LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 7 of total 7

Search options

  1. Article ; Online: Increase in the Complement Activation Product C4d and the Terminal Complement Complex sC5b-9 Is Associated with Disease Severity and a Fatal Outcome in Necrotizing Soft-Tissue Infection

    Morten Hedetoft / Martin Bruun Madsen / Cecilie Bo Hansen / Ole Hyldegaard / Peter Garred

    Journal of Innate Immunity, Pp 1-

    2021  Volume 11

    Abstract: The hyperinflammatory burden is immense in necrotizing soft-tissue infection (NSTI). The complement system is a key during the innate immune response and may be a promising target to reduce the inflammatory response, potentially improving the clinical ... ...

    Abstract The hyperinflammatory burden is immense in necrotizing soft-tissue infection (NSTI). The complement system is a key during the innate immune response and may be a promising target to reduce the inflammatory response, potentially improving the clinical outcome. However, complement activation and its association to disease severity and survival remain unknown in NSTI. Therefore, we prospectively enrolled patients with NSTI and sampled blood at admission and once daily for the following 3 days. Plasma C4c, C4d, C3bc, and C3dg and the terminal complement complex (TCC) were evaluated using ELISA techniques. In total, 242 patients were included with a median age of 62 years, with a 60% male predominance. All-cause 30-day mortality was 17% (95% confidence interval [CI] 13–23) with a follow-up of >98%. C4c and C3dg were negatively correlated with Simplified Acute Physiology Score II (Rho −0.22, p < 0.001 and Rho −0.17, p = 0.01). Patients with septic shock (n = 114, 47%) had higher levels of baseline TCC than those in non-shock patients (18 vs. 14, p < 0.001). TCC correlated with the Sequential Organ Failure Assessment (SOFA) score (Rho 0.19, p = 0.004). In multivariate Cox regression analysis (adjusted for age, sex, comorbidity, and SOFA score), high baseline C4d (>20 ng/mL) and the combination of high C4d and TCC (>31 arbitrary units/mL) were associated with increased 30-day mortality (hazard ratio [HR] 3.26, 95% CI 1.56–6.81 and HR 5.12, 95% CI 2.15–12.23, respectively). High levels of both C4d and TCC demonstrated a negative predictive value of 0.87. In conclusion, we found that in patients with NSTI, complement activation correlated with the severity of the disease. High baseline C4d and combination of high C4d and TCC are associated with increased 30-day mortality. Low baseline C4d or TCC indicates a higher probability of survival.
    Keywords necrotizing soft-tissue infection ; complement ; c4d ; terminal complement complex ; sepsis ; Medicine ; R ; Internal medicine ; RC31-1245
    Subject code 616
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher Karger Publishers
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  2. Article ; Online: Prediction of Respiratory Failure and Mortality in COVID-19 Patients Using Long Pentraxin PTX3

    Cecilie Bo Hansen / Håkon Sandholdt / Maria Elizabeth Engel Møller / Laura Pérez-Alós / Lise Pedersen / Simone Bastrup Israelsen / Peter Garred / Thomas Benfield

    Journal of Innate Immunity, Pp 1-

    2022  Volume 9

    Abstract: The course of COVID-19 is unpredictable, ranging from asymptomatic to respiratory failure and death. Prognostic biomarkers are urgently needed. We hypothesized that long pentraxin PTX3 could be a valuable plasma biomarker due to its essential role in ... ...

    Abstract The course of COVID-19 is unpredictable, ranging from asymptomatic to respiratory failure and death. Prognostic biomarkers are urgently needed. We hypothesized that long pentraxin PTX3 could be a valuable plasma biomarker due to its essential role in inflammatory processes. In a prospective hospitalized COVID-19 derivation cohort (n = 126) during the spring of 2020, we measured PTX3 within 4 days of admission. The predictive value of mechanical ventilation (MV) and 30-day mortality compared with clinical parameters and other markers of inflammation were assessed by logistic regression analysis and expressed as odds ratio (OR) with 95% confidence interval (CI). Analyses were repeated in a prospective validation cohort (n = 112) of hospitalized patients with COVID-19 treated with remdesivir and dexamethasone. Thirty-day mortality in the derivation cohort was 26.2%. In patients who died, the median PTX3 concentration upon admission was 19.5 ng/mL (IQR: 12.5–33.3) versus 6.6 ng/mL (IQR 2.9–12.3) (p < 0.0001) for survivors. After adjustment for covariates, the odds of 30-day mortality increased two-fold for each doubling of PTX3 (OR 2.03 [95% CI: 1.23–3.34], p = 0.006), which was also observed in the validation cohort (OR 1.70 [95% CI: 1.09–2.67], p = 0.02). Similarly, PTX3 levels were associated with MV. After adjustment for covariates, OR of MV was 2.34 (95% CI: 1.33–4.12, p = 0.003) in the derivation cohort and 1.64 (95% CI: 1.03–2.62, p = 0.04) in the validation cohort. PTX3 appears to be a useful clinical biomarker to predict 30-day respiratory failure and mortality risk in COVID-19 patients treated with and without remdesivir and dexamethasone.
    Keywords long pentraxin-3 ; ptx3 ; covid-19 ; inflammation ; critical illness ; Medicine ; R ; Internal medicine ; RC31-1245
    Subject code 310
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Karger Publishers
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  3. Article ; Online: Lectin Pathway Enzyme MASP-2 and Downstream Complement Activation in COVID-19

    Maximilian Peter Götz / Mikkel-Ole Skjoedt / Rafael Bayarri-Olmos / Cecilie Bo Hansen / Laura Pérez-Alós / Ida Jarlhelt / Thomas Benfield / Anne Rosbjerg / Peter Garred

    Journal of Innate Immunity, Pp 1-

    2022  Volume 14

    Abstract: Mannose-binding lectin-associated serine protease 2 (MASP-2) is the main activator of the lectin complement pathway and has been suggested to be involved in the pathophysiology of coronavirus disease 2019 (COVID-19). To study a possible association ... ...

    Abstract Mannose-binding lectin-associated serine protease 2 (MASP-2) is the main activator of the lectin complement pathway and has been suggested to be involved in the pathophysiology of coronavirus disease 2019 (COVID-19). To study a possible association between MASP-2 and COVID-19, we aimed at developing a sensitive and reliable MASP-2 ELISA. From an array of novel mouse-monoclonal antibodies using recombinant MASP-2 as antigen, two clones were selected to create a sandwich ELISA. Plasma samples were obtained from 216 healthy controls, 347 convalescent COVID-19 patients, and 147 prospectively followed COVID-19 patients. The assay was specific towards MASP-2 and did not recognize the truncated MASP2 splice variant MAP-2 (MAp19). The limit of quantification was shown to be 0.1 ng/mL. MASP-2 concentration was found to be stable after multiple freeze-thaw cycles. In healthy controls, the mean MASP-2 concentration was 524 ng/mL (95% CI: 496.5–551.6). No significant difference was found in the MASP-2 concentrations between COVID-19 convalescent samples and controls. However, a significant increase was observed in prospectively followed COVID-19 patients (mean: 834 ng/mL [95% CI: 765.3–902.7, p < 0.0001]). In these patients, MASP-2 concentration correlated significantly with the concentrations of the terminal complement complex (ρ = 0.3596, p < 0.0001), with the lectin pathway pattern recognition molecules ficolin-2 (ρ = 0.2906, p = 0.0004) and ficolin-3 (ρ = 0.3952, p < 0.0001) and with C-reactive protein (ρ = 0.3292, p = 0.0002). Overall, we developed a specific quantitative MASP-2 sandwich ELISA. MASP-2 correlated with complement activation and inflammatory markers in COVID-19 patients, underscoring a possible role of MASP-2 in COVID-19 pathophysiology.
    Keywords mannose-binding lectin-associated serine protease 2 ; masp-2 ; assay ; covid-19 ; inflammation ; outcome ; Medicine ; R ; Internal medicine ; RC31-1245
    Subject code 616
    Language English
    Publishing date 2022-07-01T00:00:00Z
    Publisher Karger Publishers
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  4. Article ; Online: Humoral and cellular immune responses eleven months after the third dose of BNT162b2 an mRNA-based COVID-19 vaccine in people with HIV – a prospective observational cohort studyResearch in context

    Line Dam Heftdal / Laura Pérez-Alós / Rasmus Bo Hasselbalch / Cecilie Bo Hansen / Sebastian Rask Hamm / Dina Leth Møller / Mia Pries-Heje / Kamille Fogh / Jan Gerstoft / Kirsten Grønbæk / Sisse Rye Ostrowski / Ruth Frikke-Schmidt / Erik Sørensen / Linda Hilsted / Henning Bundgaard / Peter Garred / Kasper Iversen / Caroline Sabin / Susanne Dam Nielsen

    EBioMedicine, Vol 93, Iss , Pp 104661- (2023)

    2023  

    Abstract: Summary: Background: We investigated long-term durability of humoral and cellular immune responses to third dose of BNT162b2 in people with HIV (PWH) and controls. Methods: In 378 PWH with undetectable viral replication and 224 matched controls ... ...

    Abstract Summary: Background: We investigated long-term durability of humoral and cellular immune responses to third dose of BNT162b2 in people with HIV (PWH) and controls. Methods: In 378 PWH with undetectable viral replication and 224 matched controls vaccinated with three doses of BNT162b2, we measured IgG-antibodies against the receptor binding domain of SARS-CoV-2 spike protein three months before third dose of BNT162b2, and four and eleven months after. In 178 PWH and 135 controls, the cellular response was assessed by interferon-γ (IFN-γ) release in whole blood four months after third dose. Differences in antibody or IFN-γ concentrations were assessed by uni- and multivariable linear regressions. Findings: Before the third dose the concentration of SARS-CoV-2 antibodies was lower in PWH than in controls (unadjusted geometric mean ratio (GMR): 0.68 (95% CI: 0.54–0.86, p = 0.002). We observed no differences in antibody concentrations between PWH and controls after four (0.90 (95% CI: 0.75–1.09), p = 0.285) or eleven months (0.89 (95% CI: 0.69–1.14), p = 0.346) after the third dose. We found no difference in IFN-γ concentrations four months after the third dose between PWH and controls (1.06 (95% CI: 0.71–1.60), p = 0.767). Interpretation: We found no differences in antibody concentrations or cellular response between PWH and controls up to eleven months after third dose of BNT162b2. Our findings indicate that PWH with undetectable viral replication and controls have comparable immune responses to three doses of the BNT162b2 vaccine. Funding: This work was funded by the Novo Nordisk Foundation (NFF205A0063505, NNF20SA0064201), the Carlsberg Foundation (CF20-476 0045), the Svend Andersen Research Foundation (SARF2021), and Bio- and Genome Bank Denmark.
    Keywords BNT162b2 ; HIV ; SARS-CoV-2 ; Immune response ; Booster dose ; Medicine ; R ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2023-07-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  5. Article ; Online: The alpha/B.1.1.7 SARS-CoV-2 variant exhibits significantly higher affinity for ACE-2 and requires lower inoculation doses to cause disease in K18-hACE2 mice

    Rafael Bayarri-Olmos / Laust Bruun Johnsen / Manja Idorn / Line S Reinert / Anne Rosbjerg / Søren Vang / Cecilie Bo Hansen / Charlotte Helgstrand / Jais Rose Bjelke / Theresa Bak-Thomsen / Søren R Paludan / Peter Garred / Mikkel-Ole Skjoedt

    eLife, Vol

    2021  Volume 10

    Abstract: The alpha/B.1.1.7 SARS-CoV-2 lineage emerged in autumn 2020 in the United Kingdom and transmitted rapidly until winter 2021 when it was responsible for most new COVID-19 cases in many European countries. The incidence domination was likely due to a ... ...

    Abstract The alpha/B.1.1.7 SARS-CoV-2 lineage emerged in autumn 2020 in the United Kingdom and transmitted rapidly until winter 2021 when it was responsible for most new COVID-19 cases in many European countries. The incidence domination was likely due to a fitness advantage that could be driven by the receptor-binding domain (RBD) residue change (N501Y), which also emerged independently in other variants of concern such as the beta/B.1.351 and gamma/P.1 strains. Here, we present a functional characterization of the alpha/B.1.1.7 variant and show an eightfold affinity increase towards human angiotensin-converting enzyme-2 (ACE-2). In accordance with this, transgenic hACE2 mice showed a faster disease progression and severity after infection with a low dose of B.1.1.7, compared to an early 2020 SARS-CoV-2 isolate. When challenged with sera from convalescent individuals or anti-RBD monoclonal antibodies, the N501Y variant showed a minor, but significant elevated evasion potential of ACE-2/RBD antibody neutralization. The data suggest that the single asparagine to tyrosine substitution remarkable rise in affinity may be responsible for the higher transmission rate and severity of the B.1.1.7 variant.
    Keywords immunology ; epidemiology ; SARS-CoV-2 ; mouse model ; human ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-11-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  6. Article ; Online: Modeling of waning immunity after SARS-CoV-2 vaccination and influencing factors

    Laura Pérez-Alós / Jose Juan Almagro Armenteros / Johannes Roth Madsen / Cecilie Bo Hansen / Ida Jarlhelt / Sebastian Rask Hamm / Line Dam Heftdal / Mia Marie Pries-Heje / Dina Leth Møller / Kamille Fogh / Rasmus Bo Hasselbalch / Anne Rosbjerg / Søren Brunak / Erik Sørensen / Margit Anita Hørup Larsen / Sisse Rye Ostrowski / Ruth Frikke-Schmidt / Rafael Bayarri-Olmos / Linda Maria Hilsted /
    Kasper Karmark Iversen / Henning Bundgaard / Susanne Dam Nielsen / Peter Garred

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 11

    Abstract: This study investigates the dynamics of immunological markers after first SARS-CoV-2 vaccination dose in cohort of healthcare professionals in Denmark. Natural infection was associated with higher antibody responses, and IgG decline varied by age, sex, T- ...

    Abstract This study investigates the dynamics of immunological markers after first SARS-CoV-2 vaccination dose in cohort of healthcare professionals in Denmark. Natural infection was associated with higher antibody responses, and IgG decline varied by age, sex, T-cell response, previous infection, and interval between vaccine doses.
    Keywords Science ; Q
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  7. Article ; Online: Antibody responses and risk factors associated with impaired immunological outcomes following two doses of BNT162b2 COVID-19 vaccination in patients with chronic pulmonary diseases

    Kasper Karmark Iversen / Pradeesh Sivapalan / Jens-Ulrik Stæhr Jensen / Tor Biering-Sørensen / Erik Sørensen / Henning Bundgaard / Rasmus Bo Hasselbalch / Peter Garred / Mia Marie Pries-Heje / Ruth Frikke-Schmidt / Torgny Wilcke / Helene Prieme / Birgitte Lindegaard / Sisse Rye Ostrowski / Zitta Barrella Harboe / Sebastian Rask Hamm / Laura Pérez-Alós / Peter Kjeldgaard / Saher Shaker /
    Alexander Svorre Jordan / Dina Leth Møller / Line Dam Heftdal / Johannes Roth Madsen / Rafael Bayarri-Olmos / Cecilie Bo Hansen / Kamille Fogh / Jose Juan Almagro Armenteros / Linda Hilsted / Andrea Browatzki / Susanne Dam Nielsen

    BMJ Open Respiratory Research, Vol 9, Iss

    2022  Volume 1

    Abstract: Introduction Responses to COVID-19 vaccination in patients with chronic pulmonary diseases are poorly characterised. We aimed to describe humoral responses following two doses of BNT162b2 mRNA COVID-19 vaccine and identify risk factors for impaired ... ...

    Abstract Introduction Responses to COVID-19 vaccination in patients with chronic pulmonary diseases are poorly characterised. We aimed to describe humoral responses following two doses of BNT162b2 mRNA COVID-19 vaccine and identify risk factors for impaired responses.Methods Prospective cohort study including adults with chronic pulmonary diseases and healthcare personnel as controls (1:1). Blood was sampled at inclusion, 3 weeks, 2 and 6 months after first vaccination. We reported antibody concentrations as geometric means with 95% CI of receptor binding domain (RBD)-IgG and neutralising antibody index of inhibition of ACE-2/RBD interaction (%). A low responder was defined as neutralising index in the lowest quartile (primary outcome) or RBD-IgG <225 AU/mL plus neutralising index <25% (secondary outcome), measured at 2 months. We tested associations using Poisson regression.Results We included 593 patients and 593 controls, 75% of all had neutralising index ≥97% at 2 months. For the primary outcome, 34.7% of patients (n=157/453) and 12.9% of controls (n=46/359) were low responders (p<0.0001). For the secondary outcome, 8.6% of patients (n=39/453) and 1.4% of controls (n=5/359) were low responders (p<0.001). Risk factors associated with low responder included increasing age (per decade, adjusted risk ratio (aRR) 1.17, 95% CI 1.03 to 1.32), Charlson Comorbidity Index (per point) (aRR 1.15, 95% CI 1.05 to 1.26), use of prednisolone (aRR 2.08, 95% CI 1.55 to 2.77) and other immunosuppressives (aRR 2.21, 95% CI 1.65 to 2.97).Discussion Patients with chronic pulmonary diseases established functional humoral responses to vaccination, however lower than controls. Age, comorbidities and immunosuppression were associated with poor immunological responses.
    Keywords Medicine ; R ; Diseases of the respiratory system ; RC705-779
    Subject code 610
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher BMJ Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top