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INTRODUCTION: Transcriptome-derived sepsis subphenotypes, termed 'adaptive', 'inflammopathic' and 'coagulopathic', have been reliably identified in sepsis cohorts, however plasma proteomics in these groups have not been well characterized. We hypothesized that inflammatory and vascular injury markers would be elevated in the inflammopathic and coagulopathic groups compared to the adaptive group. METHOD(S): We prospectively enrolled and obtained blood from 130 inpatients with COVID19-related sepsis. Severity was classified by NIH ordinal scale. Gene expression analysis was performed by Nanostring nCounter (Inflammatix). Inflammatory proteins interleukin (IL)-6, IL8, IL10, IL1RA, IL1RL1, and IFNg and vascular markers ANGPT2, sICAM, vWF, ADAMTS13, and protein C were measured with OLINK proximity extension assay. Clinical variables were compared by chi-square and protein levels were compared using ANOVA with Bonferroni adjustment. RESULT(S): The transcriptomic classifier identified 32% (41) inflammopathic, 50% (65) adaptive and 18% (24) coagulopathic subjects. The inflammopathic group had more patients requiring mechanical ventilation (39% vs 9% vs 21%;p < 0.001) and higher 90-day mortality (32% vs 8% vs 13%, p = 0.016). Inflammatory cytokines IL8 and IL10 were significantly higher in inflammopathic compared to adaptive (p=0.038 and p=0.017 respectively), but not compared to coagulopathic (p>0.99 and p=0.24, respectively). Both the inflammopathic and coagulopathic groups expressed higher IL1RL1 and interferon-gamma compared to adaptive (IL1RL1;p< 0.001, p=0.002, IFNg;p=0.007, p=0.001). Plasma IL6 and IL1RA did not differ between groups, nor did many vascular proteins. The inflammopathic group expressed higher sICAM (p=0.049 vs adaptive) and lower ADAMTS13 compared to the adaptive group, and the coagulopathic group did not differ in its vascular protein expression. CONCLUSION(S): Transcriptomic subphenotypes are present in COVID-19 sepsis at similar proportions to non-COVID-19 sepsis. Inflammopathic subjects manifested higher severity of illness at admission, higher expression of inflammatory proteins and higher mortality. Markers of vascular injury did not distinguish the coagulopathic group. Integrating RNA and protein expression may offer new insights to host immune dysregulation during COVID sepsis.
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Background. Tocilizumab (TCZ) was approved by the Food and Drug Administration under emergency use authorization for treatment of COVID-19 in patients requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation. Despite multiple clinical trials, there remain unanswered questions surrounding TCZ use. Methods. This multi-hospital retrospective cohort study included patients who received TCZ for COVID-19 between January 29th, 2021 and June 30th, 2021 at five University of Pennsylvania Health System (UPHS) hospitals. Patients were eligible for TCZ per UPHS criteria if they scored >= 5 on the World Health Organization (WHO) ordinal scale for <= 24 hours and experienced < 14 days of acute COVID-19 symptoms. Descriptive statistics were performed to characterize usage within the health system. Results. This study evaluated 134 patients who received TCZ for the treatment of COVID-19. TCZ was ordered a median of 22 hours (interquartile range [IQR], 13.2 - 41.5) after hospital admission. A majority of patients (76.1%) were admitted to the intensive care unit and a small portion (12.7%) had a WHO ordinal scale that was >5 at time of TCZ order entry. All patients received concomitant dexamethasone therapy at a total prednisone equivalent of 400 mg (IQR, 335.6 - 480). Overall 33.6% of patients experienced an adverse event (ADE) within 30 days of TCZ administration (Table 1). Most common ADEs included bacterial infection (29.9%), hepatitis (6.7%), and fungal infection (3%);other etiologies of ADEs were not accounted for. All-cause mortality (Table 2) at day 30 occurred in 20.9% of patients and median time from TCZ administration to mortality was 12.5 days (IQR 5 - 18.3). Ninety-six patients in the cohort (71.6%) were discharged by day 30. Of the subgroup discharged by day 30, the majority (70.8%) were discharged to home. Conclusion. Patients who received TCZ for severe COVID-19 experienced 20.9% mortality;mortality was higher among those with higher ordinal scale at the time of TCZ dosing. A large portion of patients (70.8%) were discharged to home within 30 days. One third of patients experienced an adverse event, primarily bacterial or fungal infection. Our experience may be useful in counseling patients about anticipated effects of TCZ.
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The COVID-19 pandemic has had a major impact on everyone’s life. Like many other professionals, social workers have been forced to adapt to these new working conditions and new challenges in order to support clients during the pandemic, as new needs have arisen. Together with professional associations from three nations (Germany, Switzerland and the Netherlands), we used a coordinated approach to explore the consequences of the pandemic for social work professionals. This study was conducted during the most severe contact and hygiene restrictions of the second wave of the COVID-19 pandemic in the winter of 2020/2021. The data addresses the changes perceived by social work professionals in relation to their contact and communication with clients, the use of digital technology in the context of work, the professional response in terms of innovation, the working conditions and the psychosocial risks they face. Methods Cross-sectional data was collected from 7,241 social workers in Germany, Switzerland and the Netherlands through online surveys. Results The results show an increase in the workload of professional social workers and compounding problems of clients, together with a negative impact of the COVID-19 pandemic on communication and contact with clients. All of this takes place within the framework of changing working conditions and contexts. Our data shows that the use of digital technologies does not cause bigger problems for most of the participating social workers. It should in fact be noted that professionals have many positive associations with the use of digital technology in general. Conclusions There are both remarkable and alarming results concerning the mental health of social workers and their working conditions, as well as the position of the social work profession in general. © This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
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Social media (SM) provides a platform to learn from pts and the public to better understand pts' needs. This research examined SM discussions on symptoms, impact of the COVID-19 pandemic, and QoL of pts with melanoma. A SML approach using melanoma-specific terminology from publicly-available blogs, forums, and SM sites, collected data retrospectively over 2 years (Nov 2018-Sep 2020) across 15 European countries. Manual and automated relevancy approaches filtered the extracted data for content that provided pt-centric insights. This contextualized data was then mined to gain insights on symptoms, QoL, and the impact of the COVID-19 pandemic. Of 182.4K mentions of melanoma, Twitter was the primary channel used (71% of conversations), followed by blogs (17%), and forums (11%). Pts were the predominant contributors to conversations (62%), with caregivers (22%), and family/friends (12%) also contributing. The top 5 regions where conversations took place were the UK (38%), Spain (16%), Italy (13%), Germany (11%), and France (11%). Female-led conversations were more common (55%), and malignant and metastatic disease accounted for 77% of the types of melanoma discussed. Of the 864 insightful conversations identified, QoL was mentioned in 255 (30%);emotional burden was the most frequent topic mentioned (70%), followed by physical (24%), social (17%), and financial (4%) impacts. Symptoms were mentioned in only 2% of conversations, with pain (36%), hardened nodules under the skin (21%), and itchy skin (14%) the most common. 5% of discussions highlighted treatments being postponed, rescheduled, or cancelled, which was often attributed to the COVID-19 pandemic. Emotional burden was the main impact on QoL identified in this study. SML is a useful tool to understand concerns surrounding the QoL of pts with melanoma.
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Background: In March 2020, the COVID-19 outbreak was declared a pandemic by the World Health Organization. Aim: Our objective was to identify risk factors predictive of severe disease and death in France. Methods: In this prospective cohort study, we included patients >= 18 years old with confirmed COVID19, hospitalised in Strasbourg and Mulhouse hospitals (France), in March 2020. We respectively compared patients who developed severe disease (admission to an intensive care unit (ICU) or death) and patients who died, to those who did not, by day 7 after hospitalisation. Results: Among 1,045 patients, 424 (41%) had severe disease, including 335 (32%) who were admitted to ICU, and 115 (11%) who died. Mean age was 66 years (range: 20-100), and 612 (59%) were men. Almost 75% of patients with body mass index (BMI) data (n = 897) had a BMI >= 25 kg/m2 (n = 661). Independent risk factors associated with severe disease were advanced age (odds ratio (OR): 1.1 per 10-year increase;95%CrI (credible interval): 1.0-1.2), male sex (OR: 2.1;95% CrI: 1.5- 2.8), BMI of 25-29.9 kg/m2 (OR: 1.8;95% CrI: 1.2-2.7) or >= 30 (OR: 2.2;95% CrI: 1.5-3.3), dyspnoea (OR: 2.5;95% CrI: 1.8-3.4) and inflammatory parameters (elevated C-reactive protein and neutrophil count, low lymphocyte count). Risk factors associated with death were advanced age (OR: 2.7 per 10-year increase;95% CrI: 2.1-3.4), male sex(OR:1.7;95%CrI:1.1- 2.7), immunosuppression (OR: 3.8;95% CrI: 1.6-7.7), diabetes (OR: 1.7;95% CrI: 1.0-2.7), chronic kidney disease (OR: 2.3;95% CrI: 1.3-3.9), dyspnoea (OR: 2.1;95% CrI: 1.2-3.4) and inflammatory parameters. Conclusions: Overweightedness, obesity, advanced age, male sex, comorbidities, dyspnoea and inflammation are risk factors for severe COVID-19 or death in hospitalised patients. Identifying these features among patients in routine clinical practice might improve COVID-19 management. <comment>Superscript/Subscript Available</comment
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The novel coronavirus, also known as Covid-19, has affected people globally. The reality of reduced working hours set in, and a contraction in consumer demand and business confidence began, leading to a reduction in spending and investment. Travel restrictions were put in place, trade was halted, and most of the way we were used to living changed drastically. To combat economic losses and complete economic shutdown, governments were forced to rollout relief policies to aid businesses and reduce financial losses. These policies include tax and bank payment holidays, underwriting of loans, job retention schemes, value-added tax (VAT) deferments, grants, and mortgage breaks. This study aimed to analyse the support policies that several European countries applied to assist businesses and compare them to South Africa. The study followed a qualitative exploratory research design using secondary data obtained from several open-source documents obtained from various government and non-governmental websites. Thematic analysis using Atlas.ti was used to analyse and report the data. Five themes emanated from the study: Business stability measures, Social support, Post-Covid recovery measures, Liquidity measures for businesses and Transmission prevention. In comparison with South Africa, several similarities were present in the Disaster Management Tax Relief Administration Bill. Yet, despite the commonalities that persist and the fact that South Africa shares in the spirit of the themes applied by the European nations, it is comparatively weaker when the breadth and scale of its interventions are compared. © 2021, Czestochowa University of Technology. All rights reserved.
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Rationale: Respiratory viruses are commonly detected pathogens in pulmonary sepsis. Prior studies have demonstrated that patients with respiratory viral infections may have transient lymphocytopenia and thrombocytopenia. Leukocyte parameters including lymphocyte to monocyte ratio (LMR) and neutrophil to lymphocyte ratio (NLR) have been reported as screening tools for viral infections. Platelet counts and dynamics have been described as quantitative traits for ARDS risk and mortality. Therefore, we hypothesized that early hematologic parameters including lymphocyte count, monocyte count, platelet count, NLR, and LMR may distinguish viral from bacterial pulmonary sepsis. Methods: We enrolled 1,158 critically ill patients with pulmonary sepsis from 2009 to 2020 and measured lymphocyte count, monocyte count, platelet count, NLR, and LMR on ICU admission and at 24-hrs. Respiratory viruses were detected via PCR panel on nasopharyngeal swabs. Pulmonary sepsis was adjudicated by a physician panel. APACHE III scores were collected during the first 24-hrs. Shock was assessed by vasopressor use or mean arterial pressure <65mmHg despite 30cc/kg fluid resuscitation. ARDS was defined per Berlin criteria. We assessed mortality at 30 days. We used multivariable linear regression to test the association between each of the laboratory studies and a positive respiratory pathogen panel (RVP) adjusting for APACHE III score, age, sex, malignancy, and race. We used multivariable logistic regression to assess for associations between a positive RVP and outcomes. Results: The incidence of respiratory virus detection was 33.9%. The incidence of ARDS and mortality were 52.7% and 49.0%, respectively. The most commonly detected pathogens were SARS-CoV-2 and rhinovirus (Table 1). Lower platelet counts at 24-hrs were significantly associated with respiratory virus detection (β-41.59 × 109/L [95%CI-79.03,-4.15], p=0.03), whereas admission platelet counts were not significantly associated (β-22.38 × 109/L [95%CI-63.26, 20.49], p=0.32). The significant association at 24-hrs was also present on sensitivity analyses excluding patients with SARS-CoV-2. There were no statistically significant differences between the populations with respect to lymphocyte count, monocyte count, NLR, LMR, ARDS, shock, and mortality. Conclusion: Lower early platelet counts were identified in patients with viral pulmonary sepsis. Although LMR and NLR have been reported as screening tools for viral infections in non-critically ill populations, we did not detect significant associations between lymphocyte count, monocyte count, NLR or LMR and viral detection in pulmonary sepsis. Our findings suggest that platelet counts in combination with other validated parameters may warrant further investigation for the early discrimination of viral versus bacterial pulmonary sepsis.
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Rationale: Obesity is a strong risk factor for acute kidney injury (AKI) in patients with COVID-19, but underlying mechanisms are unknown. Resistin is an immunomodulatory adipokine with elevated circulating levels in obese outpatients that could contribute to inflammatory kidney injury. We hypothesized that plasma resistin levels would be associated with AKI and BMI, and correlated with the inflammatory markers IL6 and MCP1 in hospitalized COVID-19 patients. Methods: We conducted a prospective cohort study of 134 patients admitted to the Hospital of the University of Pennsylvania with a primary diagnosis of COVID-19. Plasma samples were collected within 48 hours of admission and analyzed using the Olink Proximity Extension Assay, with biomarker levels expressed using normalized protein expression (NPX) values relative to common pooled control plasma. We tested the association of each biomarker with AKI, defined by Kidney Disease Improving Global Outcomes creatinine and dialysis criteria, using the Wilcoxon rank-sum test as well as multivariable logistic regression to adjust for confounders. Spearman's rho and correlation coefficients were calculated for the correlation of biomarker levels with each other. We used causal mediation models to investigate effects of BMI on AKI mediated by plasma resistin. Results: Of 134 patients enrolled, 43 (32.1%) developed AKI: 25 with stage 1, 5 with stage 2, and 13 with stage 3. Plasma resistin levels ranged from 5.26-13.01 NPX units and were strongly associated with AKI: odds ratio 2.13 (95% CI 1.43-3.17) per NPX unit. This association was diminished but remained significant after adjustment for age and APACHE III score (OR 1.69 (1.09-2.63)). Body mass index was higher in patients with AKI than without (median 31.4 (IQR 27.1-37.6) kg/m2 v. 28.3 (25.1-34.9) kg/m2, respectively), but the difference was not statistically significant (p=0.082). There was no significant correlation of BMI with resistin levels (rho 0.05, p=0.562), and causal mediation models failed to detect significant mediation of BMI-AKI association through resistin. Plasma IL6 and MCP1 were associated with AKI (p=0.044 and p=0.003, respectively) and correlated with resistin levels (rho=0.32, p<0.001 and rho=0.40, p<0.001, respectively). Conclusion: In patients hospitalized with COVID-19, plasma levels of the adipokine resistin were strongly associated with the development of AKI, and correlated with circulating inflammatory markers IL6 and MCP1. We did not detect a mediation effect of the obesity-AKI association by plasma resistin but had limited sample size to adequately power this analysis.
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Rationale: We aim to describe the clinical characteristics and outcomes of patients who received Tocilizumab for COVID-19 pneumonia at our institution between March 20 and October 26, 2020. Methods: In this single center, retrospective, observational study, we identified 55 adults admitted with COVID-19 pneumonia who received Tocilizumab. Demographic data, symptoms, laboratory values, treatments, and clinical outcomes were collected. Data was compared between those who received Tocilizumab and all patients admitted with COVID-19. Primary outcome was 28-day mortality. Secondary outcomes included role of concomitant steroid use and change in eosinophil counts, ferritin, AST, CRP and D-Dimer values. Results: Of the 589 patients admitted with COVID-19 pneumonia, 55 received Tocilizumab as part of their treatment course. Patient demographics of those who received Tocilizumab include a mean age of 58 years with 73% male, 51% with diabetes, and 58% with hypertension. 4/55 (7.3%) were immunocompromised. Common presenting symptoms on admission were fever (62%), cough (78%) and dyspnea (89%). 35/55 (64%) were admitted to the ICU during their hospitalization;their mean P/F ratio was 127. Tocilizumab was administered on average admission day 4 (1-19). A second dose was given to 17 (31%) of patients, with 11 given the following day. Average hospital length of stay (LOS) postadministration was 17 days. Average white blood cell (WBC) count on day of Tocilizumab administration was 11, with an absolute lymphocyte count of 0.96. Mean IL-6 on hospital admission was 48.3. Two days post Tocilizumab administration there was a peak in ferritin, percent eosinophils, and AST. Both two-and five-day post-Tocilizumab CRP levels decreased while D-Dimer increased (Table 1). All Tocilizumab patients received antibiotics. In addition, three received hydroxychloroquine, 16 Remdesivir, and 51 convalescent plasma. 31 (56%) received steroids. On Day 2, those who did not receive steroids had, on average, more than double the percent of eosinophils in their blood (3.21% vs 1.53%). This difference decreased by Day 5. In time period of interest, COVID-19 admission mortality was 63/589 (10.6%) and 40/77 (52%) for mechanically ventilated patients. For Tocilizumab recipients, 25/55 patients were mechanically ventilated and 12/25 (48%) died. Overall, 28-day mortality was 11/55 (20%), with hospital mortality up to 16/55 (29%). This was similar to our larger cohort ICU mortality of 29.3%. Conclusion: Tocilizumab recipients in our cohort had a mortality similar to overall COVID ICU mortality. It appeared to be well tolerated except for an increase in eosinophilia if with no concomitant steroid use.
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Rationale: To utilize high-dimensional proteomic data to identify dysregulated pathways that are associated with COVID-19 disease severity and suggest potential therapeutic targets. Methods: We enrolled 161 COVID-19 inpatients admitted at two tertiary care hospitals. Plasma samples collected within 48 hours of admission were analyzed with the Olink Proximity Extension Assay;713 unique proteins were assayed. The WHO COVID-19 ordinal severity scale at enrollment was dichotomized into moderate (levels 3-4) and severe (levels 5-7). Normalized protein expression (NPX) values were generated in relation to a common pooled control plasma on each plate. The association between NPX values and disease severity on admission was estimated with logistic regression (LR) after adjustment for age, sex, race, and select comorbidities. Ingenuity Pathway Analysis (IPA) was employed after application of the Benjamini-Hochberg procedure with a false discovery rate of 5% to all proteins for which the NPX difference was +/-0.8 between groups. Predictive models of disease severity on hospital day 7 using all proteins as potential features were fit using elastic net LR (ENLR) and gradient boosting (GBM). Performance was estimated on a held-out test set (40% of the data) with area under the receiveroperator characteristic curve (AUROC). Results: Of 161 subjects, 85 (53%) were classified as having severe COVID-19. A total of 552 proteins were differentially expressed (Figure 1), and 31 of these proteins met criteria for inclusion in pathway analysis. IPA identified the triggering receptor expressed on myeloid cells 1 (TREM-1) signaling pathway (4 members, p=3.8E-3), the tumor microenvironment (TME) pathway (5 members, p=4.1E-3), and the interleukin 17 (IL-17) signaling pathway (4 members, p=1.8E-2). Interleukin 1 receptor-like 1, a member of the TREM-1 pathway, was the protein most associated with disease severity (OR=3.18, p=1.82E-08). Tumor necrosis factor ligand superfamily member 11 (TNFSF11), a member of the IL-17 signaling pathway was the only factor whose enrichment was associated with less severe disease (OR=0.39, p=2.3E-05). ENLR and GBM predicted disease severity on day 7 with AUROC values of 0.908 (0.828, 0.968) and 0.882 (0.788, 0.957), respectively. Conclusion: We identified pathways differentially expressed between patients with severe and nonsevere COVID-19 associated with immune function and angiogenesis. Several agents currently being investigated to treat severe COVID-19 act on these dysregulated pathways, and future investigations could test whether these proteins act as enrichment markers or response indicators. Integrating protein expression with cellular immune phenotype may help explain COVID-19 pathophysiology.