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Tocilizumab for severe COVID-19 related illness - A community academic medical center experience.

ABSTRACT: The SARS-CoV-2 virus responsible for the COVID-19 pandemic can result in severe or fatal disease in a subset of infected patients. While the pathogenesis of severe COVID-19 disease has yet to be fully elucidated, an overexuberant and harmful immune response to the SARS-CoV-2 virus may be a pivotal aspect of critical illness in this patient population. The inflammatory cytokine, IL-6, has been found to be consistently elevated in severely ill COVID-19 patients, prompting speculation that IL-6 is an important driver of the pathologic process. The inappropriately elevated levels of inflammatory cytokines in COVID-19 patients is similar to cytokine release syndrome (CRS) observed in cell therapy patients. We sought to describe outcomes in a series of severely ill patients with COVID-19 CRS following treatment with anti-IL-6/IL-6-Receptor (anti-IL-6/IL-6-R) therapy, including tocilizumab or siltuximab. At our academic community medical center, we formed a multi-disciplinary committee for selecting severely ill COVID-19 patients for therapy with anti-IL-6 or IL-6-R agents. Key selection criteria included evidence of hyperinflammation, most notably elevated levels of C-reactive protein (CRP) and ferritin, and an increasing oxygen requirement. By the data cutoff point, we treated 31 patients with anti-IL-6/IL-6-R agents including 12 who had already been intubated. Overall, 27 (87%) patients are alive and 24 (77%) have been discharged from the hospital. Clinical responses to anti-IL-6/IL-6-R therapy were accompanied by significant decreases in temperature, oxygen requirement, CRP, IL-6, and IL-10 levels. Based on these data, we believe anti-IL-6/IL-6-R therapy can be effective in managing early CRS related to COVID-19 disease. Further study of anti-IL-6/IL-6-R therapy alone and in combination with other classes of therapeutics is warranted and trials are underway.

SUBMITTER: Meleveedu KS

PROVIDER: S-EPMC7467014 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Tocilizumab for severe COVID-19 related illness - A community academic medical center experience.

Meleveedu Kapil S KS Miskovsky John J Meharg Joseph J Abdelrahman Abd A Tandon Richa R Moody Ashley E AE Dasilva Priscilla P Masse Gabrielle G LaPorte Jason J Saied Calvino Abdul A Allen Greg G El-Bizri Rabih R Roberts Todd T Armenio Vincent V Katz Steven C SC

Cytokine: X 20200902 4

The SARS-CoV-2 virus responsible for the COVID-19 pandemic can result in severe or fatal disease in a subset of infected patients. While the pathogenesis of severe COVID-19 disease has yet to be fully elucidated, an overexuberant and harmful immune response to the SARS-CoV-2 virus may be a pivotal aspect of critical illness in this patient population. The inflammatory cytokine, IL-6, has been found to be consistently elevated in severely ill COVID-19 patients, prompting speculation that IL-6 is ...[more]

PMID: 32895645

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Project description:Dabigatran, an oral direct thrombin inhibitor, is FDA approved for the prevention of stroke in patients with nonvalvular atrial fibrillation. No agent exists for the reversal of dabigatran-related major bleeding. Prothrombin complex concentrate (PCC) has been studied in reversal but was not shown to affect the surrogate markers of bleeding such as the thrombin time, ecarin clotting time, or activated partial thromboplastin time (aPTT). Recombinant factor VIIa (rFVIIa) may provide benefit in patients with life-threatening or major bleeding; however, it has not been studied in dabigatran-related bleeding. PCC and rFVIIa are agents utilized at our institution for major bleeding in patients receiving anticoagulant therapy. Due to the high cost and thrombogenic risk of both rVIIa and PCC and lack of a clear reversal strategy, we reviewed the management of all reported cases of dabigatran-related bleeding.This was a retrospective chart review of patients admitted to UMass Memorial Medical Center with a bleeding event and also receiving dabigatran therapy.Eleven patients on dabigatran admitted for bleeding were identified. Seven were admitted for an intracranial hemorrhage (ICH) and four for a gastrointestinal hemorrhage (GIH). The baseline characteristics are as follows: mean age was 74.55 years (range, 63-89), and seven were male. Admission mean hemoglobin was 11.88 g/dl (range, 6.1-18), mean international normalized ratio (INR) was 2.2 (range, 1.1-7.1), and mean aPTT was 42.21 s (range, 36-81.4). Interventions received included fresh frozen plasma (n?=?6), platelets (n?=?3), packed red blood cells (n?=?4), rFVIIa (n?=?2), intravenous fluids (n?=?10), surgical intervention (n?=?3), and dialysis (n?=?2). No patients received PCC. Four patients survived in the ICH group, and four patients survived in the GIH group.Reversal strategies for dabigatran-related bleeding events at our institution are highly variable. Intracranial hemorrhage in patients on dabigatran was associated with 43 % mortality. Patients with severe dabigatran-related bleeding may benefit from a standardized approach to treatment.

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Tocilizumab for severe COVID-19 related illness - A community academic medical center experience.

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Tocilizumab for severe COVID-19 related illness - A community academic medical center experience.

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