SARS-CoV-2 specific memory B cells frequency in recovered patient remains stable while antibodies decay over time

Vaisman-Mentesh, Anna; Dror, Yael; Tur–Kaspa, Ran; Markovitch, Dana; Kournos, Tatiana; Dicker, Dror; Wine, Yariv

doi:10.1101/2020.08.23.20179796

Cited by 22 publications

(26 citation statements)

References 30 publications

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“…Our results show that the majority of patients, irrespective of disease severity, can mount specific memory B- and T-cell responses, which remain present at least 6-8 months post symptom onset. These findings are consistent with preprints showing, using flow cytometry, that RBD-specific memory B cells are generated and maintained up to 3-5 months post-SARS-CoV-2 infection in predominantly mild-moderate cohorts 32 33 34 . Importantly, we show that these memory B cells are maintained and can secrete RBD-specific IgG antibodies following stimulation.…”

Section: Discussionsupporting

confidence: 90%

Persistence of SARS-CoV-2 specific B- and T-cell responses in convalescent COVID-19 patients 6-8 months after the infection

Sherina

Piralla

et al. 2020

Preprint

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Background: The longevity of the immune response against SARS-CoV-2 is currently debated. We thus profiled the serum anti-SARS-CoV-2 antibody levels and virus specific memory B- and T-cell responses over time in convalescent COVID-19 patients. Methods: A cohort of COVID-19 patients from the Lombardy region in Italy who experienced mild to critical disease and Swedish volunteers with mild symptoms, were tested for the presence of elevated anti-spike and anti-receptor binding domain antibody levels over a period of eight months. In addition, specific memory B- and T-cell responses were tested in selected patient samples. Results: Anti-SARS-CoV-2 antibodies were present in 85% samples collected within 4 weeks after onset of symptoms in COVID-19 patients. Levels of specific IgM or IgA antibodies declined after 1 month while levels of specific IgG antibodies remained stable up to 6 months after diagnosis. Anti-SARS-CoV-2 IgG antibodies were still present, though at a significantly lower level, in 80% samples collected at 6-8 months after symptom onset. SARS-CoV-2-specific memory B- and T-cell responses were developed in vast majority of the patients tested, regardless of disease severity, and remained detectable up to 6-8 months after infection. Conclusions: Although the serum levels of anti-SARS-CoV-2 IgG antibodies started to decline, virus-specific T and/or memory B cell responses increased with time and maintained during the study period (6-8 months after infection).

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Section: Discussionsupporting

confidence: 90%

Persistence of SARS-CoV-2 specific B- and T-cell responses in convalescent COVID-19 patients 6-8 months after the infection

Sherina

Piralla

et al. 2020

Preprint

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“…There is also evidence that symptomatic COVID-19 patients mount robust antibody responses that wane very quickly over a period of 6 months (52). However, the same study suggeted that SARS-CoV-2-specific memory B cells may be sustained over a longer period of time (52). Indeed, most acute virus infections induce some level of protective and long-term immunity, albeit through a variety of mechanisms that are not necessarily the same for each pathogen and may even differ between hosts due to a variety of factors, including simultaneous viral coinfection (53,54).…”

Section: Discussionmentioning

confidence: 95%

Distinct antibody repertoires against endemic human coronaviruses in children and adults

Khan¹,

Rahman²,

Ali³

et al. 2021

JCI Insight

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Four endemic human coronaviruses (HCoVs) are commonly associated with acute respiratory infection in humans. B cell responses to these “common cold” viruses remain incompletely understood. Here we report a comprehensive analysis of CoV-specific antibody repertoires in 231 children and 1168 adults using phage immunoprecipitation sequencing. Seroprevalence of antibodies against endemic HCoVs ranged between approximately 4% and 27% depending on the species and cohort. We identified at least 136 novel linear B cell epitopes. Antibody repertoires against endemic HCoVs were qualitatively different between children and adults in that anti-HCoV IgG specificities more frequently found among children targeted functionally important and structurally conserved regions of the spike, nucleocapsid, and matrix proteins. Moreover, antibody specificities targeting the highly conserved fusion peptide region and S2′ cleavage site of the spike protein were broadly cross-reactive with peptides of epidemic human and nonhuman coronaviruses. In contrast, an acidic tandem repeat in the N-terminal region of the Nsp3 subdomain of the HCoV-HKU1 polyprotein was the predominant target of antibody responses in adult donors. Our findings shed light on the dominant species-specific and pan-CoV target sites of human antibody responses to coronavirus infection, thereby providing important insights for the development of prophylactic or therapeutic monoclonal antibodies and vaccine design.

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“…We demonstrated the persistence of specific IgG memory B cells by differentiating them into Ab-secreting cells in vitro, which also facilitated our functional analysis of the Abs secreted by the cells. Previous studies have also detected COVID-19 patients' memory B cells by staining them with labelled antigens (4,15,21,(35)(36)(37)(38)(39) and using the enzyme-linked immune absorbent spot (ELISPOT) assay (8,(40)(41)(42). Sorting the SARS-CoV-2-specific B cells and cloning their antigen-receptors provided important insights into clonal turnover and the ongoing somatic hypermutation of SARS-CoV-2-specific B cells associated with antigen persistence (15,21).…”

Section: Discussionmentioning

confidence: 99%

Persistence of functional memory B cells recognizing SARS-CoV-2 variants despite loss of specific IgG

Winklmeier

Eisenhut

Taskin

et al. 2021

Preprint

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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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SARS-CoV-2 specific memory B cells frequency in recovered patient remains stable while antibodies decay over time

Cited by 22 publications

References 30 publications

Persistence of SARS-CoV-2 specific B- and T-cell responses in convalescent COVID-19 patients 6-8 months after the infection

Persistence of SARS-CoV-2 specific B- and T-cell responses in convalescent COVID-19 patients 6-8 months after the infection

Distinct antibody repertoires against endemic human coronaviruses in children and adults

Persistence of functional memory B cells recognizing SARS-CoV-2 variants despite loss of specific IgG

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