Interleukin-6 as prognosticator in patients with COVID-19

Grifoni, Elisa; Valoriani, Alice; Cei, Francesco; Lamanna, Roberta; Gelli, Anna Maria Grazia; Ciambotti, Benedetta; Vannucchi, Vieri; Moroni, Federico; Pelagatti, Lorenzo; Tarquini, Roberto; Landini, Giancarlo; Vanni, Simone; Masotti, Luca

doi:10.1016/j.jinf.2020.06.008

Cited by 167 publications

(178 citation statements)

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“…It is related to a hyperinflammatory status comprising a number of proinflammatory cytokines and chemokines, one of the most predominant being bx;1interleukin 6 (IL-6). 11,12 Given the potential deleterious effect of IL-6 in COVID-19 pneumonia, [13][14][15] we first evaluated the benefit-risk effect of tocilizumab (TCZ), an anti-human IL-6 receptor (IL-6R) monoclonal antibody that inhibits IL-6 signaling by binding soluble IL-6R and membrane IL-6R and is approved for rheumatoid arthritis, juvenile inflammatory arthritis and refractory giant cell arteritis. Tocilizumab is also approved for systemic inflammatory response caused by the massive release of proinflammatory cytokines in response to iatrogenic disease (eg, chimeric antigen receptor T-cell therapies).…”

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confidence: 99%

Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia

et al. 2021

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; for the CORIMUNO-19 Collaborative Group IMPORTANCE Severe pneumonia with hyperinflammation and elevated interleukin-6 is a common presentation of coronavirus disease 2019 (COVID-19). OBJECTIVE To determine whether tocilizumab (TCZ) improves outcomes of patients hospitalized with moderate-to-severe COVID-19 pneumonia. DESIGN, SETTING, AND PARTICPANTS This cohort-embedded, investigator-initiated, multicenter, open-label, bayesian randomized clinical trial investigating patients with COVID-19 and moderate or severe pneumonia requiring at least 3 L/min of oxygen but without ventilation or admission to the intensive care unit was conducted between March 31, 2020, to April 18, 2020, with follow-up through 28 days. Patients were recruited from 9 university hospitals in France. Analyses were performed on an intention-to-treat basis with no correction for multiplicity for secondary outcomes. INTERVENTIONS Patients were randomly assigned to receive TCZ, 8 mg/kg, intravenously plus usual care on day 1 and on day 3 if clinically indicated (TCZ group) or to receive usual care alone (UC group). Usual care included antibiotic agents, antiviral agents, corticosteroids, vasopressor support, and anticoagulants. MAIN OUTCOMES AND MEASURES Primary outcomes were scores higher than 5 on the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) on day 4 and survival without need of ventilation (including noninvasive ventilation) at day 14. Secondary outcomes were clinical status assessed with the WHO-CPS scores at day 7 and day 14, overall survival, time to discharge, time to oxygen supply independency, biological factors such as C-reactive protein level, and adverse events. RESULTS Of 131 patients, 64 patients were randomly assigned to the TCZ group and 67 to UC group; 1 patient in the TCZ group withdrew consent and was not included in the analysis. Of the 130 patients, 42 were women (32%), and median (interquartile range) age was 64 (57.1-74.3) years. In the TCZ group, 12 patients had a WHO-CPS score greater than 5 at day 4 vs 19 in the UC group (median posterior absolute risk difference [ARD] −9.0%; 90% credible interval [CrI], −21.0 to 3.1), with a posterior probability of negative ARD of 89.0% not achieving the 95% predefined efficacy threshold. At day 14, 12% (95% CI −28% to 4%) fewer patients needed noninvasive ventilation (NIV) or mechanical ventilation (MV) or died in the TCZ group than in the UC group (24% vs 36%, median posterior hazard ratio [HR] 0.58; 90% CrI, 0.33-1.00), with a posterior probability of HR less than 1 of 95.0%, achieving the predefined efficacy threshold. The HR for MV or death was 0.58 (90% CrI, 0.30 to 1.09). At day 28, 7 patients had died in the TCZ group and 8 in the UC group (adjusted HR, 0.92; 95% CI 0.33-2.53). Serious adverse events occurred in 20 (32%) patients in the TCZ group and 29 (43%) in the UC group (P = .21). CONCLUSIONS AND RELEVANCE In this randomized clinical trial of patients with COVID-19 and pneumonia requiring oxygen support but not admitted to the intensive care...

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Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia

et al. 2021

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“…Yong et al identified the cut-off value of 24.3 pg/ml of IL-6 combining with D-Dimer for early detection of severe cases in a cohort of 43 cases [ 8 ]. Giofoni et al identified a cut-off value of 25 pg/ml of serum IL-6 as an independent risk factor of progression for severe COVID-19 and/or in-hospital mortality in a cohort of 77 patients [ 19 ]. In another cohort in Munich, elevated IL-6 (> 80 pg/ml) was strongly associated with a 22 times higher need for mechanical ventilation compared with patients with lower IL-6 levels in a cohort involving 40 patients, suggesting that high IL-6 level might predict the critical illness [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Serum interleukin-6 is an indicator for severity in 901 patients with SARS-CoV-2 infection: a cohort study

et al. 2020

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Background Interleukin-6 (IL-6) was proposed to be associated with the severity of coronavirus disease 2019 (COVID-19). The present study aimed to explore the kinetics of IL-6 levels, validate this association in COVID-19 patients, and report preliminary data on the efficacy of IL-6 receptor blockade. Methods We conducted a retrospective single-institutional study of 901 consecutive confirmed cases. Serum IL-6 concentrations were tested on admission and/or during hospital stay. Tocilizumab was given to 16 patients with elevated IL-6 concentration. Results 366 patients were defined as common cases, 411 patients as severe, and 124 patients as critical according to the Chinese guideline on diagnosis and treatment of COVID-19. The median concentration of IL-6 was < 1.5 pg/ml (IQR < 1.50–2.15), 1.85 pg/ml (IQR < 1.50–5.21), and 21.55 pg/ml (IQR 6.47–94.66) for the common, severe, and critical groups respectively (P < 0.001). The follow-up kinetics revealed serum IL-6 remained high in critical patients even when cured. An IL-6 concentration higher than 37.65 pg/ml was predictive of in-hospital death (AUC 0.97 [95% CI 0.95–0.99], P < 0.001) with a sensitivity of 91.7% and a specificity of 95.7%. In the 16 patients who received tocilizumab, IL-6 concentrations were significantly increased after administration, and survival outcome was not significantly different from that of propensity-score matched counterparts (n = 53, P = 0.12). Conclusion Serum IL-6 should be included in diagnostic work-up to stratify disease severity, but the benefit of tocilizumab needs further confirmation. Trial registration retrospectively registered.

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“…One of the most investigated cytokines in COVID-19 is IL-6, as it is one of the main mediators of the inflammatory and immune response. In fact, IL-6 levels at hospital admission are considered to have a good prognostic value for severe disease progression and/or in-hospital mortality (Grifoni et al, 2020). IL-6 can be more easily measured in blood than others cytokines and is therefore currently being used to evaluate hyperinflammation and the need for specific anti-inflammatory treatment in hospitalized COVID-19 patients.…”

Section: Discussionmentioning

confidence: 99%

Hypercytokinemia in COVID-19: Tear cytokine profile in hospitalized COVID-19 patients

Burgos-Blasco

Güemes-Villahoz

Santiago

et al. 2020

Experimental Eye Research

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Interleukin-6 as prognosticator in patients with COVID-19

Cited by 167 publications

References 6 publications

Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia

Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia

Serum interleukin-6 is an indicator for severity in 901 patients with SARS-CoV-2 infection: a cohort study

Hypercytokinemia in COVID-19: Tear cytokine profile in hospitalized COVID-19 patients

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