Specific Interleukin-1 Inhibitors, Specific Interleukin-6 Inhibitors, and GM-CSF Blockades for COVID-19 (at the Edge of Sepsis): A Systematic Review

Frontiers in Pharmacology

Pharmacology

Xin Lv¹  Rulin Dai¹  Miao Li²  Ying Wang³  Qian Yu³  Rui Li³  Kun Zhu³ 

[1] Center of Reproductive Medicine and Center of Prenatal Diagnosis, The First Hospital, Jilin University, Changchun, China;Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Jilin University, Changchun, China;Department of Pharmacy, China-Japan Union Hospital of Jilin University, Jilin University, Changchun, China;

关键词: specific interleukin-1 inhibitors;    specific interleukin-6 inhibitors;    GM-CSF blockades;    coronavirus disease 2019 (COVID-19);    SARS-CoV-2;    sepsis;   

DOI  :  10.3389/fphar.2021.804250

 received in 2021-10-29, accepted in 2021-11-23,  发布年份 2022

来源: Frontiers

【 摘 要 】

Sepsis is a syndrome with high mortality, which seriously threatens human health. During the pandemic of coronavirus disease 2019 (COVID-19), some severe and critically ill COVID-19 patients with multiple organ dysfunction developed characteristics typical of sepsis and met the diagnostic criteria for sepsis. Timely detection of cytokine storm and appropriate regulation of inflammatory response may be significant in the prevention and treatment of sepsis. This study evaluated the efficacy and safety of specific interleukin (IL)-1 inhibitors, specific IL-6 inhibitors, and GM-CSF blockades in the treatment of COVID-19 (at the edge of sepsis) patients through systematic review and meta-analysis. Methodology: A literature search was conducted on PubMed, EMBASE, Clinical Key, Cochrane Library, CNKI, and Wanfang Database using proper keywords such as “SARS-CoV-2,” “Corona Virus Disease 2019,” “COVID-19,” “anakinra,” “tocilizumab,” “siltuximab,” “sarilumab,” “mavrilimumab,” “lenzilumab,” and related words for publications released until August 22, 2021. Other available resources were also used to identify relevant articles. The present systematic review was performed based on PRISMA protocol. Results: Based on the inclusion and exclusion criteria, 43 articles were included in the final review. The meta-analysis results showed that tocilizumab could reduce the mortality of patients with COVID-19 (at the edge of sepsis) [randomized controlled trials, RCTs: odds ratio (OR) 0.71, 95%CI: 0.52–0.97, low-certainty evidence; non-RCTs: risk ratio (RR) 0.68, 95%CI: 0.55–0.84, very low-certainty evidence) as was anakinra (non-RCTs: RR 0.47, 95%CI: 0.34–0.66, very low-certainty evidence). Sarilumab might reduce the mortality of patients with COVID-19 (at the edge of sepsis), but there was no statistical significance (OR 0.65, 95%CI: 0.36–1.2, low-certainty evidence). For safety outcomes, whether tocilizumab had an impact on serious adverse events (SAEs) was very uncertain (RCTs: OR 0.87, 95%CI: 0.38–2.0, low-certainty evidence; non-RCTs 1.18, 95%CI: 0.83–1.68, very low-certainty evidence) as was on secondary infections (RCTs: OR 0.71, 95%CI: 0.06–8.75, low-certainty evidence; non-RCTs: RR 1.15, 95%CI: 0.89–1.49, very low-certainty evidence). Conclusions: This systematic review showed that tocilizumab, sarilumab, and anakinra could reduce the mortality of people with COVID-19 (at the edge of sepsis), and tocilizumab did not significantly affect SAEs and secondary infections. The current evidence of the studies on patients treated with siltuximab, mavrilimumab, and lenzilumab is insufficient. In order to establish evidence with stronger quality, high-quality studies are needed.Systematic Review Registration: PROSPERO (https://www.crd.york.ac.uk/prospero/), identifier CRD42020226545

【 授权许可】

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Copyright © 2022 Wang, Zhu, Dai, Li, Li, Lv and Yu.