4.5 Review

Efficacy and secondary infection risk of tocilizumab, sarilumab and anakinra in COVID-19 patients: A systematic review and meta-analysis

Journal

REVIEWS IN MEDICAL VIROLOGY
Volume 32, Issue 3, Pages -

Publisher

WILEY
DOI: 10.1002/rmv.2295

Keywords

anakinra; COVID-19; meta-analysis; sarilumab; tocilizumab

Categories

Funding

  1. Important and Special Project of the Science and Technology Ministry of China [2018ZX10734404]
  2. National Natural Science Foundation of China [81972949]
  3. Scientific and Technological Innovation Projects of Medicine and Health of the Chinese Academy of Medical Sciences [2016-I2M-3-021]
  4. Nanjing Incubation Program for National Clinical Research Center [2019060001]
  5. National Science and Technology Infrastructure of China [NPRC-32]
  6. National Mega-project for Innovative Drugs [2019ZX09721001]

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The use of immunosuppressants in COVID-19 patients has been shown to significantly reduce mortality rates, especially when using tocilizumab and anakinra. However, tocilizumab therapy may increase the risk of fungal co-infections in these patients.
As the pandemic progresses, the pathophysiology of coronavirus disease 2019 (COVID-19) is becoming clearer and the potential for immunotherapy is increasing. However, clinical efficacy and safety of immunosuppressants (including tocilizumab, sarilumab and anakinra) treatment in COVID-19 patients are not yet known. We searched PubMed, Embase Medline, Web of Science and MedRxiv using specific search terms in studies published from 1 January 2020 to 20 December 2020. In total, 33 studies, including 3073 cases and 6502 controls, were selected for meta-analysis. We found that immunosuppressant therapy significantly decreased mortality in COVID-19 patients on overall analysis (odds ratio = 0.71, 95% confidence interval = 0.57-0.89, p = 0.004). We also found that tocilizumab and anakinra significantly decreased mortality in patients without any increased risk of secondary infection. In addition, we found similar results in several subgroups. However, we found that tocilizumab therapy significantly increased the risk of fungal co-infections in COVID-19 patients. This represents the only systematic review and meta-analysis to investigate the efficacy and secondary infection risk of immunosuppressant treatment in COVID-19 patients. Overall, immunosuppressants significantly decreased mortality but had no effect on increased risk of secondary infections. Our analysis of tocilizumab therapy showed a significantly increased risk of fungal co-infections in these patients.

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