Rabaan Ali A, Al-Ahmed Shamsah H, Garout Mohammed A, Al-Qaaneh Ayman M, Sule Anupam A, Tirupathi Raghavendra, Mutair Abbas Al, Alhumaid Saad, Hasan Abdulkarim, Dhawan Manish, Tiwari Ruchi, Sharun Khan, Mohapatra Ranjan K, Mitra Saikat, Emran Talha Bin, Bilal Muhammad, Singh Rajendra, Alyami Salem A, Moni Mohammad Ali, Dhama Kuldeep
Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran 31311, Saudi Arabia.
Specialty Paediatric Medicine, Qatif Central Hospital, Qatif 32654, Saudi Arabia.
Pathogens. 2021 May 7;10(5):565. doi: 10.3390/pathogens10050565.
The pathogenesis of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still not fully unraveled. Though preventive vaccines and treatment methods are out on the market, a specific cure for the disease has not been discovered. Recent investigations and research studies primarily focus on the immunopathology of the disease. A healthy immune system responds immediately after viral entry, causing immediate viral annihilation and recovery. However, an impaired immune system causes extensive systemic damage due to an unregulated immune response characterized by the hypersecretion of chemokines and cytokines. The elevated levels of cytokine or hypercytokinemia leads to acute respiratory distress syndrome (ARDS) along with multiple organ damage. Moreover, the immune response against SARS-CoV-2 has been linked with race, gender, and age; hence, this viral infection's outcome differs among the patients. Many therapeutic strategies focusing on immunomodulation have been tested out to assuage the cytokine storm in patients with severe COVID-19. A thorough understanding of the diverse signaling pathways triggered by the SARS-CoV-2 virus is essential before contemplating relief measures. This present review explains the interrelationships of hyperinflammatory response or cytokine storm with organ damage and the disease severity. Furthermore, we have thrown light on the diverse mechanisms and risk factors that influence pathogenesis and the molecular pathways that lead to severe SARS-CoV-2 infection and multiple organ damage. Recognition of altered pathways of a dysregulated immune system can be a loophole to identify potential target markers. Identifying biomarkers in the dysregulated pathway can aid in better clinical management for patients with severe COVID-19 disease. A special focus has also been given to potent inhibitors of proinflammatory cytokines, immunomodulatory and immunotherapeutic options to ameliorate cytokine storm and inflammatory responses in patients affected with COVID-19.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的2019冠状病毒病（COVID-19）的发病机制仍未完全阐明。尽管预防性疫苗和治疗方法已投放市场，但尚未发现针对该疾病的特效疗法。最近的调查和研究主要集中在该疾病的免疫病理学方面。健康的免疫系统在病毒侵入后会立即做出反应，导致病毒立即被消灭并康复。然而，免疫系统受损会由于以趋化因子和细胞因子过度分泌为特征的不受控制的免疫反应而导致广泛的全身损伤。细胞因子水平升高或高细胞因子血症会导致急性呼吸窘迫综合征（ARDS）以及多器官损伤。此外，针对SARS-CoV-2的免疫反应与种族、性别和年龄有关；因此，这种病毒感染的结果在患者中存在差异。许多针对免疫调节的治疗策略已经在重症COVID-19患者中进行了测试，以缓解细胞因子风暴。在考虑缓解措施之前，全面了解由SARS-CoV-2病毒触发的各种信号通路至关重要。本综述解释了过度炎症反应或细胞因子风暴与器官损伤和疾病严重程度之间的相互关系。此外，我们还阐明了影响发病机制的各种机制和危险因素以及导致严重SARS-CoV-2感染和多器官损伤的分子途径。识别失调免疫系统的改变途径可能是识别潜在靶标标志物的一个漏洞。在失调途径中识别生物标志物有助于对重症COVID-19疾病患者进行更好的临床管理。还特别关注了促炎细胞因子的有效抑制剂、免疫调节和免疫治疗选择，以改善受COVID-19影响患者的细胞因子风暴和炎症反应。
