Tumour necrosis factor-alpha inhibitors decrease mortality in COVID-19: a systematic review and meta-analysis

Abstract

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.