Garduno Alexis, Martinez Gustavo Sganzerla, Ostadgavahi Ali Toloue, Kelvin David, Cusack Rachael, Martin-Loeches Ignacio
Department of Clinical Medicine, University of Dublin, Trinity College, D08 NHY1 Dublin, Ireland.
Department of Microbiology and Immunology, Dalhousie University, 5850 College Street, Halifax, NS B3H 4R2, Canada.
Biomedicines. 2023 Mar 3;11(3):778. doi: 10.3390/biomedicines11030778.
Critically ill COVID-19 patients start developing single respiratory organ failure that often evolves into multiorgan failure. Understanding the immune mechanisms in severe forms of an infectious disease (either critical COVID-19 or bacterial septic shock) would help to achieve a better understanding of the patient's clinical trajectories and the success of potential therapies. We hypothesized that a dysregulated immune response manifested by the abnormal activation of innate and adaptive immunity might be present depending on the severity of the clinical presentation in both COVID-19 and bacterial sepsis. We found that critically ill COVID-19 patients demonstrated a different clinical endotype that resulted in an inflammatory dysregulation in mild forms of the disease. Mild cases (COVID-19 and bacterial non severe sepsis) showed significant differences in the expression levels of CD8 naïve T cells, CD4 naïve T cells, and CD4 memory T cells. On the other hand, in the severe forms of infection (critical COVID-19 and bacterial septic shock), patients shared immune patterns with upregulated single-cell transcriptome sequencing at the following levels: B cells, monocyte classical, CD4 and CD8 naïve T cells, and natural killers. In conclusion, we identified significant gene expression differences according to the etiology of the infection (COVID-19 or bacterial sepsis) in the mild forms; however, in the severe forms (critical COVID-19 and bacterial septic shock), patients tended to share some of the same immune profiles related to adaptive and innate immune response. Severe forms of the infections were similar independent of the etiology. Our findings might promote the implementation of co-adjuvant therapies and interventions to avoid the development of severe forms of disease that are associated with high mortality rates worldwide.
危重症 COVID-19 患者开始出现单一呼吸器官衰竭,且常常会发展为多器官衰竭。了解严重形式的传染病(重症 COVID-19 或细菌性脓毒症休克)中的免疫机制,将有助于更好地理解患者的临床病程以及潜在治疗方法的成效。我们推测,根据 COVID-19 和细菌性脓毒症的临床表现严重程度,可能存在由先天性和适应性免疫异常激活所表现出的免疫反应失调。我们发现,危重症 COVID-19 患者表现出一种不同的临床内型,这在疾病的轻症形式中导致了炎症失调。轻症病例(COVID-19 和细菌性非重症脓毒症)在 CD8 初始 T 细胞、CD4 初始 T 细胞和 CD4 记忆 T 细胞的表达水平上存在显著差异。另一方面,在严重感染形式(重症 COVID-19 和细菌性脓毒症休克)中,患者在以下水平上具有上调的单细胞转录组测序共享免疫模式:B 细胞、经典单核细胞、CD4 和 CD8 初始 T 细胞以及自然杀伤细胞。总之,我们发现在轻症形式中,根据感染病因(COVID-19 或细菌性脓毒症)存在显著的基因表达差异;然而,在重症形式(重症 COVID-19 和细菌性脓毒症休克)中,患者倾向于共享一些与适应性和先天性免疫反应相关的相同免疫谱。无论病因如何,严重感染形式都相似。我们的发现可能会促进联合辅助治疗和干预措施的实施,以避免发展为与全球高死亡率相关的严重疾病形式。