Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19.
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ABSTRACT: Background
Severe coronavirus disease 2019 (COVID-19) can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers, consistent with cytokine release syndrome for which IL-6 blockade is an approved treatment.Methods
We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability postintubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared with tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability of treatment weighting (IPTW).Results
154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range, 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean: 55 vs 60 years), less likely to have chronic pulmonary disease (10% vs 28%), and had lower D-dimer values at time of intubation (median: 2.4 vs 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death (HR, .55; 95% CI, .33-.90) and improved status on the ordinal outcome scale [OR per 1-level increase, .58; .36-.94). Although tocilizumab was associated with an increased proportion of patients with superinfections (54% vs 26%; P < .001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection (22% vs 15%; P = .42). Staphylococcus aureus accounted for ~50% of bacterial pneumonia.Conclusions
In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with lower mortality despite higher superinfection occurrence.
SUBMITTER: Somers EC
PROVIDER: S-EPMC7454462 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Severe COVID-19 can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers. This presentation is consistent with cytokine release syndrome in chimeric antigen receptor T cell therapy, for which IL-6 blockade is approved treatment. We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability post-intubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared to tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability weighting (IPTW). 154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean 55 vs. 60 years), less likely to have chronic pulmonary disease (10% vs. 28%), and had lower D-dimer values at time of intubation (median 2.4 vs. 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death [hazard ratio 0.55 (95% CI 0.33, 0.90)] and improved status on the ordinal outcome scale [odds ratio per 1-level increase: 0.59 (0.36, 0.95)]. Though tocilizumab was associated with an increased proportion of patients with superinfections (54% vs. 26%; p<0.001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection [22% vs. 15%; p=0.42]. In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with a decreased likelihood of death despite higher superinfection occurrence. Randomized controlled trials are urgently needed to confirm these findings.
| S-EPMC7302290 | biostudies-literature
Project description:ObjectivesThe purpose of this study is to evaluate clinical outcomes in patients with critical COVID-19 pneumonia requiring invasive mechanical ventilation who were treated with tocilizumab DESIGN: Single-center retrospective cohort study SETTING: Stony Brook University Hospital, a 600-bed academic tertiary medical center in Suffolk County, New York PARTICIPANTS: Consecutive patients with COVID-19 confirmed by nasopharyngeal polymerase chain reaction (PCR) who were admitted to Stony Brook University Hospital between March 10 and April 2 2020 and required mechanical ventilation in any intensive care unit during their hospitalization EXPOSURE: Treatment with tocilizumab while intubated MAIN OUTCOME: Overall mortality 30 days from the date of intubation RESULTS: Forty-five patients received tocilizumab compared to seventy controls. Baseline demographic characteristics, inflammatory markers, treatment with corticosteroids, and sequential organ failure assessment (SOFA) scores were similar between the two cohorts. Patients who received tocilizumab had significantly lower Charlson co-morbidity index (2.0 vs 3.0,P = 0.01) than controls. There was a trend towards younger mean age in the tocilizumab exposed group (56.2 vs 60.6; P = 0.09). In logistic regression analysis there was no reduction in mortality associated with receipt of tocilizumab (odds ratio (OR) 1.04; 95% CI, 0.27-3.75). There was no observed increased risk of secondary infection in patients given tocilizumab (28.9 vs 25.7; OR 1.17; 95% CI, 0.51-2.71).ConclusionWhen controlling for age, severity of illness, and co-morbidities, tocilizumab was not associated with reduction in mortality in this retrospective cohort study of mechanically ventilated patients with COVID-19 pneumonia. Further studies are needed to determine the role of tocilizumab in the treatment of COVID-19.
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Project description:ObjectivesAssess the association between tocilizumab administration and clinical outcomes among mechanically ventilated patients with COVID-19 pneumonia.DesignRetrospective cohort study.SettingLarge integrated health system with 9 million members in California, USA.Participants4185 Kaiser Permanente members hospitalised with COVID-19 pneumonia requiring invasive mechanical ventilation (IMV).InterventionsReceipt of tocilizumab within 10 days of initiation of IMV.Outcome measuresUsing a retrospective cohort of consecutive patients hospitalised with COVID-19 pneumonia who required IMV in a large integrated health system in California, USA, we assessed the association between tocilizumab administration and 28-day mortality, time to extubation from IMV and time to hospital discharge.ResultsAmong 4185 patients, 184 received tocilizumab and 4001 patients did not receive tocilizumab within 10 days of initiation of IMV. After inverse probability weighting, baseline characteristics were well balanced between groups. Patients treated with tocilizumab had a similar risk of death in the 28 days after intubation compared with patients not treated with tocilizumab (adjusted HR (aHR), 1.21, 95% CI 0.98 to 1.50), but did have a significantly longer time-to-extubation (aHR 0.71; 95% CI 0.57 to 0.88) and time-to-hospital-discharge (aHR 0.66; 95% CI 0.50 to 0.88). However, patients treated with tocilizumab ≤2 days after initiation of IMV had a similar risk of mortality (aHR 1.47; 95% CI 0.96 to 2.26), but significantly shorter time-to-extubation (aHR 0.37; 95% CI 0.23 to 0.58) and time-to-hospital-discharge (aHR 0.31; 95% CI CI 0.17 to 0.56) compared with patients treated with tocilizumab 3-10 days after initiation of IMV.ConclusionsAmong mechanically ventilated patients with COVID-19, the risk of death in the 28-day follow-up period was similar, but time-to-extubation and time-to-hospital-discharge were longer in patients who received tocilizumab within 10 days of initiation of IMV compared with patients who did not receive tocilizumab.
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Project description:Potential interactions between the SARS-CoV-2 virus and the human oral microbiota are currently investigated widely. Patients with COVID-19 requiring mechanical ventilation in an intensive care unit (ICU) setting are at high risk of developing severe complications, including ventilator-associated pneumonia, thus making oral health management important. The aim of this study was to evaluate the oral health status and assess the dysbiosis of cultivable oral bacteriota in COVID-19 patients hospitalized in an ICU with acute respiratory distress within 36 h following intubation. In this prospective cohort study, we recruited 56 adult COVID-19 patients that qualified for mechanical ventilation in the Temporary ICU for COVID-19 Patients of the University Hospital in Krakow. On admission to the ICU, oral health of patients was assessed using the modified Beck Oral Assessment Score (BOAS). Four oral habitats were sampled, namely the buccal mucosa, tongue, buccal dental surface and gingival pocket. Microorganisms were identified by MALDI/TOF mass spectrometry. The mean age of the study population was 66.5 ± 12.7 years, there were 24 (42.9%) females. All patients included in this study were intubated and ventilated in the ICU, with a corresponding high mortality rate (76.8%). On admission to ICU, 76.8% subjects scored 11-20 on the BOAS scale (median 12 [IQR 10-14]), indicating moderate or severe dysfunction of oral health. Potentially pathogenic bacteria were identified in the oral microbiota samples, including Acinetobacter baumannii, Enterococcus faecalis, Escherichia coli and Klebsiella pneumoniae in 23.2%, 39.3%, 17.9%, and 19.6% of patients, respectively. Lactobacillus spp. were present in 57.1% subjects. The mean CFU counts of all bacteria strains in dental brushes were 9.3E+5 (1.4E+6) and in gingival pockets 7.6E+5 (1.4E+6). The highest CFU counts were observed for Enterococcus spp. and, Lactobacillus spp., although these did not differ significantly from CFU counts of Streptococcus spp. and Staphylococcus spp. In this report we comprehensively characterized the oral health condition and cultivable oral bacteriota in COVID-19 patients hospitalized in an ICU with acute respiratory distress within 36 h following intubation. The oral bacteriota showed significant qualitative and quantitative dysbiosis. Hospitalization in an ICU and mechanical ventilation are important factors leading to oral dysbiosis in SARS-CoV-2 patients.
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Project description:ObjectiveTo determine the incidence, predictors, and outcome of pneumothorax (PNX)/pneumomediastinum (PMD) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS).DesignObservational study.SettingTertiary-care university hospital.ParticipantsOne hundred sixteen consecutive critically ill, invasively ventilated patients with COVID-19 ARDS.InterventionsThe authors collected demographic, mechanical ventilation, imaging, laboratory, and outcome data. Primary outcome was the incidence of PNX/PMD. Multiple logistic regression analyses were performed to identify predictors of PNX/PMD.Measurements and main resultsPNX/PMD occurred in a total of 28 patients (24.1%), with 22 patients developing PNX (19.0%) and 13 developing PMD (11.2%). Mean time to development of PNX/PMD was 14 ± 11 days from intubation. The authors found no significant difference in mechanical ventilation parameters between patients who developed PNX/PMD and those who did not. Mechanical ventilation parameters were within recommended limits for protective ventilation in both groups. Ninety-five percent of patients with PNX/PMD had the Macklin effect (linear collections of air contiguous to the bronchovascular sheaths) on a baseline computed tomography scan, and tended to have a higher lung involvement at intensive care unit (ICU) admission (Radiographic Assessment of Lung Edema score 32.2 ± 13.4 v 18.7 ± 9.8 in patients without PNX/PMD, p = 0.08). Time from symptom onset to intubation and time from total bilirubin on day two after ICU admission were the only independent predictors of PNX/PMD. Mortality was 60.7% in patients who developed PNX/PMD versus 38.6% in those who did not (p = 0.04).ConclusionPNX/PMD occurs frequently in COVID-19 patients with ARDS requiring mechanical ventilation, and is associated with increased mortality. Development of PNX/PMD seems to occur despite use of protective mechanical ventilation and has a radiologic predictor sign.
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Project description:Effective treatments for the critically ill patient with novel coronavirus disease 2019 are desperately needed. Given the role of cytokine release syndrome in the pathogenesis of coronavirus disease 2019-associated respiratory distress, therapies aimed at mitigating cytokine release, such as the interleukin-6 receptor-inhibiting monoclonal antibody tocilizumab, represent potential treatment strategies. Therefore, we examined the outcomes of critically ill coronavirus disease 2019 patients treated with tocilizumab and factors associated with clinical improvement. Design:A retrospective cohort analysis of 21-day outcomes for consecutive mechanically ventilated patients treated with tocilizumab from March 24, 2020, to May 4, 2020. Setting:Nine ICUs at six hospitals within a hospital system in Houston, Texas, United States. Patients:The first 62 coronavirus disease 2019 patients on invasive mechanical ventilation who were treated with tocilizumab, which was considered for all patients with severe disease. Interventions:Tocilizumab was administered either at a weight-based dose of 4-8?mg/kg or at a flat dose of 400?mg, with repeat administration in some patients at the physician's discretion. Measurements and Main Results:The primary outcomes were mortality and clinical improvement, defined as extubation. By day 21 post-tocilizumab, clinical improvement occurred in 36 patients (58%) and 13 patients (21%) died. In both univariable and multivariable analyses, age less than 60 years was associated with clinical improvement. Transient transaminitis was the most common adverse reaction, occurring in 25 patients (40%). Conclusions:Based on clinical outcomes and mortality rates seen in previous reports of mechanically ventilated patients, tocilizumab, as part of the management strategy for severe coronavirus disease 2019, represents a promising option. These findings support the need for evaluation of tocilizumab in a randomized controlled trial.
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| S-EPMC7959453 | biostudies-literature
Project description:BackgroundSolid data on cardiovascular derangements in critically ill COVID-19 patients remain scarce. The aim of this study is to describe hemodynamic characteristics in a cohort of COVID-19-related critically ill patients.MethodsA retrospective observational cohort study in twenty-eight consecutive mechanically ventilated COVID-19 patients. Pulse contour analysis-derived data were obtained from all patients, using the PiCCO® system.ResultsThe mean arterial pressure increased from 77 ± 10 mmHg on day 1 to 84 ± 9 mmHg on day 21 (p=0.04), in combination with the rapid tapering and cessation of norepinephrine and the gradual use of antihypertensive drugs in the vast majority of patients. The cardiac index increased significantly from 2.8 ± 0.7 L/min/m2 on day 1 to 4.0 ± 0.8 L/min/m2 on day 21 (p < 0.001). Dobutamine was administered in only two patients. Mean markers of left ventricular contractility and peripheral perfusion, as well as lactate levels, remained within the normal range. Despite a constant fluid balance, extravascular lung water index decreased significantly from 17 ± 7 mL/kg on day 1 to 11 ± 4 mL/kg on day 21 (p < 0.001). Simultaneously, intrapulmonary right-to-left shunt fraction (Q s/Q t) decreased significantly from 27 ± 10% in week 1 to 15 ± 9% in week 3 (p=0.007). PaO2/FiO2 ratio improved from 159 ± 53 mmHg to 319 ± 53 mmHg (p < 0.001), but static lung compliance remained unchanged.ConclusionsIn general, this cohort of patients with COVID-19 respiratory failure showed a marked rise in blood pressure over time, not accompanied by distinctive markers of circulatory failure. Characteristically, increased extravascular lung water, vascular permeability, and intrapulmonary shunt diminished over time, concomitant with an improvement in gas exchange.
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Project description:PurposeThe outcomes of patients requiring invasive mechanical ventilation for COVID-19 remain poorly defined. We sought to determine clinical characteristics and outcomes of patients with COVID-19 managed with invasive mechanical ventilation in an appropriately resourced US health care system.MethodsOutcomes of COVID-19 infected patients requiring mechanical ventilation treated within the Inova Health System between March 5, 2020 and April 26, 2020 were evaluated through an electronic medical record review.Results1023 COVID-19 positive patients were admitted to the Inova Health System during the study period. Of these, 164 (16.0%) were managed with invasive mechanical ventilation. All patients were followed to definitive disposition. 70/164 patients (42.7%) had died and 94/164 (57.3%) were still alive. Deceased patients were older (median age of 66 vs. 55, p <0.0001) and had a higher initial d-dimer (2.22 vs. 1.31, p = 0.005) and peak ferritin levels (2998 vs. 2077, p = 0.016) compared to survivors. 84.3% of patients over 70 years old died in the hospital. Conversely, 67.4% of patients age 70 or younger survived to hospital discharge. Younger age, non-Caucasian race and treatment at a tertiary care center were all associated with survivor status.ConclusionMortality of patients with COVID-19 requiring invasive mechanical ventilation is high, with particularly daunting mortality seen in patients of advanced age, even in a well-resourced health care system. A substantial proportion of patients requiring invasive mechanical ventilation were not of advanced age, and this group had a reasonable chance for recovery.
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Project description:BackgroundNutrition therapy is essential in critically ill adults. Little is known about appropriate nutrition therapy in patients with severe coronavirus disease 2019 (COVID-19) infection.MethodsThis was a retrospective, observational study in adult patients with confirmed COVID-19 infection receiving mechanical ventilation. Data regarding patient demographics and nutrition therapy were collected. Patients that received enteral nutrition within 24 hours of starting mechanical ventilation were compared with patients starting enteral nutrition later. The primary outcome was inpatient length of stay. Propensity score matching was conducted to control for baseline differences in patient groups.ResultsOne hundred fifty-five patients were included in final analysis. Patients who received enteral nutrition within 24 hours received a significantly greater daily amount of calories (17.5 vs 15.2 kcal/kg, P = .015) and protein (1.04 vs 0.85 g/kg, P = .003). There was no difference in length of stay (18.5 vs 23.5 days, P = .37). The propensity score analysis included 100 patients. Following propensity scoring, significant differences in daily calorie (17.7 [4.6] vs 15.1 [5.1] kcal/kg/d, P = .009) and protein (1.03 [0.35] vs 0.86 [0.38] g/kg/d, P = .014) provision remained. No differences in length of stay or other outcomes were noted in the propensity score analysis.ConclusionInitiation of enteral nutrition within 24 hours was not associated with improved outcomes in mechanically ventilated adults with COVID-19. No harm was detected either. Future research should seek to clarify optimal timing of enteral nutrition initiation in patients with COVID-19 who require mechanical ventilation.
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