Dataset Information

Elevated Plasma D-Dimer Concentrations in Adults after an Outpatient-Treated COVID-19 Infection.

ABSTRACT: Elevated D-dimer plasma concentrations are common in hospitalized COVID-19 patients and are often associated with a worse prognosis, but it is not yet clear whether this also applies to outpatient cases. The present cross-sectional study evaluated D-dimer levels and their association with clinical parameters and inflammation biomarkers after a COVID-19 disease in individuals treated as outpatients. The study included 411 individuals (43.3% men) with an average age of 46.8 years (SD 15.2). Study participants who had acute COVID-19 disease at a median of 235 days (120; 323) ago were examined at the University Hospital Augsburg, Southern Germany, between 11/2020 and 05/2021. Plasma D-dimers were measured by a particle-enhanced immunoturbidimetric assay. Sixty-one subjects (15%) showed increased D-dimer concentrations (≥500 µg/L). Study participants with elevated D-dimer levels in comparison to subjects with levels in the reference range were significantly older, and more frequently reported a history of cardiovascular disease, hypertension, venous thromboembolism, and chronic venous insufficiency. In multivariable logistic regression analysis, CRP levels (OR 5.58 per mg/dL, 95% CI 1.77-17.60) and white blood cell count (OR 1.48 per nL, 95% CI 1.19-1.83) were significantly related to elevated D-dimers even after adjustment for multiple testing. However, acute or persistent symptoms were not significantly associated with increased D-dimers. Elevated D-dimer levels months after an acute COVID-19 disease seems to be associated with markers of inflammation. Further studies are needed to investigate the underlying pathophysiological mechanisms and consequences of prolonged D-dimer elevation in these patients.

SUBMITTER: Meisinger C

PROVIDER: S-EPMC9699049 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Elevated Plasma D-Dimer Concentrations in Adults after an Outpatient-Treated COVID-19 Infection.

Meisinger Christa C Kirchberger Inge I Warm Tobias D TD Hyhlik-Dürr Alexander A Goßlau Yvonne Y Linseisen Jakob J

Viruses 20221103 11

Elevated D-dimer plasma concentrations are common in hospitalized COVID-19 patients and are often associated with a worse prognosis, but it is not yet clear whether this also applies to outpatient cases. The present cross-sectional study evaluated D-dimer levels and their association with clinical parameters and inflammation biomarkers after a COVID-19 disease in individuals treated as outpatients. The study included 411 individuals (43.3% men) with an average age of 46.8 years (SD 15.2). Study ...[more]

PMID: 36366539

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Project description:BackgroundPolyclonal convalescent plasma may be obtained from donors who have recovered from coronavirus disease 2019 (Covid-19). The efficacy of this plasma in preventing serious complications in outpatients with recent-onset Covid-19 is uncertain.MethodsIn this multicenter, double-blind, randomized, controlled trial, we evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults (≥18 years of age) who had tested positive for severe acute respiratory syndrome coronavirus 2, regardless of their risk factors for disease progression or vaccination status. Participants were enrolled within 8 days after symptom onset and received a transfusion within 1 day after randomization. The primary outcome was Covid-19-related hospitalization within 28 days after transfusion.ResultsParticipants were enrolled from June 3, 2020, through October 1, 2021. A total of 1225 participants underwent randomization, and 1181 received a transfusion. In the prespecified modified intention-to-treat analysis that included only participants who received a transfusion, the primary outcome occurred in 17 of 592 participants (2.9%) who received convalescent plasma and 37 of 589 participants (6.3%) who received control plasma (absolute risk reduction, 3.4 percentage points; 95% confidence interval, 1.0 to 5.8; P = 0.005), which corresponded to a relative risk reduction of 54%. Evidence of efficacy in vaccinated participants cannot be inferred from these data because 53 of the 54 participants with Covid-19 who were hospitalized were unvaccinated and 1 participant was partially vaccinated. A total of 16 grade 3 or 4 adverse events (7 in the convalescent-plasma group and 9 in the control-plasma group) occurred in participants who were not hospitalized.ConclusionsIn participants with Covid-19, most of whom were unvaccinated, the administration of convalescent plasma within 9 days after the onset of symptoms reduced the risk of disease progression leading to hospitalization. (Funded by the Department of Defense and others; CSSC-004 ClinicalTrials.gov number, NCT04373460.).

Project description:BackgroundThe scalability of a blood-based sarcopenia assessment has generated interest in circulating markers that may enhance management strategies. Data regarding the relevance of brain derived neurotrophic factor (BDNF), a regulator of neuroplasticity, to sarcopenia in community-dwelling adults are scarce. We examined the association between plasma BDNF concentrations, sarcopenia and individual sarcopenia signatures in a well-characterised adult cohort.MethodsParticipants included 246 men and women aged 50-82 years (mean age = 63.6 years; 52% female). Muscle strength and skeletal muscle index (SMI) were assessed by hand dynamometry and dual-energy X-ray absorptiometry. Plasma BDNF concentrations were determined, in duplicate, with commercially available enzyme-linked immunosorbent assays. Sarcopenia and individual signatures of sarcopenia (i.e. low grip strength or low SMI) were diagnosed according to the EWGSOP2 algorithm.ResultsPlasma BDNF concentrations were 47.6% higher in participants with sarcopenia than controls (P = 0.005), and demonstrated acceptable diagnostic accuracy (areas under the curves = 0.702, 95%CI = 0.597-0.806, P = 0.002, optimal cut-off >1645 pg/ml). Plasma BDNF concentration >1645 pg/ml was associated with 2.83 greater odds for sarcopenia (95%CI = 1.13-7.11, P = 0.027), than ≤1645 pg/ml, whilst a BDNF Z-score ≥2 was associated with 5.14 higher odds for sarcopenia (95%CI = 1.16-22.82, P = 0.031), than a Z-score <1. Covariates included sex, age, body mass index, habitual physical activity, smoking status, alcohol consumption, comorbidity and educational attainment.ConclusionCirculating BDNF concentrations are elevated in community-dwelling men and women with sarcopenia, which may reflect increased neuromuscular remodelling in these people. Our findings complement existing data, supporting the presence of an intricate relationship between neural integrity and skeletal muscle health. Future studies are needed to establish the mechanistic pathways that may underpin the associations.

Project description:Human clinical studies investigating use of convalescent plasma (CP) for treatment of coronavirus disease 2019 (COVID-19) have produced conflicting results. Outcomes in these studies may vary at least partly due to different timing of CP administration relative to symptom onset. The mechanisms of action of CP include neutralizing antibodies but may extend beyond virus neutralization to include normalization of blood clotting and dampening of inflammation. Unresolved questions include the minimum therapeutic titer in the CP units or CP recipient as well as the optimal timing of administration. Here, we show that treatment of macaques with CP within 24 h of infection does not reduce viral shedding in nasal or lung secretions compared to controls and does not detectably improve any clinical endpoint. We also demonstrate that CP administration does not impact viral sequence diversity in vivo, although the selection of a viral sequence variant in both macaques receiving normal human plasma was suggestive of immune pressure. Our results suggest that CP, administered to medium titers, has limited efficacy, even when given very early after infection. Our findings also contribute information important for the continued development of the nonhuman primate model of COVID-19. These results should inform interpretation of clinical studies of CP in addition to providing insights useful for developing other passive immunotherapies and vaccine strategies. IMPORTANCE Antiviral treatment options for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain very limited. One treatment that was explored beginning early in the pandemic (and that is likely to be tested early in future pandemics) is plasma collected from people who have recovered from coronavirus disease 2019 (COVID-19), known as convalescent plasma (CP). We tested if CP reduces viral shedding or disease in a nonhuman primate model. Our results demonstrate that administration of CP 1 day after SARS-CoV-2 infection had no significant impact on viral loads, clinical disease, or sequence diversity, although treatment with normal human plasma resulted in selection of a specific viral variant. Our results demonstrate that passive immunization with CP, even during early infection, provided no significant benefit in a nonhuman primate model of SARS-CoV-2 infection.

Dataset Information

Elevated Plasma D-Dimer Concentrations in Adults after an Outpatient-Treated COVID-19 Infection.

Publications

Elevated Plasma D-Dimer Concentrations in Adults after an Outpatient-Treated COVID-19 Infection.

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