Title : Immune transcriptomic analysis of COVID-19 patients with varying clinical presentations
Abstract:
Background: Coronavirus disease (COVID-19) is an infectious disease with a heterogeneous clinical presentation caused by the novel coronavirus, the 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 dysregulated inflammation, endothelial dysfunction, thrombotic pulmonary microangiopathies, and multiple organ failure. However, the underlying molecular mechanisms of host responses to this infection, particularly systemic inflammation and the host immunity against SARS-CoV-2, remain largely undefined.
Methods: In this prospective study, ribonucleic acid (RNA) sequence analysis from venous blood of 228 COVID-19 patients (comprising 188 males, aged 21-87 years), was performed using a shotgun sequencing pipeline and subsequently clustered using an unsupervised algorithm. Differential gene expression was assessed, integrated pathway and network data, along with clinical information between clusters, as well as estimating circulating cell populations from the sequencing data and investigating its correlation with disease severity and mortality.
Results: This research 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.
Conclusions: The transcriptomic dataset of COVID-19 patients with diverse clinical presentations holds promise as a valuable resource for guiding clinical decisions regarding anti-inflammatory intervention, offering potential insights into the molecular underpinnings of the disease.
