Combined Anakinra and Ruxolitinib treatment to rescue extremely ill COVID-19 patients: A pilot study.

Kaplanski, Gilles; Bontemps, Denis; Esnault, Pierre; Blasco, V.; Carvelli, Julien; Delarbre, D.; Cauchois, R.; Forel, Jean Marie; Papazian, Laurent

doi:10.1016/j.autrev.2020.102726

Cited by 18 publications

(15 citation statements)

References 16 publications

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“…Another paper reported clinical resolving of COVID-19 in a 53-year-old patient with hematopoietic stem cell transplant due to chronic myeloid leukemia (CML) who was treated with a high dose of ruxolitinib (10mg twice daily) (146) . Similar results of the efficacy of ruxolitinib in critically ill COVID-19 patients have been reported [147] , [148] . To conclude, the administration of ruxolitinib has shown significant improvement in the clinical status of COVID-19 patients with ARDS (149) .…”

Section: Filgotinibsupporting

confidence: 84%

An updated overview of recent advances, challenges, and clinical considerations of IL-6 signaling blockade in severe coronavirus disease 2019 (COVID-19)

Elahi

Karami

Heidary

et al. 2022

International Immunopharmacology

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Section: Filgotinibsupporting

confidence: 84%

An updated overview of recent advances, challenges, and clinical considerations of IL-6 signaling blockade in severe coronavirus disease 2019 (COVID-19)

Elahi

Karami

Heidary

et al. 2022

International Immunopharmacology

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“…However, we did not observe any difference in VAP or BSI incidence or recurrences between centres. Lastly, some patients received rescue immunomodulatory therapies later during their ICU stays [ 33 ], which might have favoured nosocomial infections. These patients were equally split in both groups and this confounding factor was considered as a competing event and did not modify the cumulative incidence of VAP.…”

Section: Discussionmentioning

confidence: 99%

Impact of dexamethasone on the incidence of ventilator-associated pneumonia and blood stream infections in COVID-19 patients requiring invasive mechanical ventilation: a multicenter retrospective study

Gragueb-Chatti

López

Hamidi

et al. 2021

Ann. Intensive Care

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Background Dexamethasone decreases mortality in patients with severe coronavirus disease 2019 (COVID-19) and has become the standard of care during the second wave of pandemic. Dexamethasone is an immunosuppressive treatment potentially increasing the risk of secondary hospital acquired infections in critically ill patients. We conducted an observational retrospective study in three French intensive care units (ICUs) comparing the first and second waves of pandemic to investigate the role of dexamethasone in the occurrence of ventilator-associated pneumonia (VAP) and blood stream infections (BSI). Patients admitted from March to November 2020 with a documented COVID-19 and requiring mechanical ventilation (MV) for ≥ 48 h were included. The main study outcomes were the incidence of VAP and BSI according to the use of dexamethasone. Secondary outcomes were the ventilator-free days (VFD) at day-28 and day-60, ICU and hospital length of stay and mortality. Results Among the 151 patients included, 84 received dexamethasone, all but one during the second wave. VAP occurred in 63% of patients treated with dexamethasone (DEXA+) and 57% in those not receiving dexamethasone (DEXA−) (p = 0.43). The cumulative incidence of VAP, considering death, duration of MV and late immunosuppression as competing factors was not different between groups (p = 0.59). A multivariate analysis did not identify dexamethasone as an independent risk factor for VAP occurrence. The occurrence of BSI was not different between groups (29 vs. 30%; p = 0.86). DEXA+ patients had more VFD at day-28 (9 (0–21) vs. 0 (0–11) days; p = 0.009) and a reduced ICU length of stay (20 (11–44) vs. 32 (17–46) days; p = 0.01). Mortality did not differ between groups. Conclusions In this cohort of COVID-19 patients requiring invasive MV, dexamethasone was not associated with an increased incidence of VAP or BSI. Dexamethasone might not explain the high rates of VAP and BSI observed in critically ill COVID-19 patients.

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“…Thus, early intervention upon the development of acute hyperinflammatory respiratory failure in patients with COVID-19 can have a therapeutic effect (25)(26)(27). Furthermore, albeit at a different level compared to that in patients with secondary HLH/MAS, the IL-18-IFNγ axis is certainly active in patients with critical COVID-19, and targeting this and IL-1 simultaneously may constitute a rescue treatment for extremely ill patients (28). A corresponding randomized controlled trial is ongoing.…”

Section: Discussionmentioning

confidence: 99%

Discrimination of COVID‐19 From Inflammation‐Induced Cytokine Storm Syndromes Using Disease‐Related Blood Biomarkers

Kessel

Vollenberg

Masjosthusmann

et al. 2021

Arthritis & Rheumatology

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Objective Infection with the novel coronavirus SARS–CoV‐2 triggers severe illness with high mortality in a subgroup of patients. Such a critical course of COVID‐19 is thought to be associated with the development of cytokine storm, a condition seen in macrophage activation syndrome (MAS) and secondary hemophagocytic lymphohistiocytosis (HLH). However, specific data demonstrating a clear association of cytokine storm with severe COVID‐19 are still lacking. The aim of this study was to directly address whether immune activation in COVID‐19 does indeed mimic the conditions found in these classic cytokine storm syndromes. Methods Levels of 22 biomarkers were quantified in serum samples from patients with COVID‐19 (n = 30 patients, n = 83 longitudinal samples in total), patients with secondary HLH/MAS (n = 50), and healthy controls (n = 9). Measurements were performed using bead array assays and single‐marker enzyme‐linked immunosorbent assay. Serum biomarker levels were assessed for correlations with disease outcome. Results In patients with secondary HLH/MAS, we observed pronounced activation of the interleukin‐18 (IL‐18)–interferon‐γ axis, increased serum levels of IL‐1 receptor antagonist, intercellular adhesion molecule 1, and IL‐8, and strongly reduced levels of soluble Fas ligand in the course of SARS–CoV‐2 infection. These observations appeared to discriminate immune dysregulation in critical COVID‐19 from the well‐recognized characteristics of other cytokine storm syndromes. Conclusion Serum biomarker profiles clearly separate COVID‐19 from MAS or secondary HLH in terms of distinguishing the severe systemic hyperinflammation that occurs following SARS–CoV‐2 infection. These findings could be useful in determining the efficacy of drugs targeting key molecules and pathways specifically associated with systemic cytokine storm conditions in the treatment of COVID‐19.

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Combined Anakinra and Ruxolitinib treatment to rescue extremely ill COVID-19 patients: A pilot study.

Cited by 18 publications

References 16 publications

An updated overview of recent advances, challenges, and clinical considerations of IL-6 signaling blockade in severe coronavirus disease 2019 (COVID-19)

An updated overview of recent advances, challenges, and clinical considerations of IL-6 signaling blockade in severe coronavirus disease 2019 (COVID-19)

Impact of dexamethasone on the incidence of ventilator-associated pneumonia and blood stream infections in COVID-19 patients requiring invasive mechanical ventilation: a multicenter retrospective study

Discrimination of COVID‐19 From Inflammation‐Induced Cytokine Storm Syndromes Using Disease‐Related Blood Biomarkers

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