scholarly journals Complement Overactivation and Consumption Predicts In-Hospital Mortality in SARS-CoV-2 Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
György Sinkovits ◽  
Blanka Mező ◽  
Marienn Réti ◽  
Veronika Müller ◽  
Zsolt Iványi ◽  
...  

ObjectivesUncontrolled thromboinflammation plays an important role in the pathogenesis of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus. Complement was implicated as key contributor to this process, therefore we hypothesized that markers of the complement profile, indicative for the activation state of the system, may be related to the severity and mortality of COVID-19.MethodsIn this prospective cohort study samples of 102 hospitalized and 26 outpatients with PCR-confirmed COVID-19 were analyzed. Primary outcome was in-hospital, COVID-19 related mortality, and secondary outcome was COVID-19 severity as assessed by the WHO ordinal scale. Complement activity of alternative and classical pathways, its factors, regulators, and activation products were measured by hemolytic titration, turbidimetry, or enzyme-immunoassays. Clinical covariates and markers of inflammation were extracted from hospital records.ResultsIncreased complement activation was characteristic for hospitalized COVID-19 patients. Complement activation was significantly associated with markers of inflammation, such as interleukin-6, C-reactive protein, and ferritin. Twenty-five patients died during hospital stay due to COVID-19 related illness. Patients with uncontrolled complement activation leading to consumption of C3 and decrease of complement activity were more likely to die, than those who had complement activation without consumption. Cox models identified anaphylatoxin C3a, and C3 overactivation and consumption (ratio of C3a/C3) as predictors of in-hospital mortality [HR of 3.63 (1.55–8.45, 95% CI) and 6.1 (2.1–17.8), respectively].ConclusionIncreased complement activation is associated with advanced disease severity of COVID-19. Patients with SARS-CoV-2 infection are more likely to die when the disease is accompanied by overactivation and consumption of C3. These results may provide observational evidence and further support to studies on complement inhibitory drugs for the treatment of COVID-19.

Author(s):  
Yusuke Katayama ◽  
Tetsuhisa Kitamura ◽  
Kosuke Kiyohara ◽  
Kenichiro Ishida ◽  
Tomoya Hirose ◽  
...  

Abstract Purpose The aim of this study was to assess the effect of fluid administration by emergency life-saving technicians (ELST) on the prognosis of traffic accident patients by using a propensity score (PS)-matching method. Methods The study included traffic accident patients registered in the JTDB database from January 2016 to December 2017. The main outcome was hospital mortality, and the secondary outcome was cardiopulmonary arrest on hospital arrival (CPAOA). To reduce potential confounding effects in the comparisons between two groups, we estimated a propensity score (PS) by fitting a logistic regression model that was adjusted for 17 variables before the implementation of fluid administration by ELST at the scene. Results During the study period, 10,908 traffic accident patients were registered in the JTDB database, and we included 3502 patients in this study. Of these patients, 142 were administered fluid by ELST and 3360 were not administered fluid by ELST. After PS matching, 141 patients were selected from each group. In the PS-matched model, fluid administration by ELST at the scene was not associated with discharge to death (crude OR: 0.859 [95% CI, 0.500–1.475]; p = 0.582). However, the fluid group showed statistically better outcome for CPAOA than the no fluid group in the multiple logistic regression model (adjusted OR: 0.231 [95% CI, 0.055–0.967]; p = 0.045). Conclusion In this study, fluid administration to traffic accident patients by ELST was associated not with hospital mortality but with a lower proportion of CPAOA.


2021 ◽  
Author(s):  
Laura C Blomaard ◽  
Carolien M J van der Linden ◽  
Jessica M van der Bol ◽  
Steffy W M Jansen ◽  
Harmke A Polinder-Bos ◽  
...  

Abstract Background During the first wave of the coronavirus disease 2019 (COVID-19) pandemic, older patients had an increased risk of hospitalisation and death. Reports on the association of frailty with poor outcome have been conflicting. Objective The aim of the present study was to investigate the independent association between frailty and in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands. Methods This was a multicentre retrospective cohort study in 15 hospitals in the Netherlands, including all patients aged ≥70 years, who were hospitalised with clinically confirmed COVID-19 between February and May 2020. Data were collected on demographics, co-morbidity, disease severity and Clinical Frailty Scale (CFS). Primary outcome was in-hospital mortality. Results A total of 1,376 patients were included (median age 78 years (interquartile range 74–84), 60% male). In total, 499 (38%) patients died during hospital admission. Parameters indicating presence of frailty (CFS 6–9) were associated with more co-morbidities, shorter symptom duration upon presentation (median 4 versus 7 days), lower oxygen demand and lower levels of C-reactive protein. In multivariable analyses, the CFS was independently associated with in-hospital mortality: compared with patients with CFS 1–3, patients with CFS 4–5 had a two times higher risk (odds ratio (OR) 2.0 (95% confidence interval (CI) 1.3–3.0)) and patients with CFS 6–9 had a three times higher risk of in-hospital mortality (OR 2.8 (95% CI 1.8–4.3)). Conclusions The in-hospital mortality of older hospitalised COVID-19 patients in the Netherlands was 38%. Frailty was independently associated with higher in-hospital mortality, even though COVID-19 patients with frailty presented earlier to the hospital with less severe symptoms.


2011 ◽  
Vol 10 (2) ◽  
pp. 207
Author(s):  
Hemelrijck M.J.J. Van ◽  
I. Jugner ◽  
G. Walldius ◽  
H. Garmo ◽  
E. Binda ◽  
...  

2017 ◽  
Vol 199 (1) ◽  
pp. 292-303 ◽  
Author(s):  
Ádám I. Csincsi ◽  
Zsóka Szabó ◽  
Zsófia Bánlaki ◽  
Barbara Uzonyi ◽  
Marcell Cserhalmi ◽  
...  

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Makrouhi Sonikian ◽  
Aggeliki Barbatsi ◽  
Eugenia Karakou ◽  
Theodoros Chiras ◽  
Jacob Skarakis ◽  
...  

Abstract Introduction C-reactive protein (CRP) and procalcitonin (PCT) are widely used as markers of inflammation and infection in general population and in chronic hemodialysis (HD) as well. However, in dialysis (D) patients, serum CRP and PCT levels may be elevated even in the absence of inflammatory or infectious disease and diagnostic process is a challenge in such cases. We studied HD patients' laboratory profile concerning CRP and PCT. Subjects and Methods We studied 25 stable HD patients, M/F=22/3, aged 68(44-89) years, dialyzed thrice weekly for 55(6-274) months with a dialysate flow rate of 700 ml/min, with a residual daily diuresis less than 200 ml, Kt/V values of 1,44±0,3 and no signs of infection. Patients were classified in two groups. Group A included 10 patients on pre-dilution online hemodiafiltration (HDF). Group B consisted of 15 patients on conventional HD with low-flux polysulfone membrane. Twenty healthy subjects formed a control group C. Serum CRP and PCT levels were measured in duplicate in A and B groups before and at the end of mid-week dialysis sessions and also in C group. Results Pre-D serum CRP values in the total of patients were higher than those in healthy controls (10,89±19,29 vs 2,54±1,28 mg/L-p=0,004). Compared with group C, pre-D CRP values were higher only in B group (15,98±24,54 mg/L-p=0,001) but not in A group (4,09±3,33 mg/L-p=NS). There was a significant difference in pre-D serum CRP values between A and B groups (p=0,028). At the end of D session serum CRP values showed a tendency to increase in both groups A (5,16±4,81 mg/L) and B (17,00±27,00 mg/L) but differences were not significant. Pre-D serum PCT values in the total of patients were higher than those in healthy controls (0,82±0,9 vs 0,29±0,55 ng/ml-p<0,001). Compared with group C, pre-D PCT values were higher in both A group (0,52±0,15 ng/ml-p<0,001) and B group (1,01±1,13 ng/ml-p=0,006). There was no significant difference in pre-D serum PCT values between A and B groups (p=0,261). At the end of D session serum PCT values decreased in A group (0,32±0,11 ng/ml-p<0,001) and increased in B group (1,12±1,21 ng/ml-p=0,014). Conclusions In patients on both conventional low-flux HD and online HDF pre-D serum CRP and PCT levels were higher than those in healthy subjects. Dialysis modality and membrane flux did not affect post-D serum CRP values, but post-PCT values decreased in online HDF. PCT usefulness might be limited in dialysis with high-flux membranes. Cut-off values have to be established for both markers to eliminate confusion in diagnosis of inflammatory and infectious diseases in hemodialyzed patients.


Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Ahmed M Maraey ◽  
Ahmed Elzanaty ◽  
Hadeer R Elsharnoby ◽  
Mahmoud Salem ◽  
Mahmoud Khalil ◽  
...  

Background: Type 2 Myocardial infarction (T2MI) can occur in hypertensive crisis patients. The impact of T2MI in this population is poorly understood due to limited available data. Objective: To assess the impact of T2MI on patients admitted to the hospital with hypertensive crisis. Methods: We queried National Readmission Database (NRD) of year 2018 for adult patients admitted with a primary diagnosis of hypertensive crisis. Patients were excluded if they had type 1 myocardial infarction (T1MI), septic shock, or bleeding in the index admission. Primary outcome was 90-day readmission due to T1MI. Secondary outcome was in-hospital mortality. Subgroup analysis was done according to urgency and emergency presentation. Multivariate regression was done to account for confounders. Results: A total of 101211 patients were included in our cohort of whom 3644 (3.6%) were diagnosed with T2MI and 24471 (24.2%) were readmitted within 90 days of discharge. Of those, 912 (3.7%) were diagnosed with T1MI on readmission. T2MI was independently associated with increased odds of 90-day readmission with T1MI (Adjusted odds ratio (aOR): 2.67, 95% CI [1.91-3.75], P=0.000). T2MI effect was observed in hypertensive urgency, and in hypertensive emergency. T2MI was associated with increased in-hospital mortality in hypertensive urgency population (aOR: 4.21, 95% [1.58-11.25], P=0.004) but not in hypertensive emergency (table 1). Conclusion: In hypertensive crisis patients, T2MI was associated with increased 90-day readmission with T1MI. Aggressive management of cardiovascular risk factors and risk stratification should be considered at the time of diagnosis.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Hagen Schmal ◽  
Gian M. Salzmann ◽  
Philipp Niemeyer ◽  
Elia Langenmair ◽  
Renfeng Guo ◽  
...  

Cytokine regulation possibly influences long term outcome following ankle fractures, but little is known about synovial fracture biochemistry. Eight patients with an ankle dislocation fracture were included in a prospective case series and matched with patients suffering from grade 2 osteochondritis dissecans (OCD) of the ankle. All fractures needed external fixation during which joint effusions were collected. Fluid analysis was done by ELISA measuring aggrecan, bFGF, IL-1β, IGF-1, and the complement components C3a, C5a, and C5b-9. The time periods between occurrence of fracture and collection of effusion were only significantly associated with synovial aggrecan and C5b-9 levels (P<0.001). Furthermore, synovial expressions of both proteins correlated with each other (P<0.001). Although IL-1βexpression was relatively low, intra-articular levels correlated with C5a (P<0.01) and serological C-reactive protein concentrations 2 days after surgery (P<0.05). Joint effusions were initially dominated by neutrophils, but the portion of monocytes constantly increased reaching 50% at day 6 after fracture (P<0.02). Whereas aggrecan and IL-1βconcentrations were not different in fracture and OCD patients, bFGF, IGF-1, and all complement components were significantly higher concentrated in ankle joints with fractures (P<0.01). Complement activation and inflammatory cell infiltration characterize the joint biology following acute ankle fractures.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yanfei Shen ◽  
Dechang Chen ◽  
Xinmei Huang ◽  
Guolong Cai ◽  
Qianghong Xu ◽  
...  

Abstract Background Coronavirus disease has heterogeneous clinical features; however, the reasons for the heterogeneity are poorly understood. This study aimed to identify clinical phenotypes according to patients’ temperature trajectory. Method A retrospective review was conducted in five tertiary hospitals in Hubei Province from November 2019 to March 2020. We explored potential temperature-based trajectory phenotypes and assessed patients’ clinical outcomes, inflammatory response, and response to immunotherapy according to phenotypes. Results A total of 1580 patients were included. Four temperature-based trajectory phenotypes were identified: normothermic (Phenotype 1); fever, rapid defervescence (Phenotype 2); gradual fever onset (Phenotype 3); and fever, slow defervescence (Phenotype 4). Compared with Phenotypes 1 and 2, Phenotypes 3 and 4 had a significantly higher C-reactive protein level and neutrophil count and a significantly lower lymphocyte count. After adjusting for confounders, Phenotypes 3 and 4 had higher in-hospital mortality (adjusted odds ratio and 95% confidence interval 2.1, 1.1–4.0; and 3.3, 1.4–8.2, respectively), while Phenotype 2 had similar mortality, compared with Phenotype 1. Corticosteroid use was associated with significantly higher in-hospital mortality in Phenotypes 1 and 2, but not in Phenotypes 3 or 4 (p for interaction < 0.01). A similar trend was observed for gamma-globulin. Conclusions Patients with different temperature-trajectory phenotypes had different inflammatory responses, clinical outcomes, and responses to corticosteroid therapy.


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