Predictors of poor outcome in tocilizumab treated patients with Sars-CoV-2 related severe respiratory failure: A multicentre real world study

Masotti, Luca; Landini, Giancarlo; Panigada, Grazia; Grifoni, Elisa; Tarquini, Roberto; Cei, Francesco; Cimolato, Barbara; Vannucchi, Vieri; Pietro, Massimo Di; Piani, Fiorella; Fortini, Alberto; Faraone, Antonio; Nenci, Gabriele; Cipollini, Franco; Blanc, Pierluigi; Lotti, P; Natale, Massimo; Risaliti, Filippo; Aquilini, Donatella; Seravalle, Cristiana; Bribani, Andrea; Farsi, Alessandro; Micheletti, Irene; Cioni, Elisa; Pelagalli, Giulia; Mattaliano, Chiara; Pinto, Gabriele; Madonia, Elisa Maria; Sivieri, Irene; Mannini, Marianna; Valoriani, Alice; Brancati, Simona; Rosselli, Matteo; Pavone, Eleonora; Burla, Maria Chiara; Sergi, Alessandro

doi:10.1016/j.intimp.2022.108709

Cited by 4 publications

(6 citation statements)

References 35 publications

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“…Moreover, differences in lung structure, muscular atrophy, poor airway clearance, diminished lung reserve, diminished resistance to infections, the increased expression of angiotensin converting enzyme (ACE)-2, particularly among the elderly receiving ACE inhibitors and angiotensin II receptor blockers, along with prior exposure to circulating coronaviruses with reduced neutralizing capacity to SARS-CoV-2, may all contribute to an increased vulnerability of elderly individuals to this infection and poor outcomes (26). Similar to the findings of the present study, age has been reported as a predictor of mortality in patients receiving tocilizumab for SARS-CoV-2 infection in other studies (27)(28)(29)(30)(31)(32)(33).…”

Section: Discussionsupporting

confidence: 83%

“…Several studies have reported laboratory parameters, such as eosinophils, lymphocytes, PLTs, immature granulocytes, ferritin and liver enzymes as biomarkers of poor outcomes in patients with COVID-19 (36,(38)(39)(40)(41)(42). Of note, only a few studies have evaluated laboratory data as biomarkers of poor outcomes in tocilizumab-treated patients with COVID-19 (29)(30)(31)(32)(33)(34)(43)(44)(45). Some studies have examined the role of laboratory parameters on specific days following the tocilizumab administration as potential markers of mortality (31,45).…”

Section: Discussionmentioning

confidence: 99%

“…Some studies have examined the role of laboratory parameters on specific days following the tocilizumab administration as potential markers of mortality (31,45). According to the aforementioned studies, d-dimer levels (29), the WBC count (30), LDH levels (32,45), procalcitonin levels (33), ferritin (43), AST levels (44), CRP levels (34), lymphocyte count (44,45) and the number of PLTs (31,34,44), have all been identified as predictors of poor outcomes in tocilizumab-treated patients with COVID-19. Of note, the value of PTLs upon admission and following the tocilizumab administration was found to be ---------------------------------------------------------------- ---------------------------------------------------------------- (31).…”

Section: Discussionmentioning

confidence: 99%

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Factors predicting poor outcomes of patients treated with tocilizumab for COVID‑19‑associated pneumonia: A retrospective study

et al. 2022

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The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic is a significant global issue that has major implications for the healthcare system. The mortality rates associated with SARS-CoV-2 infection vary according to the geographical region and are associated with age, comorbidities and vaccination status. Organ damage is caused by the cytokine release syndrome, which plays a crucial role in the course of coronavirus disease 2019 (COVID-19) infection. Innate and adaptive immune system stimulation in patients with COVID-19 results in inappropriate cytokine release. The anti-IL-6 receptor antagonist, tocilizumab, is used in the treatment of connective tissue diseases. The present single-center retrospective study on patients with COVID-19 admitted to hospital between September, 2020 and April, 2022 aimed to identify predictors of mortality and other unfavorable outcomes in patients treated with tocilizumab for COVID-19-associated pneumonia. Demographics, vaccination status against SARS-CoV-2, the Charlson comorbidity index (CCI), laboratory data and chest X-ray scores were recorded upon admission. In total, 174 subjects (121 males; mean age, 62.43±13.47 years) fulfilling the inclusion criteria were included. Among the 174 participants, 58 (33.3%) were intubated. The mortality rate was 35.1%. The non-survivors were older, mostly females, and had a higher CCI score. At the evaluation upon admission, the survivors presented with higher levels of alanine transferase and gamma glutamyl-transferase and with a greater number of platelets (PLTs), while patients that were intubated were also older, mostly females, and had a higher CCI score (P<0.05). Age was identified as the only independent factor predicting mortality in the Cox proportional hazards multivariate regression analysis. By performing a sub-analysis regarding sex, it was revealed that the value of PLTs was an independent factor predicting intubation and 90-day mortality in male patients, and the lymphocyte count was the only factor associated with intubation in female patients. On the whole, the data of the present study may be used to identify patient subpopulations responding to treatment with tocilizumab in prospective clinical trials.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Factors predicting poor outcomes of patients treated with tocilizumab for COVID‑19‑associated pneumonia: A retrospective study

et al. 2022

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“…Although the SARS-Cov2 pandemic has mainly been overcome after more than three years, several neurological complications of the infection are still evident. Even today, there are still isolated cases of people who require treatment for severe COVID-19 infections and neurosurgery-related complications 2,3 .…”

Section: Introductionmentioning

confidence: 99%

Risk and extent of intracranial haemorrhage in patients with SARS-CoV-2 infection admitted to intensive care unit

Simion

Martínez

Klumbies

et al. 2023

Preprint

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Introduction The severe acute respiratory syndrome-coronavirus-2 (SARS-Cov2) pandemic has been overcome after more than 3 years1. Several patients were affected by neurosurgery-related complications during SARS-CoV-2 infection 2,3. The aim of the present study was to assess the incidence of SARS-Cov2-associated intracranial hemorrhage (ICH), the reasons therefore and to identify predictors of outcome. Methods We retrospectively analyzed data of patients with SARS-CoV-2 infection admitted to the intensive care unit (ICU) of our hospital in the period of 2 years. We included all patients who acquired a SARS-CoV-2 infection and required intensive care treatment. All patients were followed up until death or discharge from ICU. The primary outcome was the incidence of mortality during ICU stay and occurrence of ICH. We compared survivors and non-survivors with ICH during their ICU stay and patients who developed intracerebral hemorrhage with those who did not. Results Four hundred and sixty-seven patients with a mean age of 64.33 (± 14.76) years with confirmed SARS-CoV2-infection were registered. The mortality rate during ICU stay was 32.11%. Within the two years period, 18 out of 467 patients (3,85%) with spontaneous SARS-Cov2-associated ICH were treated in our department. In the multivariate analysis, ICH was not identified as an independent risk factor for mortality. ECMO treatment (OR 5.130, 95%: 1.739-15.133, p=0.003) was the only independent risk factor of the occurrence of ICH. Conclusion SARS-Cov2-associated ICH itself did not result in increased mortality in patients with SARS-CoV-2 infection treated on the ICU. We hypothesize, that increased mortality in patients with ICH is caused by other comorbidities such as renal failure requiring dialysis, age over 65, the use of ECMO and mechanical ventilation. The use of ECMO was found to be the strongest independent risk factor associated with the occurrence of ICH.

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“…Tocilizumab is a humanized monoclonal antibody which binds to the soluble and membrane-bound IL-6 receptor, blocking the signal transduction by which JAK-STAT is activated, perpetuating the cytokine storm [ 11 ]. Tocilizumab has demonstrated a favorable benefit–risk ratio, improving the prognosis of patients with COVID-19 [ 4 , 12 , 13 ]. The recent meta-analysis by Luo L et al concludes that tocilizumab significantly reduces the relative risk of 28–30-day mortality and the risk of invasive mechanical ventilation (IMV), without increasing the risk of infection and/or adverse events [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Application of Machine Learning in Hospitalized Patients with Severe COVID-19 Treated with Tocilizumab

Ramón

Zaragozá

Torres

et al. 2022

JCM

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Among the IL-6 inhibitors, tocilizumab is the most widely used therapeutic option in patients with SARS-CoV-2-associated severe respiratory failure (SRF). The aim of our study was to provide evidence on predictors of poor outcome in patients with COVID-19 treated with tocilizumab, using machine learning (ML) techniques. We conducted a retrospective study, analyzing the clinical, laboratory and sociodemographic data of patients admitted for severe COVID-19 with SRF, treated with tocilizumab. The extreme gradient boost (XGB) method had the highest balanced accuracy (93.16%). The factors associated with a worse outcome of tocilizumab use in terms of mortality were: baseline situation at the start of tocilizumab treatment requiring invasive mechanical ventilation (IMV), elevated ferritin, lactate dehydrogenase (LDH) and glutamate-pyruvate transaminase (GPT), lymphopenia, and low PaFi [ratio between arterial oxygen pressure and inspired oxygen fraction (PaO2/FiO2)] values. The factors associated with a worse outcome of tocilizumab use in terms of hospital stay were: baseline situation at the start of tocilizumab treatment requiring IMV or supplemental oxygen, elevated levels of ferritin, glutamate-oxaloacetate transaminase (GOT), GPT, C-reactive protein (CRP), LDH, lymphopenia, and low PaFi values. In our study focused on patients with severe COVID-19 treated with tocilizumab, the factors that were weighted most strongly in predicting worse clinical outcome were baseline status at the start of tocilizumab treatment requiring IMV and hyperferritinemia.

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Predictors of poor outcome in tocilizumab treated patients with Sars-CoV-2 related severe respiratory failure: A multicentre real world study

Cited by 4 publications

References 35 publications

Factors predicting poor outcomes of patients treated with tocilizumab for COVID‑19‑associated pneumonia: A retrospective study

Factors predicting poor outcomes of patients treated with tocilizumab for COVID‑19‑associated pneumonia: A retrospective study

Risk and extent of intracranial haemorrhage in patients with SARS-CoV-2 infection admitted to intensive care unit

Application of Machine Learning in Hospitalized Patients with Severe COVID-19 Treated with Tocilizumab

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