Immunomodulation and Reduction of Thromboembolic Risk in Hospitalized COVID-19 Patients: Systematic Review and Meta-Analysis of Randomized Trials

Background: We aimed to investigate the potential beneficial effect of immunomodulation therapy on the thromboembolic risk in hospitalized COVID-19 patients. Methods: We searched PubMed and Scopus for randomized trials reporting the outcomes of venous thromboembolism (VTE), ischemic stroke or system...

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Autores principales:	Dimitrios Sagris, Matilda Florentin, Panagiotis Tasoudis, Eleni Korompoki, Nikolaos Gatselis, Evangelos J. Giamarellos-Bourboulis, Haralampos Milionis, James Douketis, Alex C. Spyropoulos, George Dalekos, George Ntaios
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	COVID-19 thromboembolism tocilizumab anakinra hydroxycholoroquine immunomodulation Medicine R
Acceso en línea:	https://doaj.org/article/eb0a8112306749678628d0250480b520
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spelling	oai:doaj.org-article:eb0a8112306749678628d0250480b5202021-11-25T18:02:10ZImmunomodulation and Reduction of Thromboembolic Risk in Hospitalized COVID-19 Patients: Systematic Review and Meta-Analysis of Randomized Trials10.3390/jcm102253662077-0383https://doaj.org/article/eb0a8112306749678628d0250480b5202021-11-01T00:00:00Zhttps://www.mdpi.com/2077-0383/10/22/5366https://doaj.org/toc/2077-0383Background: We aimed to investigate the potential beneficial effect of immunomodulation therapy on the thromboembolic risk in hospitalized COVID-19 patients. Methods: We searched PubMed and Scopus for randomized trials reporting the outcomes of venous thromboembolism (VTE), ischemic stroke or systemic embolism, myocardial infarction, any thromboembolic event, and all-cause mortality in COVID-19 patients treated with immunomodulatory agents. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using the Mantel–Haenszel random effects method. Results: Among 8499 patients hospitalized with COVID-19, 4638 were treated with an immunomodulatory agent, 3861—with usual care only. Among the patients prescribed immunomodulatory agents, there were 1.77 VTEs per 100 patient-months compared to 2.30 among those treated with usual care (OR: 0.84, 95% CI: 0.61–1.16; I<sup>2</sup>: 0%). Among the patients who received an interleukin 6 (IL-6) antagonist, VTEs were reported in 12 among the 1075 patients compared to 20 among the 848 receiving the usual care (OR: 0.52, 95% CI: 0.22–1.20; I<sup>2</sup>: 6%). Immunomodulators as an add-on to usual care did not reduce the risk of stroke or systemic embolism (OR: 1.10, 95% CI: 0.50–2.40; I<sup>2</sup>: 0%) or of myocardial infarction (OR: 1.06, 95% CI: 0.47–2.39; I<sup>2</sup>: 0%) and there was a nonsignificant reduction in any thromboembolic event (OR: 0.86, 95% CI: 0.65–1.14; I<sup>2</sup>: 0%). Conclusions: We did not identify a statistically significant effect of immunomodulation on prevention of thromboembolic events in COVID-19. However, given the large effect estimate for VTE prevention, especially in the patients treated with IL-6 antagonists, we cannot exclude a potential effect of immunomodulation.Dimitrios SagrisMatilda FlorentinPanagiotis TasoudisEleni KorompokiNikolaos GatselisEvangelos J. Giamarellos-BourboulisHaralampos MilionisJames DouketisAlex C. SpyropoulosGeorge DalekosGeorge NtaiosMDPI AGarticleCOVID-19thromboembolismtocilizumabanakinrahydroxycholoroquineimmunomodulationMedicineRENJournal of Clinical Medicine, Vol 10, Iss 5366, p 5366 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	COVID-19 thromboembolism tocilizumab anakinra hydroxycholoroquine immunomodulation Medicine R
spellingShingle	COVID-19 thromboembolism tocilizumab anakinra hydroxycholoroquine immunomodulation Medicine R Dimitrios Sagris Matilda Florentin Panagiotis Tasoudis Eleni Korompoki Nikolaos Gatselis Evangelos J. Giamarellos-Bourboulis Haralampos Milionis James Douketis Alex C. Spyropoulos George Dalekos George Ntaios Immunomodulation and Reduction of Thromboembolic Risk in Hospitalized COVID-19 Patients: Systematic Review and Meta-Analysis of Randomized Trials
description	Background: We aimed to investigate the potential beneficial effect of immunomodulation therapy on the thromboembolic risk in hospitalized COVID-19 patients. Methods: We searched PubMed and Scopus for randomized trials reporting the outcomes of venous thromboembolism (VTE), ischemic stroke or systemic embolism, myocardial infarction, any thromboembolic event, and all-cause mortality in COVID-19 patients treated with immunomodulatory agents. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using the Mantel–Haenszel random effects method. Results: Among 8499 patients hospitalized with COVID-19, 4638 were treated with an immunomodulatory agent, 3861—with usual care only. Among the patients prescribed immunomodulatory agents, there were 1.77 VTEs per 100 patient-months compared to 2.30 among those treated with usual care (OR: 0.84, 95% CI: 0.61–1.16; I<sup>2</sup>: 0%). Among the patients who received an interleukin 6 (IL-6) antagonist, VTEs were reported in 12 among the 1075 patients compared to 20 among the 848 receiving the usual care (OR: 0.52, 95% CI: 0.22–1.20; I<sup>2</sup>: 6%). Immunomodulators as an add-on to usual care did not reduce the risk of stroke or systemic embolism (OR: 1.10, 95% CI: 0.50–2.40; I<sup>2</sup>: 0%) or of myocardial infarction (OR: 1.06, 95% CI: 0.47–2.39; I<sup>2</sup>: 0%) and there was a nonsignificant reduction in any thromboembolic event (OR: 0.86, 95% CI: 0.65–1.14; I<sup>2</sup>: 0%). Conclusions: We did not identify a statistically significant effect of immunomodulation on prevention of thromboembolic events in COVID-19. However, given the large effect estimate for VTE prevention, especially in the patients treated with IL-6 antagonists, we cannot exclude a potential effect of immunomodulation.
format	article
author	Dimitrios Sagris Matilda Florentin Panagiotis Tasoudis Eleni Korompoki Nikolaos Gatselis Evangelos J. Giamarellos-Bourboulis Haralampos Milionis James Douketis Alex C. Spyropoulos George Dalekos George Ntaios
author_facet	Dimitrios Sagris Matilda Florentin Panagiotis Tasoudis Eleni Korompoki Nikolaos Gatselis Evangelos J. Giamarellos-Bourboulis Haralampos Milionis James Douketis Alex C. Spyropoulos George Dalekos George Ntaios
author_sort	Dimitrios Sagris
title	Immunomodulation and Reduction of Thromboembolic Risk in Hospitalized COVID-19 Patients: Systematic Review and Meta-Analysis of Randomized Trials
title_short	Immunomodulation and Reduction of Thromboembolic Risk in Hospitalized COVID-19 Patients: Systematic Review and Meta-Analysis of Randomized Trials
title_full	Immunomodulation and Reduction of Thromboembolic Risk in Hospitalized COVID-19 Patients: Systematic Review and Meta-Analysis of Randomized Trials
title_fullStr	Immunomodulation and Reduction of Thromboembolic Risk in Hospitalized COVID-19 Patients: Systematic Review and Meta-Analysis of Randomized Trials
title_full_unstemmed	Immunomodulation and Reduction of Thromboembolic Risk in Hospitalized COVID-19 Patients: Systematic Review and Meta-Analysis of Randomized Trials
title_sort	immunomodulation and reduction of thromboembolic risk in hospitalized covid-19 patients: systematic review and meta-analysis of randomized trials
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/eb0a8112306749678628d0250480b520
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Immunomodulation and Reduction of Thromboembolic Risk in Hospitalized COVID-19 Patients: Systematic Review and Meta-Analysis of Randomized Trials

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