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

Abstract

<b><i>Background:</i></b> Macrophage activation-like syndrome (MALS) and complex immune dysregulation (CID) often underlie acute respiratory distress (ARDS) in COVID-19. We aimed to investigate the effect of personalized immunotherapy on clinical improvement of critical COVID-19. <b><i>Methods:</i></b> In this open-label prospective trial, 102 patients with ARDS by SARS-CoV-2 were screened for MALS (ferritin >4,420 ng/mL) and CID (ferritin ≤4,420 ng/mL and low human leukocyte antigen (HLA)-DR expression on CD14-monocytes). Patients with MALS or CID with increased aminotransferases received intravenous anakinra; those with CID and normal aminotransferases received tocilizumab. The primary outcome was ≥25% decrease in the Sequential Organ Failure Assessment (SOFA) score and/or 50% increase in the 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. <b><i>Results:</i></b> The primary study endpoint was met in 58.3% of anakinra-treated patients and in 33.3% of tocilizumab-treated patients (<i>p</i>: 0.01). Most patients in both groups received dexamethasone as standard of care. No differences were found in secondary outcomes, mortality, and SOFA score changes. Ferritin decreased among anakinra-treated patients; interleukin-6, soluble urokinase plasminogen activator receptor, and HLA-DR expression increased among tocilizumab-treated patients. Survivors by day 28 who received anakinra were distributed to lower severity levels of the WHO clinical progression scale. Greater incidence of secondary infections was found with tocilizumab treatment. <b><i>Conclusion:</i></b> Immune assessment resulted in favorable anakinra responses among critically ill patients with COVID-19 and features of MALS<i>.</i>

High-dose intravenous anakinra treatment is safe and effective in severe and critical COVID-19 patients: a propensity score-matched study in a single center

“…High-dose intravenous anakinra treatment was safe and effective in a preliminary retrospective study from Italy in patients with COVID-19 (Cavalli et al 2020 ). In another prospective controlled study (ESCAPE open label study) with critically ill COVID-19 patients, high-dose intravenous anakinra had lower mortality rate than standard of care as well as tocilizumab treatment (Karakike et al 2022 ). No increase in the frequency of severe infection as well as other complications such as myocardial infarction in anakinra group compared to controls in our study indicates that high-dose intravenous anakinra is safe in patients with COVID-19.…”

Targeting C5aR1 signaling reduced neutrophil extracellular traps and ameliorates COVID-19 pathology

“…Correlation analyses were performed with obtained levels of C5a (Fig. 1a) and the levels of different inflammatory markers that we found increased in the BAL fluid from COVID-19 patients determined in our previous study 33 . Data depicts Spearman’s correlation coefficient (r) and P-value is depicted in each graph.…”

“…Combining antiviral with immune control, including the development of specific anti-inflammatory agents to block virus-triggered inflammatory responses, might be a strategic option to treat short-living virus-caused pathology, especially in COVID-19. This hypothesis has been confirmed by the demonstration that drugs targeting the inflammatory response are, at least in part, effective to control COVID-19 severity (van de Veerdonk et al, 2022; Chen et al, 2022; Karakike et al, 2021; Durán-Méndez et al, 2021; Shankar-Hari et al, 2021; P et al, 2021). Nevertheless, these therapies need to be used with caution since they may also affect the host immune response against the virus and against secondary/opportunistic infections.…”

Calprotectin and inflammation-associated serum biomarkers determine critical illness in COVID-19

“…Ten ml of blood samples were collected the first 24 hours from admission in the emergency department or in the general ward or in the intensive care unit and collected into pyrogen-free tubes (Becton Dickinson, Cockeysville Md). Patients have already participated as comparators receiving usual care in the studies ACHIEVE 33 , SAVE 32 and ESCAPE 34 that have been approved by the National Ethics Committee of Greece and by the National Organization for Medicines of Greece (approval numbers 45/20 and IS 36/20 respectively for ACHIEVE; approval numbers 38/20 and IS 28/20 for SAVE; and approval numbers approval 30/20 and IS 021-20 respectively for ESCAPE). Patients were enrolled after written informed consent provided by themselves or legal representatives.…”