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Med Klin Intensivmed Notfmed ; 116(2): 138-145, 2021 Mar.
Article in German | MEDLINE | ID: covidwho-928406


BACKGROUND: Patients with severe COVID-19 develop hyperferritinemic inflammation, a rare sepsis-like immune dysregulation syndrome. METHODS: Stratified treatment decisions in a cross-location telemedical interdisciplinary case conference were assessed in this retrospective cohort study. A standardized treatment algorithm including continuous positive airway pressure and noninvasive ventilation was implemented. A locally developed COVID inflammation score (CIS) defined patients at risk for severe disease. Patients with life-threatening inflammation were offered off-label treatment with the immune modulator ruxolitinib. RESULTS: Between 4 March 2020 and 26 June 2020 COVID-19 patients (n = 196) were treated. Median patient age (70 years) and comorbidity were high in interstudy comparison. Mortality in all patients was 17.3%. However, advance care planning statements and physician directives limited treatment intensity in 50% of the deceased patients. CIS monitoring of ruxolitinib-treated high-risk patients (n = 20) on days 5, 7, and15 resulted in suppression of inflammation by 42% (15-70), 54% (15-77) and 60% (15-80). Here, mortality was 20% (4/20). Adjusted for patients with a maximum care directive including ICU, total mortality was 8.7% (17/196). CONCLUSION: Severe COVID-19 pneumonia with hyperferritinemic inflammation is related to macrophage activation syndrome-like sepsis. An interdisciplinary intensive care teleconference as a quality tool for ICUs is proposed to detect patients with rare sepsis-like syndromes.

COVID-19 , SARS-CoV-2 , Aged , Critical Care , Humans , Inflammation , Retrospective Studies
Leukemia ; 34(7): 1805-1815, 2020 07.
Article in English | MEDLINE | ID: covidwho-592457


A subgroup of patients with severe COVID-19 suffers from progression to acute respiratory distress syndrome and multiorgan failure. These patients present with progressive hyperinflammation governed by proinflammatory cytokines. An interdisciplinary COVID-19 work flow was established to detect patients with imminent or full blown hyperinflammation. Using a newly developed COVID-19 Inflammation Score (CIS), patients were prospectively stratified for targeted inhibition of cytokine signalling by the Janus Kinase 1/2 inhibitor ruxolitinib (Rux). Patients were treated with efficacy/toxicity guided step up dosing up to 14 days. Retrospective analysis of CIS reduction and clinical outcome was performed. Out of 105 patients treated between March 30th and April 15th, 2020, 14 patients with a CIS ≥ 10 out of 16 points received Rux over a median of 9 days with a median cumulative dose of 135 mg. A total of 12/14 patients achieved significant reduction of CIS by ≥25% on day 7 with sustained clinical improvement in 11/14 patients without short term red flag warnings of Rux-induced toxicity. Rux treatment for COVID-19 in patients with hyperinflammation is shown to be safe with signals of efficacy in this pilot case series for CRS-intervention to prevent or overcome multiorgan failure. A multicenter phase-II clinical trial has been initiated (NCT04338958).

Anti-Inflammatory Agents/therapeutic use , Coronavirus Infections/drug therapy , Cytokine Release Syndrome/drug therapy , Janus Kinase 1/antagonists & inhibitors , Janus Kinase 2/antagonists & inhibitors , Pneumonia, Viral/drug therapy , Protein Kinase Inhibitors/therapeutic use , Pyrazoles/therapeutic use , Severe Acute Respiratory Syndrome/drug therapy , Adult , Aged , Aged, 80 and over , Betacoronavirus/drug effects , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , COVID-19 , Clinical Trials as Topic , Coronavirus Infections/enzymology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Cytokine Release Syndrome/enzymology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Cytokines/antagonists & inhibitors , Cytokines/genetics , Cytokines/immunology , Drug Administration Schedule , Female , Gene Expression Regulation , Humans , Immunity, Innate/drug effects , Inflammation , Janus Kinase 1/genetics , Janus Kinase 1/immunology , Janus Kinase 2/genetics , Janus Kinase 2/immunology , Male , Middle Aged , Nitriles , Pandemics , Patient Safety , Pneumonia, Viral/enzymology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Pyrimidines , Retrospective Studies , SARS-CoV-2 , Severe Acute Respiratory Syndrome/enzymology , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/virology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , T-Lymphocytes/virology , Treatment Outcome