ABSTRACT
BACKGROUND: Accumulating evidence suggests a beneficial effective of tumour necrosis factor-alpha (TNF-α) inhibitors on the outcomes of COVID-19 disease, which, however is not validated by all studies. AIMS: To perform a systematic review and meta-analysis of existing reports to investigate the impact of anti-TNF treatments on the clinical outcomes of COVID-19 patients. METHODS: A systematic search at PubMed and SCOPUS databases using specific keywords was performed. All reports of COVID-19 outcomes for patients receiving anti-TNF therapy by September 2021 were included. Pooled effect measures were calculated using a random-effects model. The Newcastle Ottawa Scale for observational studies was used to assess bias. Studies that were not eligible for meta-analysis were described qualitatively. RESULTS: In total, 84 studies were included in the systematic review, and 35 were included in the meta-analysis. Patients receiving anti-TNF treatment, compared to non-anti-TNF, among COVID-19 cases had a lower probability of hospitalisation (eight studies, 2555 patients, pooled OR = 0.53, 95% CI: 0.42-0.67, I2 = 0) and severe disease defined as intensive care unit admission or death (two studies, 1823 patients, pooled OR = 0.63, 95% CI: 0.41-0.96, I2 = 0), after adjustment for validated predictors of adverse disease outcomes. No difference was found for the risk for hospitalisation due to COVID-19 in populations without COVID-19 for patients receiving anti-TNF treatment compared to non-anti-TNF (three studies, 5 994 958 participants, pooled risk ratio = 0.97, 95% CI: 0.68-1.39, I2 = 20) adjusted for age, sex and comorbidities. CONCLUSIONS: TNF-α inhibitors are associated with a lower probability of hospitalisation and severe COVID-19 when compared to any other treatment for an underlying inflammatory disease.