Jánosi Ágoston, Bódy Blanka, Nagy Rita, Ocskay Klementina, Kói Tamás, Müller Katalin, Túri Ibolya, Garami Miklós, Hegyi Péter, Párniczky Andrea
Centre for Translational Medicine, Semmelweis University, Budapest, Hungary.
Heim Pál National Paediatric Institute, Budapest, Hungary.
Crit Care. 2025 Jun 6;29(1):232. doi: 10.1186/s13054-025-05420-9.
Despite widespread vaccination efforts, effective treatment strategies remain critical for severe SARS-CoV-2 infection. Tumour necrosis factor-alpha (TNF-α) plays a central role in the cytokine storm characteristic of severe COVID-19. This systematic review and meta-analysis evaluates the effectiveness, efficacy, and safety of TNF-α inhibitors in the management of COVID-19.
A systematic review of PubMed, Embase, and CENTRAL was conducted, focusing on studies involving SARS-CoV-2-infected patients treated with TNF-α inhibitors compared with those receiving standard of care without prior TNF-α inhibitor use. Data from studies published up to August 12, 2024, were analysed. Outcomes assessed included mortality, invasive mechanical ventilation, and C-reactive protein (CRP) levels. Odds ratios (ORs) and mean differences (MD) were calculated with 95% confidence intervals (CI), and subgroup analyses were performed for randomised controlled trials (RCTs) and non-randomised studies.
Seven studies involving 1393 patients with moderate-to-critical COVID-19 were included. TNF-α inhibitor treatment was associated with a reduced odds of mortality (OR 0.67, 95% CI [0.44-1.00], P = 0.052), which was statistically significant in the RCT subgroup across three studies (OR 0.75, 95% CI [0.58-0.97], P = 0.042, certainty of evidence: very low). The number needed to treat for mortality was calculated to be 16 (95% CI 9.0-inf.), which indicates that one additional death could be avoided for every 16 patients treated with TNF-α inhibitors compared to standard of care. No significant reduction in the need for invasive mechanical ventilation was observed (OR 0.95 [95% CI 0.46-1.94]; P = 0.822). Additionally, TNF-α inhibitors resulted in a significant reduction in CRP levels (MD - 21.9 mg/L [95% CI - 38.46 to - 5.34]; P = 0.024) within three to seven days post-treatment.
Our study indicates a potential role for TNF-α inhibition in the treatment of COVID-19 as their use was associated with reduced mortality, but further studies are needed to provide robust evidence.
尽管进行了广泛的疫苗接种工作，但有效的治疗策略对于严重的SARS-CoV-2感染仍然至关重要。肿瘤坏死因子-α（TNF-α）在重症COVID-19的细胞因子风暴中起核心作用。本系统评价和荟萃分析评估了TNF-α抑制剂在COVID-19治疗中的有效性、疗效和安全性。
对PubMed、Embase和CENTRAL进行了系统评价，重点关注涉及接受TNF-α抑制剂治疗的SARS-CoV-2感染患者与未使用过TNF-α抑制剂且接受标准治疗的患者的研究。分析了截至2024年8月12日发表的研究数据。评估的结局包括死亡率、有创机械通气和C反应蛋白（CRP）水平。计算了比值比（OR）和平均差（MD）及其95%置信区间（CI），并对随机对照试验（RCT）和非随机研究进行了亚组分析。
纳入了7项涉及1393例中重度COVID-19患者的研究。TNF-α抑制剂治疗与死亡率降低相关（OR 0.67，95%CI[0.44-1.00]，P = 0.052），在三项研究的RCT亚组中具有统计学意义（OR 0.75，95%CI[0.58-0.97]，P = 0.042，证据确定性：极低）。计算得出的死亡治疗所需人数为16（95%CI 9.0-无穷大），这表明与标准治疗相比，每16例接受TNF-α抑制剂治疗的患者可避免1例额外死亡。未观察到有创机械通气需求的显著降低（OR 0.95[95%CI 0.46-1.94]；P = 0.822）。此外，TNF-α抑制剂在治疗后三至七天内导致CRP水平显著降低（MD -21.9 mg/L[95%CI -38.46至-5.34]；P = 0.024）。
我们的研究表明TNF-α抑制在COVID-19治疗中具有潜在作用，因为其使用与死亡率降低相关，但需要进一步研究以提供有力证据。
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