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Tumour necrosis factor-alpha inhibitors decrease mortality in COVID-19: a systematic review and meta-analysis
Ágoston Jánosi1,2, Blanka Bódy1,2, Rita Nagy1,2
1Centre for Translational Medicine, Semmelweis University, Budapest, Hungary.
Background:
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.
Patients And Methods:
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.
Results:
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.
Conclusion:
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.
Insights
Tumour necrosis factor-alpha (TNF-α) inhibitors show promise in treating severe COVID-19 by reducing mortality risk. While not impacting ventilation needs, they significantly lower C-reactive protein levels, suggesting a potential therapeutic role.
Area of Science:
- Immunology
- Infectious Diseases
- Pharmacology
Background:
- Severe COVID-19 is linked to a cytokine storm, where Tumour Necrosis Factor-alpha (TNF-α) plays a key role.
- Despite vaccination, effective treatments for severe SARS-CoV-2 infection are crucial.
- TNF-α inhibitors are being investigated for their potential in managing COVID-19 complications.
Purpose of the Study:
- To systematically review and analyze the effectiveness, efficacy, and safety of TNF-α inhibitors in treating COVID-19 patients.
- To compare outcomes of COVID-19 patients treated with TNF-α inhibitors versus standard care.
- To evaluate the impact of TNF-α inhibitors on mortality, need for mechanical ventilation, and inflammatory markers.
Main Methods:
- A systematic literature review of PubMed, Embase, and CENTRAL databases was performed.
- Studies published up to August 12, 2024, involving COVID-19 patients treated with TNF-α inhibitors were included.
- Outcomes including mortality, invasive mechanical ventilation, and C-reactive protein (CRP) levels were assessed using odds ratios and mean differences, with subgroup analyses for RCTs and non-randomized studies.
Main Results:
- Seven studies with 1393 patients indicated TNF-α inhibitor use was associated with reduced mortality risk (OR 0.67, P=0.052), particularly significant in RCTs (OR 0.75, P=0.042).
- The number needed to treat for mortality benefit was 16.
- No significant difference in the need for invasive mechanical ventilation was found (OR 0.95, P=0.822), but a significant reduction in CRP levels was observed (MD -21.9 mg/L, P=0.024).
Conclusions:
- TNF-α inhibition shows potential in managing severe COVID-19, evidenced by reduced mortality and CRP levels.
- Further high-quality research is necessary to establish definitive evidence for TNF-α inhibitors in COVID-19 treatment.
- The findings suggest a possible therapeutic avenue for cytokine storm modulation in severe SARS-CoV-2 infections.
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