Publication date: Jun 06, 2025

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.

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