SARS-CoV-2, as the causative agent of COVID-19, is an enveloped positives-sense single-stranded RNA virus that belongs to the Beta-CoVs sub-family. A sophisticated hyper-inflammatory reaction named cytokine storm is occurred in patients with severe/critical COVID-19, following an imbalance in immune-inflammatory processes and inhibition of antiviral responses by SARS-CoV-2, which leads to pulmonary failure, ARDS, and death. The miRNAs are small non-coding RNAs with an average length of 22 nucleotides which play various roles as one of the main modulators of genes expression and maintenance of immune system homeostasis. Recent evidence has shown that Homo sapiens (hsa)-miRNAs have the potential to work in three pivotal areas including targeting the virus genome, regulating the inflammatory signaling pathways, and reinforcing the production/signaling of IFNs-I. However, it seems that several SARS-CoV-2-induced interfering agents such as viral (v)-miRNAs, cytokine content, competing endogenous RNAs (ceRNAs), etc. preclude efficient function of hsa-miRNAs in severe/critical COVID-19. This subsequently leads to increased virus replication, intense inflammatory processes, and secondary complications development. In this review article, we provide an overview of hsa-miRNAs roles in viral genome targeting, inflammatory pathways modulation, and IFNs responses amplification in severe/critical COVID-19 accompanied by probable interventional factors and their function. Identification and monitoring of these interventional elements can help us in designing the miRNAs-based therapy for the reduction of complications/mortality rate in patients with severe/critical forms of the disease.

SARS-CoV-2 是 COVID-19 的病原体，是一种有包膜的正义单链 RNA 病毒，属于 Beta-CoV 亚科。在免疫炎症过程失衡和 SARS-CoV-2 抑制抗病毒反应后，严重/危重 COVID-19 患者会发生一种复杂的高炎症反应，称为细胞因子风暴，从而导致肺衰竭、ARDS 和死亡。miRNA 是平均长度为 22 个核苷酸的小型非编码 RNA，作为基因表达和维持免疫系统稳态的主要调节剂之一，发挥着多种作用。最近的证据表明，智人(hsa)-miRNA 具有在三个关键领域发挥作用的潜力，包括靶向病毒基因组、调节炎症信号通路以及增强 IFN-I 的产生/信号传导。然而，一些 SARS-CoV-2 诱导的干扰剂，如病毒 (v)-miRNA、细胞因子含量、竞争性内源性 RNA (ceRNA) 等似乎妨碍了 hsa-miRNA 在严重/危重 COVID-19 中的有效功能。这随后导致病毒复制增加、强烈的炎症过程和继发性并发症的发生。在这篇综述文章中，我们概述了 hsa-miRNA 在病毒基因组靶向、炎症途径调节和严重/危重 COVID-19 中 IFN 反应放大中的作用，以及可能的干预因素及其功能。识别和监测这些介入因素可以帮助我们设计基于 miRNA 的疗法，以减少严重/危重疾病患者的并发症/死亡率。