Gallo Alessia, Cuscino Nicola, Carcione Claudia, Busà Rosalia, Conaldi Pier Giulio, Bulati Matteo
Department of Research, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), 90127 Palermo, Italy.
Fondazione Ri.MED, Department of Research IRCCS ISMETT, via Ernesto Tricomi 5, 90145 Palermo, Italy.
Curr Issues Mol Biol. 2023 Feb 9;45(2):1471-1482. 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.
导致新冠肺炎的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）改变了世界各地的人类活动，已成为全球公共卫生危害。尽管在疫情防控技术方面取得了重大进展，其中疫苗接种发挥了关键作用，但新冠肺炎仍然是全球威胁，特别是对于体弱患者和未接种疫苗的个体，他们可能更容易发展为急性呼吸窘迫综合征（ARDS）。多项研究报告称，接受体外膜肺氧合（ECMO）治疗的新冠肺炎相关ARDS患者的生存率与非新冠肺炎相关ARDS患者相似。为了阐明新冠肺炎感染的潜在机制，我们进行了这项概念验证研究，使用B细胞的单细胞V（D）J和基因表达测序来检查新冠肺炎患者在不同阶段转录组B细胞受体（BCR）库的动态变化。我们将一名接受ECMO支持的康复新冠肺炎患者和一名死亡新冠肺炎患者与一名未接受ECMO治疗的康复新冠肺炎患者以及一名从未感染过的健康受试者进行了比较。我们的分析显示，新冠肺炎患者的记忆B细胞中FXYD、人类白细胞抗原-DRB1（HLA-DRB1）和核糖体蛋白S20（RPS20）下调；幼稚细胞中MTATP8和HLA-DQA1下调；活化B细胞中RPS4Y1下调；浆细胞中IGHV3-73下调。我们进一步描述了新冠肺炎ECMO D患者中IgA + IgG与IgD + IgM的比例增加，这表明存在强烈的记忆抗体反应。最后，我们评估了新冠肺炎患者中重链IgHV3、IGHJ4和IGHD3/IGHD2家族的V（D）J重排，无论疾病严重程度如何。
