Clinical efficacy of tocilizumab treatment in severe and critical COVID-19 patients
06 Sep 2020-World Journal of Clinical Cases (Baishideng Publishing Group Inc.)-Vol. 8, Iss: 17, pp 3763-3773
TL;DR: Tocilizumab treatment is effective against IL-6 in CO VID-19 patients, but it does not completely inhibit the inflammation and cytokine storm in all patients with COVID-19.
Abstract: Background The main pathophysiological basis of coronavirus disease 2019 (COVID-19) causing respiratory failure is a cytokine storm and interleukin-6 (IL-6) is an important component of the COVID-19 cytokine storm. As a specific antagonist of IL-6, tocilizumab may block the cytokine storm of COVID-19. The Diagnosis and Treatment Guidelines of New Coronavirus Pneumonia (7th Edition) includes tocilizumab as a recommended drug for immunotherapy in severe and critical COVID-19 patients. However, the specific clinical efficacy of tocilizumab in the treatment of COVID-19 patients is worth studying. Aim To determine the clinical efficacy of tocilizumab in inhibiting the cytokine storm in COVID-19. Methods In total, 19 severe and critical COVID-19 patients were enrolled in this study, and were treated with tocilizumab in Optical Valley Campus of Hubei Maternal and Child Health Care Hospital from February 20 to March 31, 2020. The imaging manifestations and clinical data before and after treatment were analyzed retrospectively, including routine peripheral venous blood tests, routine blood biochemical tests, coagulation test, C-reactive protein (CRP), IL-6, and arterial blood gas analysis. Results Of the 19 patients in this group, 13 (68.4%) had significantly improved symptoms of COVID-19 (5 patients were discharged directly and 8 patients were transferred after improvement) following treatment. One case was invalid, 1 case was exacerbated, and 4 deaths (21.1%) were observed (all critical cases). The lymphocyte count, CRP, lactic acid, oxygenation index, fibrinogen (FIB) and IL-6 levels were significantly different in the improved group. Conclusion Tocilizumab treatment is effective against IL-6 in COVID-19 patients, but it does not completely inhibit the inflammation and cytokine storm in all patients with COVID-19.In the clinical treatment of COVID-19 patients, attention should be paid to the timing of drug administration and other adjuvant treatments.
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TL;DR: In this paper, the authors aim to update medical evidence from controlled observational studies and randomized clinical trials (RCTs) on the use of TCZ in hospitalized patients with COVID-19.
Abstract: 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 hospital-wide 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.
21 citations
TL;DR: The main objective is to present the current most up-to-date progress in some clinical trials registered at ClinicalTrials.gov and highlight the pros and pitfalls of several SARS-CoV-2 antibody-based immunotherapeutics.
Abstract: Global efforts to contain the coronavirus disease-2019 (COVID-19) include the development of novel preventive vaccines and effective therapeutics. Passive antibody therapies using convalescent plasma, SARS-CoV-2 (Severe-Acute-Respiratory-Syndrome-Corona-Virus-2)-specific neutralizing antibodies (NAbs), and the development of monoclonal antibodies (MAbs) are among the most promising strategies for prophylaxis and treatment of SARS-CoV-2 infections. In addition, several immunomodulatory antibodies acting via several mechanisms to boost the host immune defense against SARS-CoV-2 infection as well as to avoid the harmful overreaction of the immune system are currently under clinical trial. Our main objective is to present the current most up-to-date progress in some clinical trials registered at ClinicalTrials.gov. We highlight the pros and pitfalls of several SARS-CoV-2 antibody-based immunotherapeutics.
16 citations
TL;DR: SeptiCyte RAPID can be a useful tool to identify patients with severe forms of COVID-19 in ED, as well as during follow-up, and correlation of SeptiScore with lung injury was not impacted by treatment with anti-inflammatory agents.
Abstract: 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 hours 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.
1 citations
18 Sep 2022
TL;DR: In this article , a gene expression assay measuring the relative expression levels of host response genes PLA2G7 and PLAC8, indicative of a dysregulated immune response during sepsis was used to identify patients with severe forms of COVID-19 in ED and during follow-up.
Abstract: Abstract 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 prospectively 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 hours 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.
TL;DR: In this paper, a retrospective analysis of influencing factors on the efficacy of mechanical ventilation in severe and critical COVID-19 patients was performed, and the results showed that mechanical ventilation performed well in both moderate and critical patients.
Abstract: Retrospective analysis of influencing factors on the efficacy of mechanical ventilation in severe and critical COVID-19 patients
References
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TL;DR: Defining the Epidemiology of Covid-19 Experience with MERS, pandemic influenza, and other outbreaks has shown that as an epidemic evolves, there is an urgent need to expand public health activities in response to this epidemic.
Abstract: Defining the Epidemiology of Covid-19 Experience with MERS, pandemic influenza, and other outbreaks has shown that as an epidemic evolves, we face an urgent need to expand public health activities ...
994 citations
TL;DR: This work proposes the presence of two types of patients (“nonARDS,” type 1, and ARDS, type 2) with different pathophysiology with different Pathophysiology and suggests the respiratory system compliance and possibly the response to PEEP are the only imperfect surrogates.
Abstract: Even though it can meet the ARDS Berlin definition [1, 2], the COVID-19 pneumonia is a specific disease with peculiar phenotypes. Its main characteristic is the dissociation between the severity of the hypoxemia and the maintenance of relatively good respiratory mechanics. Indeed, the median respiratory system compliance is usually around 50ml/cmH2O. Of note, the patients with respiratory compliance lower or higher than the median value experience hypoxemia of similar severity. We propose the presence of two types of patients (“nonARDS,” type 1, and ARDS, type 2) with different pathophysiology. When presenting at the hospital, type 1 and type 2 patients are clearly distinguishable by CT scan (Fig. 1). If the CT scan is not available, the respiratory system compliance and possibly the response to PEEP are the only imperfect surrogates we may suggest.
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TL;DR: A meta-analysis of clinical and epidemiological studies on confirmed cases of COVID-19 found the case severe rate and mortality is lower than that of SARS and MERS, and the most prevalent comorbidities are hypertension and diabetes which are associated with the severity of CO VID-19.
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TL;DR: It is suggested that Tocilizumab is an effective treatment in severe patients of COVID-19 to calm the inflammatory storm and reduce mortality.
Abstract: A severe pneumonia-associated respiratory syndrome caused by a new coronavirus was identified in December 2019 (COVID-19), spread rapidly and has become a world-wide public health challenge. About 25% of COVID-19 patients experienced severe complications including acute respiratory distress syndrome (ARDS), and even progressed into an intensive care unit (ICU) admission and died. The exploration for the mortality causes and advancing novel therapeutic development of severe COVID-19 is crucial at the moment. The biopsy samples analysis at autopsy suggested that increased alveolar exudate caused by aberrant host immune response and inflammatory cytokine storm probably impedes alveolar gas exchange and contributes to the high mortality of severe COVID-19 patients. Our research has identified that pathogenic T cells and inflammatory monocytes incite inflammatory storm with large amount of interleukin 6, therefore monoclonal antibody that targets the IL-6 pathways may potentially curb inflammatory storm. Moreover, Tocilizumab treatment that blocking IL-6 receptors showed inspiring clinical results including temperature returned to normal quickly and respiratory function improved. Therefore, we suggest that Tocilizumab is an effective treatment in severe patients of COVID-19 to calm the inflammatory storm and reduce mortality.
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261 citations