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  • 1
    In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 11 ( 2022-1-24)
    Kurzfassung: To develop and validate a prognostic model for in-hospital mortality after four days based on age, fever at admission and five haematological parameters routinely measured in hospitalized Covid-19 patients during the first four days after admission. Methods Haematological parameters measured during the first 4 days after admission were subjected to a linear mixed model to obtain patient-specific intercepts and slopes for each parameter. A prediction model was built using logistic regression with variable selection and shrinkage factor estimation supported by bootstrapping. Model development was based on 481 survivors and 97 non-survivors, hospitalized before the occurrence of mutations. Internal validation was done by 10-fold cross-validation. The model was temporally-externally validated in 299 survivors and 42 non-survivors hospitalized when the Alpha variant (B.1.1.7) was prevalent. Results The final model included age, fever on admission as well as the slope or intercept of lactate dehydrogenase, platelet count, C-reactive protein, and creatinine. Tenfold cross validation resulted in a mean area under the receiver operating characteristic curve (AUROC) of 0.92, a mean calibration slope of 1.0023 and a Brier score of 0.076. At temporal-external validation, application of the previously developed model showed an AUROC of 0.88, a calibration slope of 0.95 and a Brier score of 0.073. Regarding the relative importance of the variables, the (apparent) variation in mortality explained by the six variables deduced from the haematological parameters measured during the first four days is higher (explained variation 0.295) than that of age (0.210). Conclusions The presented model requires only variables routinely acquired in hospitals, which allows immediate and wide-spread use as a decision support for earlier discharge of low-risk patients to reduce the burden on the health care system. Clinical Trial Registration Austrian Coronavirus Adaptive Clinical Trial (ACOVACT); ClinicalTrials.gov, identifier NCT04351724.
    Materialart: Online-Ressource
    ISSN: 2235-2988
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2022
    ZDB Id: 2619676-1
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 12 ( 2021-6-18)
    Kurzfassung: Male sex is related to increased COVID-19 severity and fatality although confirmed infections are similarly distributed between men and women. The aim of this retrospective analysis was to investigate the impact of sex hormones on disease progression and immune activation in men with COVID-19. Patients and Methods We studied for effects of sex hormones on disease severity and immune activation in 377 patients (230 men, 147 women) with PCR-confirmed SARS-CoV-2 infections hospitalized at the Innsbruck University Hospital between February and December 2020. Results Men had more severe COVID-19 with concomitant higher immune system activation upon hospital admission when compared to women. Men with a severe course of infection had lower serum total testosterone (tT) levels whereas luteinizing hormone (LH) and estradiol (E 2 ) levels were within the normal range. tT deficiency was associated with elevated CRP (rs = - 0.567, p & lt; 0.001), IL-6 levels (rs = - 0.563, p & lt; 0.001), lower cholesterol levels (rs = 0.407, p & lt; 0.001) and an increased morbidity and mortality. Men with tT levels & lt; 100 ng/dL had a more than eighteen-fold higher in-hospital mortality risk (OR 18.243 [95%CI 2.301 – 144.639], p = 0.006) compared to men with tT levels & gt; 230 ng/dL. Moreover, while morbidity and mortality showed a positive correlation with E 2 levels at admission, we detected a negative correlation with the tT/E 2 ratio upon hospital admission. Conclusion Hospitalized men with COVID-19 present with rather low testosterone levels linked to more advanced immune activation, severe clinical manifestations translating into an increased risk for ICU admission or death. The underlying mechanisms remain elusive but may include infection driven hypogonadism as well as inflammation mediated cholesterol reduction causing gonadotropin suppression and impaired androgen formation. Finally, in elderly late onset hypogonadism might also contribute to lower testosterone levels.
    Materialart: Online-Ressource
    ISSN: 1664-2392
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2021
    ZDB Id: 2592084-4
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    Online-Ressource
    Online-Ressource
    Frontiers Media SA ; 2019
    In:  Frontiers in Forests and Global Change Vol. 2 ( 2019-12-17)
    In: Frontiers in Forests and Global Change, Frontiers Media SA, Vol. 2 ( 2019-12-17)
    Materialart: Online-Ressource
    ISSN: 2624-893X
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2019
    ZDB Id: 2968523-0
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-6-14)
    Kurzfassung: T cells play a fundamental role in the early control and clearance of many viral infections of the respiratory system. In SARS-CoV-2-infected individuals, lymphopenia with drastically reduced CD4 + and CD8 + T cells correlates with Coronavirus disease 2019 (COVID-19)-associated disease severity and mortality. In this study, we characterized cellular and humoral immune responses induced in patients with mild, severe and critical COVID-19. Peripheral blood mononuclear cells of 37 patients with mild, severe and critical COVID-19 and 10 healthy individuals were analyzed by IFNγ ELISpot and multi-color flow cytometry upon stimulation with peptide pools covering complete immunodominant SARS-CoV-2 matrix, nucleocapsid and spike proteins. In addition SARS-CoV-2 antibody levels, neutralization abilities and anaphylatoxin levels were evaluated by various commercially available ELISA platforms. Our data clearly demonstrates a significantly stronger induction of SARS-CoV-2 specific CD8 + T lymphocytes and higher IFNγ production in patients with mild compared to patients with severe or critical COVID-19. In all patients SARS-CoV-2-specific antibodies with similar neutralizing activity were detected, but highest titers of total IgGs were observed in critical patients. Finally, elevated anaphylatoxin C3a and C5a levels were identified in severe and critical COVID-19 patients probably caused by aberrant immune complex formation due to elevated antibody titers in these patients. Crucially, we provide a full picture of cellular and humoral immune responses of COVID-19 patients and prove that robust polyfunctional CD8 + T cell responses concomitant with low anaphylatoxin levels correlate with mild infections. In addition, our data indicates that high SARS-CoV-2 antibody titers are associated with severe disease progression.
    Materialart: Online-Ressource
    ISSN: 1664-3224
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2021
    ZDB Id: 2606827-8
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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