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TNF-α inhibitors may reduce mortality and inflammation in moderate-to-severe COVID-19 cases. However, further studies are needed to confirm their effectiveness and safety. 

A study published in the June 2025 issue of Critical Care discussed about the effective treatment strategies for severe SARS-CoV-2 infection remained critical despite widespread vaccination efforts, as tumor necrosis factor-alpha (TNF-α) played a central role in the cytokine storm characteristic of severe COVID-19.  

Researchers conducted a retrospective study that evaluated the effectiveness, efficacy, and safety of TNF-α inhibitors in the management of COVID-19.  

They performed a systematic review of PubMed, Embase, and CENTRAL, focusing on studies involving patients infected with SARS-CoV-2 treated with TNF-α inhibitors compared to those receiving standard of care without prior TNF-α inhibitor use. Data from studies published up to August 12, 2024, were analyzed. Outcomes assessed included mortality, invasive mechanical ventilation, and C-reactive protein (CRP) levels. Odds ratios (ORs) and mean differences (MD) were calculated with 95%CIs, and subgroup analyses were performed for randomized controlled trials (RCTs) and non-randomized studies.  

The results showed that 7 studies involving 1,393 patients with moderate-to-critical COVID-19 were included. The 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 3 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.), indicating that 1 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 3 to 7 days post-treatment.  

Investigators concluded that TNF-α inhibition potentially played a role in COVID-19 treatment due to an association with reduced mortality, though further studies were needed for robust evidence. 

Source: ccforum.biomedcentral.com/articles/10.1186/s13054-025-05420-9