Thoyaja Koritala1, Vishwanath Pattan2, Raghavendra Tirupathi3, Ali A Rabaan4,5, Abbas Al Mutair6,7,8, Saad Alhumaid9, Ramesh Adhikari10, Keerti Deepika11, Nitesh Kumar Jain12, Vikas Bansal13, Aysun Tekin13, Simon Zec13, Amos Lal14, Syed Anjum Khan12, Juan Pablo Domecq Garces15, Omar M Abu Saleh16, Salim R Surani17,18, Rahul Kashyap19. 1. Division of Hospital Internal Medicine, Mayo Clinic Health System, Mankato, USA. 2. Department of Endocrinology, Wyoming Medical Center, Casper, USA. 3. Department of Medicine, Keystone Health, Chambersburg, USA. 4. Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia. 5. Department of Public Health and Nutrition, University of Haripur, Haripur, Pakistan. 6. Research Center, Almoosa Specialist Hospital, Al-Ahsa, Saudi Arabia. 7. College of Nursing, Princess Norah Bint Abdulrahman University, Riyadh, Saudi Arabia. 8. School of Nursing, Wollongong University, Wollongong, Australia. 9. Administration of Pharmaceutical Care, Al-Ahsa Health Cluster, Al-Ahsa, Saudi Arabia. 10. Department of Hospital Medicine, Franciscan Health, Lafayette, USA. 11. Translational Health Disparities Science Research Program, Nemours Healthcare System for Children, Wilmington, USA. 12. Division of Community Critical Care, Mayo Clinic Health System, Mankato, USA. 13. Research Fellow, Mayo Clinic College of Medicine and Science, Rochester, USA. 14. Critical Care Internal Medicine Fellow, Mayo Clinic College of Medicine and Science, Rochester, USA. 15. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, USA. 16. Division of Infectious Diseases, Mayo Clinic, Rochester, USA. 17. Adjunct Clinical Professor of Medicine and Pharmacy, Texas A&M University, College Station, USA. 18. Research Collaborator (limited tenure), Mayo Clinic, Rochester, USA. 19. Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, USA.
Abstract
INTRODUCTION: To date, only corticosteroids and interleukin-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 Database 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 identified using the search terms COVID-19 or SARS-coronavirus-2, infections, interleukins, inpatients, adults, and i ncidence. 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 sarilumab was compared with placebo, one study reported an increased risk of infection. Nine studies comparing tocilizumab with placebo reported decreased or no difference 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.
INTRODUCTION: To date, only corticosteroids and interleukin-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 Database 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 identified using the search terms COVID-19 or SARS-coronavirus-2, infections, interleukins, inpatients, adults, and i ncidence. 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 sarilumab was compared with placebo, one study reported an increased risk of infection. Nine studies comparing tocilizumab with placebo reported decreased or no difference 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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