Most SARS-CoV-2-infected individuals develop durable B cell-mediated immunity

Most SARS-CoV-2-infected individuals develop durable B cell-mediated immunity

By Susha Cheriyedath, M.Sc.Nov 3 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus behind the ongoing global pandemic, causes coronavirus disease 2019 (COVID-19). This disease can cause acute respiratory distress syndrome (ARDS), pulmonary inflammation, respiratory failure, and even death. Despite the high level of morbidity and mortality associated with COVID-19, most people infected with SARS-CoV-2 survive the illness. However, whether they still have immunity against SARS-CoV-2 following their recovery is still not clear. The durability of immunity plays a crucial role in minimizing the reinfection risk in millions of people recovering from SARS-CoV-2 infection.

Several studies have shown that SARS-CoV-2 specific antibodies deplete over time following infection and recovery. This raises concerns that humoral immunity against SARS-CoV-2 is not durable. If immunity does wane over time, millions of people who have recovered from the infection might be at risk for reinfection.

Although some studies have reported that memory B cells can provide durable humoral immunity even when serum antibody titers decline, not much is known about the frequency and phenotype of SARS-CoV-2-specific memory B cells developed in response to severe or mild infection. B cells specific to the SARS-CoV-2 Spike (S) protein have been isolated from patients having very low antibody titers. However, the relatively low frequency of these cells hinders further characterization.

Flow cytometric analysis helps quantify B cells specific to SARS-CoV-2 protein receptor-binding domain

Researchers from the Johns Hopkins University and The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA, investigated the durability of B cell immunity following SARS-CoV-2 infection and recovery in their recent work published on the preprint server medRxiv*.

The researchers developed a precise and sensitive flow cytometry-based assay for quantitating B cells specific to the SARS-CoV-2 protein receptor-binding domain (S-RBD). They also designed a cell surface phenotyping panel to characterize these B cells. They focused on B cells specific to S-RBD because most human monoclonal antibodies that neutralize viruses target this domain. The neutralizing activity has been linked to protection against reinfection by similar coronaviruses in animal models of SARS-CoV-2 infection.

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They performed a multi-dimensional flow cytometric analysis of memory B cells specific to the S-RBD. Their study cohorts comprised ambulatory COVID-19 patients who had a mild disease as well as hospitalized COVID-19 patients with moderate or severe disease. The analyses were performed at a median of 54 (39-104) days following the onset of symptoms.

Resting memory B cells are the most abundant S-RBD-specific memory B cells detected in the study

The researchers detected S-RBD-specific memory B cells in 13 out of 14 patients, including 4 of the 5 participants with deficient levels of anti-S-RBD IgG and neutralizing antibodies in plasma. Resting memory B cells (rMBC) constituted the largest proportion of S-RBD-specific memory B cells detected in both study cohorts. A marker of functional memory, FCRL5, was drastically upregulated on S-RBD-specific rMBC, especially in patients with mild disease.

“FCRL5, a marker of a functional memory response when expressed on antigen-specific rMBC, was dramatically upregulated on S-RBD-specific rMBC, particularly after mild infection.”

Most patients develop S-RBD-specific B cells that phenotypically resemble B cells induced by vaccination

To summarize, the researchers demonstrated that S-RBD-specific memory B cells are developed in most SARS-CoV-2-infected patients, including those with mild symptoms or very low levels of anti-S-RBD IgG and neutralizing antibodies in plasma. The least abundant S-RBD specific memory B cells in both cohorts were atypical memory B cells (atyMBC).

Based on these data, the team concluded that most individuals infected with SARS-CoV-2 develop S-RBD-specific, class-switched memory B cells that phenotypically resemble germinal center-derived B cells that are induced following vaccination. This provides evidence for durable B cell-mediated immunity against the SARS-CoV-2 virus post recovery from mild to severe COVID-19. The authors believe that their findings offer a standard against which B cell responses to new SARS-CoV-2 vaccines could be compared in the future.

“These data have implications for risk of reinfection after recovery from COVID-19, and also provide a standard against which B cell responses to novel SARS-CoV-2 vaccines could be compared.”

*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.

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