Tocilizumab In COVID-19 Research Articles

Impact of FCGR2A rs1801274 and IL-6R rs2228145 polymorphisms on tocilizumab response in the Iranian population with severe COVID-19

BackgroundAlthough several genetic biomarkers have been reported in the tocilizumab (TCZ) response in rheumatoid arthritis, no studies have addressed the pharmacogenomics effect of TCZ in COVID-19.MethodsIn this prospective longitudinal study, 95 individuals with severe COVID-19 were selected between 2020–2022. The recovery process was measured at 24 h, 48 h, and 10 days before and after taking TCZ. All participants were genotyped using RFLP-PCR. Different genotypes of FCGR2A rs1801274 and IL-6R rs2228145 were compared in terms of the recovery process.Results43.2% of patients were male and 56.8% were female with an average age of 58.20(± 16.214) years. The GA genotype for FCGR2A rs1801274 increased the risk of death (OR = 2.83, P = 0.038) and ventilation (OR = 2.71, P = 0.047) in TCZ-treated individuals. However, there was no risk of death and ventilation with IL-6R rs2228145 (P > 0.05). Additionally, docking analysis showed that not only IL6R but also FCGR2A can be a ligand for TCZ.ConclusionThis study provides valuable insights into the impact of genetic variations on the response rate of TCZ in COVID-19 patients. The GA genotype for FCGR2A rs1801274 was associated with poor treatment outcomes.

The effect of tocilizumab administration on inflammatory markers in COVID-19 patients

BackgroundThe COVID-19 outbreak was declared a worldwide emergency as a result of its rapid spread. The number of people infected with COVID-19 is increasing rapidly around the world, and pneumonia can develop in COVID-19 cases. The monoclonal antibody tocilizumab blocks the interleukin-6 receptor, which in turn reduces inflammation.Aimof the workThe study aims to determine how tocilizumab affects inflammatory markers, laboratory indices, and oxygen therapy.Subjects and methodsThis retrospective observational study aimed to assess the effect of tocilizumab on inflammatory markers, laboratory parameters, and short-term outcomes in COVID-19 cases. Data was collected from 55 patients with COVID-19 who tested positive for SARS-CoV-2 using PCR. These patients were admitted to Ain Shams University Specialized Hospital—Obour between June 1, 2021, and May 31, 2022.ResultsAfter tocilizumab administration, C-reactive protein levels decreased significantly, but there was no statistically significant change in hemoglobin, serum ferritin, or D-dimer levels. Following tocilizumab administration, the leukocyte counts, and platelet count increased significantly. There was a significant correlation between the presence of comorbidities in the studied patients (e.g., heart failure, post-renal transplantation, and hepatitis C virus) and the risk of mortality. The study's final result showed a significant decrease in platelet count in dead patients compared to discharged patients after receiving tocilizumab. Regarding oxygen therapy following tocilizumab administration, the use of face masks and non-rebreather facemasks was high in dead patients, while nasal prong usage was high in discharged patients. After receiving tocilizumab, there was an increase in the mean liters of oxygen required in dead patients compared to discharged patients.ConclusionAfter administration of tocilizumab in COVID-19 hospitalized patients who have progressing disease, there was highly and significantly decrease in CRP level with no statistically significant alteration in the levels of hemoglobin, serum ferritin, and D-dimer and an increase in TLC and platelets was observed. Following tocilizumab administration, there was a decrease in oxygen demands, an improvement in oxygen therapy and oxygen saturation. Tocilizumab is a recommended therapy option.

The use of Tocilizumab in COVID-19 critically ill patients with renal impairment: a multicenter, cohort study

Tocilizumab (TCZ) is recommended in patients with COVID-19 who require oxygen therapy or ventilatory support. Despite the wide use of TCZ, little is known about its safety and effectiveness in patients with COVID-19 and renal impairment. Therefore, this study evaluated the safety and effectiveness of TCZ in critically ill patients with COVID-19 and renal impairment. A multicenter retrospective cohort study included all adult COVID-19 patients with renal impairment (eGFR˂60 mL/min) admitted to the ICUs between March 2020 and July 2021. Patients were categorized into two groups based on TCZ use (Control vs. TCZ). The primary endpoint was the development of acute kidney injury (AKI) during ICU stay. We screened 1599 patients for eligibility; 394 patients were eligible, and 225 patients were included after PS matching (1:2 ratio); there were 75 TCZ-treated subjects and 150 controls. The rate of AKI was higher in the TCZ group compared with the control group (72.2% versus 57.4%; p = 0.03; OR: 1.83; 95% CI: 1.01, 3.34; p = 0.04). Additionally, the ICU length of stay was significantly longer in patients who received TCZ (17.5 days versus 12.5 days; p = 0.006, Beta coefficient: 0.30 days, 95% CI: 0.09, 0.50; p = 0.005). On the other hand, the 30-day and in-hospital mortality were lower in patients who received TCZ compared to the control group (HR: 0.45, 95% CI: 0.27, 0.73; p = 0.01 and HR: 0.63, 95% CI: 0.41, 0.96; p = 0.03, respectively). The use of TCZ in this population was associated with a statistically significantly higher rate of AKI while improving the overall survival on the other hand. Further research is needed to assess the risks and benefits of TCZ treatment in critically ill COVID-19 patients with renal impairment.

Utility Of Inflammatory Markers For Tocilizumab In Covid-19 Patients: A Single-Site Retrospective Study.

Studies are available on the use of inflammatory biomarkers for profiling and patient prognosis, but literature for tocilizumab monitoring parameters is scarce. Thus, we aim to evaluate different inflammatory markers that can relate to the effectiveness of tocilizumab in hospitalized patients suffering from severe covid. We analyzed a retrospective cohort of 227 patients who were admitted due to SAR-Co2 in one of the largest hospitals in Pakistan, Lady Reading Hospital. Using in-hospital mortality as the primary parameter for the effectiveness of tocilizumab. Wilcoxon rank-sum test, chi-square test and ROC curve analysis were performed to evaluate inflammatory biomarkers. The p- values less than 0.05 were considered statistically significant. A total of 1639 tests were identified from 227 patients admitted to the hospital. CRP (28%), LDH (27.3%) were the most commonly prescribed and 40% of the total test were prescribed pre-dose. D-dimer, ferritin and CRP were found to have a clinically significant impact of the dose. D-dimer, ferritin and LDH do not seem to relate proportionally with tocilizumab effectiveness. CRP can be utilized for monitoring tocilizumab effectiveness.

Factors Influencing Disease Stability and Response to Tocilizumab Therapy in Severe COVID-19: A Retrospective Cohort Study.

(1) Background: The efficacy of tocilizumab in COVID-19 has been doubted. The study aimed to investigate factors affecting disease stability and response to tocilizumab among severe COVID-19 patients. (2) Methods: This was a cohort study of 70 severe COVID-19 patients at NMC Royal Hospital, UAE, from April to June 2020. (3) Results: Elderly patients and those with cardiovascular comorbidities had a higher risk of unstable COVID-19 (p = 0.025). Regarding tocilizumab therapy timing, compared to the critical group receiving tocilizumab, the unstable severe patients receiving tocilizumab had a significantly higher rate of improvement (86%). In contrast, the late critical subgroup showed a significantly increased mortality rate (52.9%). The risk for secondary infection and adverse events following tocilizumab was higher in the late critical group than in the unstable severe and early critical groups (p = 0.024 and p = 0.006, respectively). Therapeutic doses of anticoagulation and high-dose vitamin D were correlated with better outcomes than the prophylactic dose and the treatment dose of vitamin D (p < 0.001 and p = 0.07, respectively). (4) Conclusions: elderly patients and those with cardiovascular disease developed unstable COVID-19. Tocilizumab is a potentially effective choice against severe and critical COVID-19. Early tocilizumab administration combined with therapeutic dose anticoagulation and high vitamin D doses could improve the patients’ outcomes.

Appropriate Use of Tocilizumab in COVID-19: Early Use is Beneficial.

Interleukin-6 inhibitor Tocilizumab (TCZ) is effective to prevent the mortality of severe COVID-19 by suppressing the cytokine storm, however, its appropriate use needs to be detailed. We aimed to describe the appropriate use of TCZ in severe to critical cases with COVID-19 pneumonia in the early phase of the pandemic. This single-center, retrospective, observational study was conducted in a polymerase chain reaction (PCR) positive COVID-19 patients who received TCZ between April 01, 2020 and June 30, 2020, in Ümraniye Research and Training Hospital İstanbul, Turkey. The factors affecting mortality were compared. A total of 67 patients met the inclusion criteria during the study period. Overall, 76% of those patients were male, with a median age of 61 years. The 28-day mortality rate was 51% among all patients who were hospitalised for COVID-19 pneumonia. A logistic regression model identified the predictors of 28-day fatality; the number of comorbidities, high levels of C-reactive protein (CRP) before initiation of TCZ, initiation of TCZ in the intensive care unit (ICU) and not receiving an additional dose of TCZ. The number of comorbidities, high levels of CRP, initiation of TCZ in the ICU and not receiving the additional dose of TCZ were significant risk factors for fatality among patients with COVID-19 who received TCZ. Early initiation of TCZ when cytokine storm is suspected is appropriate for the prevention of fatality.

Predictive factors of clinical outcomes in patients with COVID-19 treated with tocilizumab: A monocentric retrospective analysis.

The aim of this retrospective observational study is to analyse clinical, serological and radiological predictors of outcome in patients with COVID-19 pneumonia treated with tocilizumab, providing clinical guidance to its use in real-life. This is a retrospective, monocentric observational cohort study. All consecutive patients hospitalized between February the 11th and April 14th 2020 for severe COVID-19 pneumonia at Reggio Emilia AUSL and treated with tocilizumab were enrolled. The patient's clinical status was recorded every day using the WHO ordinal scale for clinical improvement. Response to treatment was defined as an improvement of one point (from the status at the beginning of tocilizumab treatment) during the follow-up on this scale. Bivariate association of main patients' characteristics with outcomes was explored by descriptive statistics and Fisher or Kruskal Wallis tests (respectively for qualitative or quantitative variables). Each clinically significant predictor was checked by a loglikelihood ratio test (in univariate logistic models for each of the considered outcomes) against the null model. A total of 173 patients were included. Only hypertension, the use of angiotensin-converting enzyme inhibitors, PaO2/FiO2, respiratory rate and C-reactive protein were selected for the multivariate analysis. In the multivariable model, none of them was significantly associated with response. Evaluating a large number of clinical variables, our study did not find new predictors of outcome in COVID19 patients treated with tocilizumab. Further studies are needed to investigate the use of tocilizumab in COVID-19 and to better identify clinical phenotypes which could benefit from this treatment.

Efficacy of Tocilizumab in COVID-19: Single-Center Experience.

Background Cytokine release syndrome can be observed during the course of COVID-19. Tocilizumab is used for treating this highly fatal syndrome. We think that the starting time of tocilizumab is important. In this article, we aimed to discuss the efficacy of tocilizumab and to review the necessity of starting it in the early period and the laboratory values that guide us in determining the time of this early period. Methods This retrospective study includes a total of 308 patients with a diagnosis of COVID-19 who were treated with tocilizumab, who were hospitalized in the University of Health Sciences, Gazi Yaşargil Training and Research Hospital between July 2020 and December 2020. The data of the patients were recorded on the day of hospitalization, the day of taking tocilizumab (day 0), and the 1st day, 3rd day, 7th day, and 14th day after taking tocilizumab. Data included age, gender, underlying diseases, where the patient was followed, duration of symptoms before admission to the hospital, duration of oxygen demand before tocilizumab, fever, saturation, and laboratory values. Patients were divided into the mortality group (group 1) and the survival group (group 2), and all data were compared. Results The study consisted of 308 COVID-19 patients divided into two groups: the mortality group (group 1, n = 135) and the survival group (group 2, n = 173). The median age of the patients was 60 (min–max: 50-70) years, 75.3% (n = 232) were male, and 56.8% had at least one comorbidity. While 88.9% of group 1 was in the intensive care unit, 26.6% of group 2 received tocilizumab while in the intensive care unit, and there was a statistically significant difference. Median SpO2 values and lymphocyte counts were significantly lower in group 1 than in group 2, both on the day of hospitalization and on the day of the first dose of tocilizumab treatment (p < 0.001 for both). C-reactive protein, d-dimer, and alanine aminotransferase values were higher in the mortal group on the first day of hospitalization, and this was significant (p = 0.021, p = 0.001, and p = 0.036, respectively). In our study, d-dimer was 766.5 ng/mL in the survivor group and 988.5 ng/mL in the mortal group. In our patient group, the mean lymphocyte count was 700 × 103/mm3 in the group that survived the first day of TCZ and 500 × 103/mm3 in the mortal group. In addition, the CRP value was 135.5 mg/L in the survivor group and 169 mg/L in the mortal group. There was no difference between ferritin values. Conclusions Tocilizumab is still among the COVID-19 treatment options and appears to be effective. But the start time is important. In order to increase its effectiveness, it may be important to know a cut-off value of the laboratory findings required for the diagnosis of cytokine release syndrome. Further studies are needed for this.

Changes in Inflammatory Markers after Administration of Tocilizumab in COVID-19: A Single-Center Retrospective Study.

The COVID-19 pandemic requires the development of effective methods for the treatment of severe cases. We aimed to describe clinical outcomes and changes in inflammatory markers in Polish patients treated with tocilizumab. The medical charts of SARS-CoV-2-positive patients treated in the Department of Infectious Diseases between 4 March and 2 September 2020 were retrospectively analyzed. The patients who received tocilizumab according to the Polish Association of Epidemiologists and Infectiologists guidelines were selected for the study. We identified 29 individuals who received tocilizumab, out of whom 11 (37.9%) died. The individuals who died had significantly higher maximal interleukin-6 (IL-6) and lactate dehydrogenase (LDH) serum levels than survivors. After administration of tocilizumab, further increase in LDH and IL-6 was a prognostic factor for unfavorable outcomes. Among inflammatory markers, 7-day mean of IL-6 serum concentration was the best predictor of death (cut-off: ≥417 pg/mL; area under ROC curve = 0.81 [95% Confidence Interval: 0.63–0.98]). The serum concentrations of inflammatory markers before administration of tocilizumab did not predict the outcome, whereas IL-6 and LDH measurements after administration of tocilizumab seemed to be of predictive value.

The Use of Corticosteroids or Tocilizumab in COVID-19 Based on Inflammatory Markers.

BackgroundThe inflammatory cascade is the main cause of death in COVID-19 patients. Corticosteroids (CS) and tocilizumab (TCZ) are available to treat this escalation but which patients to administer it remains undefined.ObjectiveWe aimed to evaluate the efficacy of immunosuppressive/anti-inflammatory therapy in COVID-19, based on the degree of inflammation.DesignA retrospective cohort study with data on patients collected and followed up from March 1st, 2020, to May 1st, 2021, from the nationwide Spanish SEMI-COVID-19 Registry. Patients under treatment with CS vs. those under CS plus TCZ were compared. Effectiveness was explored in 3 risk categories (low, intermediate, high) based on lymphocyte count, C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, and d-dimer values.PatientsA total of 21,962 patients were included in the Registry by May 2021. Of these, 5940 met the inclusion criteria for the present study (5332 were treated with CS and 608 with CS plus TCZ).Main MeasuresThe primary outcome of the study was in-hospital mortality. Secondary outcomes were the composite variable of in-hospital mortality, requirement for high-flow nasal cannula (HFNC), non-invasive mechanical ventilation (NIMV), invasive mechanical ventilation (IMV), or intensive care unit (ICU) admission.Key ResultsA total of 5940 met the inclusion criteria for the present study (5332 were treated with CS and 608 with CS plus TCZ). No significant differences were observed in either the low/intermediate-risk category (1.5% vs. 7.4%, p=0.175) or the high-risk category (23.1% vs. 20%, p=0.223) after propensity score matching. A statistically significant lower mortality was observed in the very high–risk category (31.9% vs. 23.9%, p=0.049).ConclusionsThe prescription of CS alone or in combination with TCZ should be based on the degrees of inflammation and reserve the CS plus TCZ combination for patients at high and especially very high risk.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-07146-0.

Systematic Review and Meta-Analysis of Tocilizumab Therapy versus Standard of Care in over 15,000 COVID-19 Pneumonia Patients during the First Eight Months of the Pandemic.

Background. Tocilizumab is an anti-IL-6 therapy widely adopted in the management of the so-called “cytokine storm” related to SARS-CoV-2 virus infection, but its effectiveness, use in relation to concomitant corticosteroid therapy and safety were unproven despite widespread use in numerous studies, mostly open label at the start of the pandemic. Methods: We performed a systematic review and meta-analysis of case-control studies utilising tocilizumab in COVID-19 on different databases (PubMed/MEDLINE/Scopus) and preprint servers (medRxiv and SSRN) from inception until 20 July 2020 (PROSPERO CRD42020195690). Subgroup analyses and meta-regressions were performed. The impact of tocilizumab and concomitant corticosteroid therapy or tocilizumab alone versus standard of care (SOC) on the death rate, need for mechanical ventilation, ICU admission and bacterial infections were assessed. Results. Thirty-nine studies with 15,531 patients (3657 cases versus 11,874 controls) were identified. Unadjusted estimates (n = 28) failed to demonstrate a protective effect of tocilizumab on survival (OR 0.74 ([95%CI 0.55–1.01], p = 0.057), mechanical ventilation prevention (OR 2.21 [95%CI 0.53–9.23], p = 0.277) or prevention of ICU admission (OR 3.79 [95%CI 0.38–37.34], p = 0.254). Considering studies with adjusted, estimated, tocilizumab use was associated with mortality rate reduction (HR 0.50 ([95%CI 0.38–0.64], p < 0.001) and prevention of ICU admission (OR 0.16 ([95%CI 0.06–0.43], p < 0.001). Tocilizumab with concomitant steroid use versus SOC was protective with an OR of 0.49 ([95%CI 0.36–0.65], p < 0.05) as was tocilizumab alone versus SOC with an OR of 0.59 ([95%CI 0.34–1.00], p < 0.001). Risk of infection increased (2.36 [95%CI 1.001–5.54], p = 0.050; based on unadjusted estimates). Conclusion: Despite the heterogeneity of included studies and large number of preprint articles, our findings from the first eight of the pandemic in over 15,000 COVID-19 cases suggested an incremental efficacy of tocilizumab in severe COVID-19 that were confirmed by subsequent meta-analyses of large randomized trials of tocilizumab. This suggests that analysis of case-control studies and pre-print server data in the early stages of a pandemic appeared robust for supporting incremental benefits and lack of major therapeutic toxicity of tocilizumab for severe COVID-19.

Antirheumatic drugs and COVID-19: frustrations and hopes

In accordance with current views on the pathogenesis of the new coronavirus infection, some antirheumatic drugs are considered as therapeutic agents for suppressing the hyperinflammatory response in severe COVID-19. The review presents literature data on the efficacy and safety of certain basic anti-inflammatory and genetically engineered drugs in patients with COVID-19. Hydroxychloroquine is not indicated for the treatment of SARS-CoV-2 infection of any severity due to the lack of therapeutic benefits, the likelihood of a worse prognosis in more severe patients and the development of adverse reactions, especially when used concomitantly with azithromycin. The use of systemic glucocorticoids (GC) in patients with COVID-19 who require oxygen support leads to a decrease in mortality and an improvement in the prognosis of the disease. However, the optimal time of administration, dose and duration of HA administration remain the subject of further research. Despite the encouraging data, it is too early to draw final conclusions about the feasibility of using tocilizumab in COVID-19, since no randomized clinical trials have demonstrated a clear advantage of the drug in terms of reducing mortality. The use of anakinra does not reduce the need for noninvasive / invasive lung ventilation or the mortality of patients with COVID-19. Two drugs from the group of tumor necrosis factor inhibitors - infliximab and adalimumabare currently being considered as possible treatment options for COVID-19. The use of a combination of baricitinib and remdesivir for the treatment of COVID-19 patients requiring oxygen support has been approved. New RCTs are needed to study the effectiveness of other anti-rheumatic drugs in COVID-19.

Remdesivir vs tocilizumab in COVID-19: adverse event profiles

Remdesivir vs tocilizumab in COVID-19: adverse event profiles

Tocilizumab for the treatment of non‐critical COVID‐19 pneumonia: an overview of the rationale and clinical evidence to date

ABSTRACT Introduction: Tocilizumab is one of the main repurposed therapies investigated for COVID-19 pneumonia since the start of the pandemic, but there has been conflicting evidence for its use. Areas covered: This review covers the physiology of interleukin-6 and its role in the pathophysiology of COVID-19. We discuss the use of tocilizumab in other diseases and the rationale for its use in COVID-19. We summarize the design, contrasting results, and implications of the clinical trials of tocilizumab in COVID-19 to date and discuss the current guidance for its use. Expert opinion: The evidence to date suggests benefit with the use of tocilizumab in some but not all patients with COVID-19. Benefit seems to be greatest when given early after clinical deterioration with the presence of systemic inflammation. However, questions remain around the optimal timing, patient selection, and concomitant treatments.

Efficacy of tocilizumab in COVID-19: A review of the current evidence.

As cases of coronavirus 2019 (COVID-19) keep rising, reported deaths are increasing. Public health measures have been implemented with mixed efficacy. As vaccines are becoming more widely available and accessible globally, treating critically ill COVID-19 patients remains an issue with only dexamethasone found to be therapeutically effective to date. However, trials studying the efficacy of IL-6 inhibitors, namely tocilizumab have been underway with promising results. This paper is a narrative review that aims to review the current evidence provided by randomized clinical trials (RCT) for the use of tocilizumab in COVID-19. Electronic database searches were carried out in Medline, PubMed, Embase, Google Scholar, and ongoing clinical trial registries with the period set from January 1, 2020 to February 20, 2021. Prepublication manuscripts were found using the pre-print repository medRxiv. Keywords included "COVID-19,""coronavirus,""SARS-CoV-2,""sepsis,""pneumonia,""cytokine storm,""cytokine release syndrome,""IL-6 inhibitors," and "tocilizumab," as exact phrases, and a combination of subject headings according to databases syntax. Only trials with a clear and well-defined methodology, at least 100 patients recruited, and which have had results published either after peer review or in pre-print were included. In hospitalized patients with severe COVID-19, who are hypoxic and have a CRP ≥ 75 mg/L, the current evidence favors the use of a combination of tocilizumab and corticosteroids to reduce mortality, among other clinical benefits. There is also overwhelming evidence of the good safety profile of tocilizumab with only few cases of neutropenia reported with a decrease in infection rates. Tocilizumab is currently thought to work through the inhibition of IL-6 receptors (IL-6R), preventing downstream activation of pro-inflammatory reactions and cytokine release syndrome.

Tocilizumab in COVID-19: Factors Associated With Mortality Before and After Treatment.

Tocilizumab (TCZ) has been administered in SARS-CoV-2 pneumonia but the factors associated with mortality before and after treatment remain unclear. Cox regression models were used to estimate the predictors of time to death in a cohort of hospitalized patients with COVID-19 receiving TCZ. In addition, the mean differences between discharged and deceased patients in laboratory parameters measured before and 3, 6 and 9 days after TCZ administration were estimated with weighted generalized estimation equations. The variables associated with time to death were immunosuppression (Hazard Ratio-HR 3.15; 95% confidence interval-CI 1.17, 8.51), diabetes mellitus (HR 2.63; 95% CI 1.23–5.64), age (HR 1.05; 95% CI 1.02–1.09), days since diagnosis until TCZ administration (HR 1.05, 95% CI 1.00–1.09), and platelets (HR 0.27; 95% CI: 0.11, 0.69). In the post-TCZ analysis and compared to discharged patients, deceased patients had more lactate dehydrogenase (p = 0.013), troponin I (p = 0.013), C-reactive protein (p = 0.013), neutrophils (p = 0.024), and fewer platelets (p = 0.013) and lymphocytes (p = 0.013) as well as a lower average PaO2/FiO2 ratio. In conclusion, in COVID-19 diagnosed patients receiving TCZ, early treatment decreased the risk of death, while age, some comorbidities and baseline lower platelet counts increased that risk. After TCZ administration, lower platelet levels were again associated with mortality, together with other laboratory parameters.

Tocilizumab in COVID-19: a study of adverse drug events reported in the WHO database

ABSTRACT Background: Elevated inflammatory cytokines in Coronavirus disease 2019 (COVID‐19) affect the lungs leading to pneumonitis with a poor prognosis. Tocilizumab, a type of humanized monoclonal antibody antagonizing interleukin-6 receptors, is currently utilized to treat COVID-19. The present study reviews tocilizumab adverse drug events (ADEs) reported in the World Health Organization (WHO) pharmacovigilance database. Research design and methods: All suspected ADEs associated with tocilizumab between April to August 2020 were analyzed based on COVID-19 patients’ demographic and clinical variables, and severity of involvement of organ system. Results: A total of 1005 ADEs were reported among 513 recipients. The majority of the ADEs (46.26%) were reported from 18–64 years, were males and reported spontaneously. Around 80%, 20%, and 64% were serious, fatal, and administered intravenously, respectively. ‘Injury, Poisoning, and Procedural Complications’ remain as highest (35%) among categorized ADEs. Neutropenia, hypofibrinogenemia were common hematological ADEs. The above 64 years was found to have significantly lower odds than of below 45 years. In comparison, those in the European Region have substantially higher odds compared to the Region of Americas. Conclusion: Neutropenia, superinfections, reactivation of latent infections, hepatitis, and cardiac abnormalities were common ADEs observed that necessitate proper monitoring and reporting.

Tocilizumab in COVID-19: a meta-analysis, trial sequential analysis, and meta-regression of randomized-controlled trials.

PurposeInterleukin-6 (IL-6) levels discriminate between patients with mild and severe COVID-19, making IL-6 inhibition an attractive therapeutic strategy. We conducted a systematic review, meta-analysis, trial sequential analysis (TSA), and meta-regression of randomized-controlled trials to ascertain the benefit of IL-6 blockade with tocilizumab for COVID-19.MethodsWe included randomized-controlled trials (RCTs) allocating patients with COVID-19 to tocilizumab. Our control group included standard care or placebo. Trials co-administering other pharmacological interventions for COVID-19 were not excluded. Primary outcome was 28–30 day mortality. Secondary outcomes included progression-to-severe disease defined as need for mechanical ventilation, intensive-care unit (ICU) admission, or a composite.ResultsWe identified 10 RCTs using tocilizumab, 9 of which reported primary outcome data (mortality), recruiting 6493 patients with 3358 (52.2%) allocated to tocilizumab. Tocilizumab may be associated with an improvement in mortality (24.4% vs. 29.0%; OR 0.87 [0.74–1.01]; p = 0.07; I2 = 10%; TSA adjusted CI 0.66–1.14). Meta-regression suggested a relationship between treatment effect and mortality risk, with benefit at higher levels of risk (logOR vs %risk beta = −0.018 [−0.037 to −0.002]; p = 0.07). Tocilizumab did reduce the need for mechanical ventilation and was associated with a benefit in the composite secondary outcome but did not reduce ICU admission.ConclusionsFor hospitalized COVID-19 patients, there is some evidence that tocilizumab use may be associated with a short-term mortality benefit, but further high-quality data are required. Its benefits may also lie in reducing the need for mechanical ventilation.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00134-021-06416-z.

Tocilizumab in COVID-19: some clarity amid controversy

Hyperactivation of the immune response, including release of pro-inflammatory cytokines such as interleukin-6 (IL-6), might play a key role in the pathophysiology of severe illness from COVID-19.1 Consistent with this notion, one of the few therapies that reduces mortality in hospitalised patients with COVID-19 is the corticosteroid, dexamethasone.2 Accordingly, there has been great interest in examining whether treatment with additional, more targeted anti-inflammatory agents beyond steroids could provide further benefit.

565. Tocilizumab Use in COVID-19: Act(emra) to Inhibit Intubation and Decompensation

BackgroundTocilizumab is an IL-6 receptor inhibitor that has been utilized for the prevention and treatment of the cytokine storm inflammatory reaction in COVID-19. The objectives of this analysis were to evaluate clinical outcomes of tocilizumab treatment in relation to respiratory status improvements and to analyze the association between initial inflammatory markers and treatment outcomes.MethodsIRB approved retrospective chart review of adult patients with confirmed COVID-19 treated with tocilizumab from March- May 2020. Data collection focused on relevant past medical history, hematologic and inflammatory markers before and after tocilizumab administration, concomitant COVID-19 treatments, and disease outcomes such as mortality and discharge. Assessed baseline characteristics and treatment outcomes in patients who received tocilizumab prior to intubation versus after intubation, and evaluated for any significant markers of treatment success and failure.Results84 patients were evaluated. Baseline characteristics did not vary between intubated and not intubated patients (Figure 1). Overall mortality in patients who received an IL-6 inhibitor was 43%. Mortality in patients who received IL-6 inhibitor when intubated (63%) compared to patients who were not intubated (26%) was significantly higher (p = 0.005). Patients with BMI’s of 30 or above and patients with diabetes had a higher rate of treatment failure (p < 0.05) (Figure 2). Patients with IL-6 levels of 1000 or above had higher rates of treatment failure (p = 0.0001); however, given the small sample size larger studies are required for further analysis (Figure 3).Baseline Characteristics by Respiratory Status Pre-Tocilizumab Administration Subgroup Analysis Outcome by Baseline IL-6 Levels ConclusionOverall mortality in our patients was 43%; however, our sample size was small and the study did not have a control group to fully assess treatment success or failure. Comorbidities such as diabetes and obesity, and elevated IL-6 levels were associated with significantly higher rates of treatment failure. Randomized control trials are needed to determine the true benefit of tocilizumab in COVID-19.Disclosures All Authors: No reported disclosures