Favorable Anakinra Responses in Severe Covid-19 Patients with Secondary Hemophagocytic Lymphohistiocytosis

Dimοpoulos, George; Mast, Quirijn de; Μάρκου, Νικόλαος; Θεοδωρακοπούλου, Μαρία; Komnos, Apostolos; Mouktaroudi, Maria; Netea, Mihai G.; Spyridopoulos, Theodoros; Verheggen, Rebecca J. H. M.; Hoogerwerf, Jacobien J.; Lachana, Alexandra; Veerdonk, Frank L. van de; Giamarellos‐Bourboulis, Evangelos J.

doi:10.1016/j.chom.2020.05.007

Cited by 227 publications

(268 citation statements)

References 14 publications

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“…The usefulness of anakinra therapy in patients with SARS-CoV-2 pneumonia who develop secondary hemophagocytic lymphohistiocytosis was recently reported [32]. This result together with the present ndings suggests that anakinra could be administered instead of tocilizumab in patients with hyperin ammation associated with severe COVID-19 who have low serum IL-6 levels (<40) after failed corticosteroid therapy.…”

Section: Discussionsupporting

confidence: 70%

Anakinra After Corticosteroid and/or Tocilizumab Treatment in Patients with Severe COVID-19 Pneumonia and Moderate Hyperinflammation. A Retrospective Cohort Study.

Aomar-Millán

Salvatierra

Torres-Parejo

et al. 2020

Preprint

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Introduction: Little evidence appears to exists for the use of anakinra, a recombinant interleukin-1 receptor antagonist, after non-response to treatment with corticosteroids alone or combined with tocilizumab in patients with severe COVID-19 pneumonia and moderate hyperinflammatory state. Patients and Methods: A retrospective observational cohort study was carried out involving 143 patients with severe COVID-19 pneumonia and moderate hyperinflammation. They received standard therapy along with pulses of methylprednisolone (group 1) or methylprednisolone plus tocilizumab (group 2), with the possibility of receiving anakinra (group 3) according to protocol. The aim of this study was to assess the role of anakinra in the clinical course (death, admission to the intensive care ward) during the first 60 days after the first corticosteroid pulse. Clinical, laboratory, and imaging characteristics as well as infectious complications were also analyzed.Results: 74 patients (51.7%) in group 1, 59 (41.3%) patients in group 2, and 10 patients (7%) in group 3 were included. 8 patients (10.8%) in group 1 died, 6 (10.2%) in group 2, and 0 (0%) in group 3. After adjustment for age and clinical severity indices, treatment with anakinra was associated with a reduced risk of mortality (adjusted hazard ratio 0.518, 95% CI 0.265-0.910; p=0.0437). Patients in group 3 had a lower mean CD4 count after 3 days of treatment. No patients in this group presented infectious complications.Conclusions: In patients with moderate hyperinflammatory state associated with severe COVID-19 pneumonia, treatment with anakinra after non-response to corticosteroids or corticosteroids plus tocilizumab therapy may be an option for the management of these patients, and may improve their prognosis.

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Section: Discussionsupporting

confidence: 70%

Anakinra After Corticosteroid and/or Tocilizumab Treatment in Patients with Severe COVID-19 Pneumonia and Moderate Hyperinflammation. A Retrospective Cohort Study.

Aomar-Millán

Salvatierra

Torres-Parejo

et al. 2020

Preprint

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“…Hemophagocyosis is a morphological feature of the makrophage activation syndrome (MAS) or the hemophagocytic lymphohistiocytosis (HLH) 43,44 . The clinical characteristics of COVID-19, including very high ferritin levels and very high proinflammatory interleukins, resemble MAS and HLH 45 and have already encouraged therapeutically attempts 46 .Further studies are needed in order to clarify this aspect.…”

Section: Discussionmentioning

confidence: 99%

Early postmortem mapping of SARS-CoV-2 RNA in patients with COVID-19 and correlation to tissue damage

Deinhardt‐Emmer

Wittschieber

Sanft

et al. 2020

Preprint

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AbstractClinical observations indicate that COVID-19 is a systemic disease. An investigation of the viral distribution within the human body in correlation to tissue damage can help understanding the pathophysiology of SARS-CoV-2 infection.We present a detailed mapping of viral RNA in 61 tissues and organs of 11 deceased patients with the diagnosis COVID-19. The autopsies were performed within the (very) early postmortem interval (mean: 5.6 hours) to avoid bias due to viral RNA and tissue degradation. Viral loads, blood levels of cytokines, prothrombotic factors as well as macro- and micro-morphology were correlated.Very high (> 104 copies/ml) viral loads were detected in the lungs of most patients and then correlated to severe tissue damage. Intact viral particles could be verified in the lung tissue by transmission electron microscopy. Viral loads in the lymph nodes were associated with a loss of follicular architecture. Viral RNA was detected throughout further extra-pulmonary tissues and organs without visible tissue damage. Inflammatory cytokines as well as the prothrombotic factors were elevated in all patients.In conclusion, the dissemination of SARS-CoV-2-RNA throughout the body supports the hypothesis of a maladaptive host response with viremia and multi-organ dysfunction.

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“…Vor dem Hintergrund einer fehlenden Standardtherapie bei lebensbedrohlicher COVID-19-Erkrankung wurden weltweit Patienten mit individuell indizierter Immunmodulation durch selektiv Zytokin-gerichtete Substanzen (Tocilizumab, Anakinra) oder Kinaseinhibitoren des Zytokin-Signalweges JAK/STAT (Ruxolitinib, Baricitinib) zur Dämpfung der Inflammation behandelt [ 5 , 6 , 9 , 17 , 26 ].…”

Section: Hintergrund Und Fragestellungunclassified

Interdisziplinäres COVID-Board bei SARS-CoV-2-getriggerter hyperferritinämischer Inflammation

Rosée

Bremer

Rosée

et al. 2020

Med Klin Intensivmed Notfmed

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Zusammenfassung Hintergrund Patienten mit schwerer COVID-19-Erkrankung entwickeln eine hyperferritinämische Inflammation, ein sepsisähnliches Immundysregulationssyndrom. Methode Retrospektive Kohortenanalyse nach Therapiestratifizierung in einer standortübergreifenden telemedizinischen Fallkonferenz. Frühzeitige, standardisierte Identifizierung von Patienten mit einem Risiko für einen schweren Verlauf (COVID-Inflammation-Score; CIS) und Intubationsvermeidung mit Schwerpunkt auf nichtinvasive Ventilation (NIV) sind Kernelemente des Behandlungsalgorithmus. Patienten mit lebensbedrohlicher Inflammation wurde ein individueller Heilversuch mit dem Immunmodulator Ruxolitinib angeboten. Ergebnisse Zwischen 04.03.2020 und 26.06.2020 wurden 196 COVID-19-Patienten behandelt. Der Altersmedian (70 Jahre) und die Komorbidität waren im Interstudienvergleich hoch. Die Gesamtmortalität lag bei 17,3 %, wobei bei der Hälfte der verstorbenen Patienten eine A‑priori-Therapielimitierung festgelegt war. Das CIS-Monitoring der mit Ruxolitinib behandelten Hochrisikopatienten (n = 20) ergab nach 5, 7 und 15 Tagen eine Inflammationssuppression um 42 % (15–70), 54 % (15–77) und 60 % (15–80). In dieser Gruppe lag die Mortalität bei 20 % (4/20). Die Gesamtmortalität adjustiert auf Patienten mit intendierter Maximaltherapie lag bei 8,7 % (17/196). Schlussfolgerung Die COVID-19-Pneumonie mit hyperferritinämischer Inflammation ist verwandt mit der Makrophagen-Aktivierungssyndrom-ähnlichen Sepsis. Eine interdisziplinäre Fallkonferenz als Qualitätsinstrument der Intensivmedizin zur Erfassung seltener sepsisähnlicher Krankheitsbilder wird vorgestellt.

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Favorable Anakinra Responses in Severe Covid-19 Patients with Secondary Hemophagocytic Lymphohistiocytosis

Abstract: Highlights d Anakinra treatment was administered to eight severe COVID-19 patients d All patients had secondary hemophagocytic lymphohistiocytosis d Respiratory function was improved at the end of treatment d In one patient, the need for mechanical ventilation was prevented

Cited by 227 publications

References 14 publications

Anakinra After Corticosteroid and/or Tocilizumab Treatment in Patients with Severe COVID-19 Pneumonia and Moderate Hyperinflammation. A Retrospective Cohort Study.

Anakinra After Corticosteroid and/or Tocilizumab Treatment in Patients with Severe COVID-19 Pneumonia and Moderate Hyperinflammation. A Retrospective Cohort Study.

Early postmortem mapping of SARS-CoV-2 RNA in patients with COVID-19 and correlation to tissue damage

Interdisziplinäres COVID-Board bei SARS-CoV-2-getriggerter hyperferritinämischer Inflammation

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