Outcomes in patients with severe COVID-19 disease treated with tocilizumab: a case-controlled study

© The Author(s) 2020. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: [email protected]. BACKGROUND: COVID-19 is an ongoing threat to society. Patients who develop the most severe forms of the disease have high mortality. The interleukin-6 inhibitor tocilizumab has the potential to improve outcomes in these patients by preventing the development of cytokine release storm. AIMS: To evaluate the outcomes of patients with severe COVID-19 disease treated with the interleukin-6 inhibitor tocilizumab. METHODS: We conducted a retrospective, case-control, single-center study in patients with severe to critical COVID-19 disease treated with tocilizumab. Disease severity was defined based on the amount of oxygen supplementation required. The primary endpoint was the overall mortality. Secondary endpoints were mortality in non-intubated patients and mortality in intubated patients. RESULTS: A total of 193 patients were included in the study. Ninety-six patients received tocilizumab, while 97 served as the control group. The mean age was 60 years. Patients over 65 years represented 43% of the population. More patients in the tocilizumab group reported fever, cough and shortness of breath (83%, 80% and 96% vs. 73%, 69% and 71%, respectively). There was a non-statistically significant lower mortality in the treatment group (52% vs. 62.1%, P = 0.09). When excluding intubated patients, there was statistically significant lower mortality in patients treated with tocilizumab (6% vs. 27%, P = 0.024). Bacteremia was more common in the control group (24% vs. 13%, P = 0.43), while fungemia was similar for both (3% vs. 4%, P = 0.72). CONCLUSION: Our study showed a non-statistically significant lower mortality in patients with severe to critical COVID-19 disease who received tocilizumab. When intubated patients were excluded, the use of tocilizumab was associated with lower mortality

Outcomes in Patients With COVID-19 Disease and High Oxygen Requirements.

Background Approximately 19% of people infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) progress to severe or critical stages of the coronavirus disease 2019 (COVID-19) with a mortality rate exceeding 50%. We aimed to examine the characteristics, mortality rates, intubation rate, and length of stay (LOS) of patients hospitalized with COVID-19 disease with high oxygen requirements (critically ill). Methods We conducted a retrospective analysis in a single center in Brooklyn, New York. Adult hospitalized patients with confirmed COVID-19 disease and high oxygen requirements were included. We performed multivariate logistic regression analyses for statistically significant variables to reduce any confounding. Results A total of 398 patients were identified between March 19th and April 25th, 2020 who met the inclusion criteria, of which 247 (62.1%) required intubation. The overall mortality rate in our study was 57.3% (n = 228). The mean hospital LOS was 19.1 ± 17.4 days. Patients who survived to hospital discharge had a longer mean LOS compared to those who died during hospitalization (25.4 ± 22.03 days versus10.7 ± 1.74 days). In the multivariate analysis, increased age, intubation and increased lactate dehydrogenase (LDH) were each independently associated with increased odds of mortality. Diarrhea was associated with decreased mortality (OR 0.4; CI 0.16, 0.99). Obesity and use of vasopressors were each independently associated with increased intubation. Conclusions In patients with COVID-19 disease and high oxygen requirements, advanced age, intubation, and higher LDH levels were associated with increased mortality, while diarrhea was associated with decreased mortality. Gender, diabetes, and hypertension did not have any association with mortality or length of hospital stay

Should COVID-19 Patients \u3e 75 Years be Ventilated? An Outcome Study.

Background Elderly patients with COVID-19 disease are at increased risk for adverse outcomes. Current data regarding disease characteristics and outcomes in this population is limited. Aim To delineate the adverse factors associated with outcomes of COVID- 19 patients ≥75 years of age. Design Retrospective cohort study. Methods Patients were classified into mild/moderate, severe/very severe, and critical disease (intubated) based on oxygen requirements. The primary outcome was in-hospital mortality. Results 355 patients aged ≥75 years hospitalized with COVID-19 between March 19th and April 25th, 2020 were included. Mean age was 84.3 years. One-third of the patients developed critical disease. Mean length of stay was 7.10 days. Vasopressors were required in 27%, with the highest frequency in the critical disease group (74.1%). Overall mortality was 57.2%, with a significant difference between severity groups (mild/moderate disease : 17.4%, severe/very severe disease : 71.3%, critical disease: 94.9%, p \u3c 0.001). Increased age, dementia, and severe/very severe and critical disease groups were each significantly associated with increased odds for mortality while diarrhea was associated with decreased odds for mortality (OR : 0.12, 95% CI : 0.02-0.60, p \u3c 0.05)]. None of the cardiovascular comorbidities were significantly associated with mortality. Conclusion Age and dementia are associated with increased odds for mortality in patients ≥75 years of age hospitalized with COVID-19. Those who require intubation have the greatest odds for mortality. Diarrhea as a presenting symptom was associated with lower odds for mortality

Should COVID-19 patients \u3e75 years be Ventilated? An Outcome Study

Background: Elderly patients with COVID-19 disease are at increased risk for adverse outcomes. Current data regarding disease characteristics and outcomes in this population are limited. Aim: To delineate the adverse factors associated with outcomes of COVID-19 patients ≥ 75 years of age. Design: Retrospective cohort study. Methods: Patients were classified into mild/moderate, severe/very severe and critical disease (intubated) based on oxygen requirements. The primary outcome was in-hospital mortality. Results: A total of 355 patients aged ≥ 75 years hospitalized with COVID-19 between 19 March and 25 April 2020 were included.Mean age was 84.3 years. One-third of the patients developed critical disease. Mean length of stay was 7.10 days. Vasopressors were required in 27%, with the highest frequency in the critical disease group (74.1%). Overall mortality was 57.2%, with a significant difference between severity groups (mild/moderate disease: 17.4%, severe/very severe disease: 71.3%, critical disease: 94.9%, P \u3c 0.001).Increased age, dementia, and severe/very severe and critical disease groups were in- dependently associated with increased odds for mortality while diarrhea was associated with decreased odds for mortality (OR: 0.12, 95% CI: 0.02–0.60, P \u3c 0.05). None of the cardiovascular comorbidities were significantly associated with mortality. Conclusion: Age and dementia are associated with increased odds for mortality in patients ≥ 75 years of age hospitalized with COVID-19. Those who require intubation have the greatest odds for mortality. Diarrhea as a presenting symptom was associated with lower odds for mortality

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication