Reduction of ADAMTS13 Levels Predicts Mortality in SARS-CoV-2 Patients.
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ABSTRACT:
SUBMITTER: Tiscia GL
PROVIDER: S-EPMC7456602 | biostudies-literature | 2020 Jul
REPOSITORIES: biostudies-literature
Publications
Reduction of ADAMTS13 Levels Predicts Mortality in SARS-CoV-2 Patients.
Tiscia Giovanni L GL Favuzzi Giovanni G De Laurenzo Antonio A Cappucci Filomena F Fischetti Lucia L di Mauro Lazzaro L Miscio Giuseppe G Mirijello Antonio A Chinni Elena E Grandone Elvira E
TH open : companion journal to thrombosis and haemostasis 20200701 3
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Project description:Background and aimsLow HDL-cholesterol (HDLc) concentration is associated with a greater risk of infection-related mortality. We wanted to evaluate the relationship between pre-infection HDLc levels and mortality among older patients infected with SARS-Cov-2.MethodsThis is a population-based, cohort study, comprising all individuals residing in Madrid (Spain) born before 1 January 1945, and alive on 31 December 2019. Demographic, clinical, and analytical data were obtained from the primary care electronic clinical records. Confirmed SARS-CoV-2 infection was defined as a positive result in the RT-qPCR or in the antigen test. A death from COVID-19 was defined as that registered in the hospital chart, or as any death occurring in the 15 days following a confirmed SARS-CoV-2 infection. Data on infection, hospitalization, or death due to SAR-CoV-2 were collected from 1 March 2020 through 31 December 2020.ResultsOf the 593,342 individuals comprising the cohort, 36,966 had a SARS-CoV-2 infection during 2020, and at least one HDLc measurement in the previous five years. Among them, 9689 (26.2%) died from COVID-19. After adjustment for age and sex, the relative risk (95% confidence interval) of COVID-19 death across increasing quintiles of HDLc was 1.000, 0.896 (0.855-0.940), 0.816 (0.776-0.860), 0.758 (0.719-0.799), and 0.747 (0.708-0.787). The association was maintained after further adjustment for comorbidities, statin treatment and markers of malnutrition. While in females this association was linear, in males it showed a U-shaped curve.ConclusionsIn older subjects, a higher HDLc measured before SARS-CoV-2 infection was associated with a lower risk of death.
| S-EPMC8692242 | biostudies-literature
Project description:IntroductionSevere COVID-19 is often compounded by a prothrombotic state that is associated with poor outcomes. In this investigation, we aimed to evaluate ADAMTS13 activity, von Willebrand factor level (VWF:Ag), and the corresponding ADAMTS13 activity/VWF:Ag ratio, in patients with COVID-19 and for associations with disease progression and acute kidney injury (AKI).MethodsPatients presenting to the emergency department (ED) with COVID-19 were enrolled in this prospective, observational study. ADAMTS13 activity and VWF:Ag were measured at index ED visit. The primary endpoint was severe AKI defined by KDIGO stage 2 + 3 criteria, while the secondary endpoint was peak 30-day COVID-19 severity.ResultsA total of 52 adult COVID-19 patients were enrolled. Overall, we observed that 23.1% of the cohort had a relative deficiency in ADAMTS13 activity, while 80.8% had elevated VWF:Ag. The ADAMTS13 activity/VWF:Ag ratio was significantly lower in patients with severe AKI (P = .002) and those who developed the severe form of COVID-19 (P = .020). The ADAMTS13 activity/VWF:Ag ratio was negatively correlated with age (P < .001) and LDH (P < .001), while positively correlated with hemoglobin (P = .041). After controlling for confounders, a one-unit increase in ADAMTS13/VWF:Ag ratio was associated with 20% decreased odds of severe AKI.ConclusionA low ADAMTS13 activity:VWF:Ag ratio at ED presentation is associated with progression to severe COVID-19 disease and severe AKI, with a pattern suggestive of a secondary microangiopathy. Further interventional studies should be conducted to assess the restoration of ADAMTS13:VWF:Ag ratio in hospitalized patients with COVID-19.
| S-EPMC7753610 | biostudies-literature
Project description:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began proliferating widely throughout the world in late 2019/early 2020, creating a global pandemic and health crisis. Although vaccines became available to the public approximately one year after the onset of the pandemic, there still remains much hesitancy surrounding vaccination even two years into the pandemic. One key concern comes from reports of breakthrough infections among the vaccinated that show comparable levels of peak viral load as the unvaccinated, calling into question the ability of vaccines to slow or prevent transmission. Therefore young, healthy individuals who are at low risk of serious complications themselves have little incentive to receive a vaccine that they are not convinced will protect others around them. To address this important concern, this article analyzes COVID-19 incidence in the United States as a function of each state's vaccination rate. Results show that states with higher percentages of fully vaccinated individuals report fewer new cases among the remaining unvaccinated population. These data add to accumulating evidence that COVID-19 vaccinations can indeed slow the spread of SARS-CoV-2, and are an important tool in society's arsenal to put this pandemic behind us.
| S-EPMC8609904 | biostudies-literature
Project description:The recent SarsCov2 pandemic has disrupted healthcare system notably impacting intensive care units (ICU). In severe cases, the immune system is dysregulated, associating signs of hyperinflammation and immunosuppression. In the present work, we investigated, using a joint modeling approach, whether the trajectories of cellular immunological parameters were associated with survival of COVID-19 ICU patients. This study is based on the REA-IMMUNO-COVID cohort including 538 COVID-19 patients admitted to ICU between March 2020 and May 2022. Measurements of monocyte HLA-DR expression (mHLA-DR), counts of neutrophils, of total lymphocytes, and of CD4+ and CD8+ subsets were performed five times during the first month after ICU admission. Univariate joint models combining survival at day 28 (D28), hospital discharge and longitudinal analysis of those biomarkers' kinetics with mixed-effects models were performed prior to the building of a multivariate joint model. We showed that a higher mHLA-DR value was associated with a lower risk of death. Predicted mHLA-DR nadir cutoff value that maximized the Youden index was 5414 Ab/C and led to an AUC = 0.70 confidence interval (95%CI) = [0.65; 0.75] regarding association with D28 mortality while dynamic predictions using mHLA-DR kinetics until D7, D12 and D20 showed AUCs of 0.82 [0.77; 0.87], 0.81 [0.75; 0.87] and 0.84 [0.75; 0.93]. Therefore, the final joint model provided adequate discrimination performances at D28 after collection of biomarker samples until D7, which improved as more samples were collected. After severe COVID-19, decreased mHLA-DR expression is associated with a greater risk of death at D28 independently of usual clinical confounders.
| S-EPMC11247117 | biostudies-literature
Project description:BackgroundVon Willebrand Factor (VWF) multimers are cleaved into smaller and less coagulant forms by the metalloprotease ADAMTS13. The aim of this study was to investigate the association between VWF and ADAMTS13 and mortality in dialysis patients.MethodsWe prospectively followed 956 dialysis patients. VWF levels and ADAMTS13 activity were measured. Cox proportional hazard analyses were used to calculate hazard ratios (HRs) with 95 % confidence intervals (CIs) to investigate the association between quartiles of VWF levels and ADAMTS13 activity and all-cause mortality. HRs were adjusted for age, sex, body mass index, cardiovascular disease, dialysis modality, primary kidney disease, use of antithrombotic medication, systolic blood pressure, albumin, C-reactive protein and residual GFR.ResultsOf the 956 dialysis patients, 288 dialysis patients died within three years (mortality rate 151 per 1000 person-years). The highest quartile of VWF as compared with lower levels of VWF was associated with a 1.4-fold (95 %CI 1.1-1.8) increased mortality risk after adjustment. The lowest quartile of ADAMTS13 activity as compared with other quartiles was associated with a 1.3-fold (95 %CI 1.0-1.7) increased mortality risk after adjustment. The combination of the highest VWF quartile and lowest ADAMTS13 quartile was associated with a 2.0-fold (95 %CI 1.3-3.0) increased mortality risk as compared with the combination of the lowest VWF quartile and highest ADAMTS13 quartile.ConclusionsHigh VWF levels and low ADAMTS13 activity were associated with increased mortality risks in dialysis patients.
| S-EPMC8207579 | biostudies-literature
Project description:Patients with cancer may be at increased risk of severe coronavirus disease 2019 (COVID-19), but the role of viral load on this risk is unknown. We measured SARS-CoV-2 viral load using cycle threshold (CT) values from reverse-transcription polymerase chain reaction assays applied to nasopharyngeal swab specimens in 100 patients with cancer and 2,914 without cancer who were admitted to three New York City hospitals. Overall, the in-hospital mortality rate was 38.8% among patients with a high viral load, 24.1% among patients with a medium viral load, and 15.3% among patients with a low viral load (p < 0.001). Similar findings were observed in patients with cancer (high, 45.2% mortality; medium, 28.0%; low, 12.1%; p = 0.008). Patients with hematologic malignancies had higher median viral loads (CT = 25.0) than patients without cancer (CT = 29.2; p = 0.0039). SARS-CoV-2 viral load results may offer vital prognostic information for patients with and without cancer who are hospitalized with COVID-19.
| S-EPMC7492074 | biostudies-literature
Project description: Not available
| S-BSST379 | biostudies-other
Project description:RNA vaccines elicit protective immunity against SARS-CoV-2, but the use of mRNA as antiviral immunotherapeutic is unexplored. Here, we investigate the activity of lipidoid nanoparticle (LNP)-formulated mRNA encoding human IFNλ1 (ETH47), which is a critical driver of innate immunity at mucosal surfaces protecting from viral infections. IFNλ1 mRNA administration promotes dose-dependent protein translation, induction of interferon-stimulated genes without relevant signs of unspecific immune stimulation, and dose-dependent inhibition of SARS-CoV-2 replication in vitro. Pulmonary administration of IFNλ1 mRNA in mice results in potent reduction of virus load, virus-induced body weight loss and significantly increased survival. These data support the development of inhaled administration of IFNλ1 mRNA as potential prophylactic option for individuals exposed to SARS-CoV-2 or at-risk suffering from COVID-19. Based on the broad antiviral activity of IFNλ1 regardless of virus or variant, this approach might also be utilized for other respiratory viral infections or pandemic preparedness.
| S-SCDT-10_1038-S44319-024-00216-4 | biostudies-other
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