Rabiu Abubakar Abdullahi, Ahmad Rahnuma, Rowaiye Adekunle Babajide, Rahman Sayeeda, Iskandar Katia, Dutta Siddhartha, Oli Angus Nnamdi, Dhingra Sameer, Tor Maryam Abba, Etando Ayukafangha, Kumar Santosh, Irfan Mohammed, Gowere Marshall, Chowdhury Kona, Akter Farhana, Jahan Dilshad, Schellack Natalie, Haque Mainul
Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Bayero University, PMB 3452, Kano 700233, Nigeria.
Department of Physiology, Medical College for Women and Hospital, Dhaka 1230, Bangladesh.
Life (Basel). 2022 Mar 25;12(4):478. doi: 10.3390/life12040478.
COVID-19-infected patients require an intact immune system to suppress viral replication and prevent complications. However, the complications of SARS-CoV-2 infection that led to death were linked to the overproduction of proinflammatory cytokines known as cytokine storm syndrome. This article reported the various checkpoints targeted to manage the SARS-CoV-2-induced cytokine storm. The literature search was carried out using PubMed, Embase, MEDLINE, and China National Knowledge Infrastructure (CNKI) databases. Journal articles that discussed SARS-CoV-2 infection and cytokine storm were retrieved and appraised. Specific checkpoints identified in managing SARS-CoV-2 induced cytokine storm include a decrease in the level of Nod-Like Receptor 3 (NLRP3) inflammasome where drugs such as quercetin and anakinra were effective. Janus kinase-2 and signal transducer and activator of transcription-1 (JAK2/STAT1) signaling pathways were blocked by medicines such as tocilizumab, baricitinib, and quercetin. In addition, inhibition of interleukin (IL)-6 with dexamethasone, tocilizumab, and sarilumab effectively treats cytokine storm and significantly reduces mortality caused by COVID-19. Blockade of IL-1 with drugs such as canakinumab and anakinra, and inhibition of Bruton tyrosine kinase (BTK) with zanubrutinib and ibrutinib was also beneficial. These agents' overall mechanisms of action involve a decrease in circulating proinflammatory chemokines and cytokines and or blockade of their receptors. Consequently, the actions of these drugs significantly improve respiration and raise lymphocyte count and PaO/FiO ratio. Targeting cytokine storms' pathogenesis genetic and molecular apparatus will substantially enhance lung function and reduce mortality due to the COVID-19 pandemic.
新冠病毒感染患者需要完整的免疫系统来抑制病毒复制并预防并发症。然而，导致死亡的新冠病毒感染并发症与称为细胞因子风暴综合征的促炎细胞因子过度产生有关。本文报道了针对管理新冠病毒诱导的细胞因子风暴的各种检查点。使用PubMed、Embase、MEDLINE和中国知网（CNKI）数据库进行文献检索。检索并评估了讨论新冠病毒感染和细胞因子风暴的期刊文章。在管理新冠病毒诱导的细胞因子风暴中确定的特定检查点包括降低Nod样受体3（NLRP3）炎性小体水平，槲皮素和阿那白滞素等药物对此有效。托珠单抗、巴瑞替尼和槲皮素等药物可阻断Janus激酶2和信号转导及转录激活因子1（JAK2/STAT1）信号通路。此外，地塞米松、托珠单抗和沙瑞鲁单抗抑制白细胞介素（IL）-6可有效治疗细胞因子风暴，并显著降低新冠病毒感染导致的死亡率。用卡那单抗和阿那白滞素等药物阻断IL-1，以及用泽布替尼和伊布替尼抑制布鲁顿酪氨酸激酶（BTK）也有益处。这些药物的总体作用机制包括循环促炎趋化因子和细胞因子的减少和/或其受体的阻断。因此，这些药物的作用显著改善呼吸，提高淋巴细胞计数和氧合指数（PaO/FiO）。针对细胞因子风暴的发病机制、基因和分子机制将显著增强肺功能，并降低新冠疫情导致的死亡率。
