Abdallah Abdallah Musa, Ansari Hifzur Rahman, Shuaib Muhammad, Doudin Asmma, Yassine Hadi M, Shah Syed Shahab Ud Din, Mir Fayaz Ahmad, Emara Mohamed M, Elzouki Abdel-Naser, Cyprian Farhan S
College of Medicine, QU Health, Qatar University, Doha, Qatar.
King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard-Health Affairs (MNG-HA), Jeddah, Saudi Arabia.
Sci Rep. 2025 Jul 2;15(1):23416. doi: 10.1038/s41598-025-04837-0.
Coronavirus disease (COVID-19) is a heterogeneous infectious disease caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The distinctive features of COVID-19 infection encompass a clinical spectrum ranging from asymptomatic forms to severe illness involving diverse underlying pathophysiological processes such as hyperinflammation, endothelial dysfunction, thrombotic microangiopathies, and multiple organ failure. However, the host responses to COVID-19, including systemic inflammation and immunity against SARS-CoV-2, remain largely undefined across different disease states. Here, we performed global transcriptome profiling of 228 peripheral blood samples of COVID-19 patients with different clinical manifestations and subsequent clustering using an unsupervised algorithm. We identified various transcriptomic clusters and globally dysregulated immune-related pathways, leading to distinct host inflammatory cytokine profiles in severe and critical SARS-CoV-2 infected patients. This underscores the association between COVID-19 pathogenesis and excessive cytokine release. Additionally, our results reveal variances in circulating cell populations and the activation of apoptosis and the p53 signaling pathway in lymphocytes induced by SARS-CoV-2 infection. The transcriptome dataset of COVID-19 patients with diverse clinical presentations offers valuable insights into molecular mechanisms and may inform clinical decisions on anti-inflammatory therapies.
冠状病毒病（COVID-19）是一种由新型冠状病毒严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的异质性传染病。COVID-19感染的显著特征包括从无症状形式到严重疾病的临床谱，涉及多种潜在的病理生理过程，如过度炎症、内皮功能障碍、血栓性微血管病和多器官衰竭。然而，宿主对COVID-19的反应，包括全身炎症和针对SARS-CoV-2的免疫，在不同疾病状态下仍 largely undefined。在此，我们对具有不同临床表现的COVID-19患者的228份外周血样本进行了全转录组分析，并使用无监督算法进行了后续聚类。我们鉴定了各种转录组簇和全局失调的免疫相关途径，导致严重和危重型SARS-CoV-2感染患者出现不同的宿主炎症细胞因子谱。这突出了COVID-19发病机制与细胞因子过度释放之间的关联。此外，我们的结果揭示了循环细胞群体的差异以及SARS-CoV-2感染诱导的淋巴细胞凋亡和p53信号通路的激活。具有不同临床表现的COVID-19患者的转录组数据集为分子机制提供了有价值的见解，并可能为抗炎治疗的临床决策提供参考。
