Translational and Clinical Research Program, Cancer Research Center (IBMCC, CSIC - University of Salamanca); Cytometry Service, NUCLEUS, University of Salamanca (Universidad de Salamanca), Salamanca, Spain.
Department of Medicine, University of Salamanca (Universidad de Salamanca), Salamanca, Spain.
Am J Hematol. 2023 Dec;98(12):1909-1922. doi: 10.1002/ajh.27119. Epub 2023 Oct 4.
Low-count monoclonal B-cell lymphocytosis (MBL ) has been associated with an underlying immunodeficiency and has recently emerged as a new risk factor for severe COVID-19. Here, we investigated the kinetics of immune cell and antibody responses in blood during COVID-19 of MBL versus non-MBL patients. For this study, we analyzed the kinetics of immune cells in blood of 336 COVID-19 patients (74 MBL and 262 non-MBL), who had not been vaccinated against SARS-CoV-2, over a period of 43 weeks since the onset of infection, using high-sensitivity flow cytometry. Plasma levels of anti-SARS-CoV-2 antibodies were measured in parallel by ELISA. Overall, early after the onset of symptoms, MBL COVID-19 patients showed increased neutrophil, monocyte, and particularly, plasma cell (PC) counts, whereas eosinophil, dendritic cell, basophil, and lymphocyte counts were markedly decreased in blood of a variable percentage of samples, and with a tendency toward normal levels from week +5 of infection onward. Compared with non-MBL patients, MBL COVID-19 patients presented higher neutrophil counts, together with decreased pre-GC B-cell, dendritic cell, and innate-like T-cell counts. Higher PC levels, together with a delayed PC peak and greater plasma levels of anti-SARS-CoV-2-specific antibodies (at week +2 to week +4) were also observed in MBL patients. In summary, MBL COVID-19 patients share immune profiles previously described for patients with severe SARS-CoV-2 infection, associated with a delayed but more pronounced PC and antibody humoral response once compared with non-MBL patients.
低计数单克隆 B 细胞淋巴细胞增多症 (MBL) 与潜在免疫缺陷有关，最近已成为严重 COVID-19 的新危险因素。在这里，我们研究了 MBL 与非 MBL 患者 COVID-19 期间血液中免疫细胞和抗体反应的动力学。为此，我们使用高灵敏度流式细胞术分析了 336 名未接种 SARS-CoV-2 疫苗的 COVID-19 患者（74 名 MBL 和 262 名非 MBL）的血液中免疫细胞的动力学，感染发作后 43 周。同时通过 ELISA 平行测量血浆中抗 SARS-CoV-2 抗体的水平。总的来说，在症状发作后早期，MBL COVID-19 患者的中性粒细胞、单核细胞计数增加，特别是浆细胞 (PC) 计数增加，而嗜酸性粒细胞、树突状细胞、嗜碱性粒细胞和淋巴细胞计数在血液中的百分比显著降低，并且从感染后第 5 周开始趋于正常水平。与非 MBL 患者相比，MBL COVID-19 患者的中性粒细胞计数较高，同时前 GC B 细胞、树突状细胞和固有样 T 细胞计数减少。MBL 患者还观察到更高的 PC 水平，以及 PC 峰值延迟和更大的 SARS-CoV-2 特异性抗体血浆水平（在第 2 周到第 4 周）。总之，MBL COVID-19 患者与严重 SARS-CoV-2 感染患者先前描述的免疫特征相似，与非 MBL 患者相比，PC 和抗体体液反应延迟但更为明显。
