Our study, through the integration of transcriptomic data and single-cell paired BCR profiles, revealed BCR repertoire changes in COVID-19 patients with severe illness, which is consistent with other studies focusing on subjects infected and/or vaccinated against SARS-CoV-2 subjects [29]. == 5. HLA-DRB1, and RPS20 in memory B cells; MTATP8 and HLA-DQA1 in nave cells; RPS4Y1 in activated B cells; and IGHV3-73 in plasma cells in COVID-19 patients. We further described an increased ratio of IgA + IgG to IgD + IgM, suggestive of an intensive memory antibody response, in the COVID ECMO D patient. Finally, we assessed a V(D)J rearrangement of heavy chain IgHV3, IGHJ4, and IGHD3/IGHD2 families in COVID-19 patients regardless of the severity of the disease. Keywords:COVID-19, BCR repertoire, ECMO, V(D)J, transcriptome == 1. Introduction == Since December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a hazard to global public health. The coronavirus disease 2019 (COVID-19) shows a wide range of clinical manifestations, ranging from asymptomatic presentation to critical illness with severe pneumonia, acute respiratory Nutlin-3 distress syndrome (ARDS), or multiple organ failure [1]. The similarities between the worst SARS-CoV-2 consequences and seasonal influenza problems, such as ARDS or multiple organ failure, have suggested a role for extracorporeal membrane oxygenation (ECMO) implantation in patients with the most severe pulmonary decompensation [2,3]. It has recently been established that ECMO can be utilized as a rescue therapy due to Nutlin-3 the temporary alternative of lung and/or cardiac function [4]. Several studies have reported that patients with COVID-19-related ARDS who were treated with ECMO showed a survival rate comparable with those with COVID-19-unrelated ARDS [5,6,7]. Clearing the SARS-CoV-2 contamination and hence influencing patients clinical outcomes is also mediated by humoral and adaptive immune responses [8]. A crucial role is played by the B cell antigen receptor (BCR) responsible for the recognition of pathogens. The processes of recombination and assembly of the variable and constant regions of the V, D, and J segments are Nutlin-3 crucial in generating an immense repertoire of antibodies responsible for the recognition of diverse pathogens [9]. Briefly, the antigen-binding domain name of immunoglobulins is composed of two polypeptide chains. The exons that encode the antigen-binding domains are assembled from V (variable), D (diversity), and J (joining) gene segments by a process defined as cut-and-paste DNA rearrangements. This process, named V(D)J recombination, selects a pair of segments, introduces double-strand breaks next to each segment, deletes the intermediate DNA, Nutlin-3 and ligates the segments together. Rearrangements take place in a well-ordered way, with D-to-J joining proceeding before a V segment is joined to the rearranged DJ segments (Physique 1) [10]. Getting together with a pathogen then unleashes rapid hypermutation (SHM) and class-switch recombination (CSR), thereby increasing antigen binding [11]. == Figure 1. == The antigen-binding domain of immunoglobulins is composed of two polypeptide chains, namely heavy and light chains. The exons that encode the antigen-binding domains of the heavy chain are assembled Nutlin-3 from Ednra V (variable), D (diversity), and J (joining) gene segments by a process defined as cut-and-paste DNA rearrangements. This process, named V(D)J recombination, selects a pair of segments, introduces double-strand breaks next to each segment, deletes the intermediate DNA, and ligates the segments together. Rearrangements take place in a well-ordered way, with D-to-J joining proceeding before a V segment is joined to the rearranged DJ segments. The rearrangement of the light chain is identical except for the absence of D gene fragments. In this study, we used a single-cell approach to look at the dynamic changes in the transcriptomic BCR repertoire in patients with COVID-19 at various stages, comparing a recovered and a deceased COVID-19 patient who had been supported with ECMO with one COVID-19-recovered patient who had.
Our study, through the integration of transcriptomic data and single-cell paired BCR profiles, revealed BCR repertoire changes in COVID-19 patients with severe illness, which is consistent with other studies focusing on subjects infected and/or vaccinated against SARS-CoV-2 subjects [29]