Clinical efficacy of tocilizumab treatment in severe and critical COVID-19 patients

Zeng, Jia; Xie, Minghui; Yang, Jing; Chao, Sheng-Wu; Xu, Er-li

doi:10.12998/wjcc.v8.i17.3763

Cited by 6 publications

(5 citation statements)

References 13 publications

(11 reference statements)

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“…Overall, 71.7% of patients achieved a good clinical response with respiratory function improvement. The mortality rate in the studied group was 16.7% and secondary infections occurred in 13.3% after TCZ initiation, which is comparable to data reported in earlier trials [ 73 ]. Respiratory deterioration between TCZ administration and the fourth day after it was noted significantly more often in the non-responder group than in clinical responders (76.5% vs. 15.1%).…”

Section: Discussionsupporting

confidence: 88%

Identification of Clinical Response Predictors of Tocilizumab Treatment in Patients with Severe COVID-19 Based on Single-Center Experience

Schmidt

Pawlak-Buś

Jóźwiak³

et al. 2023

JCM

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Hyperinflammation in COVID-19 plays a crucial role in pathogenesis and severity; thus, many immunomodulatory agents are applied in its treatment. We aimed to identify good clinical response predictors of tocilizumab (TCZ) treatment in severe COVID-19, among clinical, laboratory, and radiological variables. We conducted a prospective, observational study with 120 patients with severe COVID-19 not improving despite dexamethasone (DEX) treatment. We used parametric and non-parametric statistics, univariate logistic regression, receiver operating characteristic (ROC) curves, and nonlinear factors tertile analysis. In total, 86 (71.7%) patients achieved the primary outcome of a good clinical response to TCZ. We identified forty-nine predictive factors with potential utility in patient selection and treatment monitoring. The strongest included time from symptom onset between 9 and 12 days, less than 70% of estimated radiological lung involvement, and lower activity of lactate dehydrogenase. Additional predictors were associated with respiratory function, vitamin D concentration, comorbidities, and inflammatory/organ damage biomarkers. Adverse events analysis proved the safety of such a regimen. Our study confirmed that using TCZ early in the hyperinflammatory phase, before severe respiratory failure development, is most beneficial. Considering the described predictive factors, employing simple and widely available laboratory, radiological, and clinical tools can optimize patient selection for immunomodulatory treatment with TCZ.

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Section: Discussionsupporting

confidence: 88%

Identification of Clinical Response Predictors of Tocilizumab Treatment in Patients with Severe COVID-19 Based on Single-Center Experience

Schmidt

Pawlak-Buś

Jóźwiak³

et al. 2023

JCM

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“…The Abbé plot of variance-weighted values showed four studies as outliers in effect size. 42,48,64,65 The Forest plot in the retrospective studies by country is shown in the Supporting Information S4. It was found that the country of the study was a significant cause of heterogeneity, but sensitivity analyses excluding country by country did not show significant impact on pooled ORs, with nonsignificant changes after excluding individually country of study in ORs from +1% (excluding IDN, PAK, SWE, and the US) to −3% (excluding SPA).…”

Section: In-hospital Mortalitymentioning

confidence: 99%

Beneficial and harmful outcomes of tocilizumab in severe COVID‐19: A systematic review and meta‐analysis

et al. 2021

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Introduction:The results of studies of tocilizumab (TCZ) in COVID-19 are contradictory. Our study aims to update medical evidence from controlled observational studies and randomized clinical trials (RCTs) on the use of TCZ in hospitalized patients with COVID-19. Methods:We searched the following databases from January 1, 2020 to April 13, 2021 (date of the last search): MEDLINE database through the PubMed search engine and Scopus, using the terms ("COVID-19" [Supplementary Concept]) AND "tocilizumab" [Supplementary Concept]).Results: Sixty four studies were included in the present study: 54 were controlled observational studies (50 retrospective and 4 prospective) and 10 were RCTs. The overall results provided data from 20,616 hospitalized patients with COVID-19: 7668 patients received TCZ in addition to standard of care (SOC) (including 1915 patients admitted to intensive care units (ICU) with reported mortality) and 12,948 patients only receiving SOC (including 4410 patients admitted to the ICU with reported mortality). After applying the random-effects model, the hospital-wide (including ICU) pooled mortality odds ratio (OR) of patients with COVID-19 treated with TCZ was 0.73 (95% confidence interval (CI) = 0.56-0.93). The pooled hospital-wide mortality OR was 1.25 (95% CI = 0.74-2.18) in patients admitted at conventional wards versus 0.66 (95% CI = 0.59-0.76) in patients admitted to the ICU. The pooled OR of hospitalwide mortality (including ICU) of COVID-19 patients treated with TCZ plus corticosteroids (CS) was 0.67 (95% CI = 0.54-0.84). The pooled in-hospital mortality OR was 0.71 (95% CI = 0.35-1.42) when TCZ was early administered (≤10 days from symptom onset) versus 0.83 (95% CI 0.48-1.45) for late administration (>10 days from symptom onset). The meta-analysis did not find significantly higher risk for secondary infections in COVID-19 patients treated with TCZ.Conclusions: TCZ prevented mortality in patients hospitalized for COVID-19. This benefit was seen to a greater extent in patients receiving concomitant CS and when TCZ administration occurred within the first 10 days after symptom onset.

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“…The study cohort was heavily treated with both corticosteroids (59/94 = 63%) and tocilizumab (24/94 = 26%), with some patients receiving both therapies (22/94 = 23%). It is well-known that CRP is negatively modulated by both corticosteroids and tocilizumab [ 34 , 35 , 36 , 37 , 38 , 39 ]. Thus, in treated patients, CRP may no longer be a useful indicator of progression to more severe states, e.g., secondary bacterial infections [ 36 , 40 ], whereas SeptiScore values were not impacted, consistent with its original function as an indicator of sepsis.…”

Section: Discussionmentioning

confidence: 99%

Stratification of COVID-19 Severity Using SeptiCyte RAPID, a Novel Host Immune Response Test

Gravrand

Mellot

Ackermann

et al. 2023

Viruses

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SeptiCyte® RAPID is a gene expression assay measuring the relative expression levels of host response genes PLA2G7 and PLAC8, indicative of a dysregulated immune response during sepsis. As severe forms of COVID-19 may be considered viral sepsis, we evaluated SeptiCyte RAPID in a series of 94 patients admitted to Foch Hospital (Suresnes, France) with proven SARS-CoV-2 infection. EDTA blood was collected in the emergency department (ED) in 67 cases, in the intensive care unit (ICU) in 23 cases and in conventional units in 4 cases. SeptiScore (0–15 scale) increased with COVID-19 severity. Patients in ICU had the highest SeptiScores, producing values comparable to 8 patients with culture-confirmed bacterial sepsis. Receiver operating characteristic (ROC) curve analysis had an area under the curve (AUC) of 0.81 for discriminating patients requiring ICU admission from patients who were immediately discharged or from patients requiring hospitalization in conventional units. SeptiScores increased with the extent of the lung injury. For 68 patients, a chest computed tomography (CT) scan was performed within 24 h of COVID-19 diagnosis. SeptiScore >7 suggested lung injury ≥50% (AUC = 0.86). SeptiCyte RAPID was compared to other biomarkers for discriminating Critical + Severe COVID-19 in ICU, versus Moderate + Mild COVID-19 not in ICU. The mean AUC for SeptiCyte RAPID was superior to that of any individual biomarker or combination thereof. In contrast to C-reactive protein (CRP), correlation of SeptiScore with lung injury was not impacted by treatment with anti-inflammatory agents. SeptiCyte RAPID can be a useful tool to identify patients with severe forms of COVID-19 in ED, as well as during follow-up.

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Clinical efficacy of tocilizumab treatment in severe and critical COVID-19 patients

Cited by 6 publications

References 13 publications

Identification of Clinical Response Predictors of Tocilizumab Treatment in Patients with Severe COVID-19 Based on Single-Center Experience

Identification of Clinical Response Predictors of Tocilizumab Treatment in Patients with Severe COVID-19 Based on Single-Center Experience

Beneficial and harmful outcomes of tocilizumab in severe COVID‐19: A systematic review and meta‐analysis

Stratification of COVID-19 Severity Using SeptiCyte RAPID, a Novel Host Immune Response Test

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