PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 40400480

Impact of High-Titer Convalescent Plasma on Clinical and Virologic Outcomes Among Veterans Hospitalized With SARS-CoV-2 Infection: VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1).

Edward N Janoff·Mei-Chiung Shih·Curtis Donskey·Ilana Belitskaya-Levy·Norbert Brau·Maria C Rodriguez-Barradas·Ernest Chan·Peter Zimmerman·Elliott K Miller·Leroy B Vaughan·J Daniel Markley·Alexa M Goldberg·Peruvemba Sriram·Antonio Anzueto·Lauren Uyeda·Lisa Zehm·Ashlea Wills·Caitlin Hutchinson·Lucas Jones·Dianne Peterson·Robert J Ringer·Larry Dumont·Theresa Gleason·Robert A Bonomo·Jeffrey L Curtis·Sheldon T Brown·CURES‐1 Trials Consortium
View original source ↗Export metadata ↓

Abstract

In the initial absence of proven therapies, empirical COVID-19 convalescent plasma (CCP) was rapidly introduced for individuals hospitalized for COVID-19. Seventy-five participants were randomized from November 2020 to June 2021 in a double-blind, multi-site, placebo-controlled, randomized trial (VA CURES-1) evaluating the impact of CCP vs. saline in Veterans hospitalized with COVID-19 with hypoxemia. The composite primary outcome was acute hypoxemic respiratory failure or all-cause death by Day 29. We analyzed clinical outcomes, nasal viral RNA, plasma cytokines and viral evolution over time. Among 40 participants receiving saline and 35 receiving CCP with high neutralizing titers (median 1:1420), the percent reaching the primary outcome was similar (10%), as were time to clinical recovery and to nasal viral clearance. By whole genome sequencing, viral molecular complexity evolved pre- to posttreatment more frequently in recipients of saline vs. CCP (4 of 7 (57.1%) vs. 1 of 4 (25%), respectively), based on numbers of mixed allele positions. Numbers of amino acid-changing, non-synonymous mutations in the spike protein were greater in saline vs. CCP recipients. Both outcomes suggested purifying selection (reduced overall viral infection complexity) following CCP. In conclusion, convalescent plasma showed no significant clinical impact but may influence SARS-CoV-2 complexity. Trial Registration: ClinicalTrials.gov Identifier: NCT04539275.

Explore related subjects

AgedFemaleHumansMaleMiddle AgedAntibodies, NeutralizingAntibodies, ViralCOVID-19COVID-19 SerotherapyCytokinesDouble-Blind MethodHospitalizationImmunization, PassiveRNA, ViralSARS-CoV-2Treatment OutcomeVeteransCOVID‐19convalescent plasmahypoxemiarandomized controlled trialrespiratory failureviral complexityClinical Trial, Phase IIIJournal ArticleMulticenter StudyRandomized Controlled TrialResearch Support, U.S. Gov't, Non-P.H.S.

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Edward N Janoff, Mei-Chiung Shih, Curtis Donskey, Ilana Belitskaya-Levy, Norbert Brau, Maria C Rodriguez-Barradas, Ernest Chan, Peter Zimmerman, Elliott K Miller, Leroy B Vaughan, J Daniel Markley, Alexa M Goldberg, Peruvemba Sriram, Antonio Anzueto, Lauren Uyeda, Lisa Zehm, Ashlea Wills, Caitlin Hutchinson, Lucas Jones, Dianne Peterson, Robert J Ringer, Larry Dumont, Theresa Gleason, Robert A Bonomo, Jeffrey L Curtis, Sheldon T Brown, CURES‐1 Trials Consortium. 2025. Impact of High-Titer Convalescent Plasma on Clinical and Virologic Outcomes Among Veterans Hospitalized With SARS-CoV-2 Infection: VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1).. https://doi.org/10.1002/jmv.70349

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2026

Prognostic Value of Blood-Based P-Tau217 Levels for Progression to Cognitive Impairment.

IMPORTANCE: Blood-based biomarkers for Alzheimer disease, particularly plasma phosphorylated tau 217 (p-tau217), accurately reflect early Alzheimer disease brain pathology in cognitively unimpaired individuals, but estimates of absolute risk of progression to cognitive impairment across multiple cohorts are needed. OBJECTIVE: To estimate absolute risk of progression to cognitive impairment and rates of cognitive decline based on plasma p-tau217 across cognitively unimpaired older adults. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal cohort study using harmonized data from 2684 cognitively unimpaired older adults (defined within cohort) across 6 observational and clinical trial cohorts based in North America, Japan, and Australia. The earliest enrollment was in 2004, with most recent follow-up in 2025. EXPOSURE: Baseline plasma p-tau217. MAIN OUTCOMES AND MEASURES: The primary outcome was time to progression to cognitive impairment (mild cognitive impairment, dementia, or 2 consecutive global Clinical Dementia Rating scores ≥0.5). The secondary outcome was longitudinal change on the latent Preclinical Alzheimer Cognitive Composite (PACC; higher values indicate better performance). RESULTS: Among the 2684 participants (median [IQR] age, 69.6 [66.2-74.2] years; 1697 [63%] female), there were 478 events of progression to cognitive impairment over a median follow-up of 5.4 years (maximum follow-up of 13.5 years). Each 1-SD increase in baseline p-tau217 level was associated with an increased risk of progression to cognitive impairment (hazard ratio, 1.38 [95% CI, 1.30-1.46]), and the association remained significant after adjustment, including β-amyloid positron emission tomography scan Centiloids (hazard ratio, 1.32 [95% CI, 1.24-1.41]). Participants with high (1.1-2.4 SD) and very high (>2.5 SD) baseline p-tau217 had 24% (95% CI, 20%-28%) and 38% (95% CI, 33%-43%) absolute risk of progression over 5 years, respectively, and risk was markedly higher over 10 years, although longer-term estimates were constrained by limited data. Elevated p-tau217 was also associated with faster cognitive decline based on change in latent PACC score. Among the overall sample, baseline latent PACC scores ranged from -0.8 to 2.7. The 5-year annualized decline for the very high p-tau217 group was -0.07 latent PACC units/y (95% CI, -0.10 to -0.05), relative to 0.03 units/y (95% CI, 0.02-0.04) in the low p-tau217 group. CONCLUSIONS AND RELEVANCE: In a pooled sample of multiple selected cohorts of cognitively unimpaired older adults, higher plasma p-tau217 levels were consistently associated with increased risk of clinical progression and accelerated cognitive decline. By providing time-specific absolute risk estimates, these findings support the potential of p-tau217 for prognostic model development, with direct implications for future trial design. Further validation in unselected populations is needed to inform individual prognosis and clinical decision-making in cognitively unimpaired individuals.

Aged↗
PubMed2026

Lifestyle, anthropometric factors and clinically significant prostate cancer diagnosis in men with suspected prostate cancer.

OBJECTIVE: Lifestyle and anthropometric factors may influence prostate cancer (PCa) risk, yet evidence remains inconclusive. This study reports the associations between lifestyle and anthropometric factors and clinically significant PCa (csPCa; ISUP grade > 1) among men with clinical suspicion of PCa. MATERIALS AND METHODS: In this registered (NCT06116851), single-institution, prospective cohort trial, men referred for PCa diagnostics due to elevated prostate-specific antigen or abnormal digital rectal examination were included. Subjects underwent prostate diagnostics and completed detailed surveys of lifestyle, medical and family history. Physical activity was measured using a triaxial accelerometer. Anthropometric assessments included body mass index, waist circumference and magnetic resonance imaging-based body composition analyses. RESULTS: Among 298 included men, 143 (48%) were diagnosed with csPCa. In multivariate logistic regression, higher physical activity, measured by step count (odds ratio [OR]: 0.91, 95% confidence interval [CI]: 0.82-0.99) and active smoking compared to never-smokers (OR: 0.38, 95% CI: 0.14-0.96) were inversely associated with detection of csPCa. Higher prostate-specific antigen density was associated with increased risk (OR: 1.78, 95% CI: 1.39-2.35). Body composition was not associated with csPCa. Study strengths include comprehensive data collection. Primary limitation is partial reliance on self-reported data. CONCLUSIONS: Higher measured physical activity was inversely associated with detection of csPCa in men with suspicion of PCa. Active smoking also showed an inverse association. Both findings merit further investigation.

Aged↗
PubMed2026

Oral and gut microbiota profiles in patients with locally advanced rectal cancer with varying responses to neoadjuvant chemoradiotherapy.

Recent research has focused on gut bacteria in colorectal cancer, but the influence of other microbiota, including oral and nonbacterial gut microbiota, on treatment efficacy remains insufficiently explored. This study aimed to investigate their relationship with the efficacy of neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). Saliva and fecal samples were collected from patients with LARC before treatment. Shotgun metagenomic sequencing was used to profile bacterial, archaeal, eukaryotic, and viral taxonomic groups and to examine oral and gut microbial functions. An artificial intelligence-based prediction model was developed by integrating oral and gut microbiome data with clinical information. Statistical analyses compared diversity and response-associated microbial features between responders and non-responders to nCRT. Response-associated differences were observed in bacterial and nonbacterial taxonomic profiles and in oral and gut microbial functional profiles. In the internal test subset, the integrated analysis yielded an observed AUC of 0.917. Given the small cohort and the exploratory comparison of candidate classifiers, this estimate requires confirmation in larger, independent cohorts. Baseline oral and gut microbiome profiles were associated with response to nCRT. Integrating microbiome and clinical features showed potential for response prediction, but the model remains exploratory and requires validation in larger, independent cohorts before clinical application. Retrospectively registered on 01/08/2026, NCT07346729.

Aged↗