\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Characterization of B-cell receptor clonality and immunoglobulin gene
usage at multiple time points during active SARS-CoV-2 infection}



\author[1]{Robert J. Kreitman}%
\author[1]{Evgeny Arons}%
\author[2]{Kiersten Henry}%
\author[3]{Christopher Haas}%
\author[1]{Mory Gould}%
\author[1]{Jack Tsintolas}%
\author[1]{Jack Mauter}%
\author[1]{Hong Zhou}%
\author[4]{Peter Burbelo}%
\author[5]{Jeffrey Cohen}%
\affil[1]{National Cancer Institute Laboratory of Molecular Biology}%
\affil[2]{MedStar Montgomery Medical Center}%
\affil[3]{MedStar Franklin Square Medical Center}%
\affil[4]{National Institute of Dental and Craniofacial Research}%
\affil[5]{National Institute of Allergy and Infectious Diseases Laboratory of Infectious Diseases}%


\vspace{-1em}



  
  \date{May 25, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
\textbf{Purpose} Although monoclonal antibodies specific to the severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are known,
information about the B-cell receptor (BCR) repertoire and its change in
patients during COVID-19 disease progression is underreported.
\textbf{Methods} We used immunoglobulin heavy chain (IGH) variable
region (IGHV) spectratyping and next-generation sequencing of peripheral
blood B-cell genomic DNA collected at multiple time points during
disease evolution to study B-cell response to SARS-CoV-2 infection in 14
individuals with acute COVID-19. \textbf{Results} We found a broad
distribution of responding B-cell clones. The IGH gene usage was not
significantly skewed but frequencies of individual IGH genes changed
repeatedly. We found predominant usage of unmutated and low
mutation-loaded IGHV rearrangements characterizing na\selectlanguage{ngerman}ïve and
extrafollicular B-cells among the majority of expanded peripheral B-cell
clonal lineages at most tested time points in most patients. IGH
rearrangement usage showed no apparent relation to anti-SARS-CoV-2
antibody titers. Some patients demonstrated mono/oligoclonal populations
carrying highly mutated IGHV rearrangements indicating antigen
experience at some of the time points tested, including even before
anti-SARS-CoV-2 antibodies were detected. \textbf{Conclusion} We present
evidence demonstrating that the B-cell response to SARS-CoV-2 is
individual and includes different lineages of B-cells at various time
points during COVID-19 progression.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{Hosted file}

\verb`arons,JMedVirol.docx`  available at \url{https://authorea.com/users/650846/articles/659131-characterization-of-b-cell-receptor-clonality-and-immunoglobulin-gene-usage-at-multiple-time-points-during-active-sars-cov-2-infection}

\textbf{Hosted file}

\verb`arons,2022b.pptx`  available at \url{https://authorea.com/users/650846/articles/659131-characterization-of-b-cell-receptor-clonality-and-immunoglobulin-gene-usage-at-multiple-time-points-during-active-sars-cov-2-infection}

\selectlanguage{english}
\FloatBarrier
\end{document}

