Anakinra combined with methylprednisolone in patients with severe COVID-19 pneumonia and hyperinflammation: An observational cohort study

Bozzi, Giorgio; Mangioni, Davide; Minoia, Francesca; Aliberti, Stefano; Grasselli, Giacomo; Barbetta, Laura; Castelli, Valeria; Palomba, Emanuele; Alagna, Laura; Lombardi, Andrea; Ungaro, Riccardo; Agostoni, Carlo; Baldini, Marina; Blasi, Francesco; Cesari, Matteo; Costantino, Giorgio; Fracanzani, Anna Ludovica; Montano, Nicola; Monzani, Valter; Peyvandi, Flora; Sottocorno, Marcello; Muscatello, Antonio; Filocamo, G; Gori, Andrea; Bandera, Alessandra

doi:10.1016/j.jaci.2020.11.006

Cited by 95 publications

(112 citation statements)

References 17 publications

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“…Nevertheless, various other clinical trials with anti-IL-6 receptor antibodies [ 32 ] concluded that mortality is subject to virtually a high state of hyper-inflammation. Bozzi et al [ 33 ] reported that IL-1 antagonists, such as anakinra, may have promising results in patients with high inflammation state towards survival and recovery from COVID-19. The authors of this study also concluded that treatment of COVID-19 patients with anakinra in combination with methylprednisolone may be beneficial for survival of patients on mechanical ventilators.…”

Section: Resultsmentioning

confidence: 99%

EGCG, a Green Tea Catechin, as a Potential Therapeutic Agent for Symptomatic and Asymptomatic SARS-CoV-2 Infection

Chourasia

Koppula

Battu³

et al. 2021

Molecules

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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged to be the greatest threat to humanity in the modern world and has claimed nearly 2.2 million lives worldwide. The United States alone accounts for more than one fourth of 100 million COVID-19 cases across the globe. Although vaccination against SARS-CoV-2 has begun, its efficacy in preventing a new or repeat COVID-19 infection in immunized individuals is yet to be determined. Calls for repurposing of existing, approved, drugs that target the inflammatory condition in COVID-19 are growing. Our initial gene ontology analysis predicts a similarity between SARS-CoV-2 induced inflammatory and immune dysregulation and the pathophysiology of rheumatoid arthritis. Interestingly, many of the drugs related to rheumatoid arthritis have been found to be lifesaving and contribute to lower COVID-19 morbidity. We also performed in silico investigation of binding of epigallocatechin gallate (EGCG), a well-known catechin, and other catechins on viral proteins and identified papain-like protease protein (PLPro) as a binding partner. Catechins bind to the S1 ubiquitin-binding site of PLPro, which might inhibit its protease function and abrogate SARS-CoV-2 inhibitory function on ubiquitin proteasome system and interferon stimulated gene system. In the realms of addressing inflammation and how to effectively target SARS-CoV-2 mediated respiratory distress syndrome, we review in this article the available knowledge on the strategic placement of EGCG in curbing inflammatory signals and how it may serve as a broad spectrum therapeutic in asymptomatic and symptomatic COVID-19 patients.

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Section: Resultsmentioning

confidence: 99%

EGCG, a Green Tea Catechin, as a Potential Therapeutic Agent for Symptomatic and Asymptomatic SARS-CoV-2 Infection

Chourasia

Koppula

Battu³

et al. 2021

Molecules

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“…An increasing number of studies on adult population affected by severe COVID-19 pneumonia are demonstrating the effectiveness of IL-1 blockade in reducing oxygen requirement and mechanical invasive ventilation as well as a significantly rapid improvement of patient's clinical conditions and reduction of inflammatory markers (27,28). Furthermore, an Italian study reported the efficacy of treatment with anakinra as add-on therapy to glucocorticoids in reducing the mortality of adult patients with severe COVID-19 pneumonia and hyperinflammation with a good safety profile (29). Our experience was in line with these recent evidences.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Use of Anakinra in Multisystem Inflammatory Syndrome During COVID-19 Pandemic

et al. 2021

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During COVID-19 outbreak, a large number of children with severe inflammatory disease has been reported. This condition, named Pediatric Multi-inflammatory Syndrome temporally associated with COVID-19 (PIMS-TS) or Multisystem Inflammatory Syndrome associated with Coronavirus Disease 2019 (MIS-C), shares some clinical features with Kawasaki disease and is frequently complicated by myocarditis or shock. It has been suggested that MIS-C belongs to the group of cytokine storm syndromes triggered by SARS-CoV-2 infection. So far, intravenous immunoglobulin (IVIG) and systemic glucocorticoids are the most common therapeutic approaches reported in this group of patients. However, the use of anakinra in patients with severe forms of COVID-19 is showing promising results. Here we reported two patients with multisystem inflammatory syndrome complicated with shock. Both the patients presented a poor response to IVIG and systemic glucocorticoids and received anakinra. Treatment with IL-1 receptor antagonist showed a rapid improvement of clinical conditions and biochemical analysis in both patients and demonstrated a good safety profile. Thus, we look forward for future controlled clinical trials with the aim to demonstrate the effectiveness of anakinra in patients with MIS-C and established precise criteria for its use.

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“…Most of benefit is shown so far in cohorts of patients who are not under mechanical ventilation and who present signs of hyper-inflammation. Retrospective data of the efficacy of anakinra administered intravenously are coming from France and Italy analysing cohorts of 12 patients (13), 29 patients (14) and 65 (15) patients and using concurrent comparators. The minority of patients were under mechanical ventilation and anakinra treatment provided survival benefit after 28 days.…”

Section: Discussionmentioning

confidence: 99%

ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically Ill COVID-19 Patients

Karakike¹,

Dalekos

Koutsodimitropoulos³

et al. 2021

Preprint

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RationaleMacrophage activation syndrome (MAS) and complex immune dysregulation (CID) often underlie acute respiratory distress (ARDS) in COVID-19.ObjectiveTo investigate the outcome of personalized immunotherapy in critical COVID-19.MethodsIn this open-label prospective trial, 102 patients with SOFA (sequential organ failure assessment) score ≥2 or ARDS by SARS-CoV-2 were screened for MAS (ferritin more than 4420 ng/ml) and CID (ferritin ≤4420 ng/ml and low expression of HLA-DR on CD14-monocytes). Patients with MAS and CID with increased aminotransferases were assigned to intravenous anakinra; those with CID and normal aminotransferases to tocilizumab. The primary outcome was at least 25% decrease of SOFA score and/or 50% increase of respiratory ratio by day 8; 28-day mortality, change of SOFA score by day 28; serum biomarkers and cytokine production by mononuclear cells were secondary endpoints.Measurements and Main ResultsThe primary study endpoint was met in 58.3% of anakinra-treated patients and in 33.3% of tocilizumab-treated patients (odds ratio 3.11; 95% CIs 1.29-7.73; P: 0.011). No differences were found in mortality and in SOFA score changes. By day 4, ferritin was decreased among anakinra-treated patients; interleukin (IL)-6, soluble urokinase plasminogen activator receptor (suPAR) and the expression of HLA-DR were increased among tocilizumab-treated patients. Anakinra increased capacity of mononuclear cells to produce IL-6. Survivors by day 28 who received anakinra were distributed to scales of the WHO clinical progression of lower severity. Greater incidence of secondary infections was found with tocilizumab treatment.ConclusionsBiomarkers may guide favourable anakinra responses in critically ill patients with COVID-19.Trial RegistrationClinicalTrials.gov, NCT04339712

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Anakinra combined with methylprednisolone in patients with severe COVID-19 pneumonia and hyperinflammation: An observational cohort study

Cited by 95 publications

References 17 publications

EGCG, a Green Tea Catechin, as a Potential Therapeutic Agent for Symptomatic and Asymptomatic SARS-CoV-2 Infection

EGCG, a Green Tea Catechin, as a Potential Therapeutic Agent for Symptomatic and Asymptomatic SARS-CoV-2 Infection

Case Report: Use of Anakinra in Multisystem Inflammatory Syndrome During COVID-19 Pandemic

ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically Ill COVID-19 Patients

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