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Viral Immunol . Continued Virus-Specific Antibody-Secreting Cell Production, Avidity Maturation and B Cell Evolution in Patients Hospitalized with

tetano

Editor, Senior Moderator
Viral Immunol


. 2022 Mar 14.
doi: 10.1089/vim.2021.0191. Online ahead of print.
Continued Virus-Specific Antibody-Secreting Cell Production, Avidity Maturation and B Cell Evolution in Patients Hospitalized with COVID-19


Maggie L Bartlett[SUP] 1 [/SUP], San Suwanmanee[SUP] 1 [/SUP], Nadine Peart Akindele[SUP] 1 2 [/SUP], Shristi Ghimire[SUP] 1 [/SUP], Andy K P Chan[SUP] 1 [/SUP], Chenxu Guo[SUP] 3 [/SUP], Stephen J Gould[SUP] 3 [/SUP], Andrea L Cox[SUP] 1 4 [/SUP], Diane E Griffin[SUP] 1 [/SUP]



Affiliations

Abstract

Understanding the development and sustainability of the virus-specific protective immune response to infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains incomplete with respect to the appearance and disappearance of virus-specific antibody-secreting cells (ASCs) in circulation. Therefore, we performed cross-sectional and longitudinal analyses of peripheral blood mononuclear cells and plasma collected from 55 hospitalized patients up to 4 months after onset of COVID-19 symptoms. Spike (S)- and nucleocapsid (N)-specific IgM and IgG ASCs appeared within 2 weeks accompanied by flow cytometry increases in double negative plasmablasts consistent with a rapid extrafollicular B cell response. Total and virus-specific IgM and IgG ASCs peaked at 3-4 weeks and were still being produced at 3-4 months accompanied by increasing antibody avidity consistent with a slower germinal center B cell response. N-specific ASCs were produced for longer than S-specific ASCs and avidity maturation was greater for antibody to N than S. Patients with more severe disease produced more S-specific IgM and IgG ASCs than those with mild disease and had higher levels of N- and S-specific antibody. Women had more B cells in circulation than men and produced more S-specific IgA and IgG and N-specific IgG ASCs. Flow cytometry analysis of B cell phenotypes showed an increase in circulating B cells at 4-6 weeks with decreased percentages of switched and unswitched memory B cells. These data indicate ongoing antigen-specific stimulation, maturation, and production of ASCs for several months after onset of symptoms in patients hospitalized with COVID-19.

Keywords: SARS-CoV-2; antibody-secreting cells; antiviral antibody; avidity.
 
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