healthy controls.
Serum was tested to determine levels of RBD-specific immunoglobulins (Igs) and their ability to neutralize SARS-CoV-2. B cells isolated from recovered patients using fluorescence-activated cell sorting were used to assess the frequency of RBD-specific subsets of B cells.
RBD-specific antibodies increased in symptomatic patients and declined in recovered patients
The team found that levels of RBD-specific antibodies quickly increased among symptomatic patients.
Levels of RBD-specific IgG strongly correlated with their neutralizing capacity, which suggests RBD-specific antibody titers alone could be used as a proxy for assessing neutralization capacity, says the team.
Among recovered patients, the team found that the RBD-specific antibody titers declined over six months following symptom onset, pointing to decay in serological memory over time.
By contrast, RBD-specific memory B cells were found to be stable during the six month period.
Since the virus-specific antibodies declined over time, the team hypothesized that the differentiation of B cells into LLPCs following SARS-CoV-2 infection is impaired.
To test this, the researchers studied the association between the frequency of RBD-specific subsets of plasmablasts and the frequency of RBD-specific memory B cells, which revealed that the frequency of both subsets was strongly correlated.
Cellular arm of adaptive immunity may provide robust recall immune response
Next, they investigated the association between RBD-specific plasmablasts and antibody titers to test whether the main contributor to serum antibody levels was short-lived plasmablasts.
The team reports that the frequency of SARS-CoV-2-specific B cell plasmablasts was indeed associated with levels of virus-specific antibodies.
“The persistence of RBD-specific mBC [memory B cell] suggests that the cellular arm of the adaptive immunity may provide robust recall immune response in cases of re-infection,” say the researchers.
However, “will this suffice in providing sufficient protection especially due to the decay of the serological memory?” they ask.
“These aspects should be further investigated in follow up temporal studies when samples from recovered patients one year following the onset of symptoms will be available,” concludes the team.
*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:
- Preliminary scientific report.
Wine Y, et al. SARS-CoV-2 specific memory B cells frequency in recovered patient remains stable while antibodies decay over time. medRxiv 2020. doi: https://doi.org/10.1101/2020.08.23.20179796
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