Infection risk with the use of interleukin inhibitors in hospitalized patients with COVID-19: A narrative review

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Infezioni in Medicina


Introduction: To date, only corticosteroids and inter-leukin-6 (IL-6) inhibitors have been shown to reduce mortality of hospitalized patients with COVID-19. In this literature review, we aimed to summarize infection risk of IL inhibitors, with or without the use of corticosteroids, used to treat hospitalized patients with COVID-19. Methods: A literature search was conducted using the following evidence-based medicine reviews: Cochrane Central Register of Controlled Trials; Cochrane Data-base of Systematic Reviews; Embase; Ovid Medline; and Epub Ahead of Print, In-Process, In-Data-Review & Other Non-Indexed Citations, Daily and Versions 1946 to April 28, 2021. All relevant articles were identi-fied using the search terms COVID-19 or SARS-coro-navirus-2, infections, interleukins, inpatients, adults, and incidence. Results: We identified 36 studies of which 2 were meta-analyses, 5 were randomized controlled trials, 9 were prospective studies, and 20 were retrospective studies. When anakinra was compared with control, 2 studies reported an increased risk of infection, and 3 studies reported a similar or decreased incidence of infection. Canakinumab had a lower associated incidence of infection compared with placebo in one study. When sari-lumab was compared with placebo, one study reported an increased risk of infection. Nine studies comparing tocilizumab with placebo reported decreased or no dif-ference in infection risk (odds ratio [OR] for the studies ranged from 0.39-1.21). Fourteen studies comparing tocilizumab with placebo reported an increased risk of infection, ranging from 9.1% to 63.0% (OR for the studies ranged from 1.85-5.04). Infection most commonly presented as bacteremia. Of the 6 studies comparing tocilizumab and corticosteroid use with placebo, 4 reported a nonsignificant increase toward corticosteroids being associated with bacterial infections (OR ranged from 2.76-3.8), and 2 studies reported no increased association with a higher infection risk. Conclusions: Our literature review showed mixed results with variable significance for the association of IL-6 inhibitors with risk of infections in patients with COVID-19.

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