While some COVID-19 patients maintain SARS-CoV-2-specific serum IgGs for more than 6 months post-infection, others eventually lose IgG levels. We assessed the persistence of SARS-CoV-2-specific B cells in 17 patients, five of whom had lost specific IgGs after 5–8 months. Differentiation of blood-derived B cells in vitro revealed persistent SARS-CoV-2-specific IgG B-cells in all patients, whereas IgA-B cells were maintained in 11. Antibodies derived from cultured B cells blocked binding of viral receptor-binding domain (RBD) to the cellular receptor ACE-2, had neutralizing activity to authentic virus and recognized the RBD of the variant of concern Alpha similarly to the wild-type, while reactivity to Beta and Gamma were decreased. Thus, differentiation of memory B-cells could be more sensitive for detecting previous infection than measuring serum antibodies. Understanding the persistence of SARS-CoV-2 specific B cells even in the absence of specific serum IgG will help to promote long-term immunity.
While some COVID-19 patients maintain SARS-CoV-2-specific serum IgGs for more than 6 months post-infection, others, especially mild cases, eventually lose IgG levels. We aimed to assess the persistence of SARS-CoV-2-specific B cells in patients who have lost specific IgGs and analyzed the reactivity of the immunoglobulins produced by these B cells. Circulating IgG memory B cells specific for SARS-CoV-2 were detected in all 16 patients 1-8 months post-infection, and 11 participants had specific IgA B cells. Four patients lost specific serum IgG after 5-8 months but had SARS-CoV-2-specific-B-cell levels comparable to those of seropositive donors. Immunoglobulins produced after in vitro differentiation blocked receptor-binding domain (RBD) binding to the cellular receptor ACE-2, indicating neutralizing activity. Memory-B-cell-derived IgGs recognized the RBD of B.1.1.7 similarly to the wild-type, while reactivity to B.1.351 and P.1. decreased by 30% and 50%, respectively. Memory-B-cell differentiation into antibody-producing cells is a more sensitive method for detecting previous infection than measuring serum antibodies. Circulating SARS-CoV-2 IgG memory B cells persist, even in the absence of specific serum IgG; produce neutralizing antibodies; and show differential cross-reactivity to emerging variants of concern. These features of SARS-CoV-2-specific memory B cells will help to understand and promote long-term protection.
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