Proof-of-Concept Analysis of B Cell Receptor Repertoire in COVID-19 Patients Undergoing ECMO by Single-Cell V(D)J and Gene Expression Sequencing

• Published in: Current issues in molecular biology 2023-02, Vol.45 (2), p.1471-1482
• Main Authors: Gallo, Alessia, Cuscino, Nicola, Carcione, Claudia, Busà, Rosalia, Conaldi, Pier Giulio, Bulati, Matteo
• Format: Article
• Language: English
• Subjects: BCR repertoire; Communication; COVID-19; ECMO; transcriptome; V(D)J
• ISSN: 1467-3045; 1467-3037; 1467-3045
• DOI: 10.3390/cimb45020095

SARS-CoV-2, which causes COVID-19, has altered human activities all over the world and has become a global hazard to public health. Despite considerable advancements in pandemic containment techniques, in which vaccination played a key role, COVID-19 remains a global threat, particularly for frail patients and unvaccinated individuals, who may be more susceptible to developing ARDS. Several studies reported that patients with COVID-19-related ARDS who were treated with ECMO had a similar survival rate to those with COVID-19-unrelated ARDS. In order to shed light on the potential mechanisms underlying the COVID-19 infection, we conducted this proof-of-concept study using single-cell V(D)J and gene expression sequencing of B cells to examine the dynamic changes in the transcriptomic BCR repertoire present in patients with COVID-19 at various stages. We compared a recovered and a deceased COVID-19 patient supported by ECMO with one COVID-19-recovered patient who did not receive ECMO treatment and one healthy subject who had never been infected previously. Our analysis revealed a downregulation of FXYD, HLA-DRB1, and RPS20 in memory B cells; MTATP8 and HLA-DQA1 in naïve 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.