Search NASA⌕ Search

SEARCH · Search NASA

Results for “Vascularization”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 415 records · Page 23
All sourcesNASA NTRSDOE OSTI
NASA NTRS1962

Effect of Alpha-Particle Irradiation on Brain Glycogen in the Rat

The studies of Klatzo, Miquel, Tobias and Haymaker (1961) have shown that one of the earliest and most sensitive indications of the effects of alpha-particle irradiation on rat bran is the appearance of glycogen granules mainly in the neuroglia of the exposed area of the brain. Periodic acid-Schiff (PAS) positive, alpha-amylase soluble granules were demonstrated within 12 hr after irradiation, preceding by approximately 36 hr the first microscopically detectable vascular permeability disturbances, as shown by the fluorescein labeled serum protein technique. These studies suggested that the injurious effects of alpha-particle energy were on cellular elements primarily, according to the physical properties and distribution of the radiation in the tissue, and that the vascular permeability disturbances played a secondary role in pathogenesis. The purpose of this study was to correlate the histochemical observations on glycogen with a quantitative assessment of the glycogen in the irradiated brain tissue. It is felt that such a study may contribute to the understanding of radiation injury at the molecular level. A practical aspect of this problem is that the information on biological radiation effects due to accelerated particles from the cyclotron source, is employed in this study, is applicable to radiation from cosmic particles both in free space and entrapped in the Van Allen belts.

Wolfe, L. S.↗
NASA NTRS2015

Retinal Image Quality Assessment for Spaceflight-Induced Vision Impairment Study

Long-term exposure to space microgravity poses significant risks for visual impairment. Evidence suggests such vision changes are linked to cephalad fluid shifts, prompting a need to directly quantify microgravity-induced retinal vascular changes. The quality of retinal images used for such vascular remodeling analysis, however, is dependent on imaging methodology. For our exploratory study, we hypothesized that retinal images captured using fluorescein imaging methodologies would be of higher quality in comparison to images captured without fluorescein. A semi-automated image quality assessment was developed using Vessel Generation Analysis (VESGEN) software and MATLAB® image analysis toolboxes. An analysis of ten images found that the fluorescein imaging modality provided a 36% increase in overall image quality (two-tailed p=0.089) in comparison to nonfluorescein imaging techniques.

retina↗
NASA NTRS2017

Effects of Spaceflight on Venous and Arterial Compliance

The visual impairment and intracranial pressure (VIIP) syndrome is a spaceflight-associated set of symptoms affecting more than 50% of American astronauts who have flown International Space Station (ISS) missions. VIIP is defined primarily by visual acuity deficits and anatomical changes to eye structures (e.g. optic disc edema, choroidal folds, and globe flattening) and is hypothesized to be related to elevated intracranial pressure secondary to a cephalad fluid shift. However, ocular symptoms have not been replicated in subjects completing prolonged bed rest, a well-accepted spaceflight analog. Altered vascular compliance along with spaceflight factors such as diet, radiation exposure, or environmental factors may cause alterations in the cardiovascular system that contribute to the manifestation of ocular changes. Loss of visual acuity could be a significant threat to crew health and performance during and after an exploration mission and may have implications for years post-flight. The overall objective of this project is to determine if spaceflight alters vascular compliance and whether such an adaptation is related to the incidence of VIIP. This objective will be met by completing three separate but related projects.

Ribeiro, L. C.↗
NASA NTRS2017

Effects of Long Duration Spaceflight on Venous and Arterial Compliance: Bed Rest

The primary objective was to determine whether a high sodium diet during bed rest induced alterations in vascular compliance and was related to the incidence of VIIP. Ocular structural and functional measures and vascular ultrasound of the head and neck were acquired in bed rest subjects completing 10-14 days in 6deg head-down tilt.

Ribeiro, L. Christine↗
NASA NTRS2017

The Effects of CDKN1a/p21 on Oxidative Stress and Mitochondrial Function During Long Duration Spaceflight

Spaceflight factors, such as microgravity and space radiation, are known to put astronauts at risk for negative effects to their tissue regeneration and degenerative conditions. On our previous spaceflight research, we found that long duration spaceflight produced increased oxidative stress and activation of the inflammatory response as a major contributor to physiological changes, including alterations to the cardiovascular and musculoskeletal systems, metabolism, and the liver. Proliferation, apoptosis, and ion-channel remodeling of vascular smooth muscle cells, as well as endothelial inflammation, and nitric oxide synthase-nitric oxide system regulation have been shown by spaceflight and simulated spaceflight projects. CDKN1ap21 is a regulatory gene for tissue regeneration and also plays an important role in upregulating oxidative stress caused by radiation. In further research, we have also determined CDKN1ap21 to be overexpressed during spaceflight. When knocked out in mice, however, it protects against unloading-induced changes to the morphology and physiology of carotid arteries. In this proposal, we seek to test a potential dietary countermeasure to down-regulate CDKN1ap21 in the mice and protect against oxidative stress in the rodents. Specifically, we will expose both Wildtype and CDKN1ap21-null mice to hydrogen peroxide to induce oxidative stress and observe the molecular mechanisms in which a dietary supplement protects vascular smooth muscle cells against the consequences of the apoptotic environment within Wildtype mice versus the, hypothetically, sound physiology of CDKN1ap21-null mice. The successful completion of this experiment will conclusively determine accuracy of a dietary supplement as a CDKN1ap21 suppressor. This will provide a new perspective on the problem of increased oxidative stress developing into cardiovascular disease as a result of long-term space flight. This research will address the Human Research Plan Roadmaps Risk of Cardiac Rhythm Problems including CV-8, the Risk of Cardiovascular Disease and Other Degenerative Tissue Effects from Radiation Exposure including Degen-6 and Degen-7, and the Risk of Adverse Health Event from Radiation Exposure including IM-8. Additionally, this research will address Space Biology Research Plans questions SBP CMB-1, SBP CMB-3, and SB AN-2.

Oxidative Stress↗
NASA NTRSDate not supplied

Circulating miRNA Signature Predicts and Rescues Spaceflight Associated Health Risks

We have identified and validated a spaceflight-associated microRNA (miRNA) signature that is shared by rodents and humans in response to simulated and real spaceflight and regulates vascular damage by simulated deep space radiation. In previous studies, we identified miRNAs that are predicted to regulate rodent responses to spaceflight in low-Earth orbit. Here we have validated the expression of key spaceflight-associated miRNAs in rodents reacting to simulated spaceflight conditions (exposure to ionizing radiation combined with simulated microgravity) and in astronaut samples from the NASA Twin Study. We demonstrate that this circulating miRNA siganture is conserved between these different species and will serve as an ideal biomarker to monitor increase health risk due to exposure to the space environment. Lastly, to demonstrate their physiological relevance, we have utilized antagomirs to target a subset of miRNAs from the spaceflight associated signature to successfully rescue simulated deep space radiation-mediated damage in human 3D vascular constructs. These results provide strong evidence to further develop a miRNA based countermeasure in astronauts.

Afshin Beheshti↗
NASA NTRS2020

Circulating Mirna Spaceflight Signature Reveals Targets to Mitigate Associated Health Risks

We have identified and validated a spaceflight-associated microRNA (miRNA) signature that is shared by rodents and humans in response to simulated, short-duration, and long-duration spaceflight and regulates vascular damage caused by simulated deep space radiation. In previous studies, we had identified miRNAs that are predicted to regulate rodent responses to spaceflight in low-Earth orbit. Here we have confirmed the expression of these proposed spaceflight associated miRNAs in rodents reacting to simulated spaceflight conditions (exposure to ionizing radiation combined with simulated microgravity) and in astronaut samples from the NASA Twins Study via direct quantification of miRNAs, miRNA sequencing, and inferring miRNA target levels based on single-cell RNA (scRNA-seq) and single-cell chromatin (scATAC-seq) sequencing data. To demonstrate the physiological relevance of key spaceflight associated miRNAs, we utilized antagomirs to inhibit their expression and successfully rescue simulated deep space radiation-mediated damage in human 3D vascular constructs.

Sherina Malkani↗
NASA NTRSDate not supplied

Mitigating Headward Fluid Shifts with Venoconstrictive Thigh Cuffs during Spaceflight

Venoconstrictive thigh cuffs (VTC) are a mechanical countermeasure capable of attenuating the spaceflight induced headward fluid shift, and thus may be a viable spaceflight associated neuro-ocular syndrome (SANS) countermeasure. Crewmembers can use VTC to mitigate the headward fluid shift to aid in adapting to spaceflight. However, data are needed to determine if VTC affect ocular structures. PURPOSE The purpose of this study is to determine the efficacy of long duration use of VTC application to mitigate the spaceflight-induced headward fluid shift. We hypothesize that a VTC countermeasure will temporarily reverse the headward fluid shift and attenuate spaceflight-induced changes of internal jugular vein (IJV) cross-sectional area, IJV pressure, stroke volume, cardiac output, intraocular pressure (IOP), and optic nerve head and retinal morphology. METHODS This study will evaluate the effectiveness of VTC countermeasure application on the headward fluid shift, as well as cardiovascular and ocular variables. VTC during spaceflight will be worn for an extended duration (up to 6 hours) with data collected at three time points (30 minutes, 3 hours, and 6 hours) to characterize the temporal profile of key fluid shift outcome measures of the vascular fluid shift, IOP, and ocular structure changes. Ten astronauts will be recruited to participate and will be studied before and during approximately 180-day International Space Station (ISS) spaceflight missions. Baseline data collection will occur approximately 90-days before launch (Figure). Preflight, each leg of the crewmember will be measured to determine the VTC cuff size and a cuff fit check session will occur prior to the preflight baseline ground imaging to verify the appropriate fit measured via a surface contact pressure. Prior to donning the VTC, baseline measures without VTC will be collected seated, supine, and supine followed by data collection with the VTC. The baseline data collection will include ultrasound (IJV area and pressure, stroke volume and cardiac output), brachial blood pressure and heart rate, optical coherence tomography (OCT) imaging (total retinal thickness and choroid thickness), and IOP. An inflight cuff fit check session, same as the preflight fit check, will occur prior to VTC use on ISS. The inflight VTC experiment will be conducted early (FD45) and late (R-45) to determine if mission duration affects VTC fit and the efficacy of fluid redistribution. A system usability scale comfort questionnaire will be included in each VTC session to capture feedback from crewmembers regarding the comfort and usability of the VTC. SCIENTIFIC & MISSION IMPACT Results will narrow knowledge gaps described in the Human Research Roadmap to mitigate the headward fluid shift during spaceflight and help NASA to 1) determine the efficacy of extended use VTC application to mitigate the spaceflight-induced headward fluid shift and 2) further the understanding of the use of VTC on vascular fluid shifts, IOP, and ocular structure during spaceflight. Supported by NASA Human Research Program Directed Research. Figure. Detailed Testing Schedule. Baseline data collection at L-90 will be performed in a randomized order of position.

J V Jasien↗
NASA NTRS2021

Vegetation structural complexity and biodiversity in the Great Smoky Mountains

Vegetation structural complexity and biodiversity tend to be positively correlated, but understanding of this relationship is limited in part by structural metrics tending to quantify only horizontal or vertical variation, and that do not reflect internal structure. We developed new metrics for quantifying internal vegetation structural complexity using terrestrial LiDAR scanning and applied them to 12 NEON forest plots across an elevational gradient in Great Smoky Mountains National Park, USA. We asked (1) How do our newly developed structure metrics compare to traditional metrics? (2) How does forest structure vary with elevation in a high-biodiversity, high topographic complexity region? (3) How do forest structural metrics vary in the strength of their relationships with vascular plant biodiversity? Our new measures of canopy density (Depth) and structural complexity (σDepth), and their canopy height-normalized counterparts, were sensitive to structural variations and effectively summarized horizontal and vertical dimensions of structural complexity. Forest structure varied widely across plots spanning the elevational range of GRSM, with taller, more structurally complex forests at lower elevation. Vascular plant biodiversity was negatively correlated with elevation and more strongly positively correlated with vegetation structure variables. The strong correlations we observed between canopy structural complexity and biodiversity suggest that structural complexity metrics could be used to assay plant biodiversity over large areas in concert with airborne and spaceborne platforms.

Jonathan A. Walter↗
NASA NTRSDate not supplied

Neurovascular Responses to Simulated Deep Space Radiation in a Human Organ-on-a-Chip Model

A major health risk for human deep space exploration is central nervous system (CNS) damage by galactic cosmic ray radiation. Simulated galactic cosmic rays or their components, especially the high-linear energy transfer (LET) particles such as 56Fe ions, have been shown to cause CNS damage, neuroinflammation and cognitive dysfunction in rodent models, but their effects on human CNS remain to be investigated. CNS damage from any insult, including ionizing radiation, is partially mediated by the blood-brain barrier (BBB), which regulates interactions between CNS and the rest of the body. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuroinflammation. However, there have been few studies on BBB and astrocyte functions in regulating CNS responses, especially in human tissue analogs. Therefore, we utilized a high-throughput 3D organ-on-a-chip system, seeded with human induced pluripotent stem cell-derived astrocytes and brain endothelial cells, or brain endothelial cells alone, to study human neurovascular responses to simulated deep space radiation. We investigated the permeability and morphology of vascular structures formed by endothelial cells, as well as oxidative stress and secreted cytokines and chemokine levels over 1-7 days after irradiation with 0.25 – 0.5 Gy 5-ion simplified simulated galactic cosmic rays or 0.3 – 0.8 Gy high-LET 600 MeV/n 56Fe particles, and compared the outcomes to low-LET X-ray irradiation. We observed that simulated deep space radiation caused delayed astrocyte activation in a pattern resembling CNS responses to brain injury, caused oxidative stress and the production of inflammatory cytokines, and compromised BBB integrity by damaging tight junctions, thus increasing vascular permeability. Furthermore, our results indicate that astrocytes have a dual role in regulating radiation responses: they exacerbate blood-brain barrier permeability early after irradiation, followed by switching to a more protective scar-like phenotype by reducing oxidative stress and pro-inflammatory cytokine and chemokine secretion. In a follow-up study using the same platform, we investigated the dose-rate effects of ionizing radiation, by exposing our model to chronic, low dose-rate, gamma radiation. Our model was significantly improved by adding additional cell types composing the BBB, modelling immune cell infiltration into the brain, and studying the effect of an antioxidant, to measure more complex outcomes and model more closely the effect of deep space radiation on the human BBB. In summary, our results present a human neurovascular model for space radiation studies and potential future automated payload adaptation, and suggest astrocyte regulatory mechanisms as targets for countermeasures to mitigate human neurovascular impairments during deep space exploration.

Ionizing radiation↗
NASA NTRSDate not supplied

Surveillance for Jugular Venous Thrombosis in Long-Duration Space Flight: Findings From Twenty-Eight U.S. Astronauts

BACKGROUND: Given the high incidence of internal jugular vein (IJV) flow anomalies aboard the International Space Station and a case of thrombosis, the National Aeronautics and Space Administration (NASA) instituted an occupational surveillance program to evaluate astronauts for venous thromboembolism (VTE). Current findings of the program are presented. METHODS: NASA astronauts undergo pre- and in-flight VTE surveillance examinations using a standardized vascular ultrasound protocol, which includes evaluation for bilateral IJV compressibility, filling, flow, and spontaneous echo contrast (SEC). RESULTS: Twenty-eight NASA astronauts had terrestrial baseline examinations and at least one in-flight imaging session. The reduction of in-flight peak IJV flow speeds was significant and more pronounced on the left. Comparing the first in-flight measurement to the terrestrial baseline, peak flow speeds were reduced from 90.1±41.9 cm/s (average ±SD) to 62.1±31.6 cm/s on the right and from 76.9±41.8 cm/s to 26.8±18.2 cm/s on the left. Seven astronauts showed stagnant or retrograde flow in the left IJV. Fourteen developed appreciable SEC in the left IJV (7 greater than mild); none developed significant right-sided SEC. All IJVs were fully compressible and free from thrombi. DISCUSSION: Bilateral IJV flow speed reduction is observed in microgravity, possibly due to the multitude of available flow redistribution paths for cranial drainage. In a subset of astronauts, significant flow anomalies develop that may facilitate thrombus formation through changes in blood viscosity and speed, especially if combined with other thrombogenic factors. These findings warrant attention to the interplay between individual vascular configurations and the dynamic properties of blood as a non-Newtonian fluid in the reduced-shear flow environment of microgravity.

Ashot Sargsyan↗
DOE OSTI2025

Design and structural basis of selective 1,4-dihydropyridine inhibitors of the calcium-activated potassium channel K Ca 3.1

The 1,4-dihydropyridines, drugs with well-established bioavailability and toxicity profiles, have proven efficacy in treating human hypertension, peripheral vascular disorders, and coronary artery disease. Every 1,4-dihydropyridine in clinical use blocks L-type voltage-gated calcium channels. We now report our development, using selective optimization of a side activity (SOSA), of a class of 1,4-dihydropyridines that selectively and potently inhibit the intermediate-conductance calcium-activated K + channel K Ca 3.1, a validated therapeutic target for diseases affecting many organ systems. One of these 1,4-dihydropyridines, DHP-103, blocked K Ca 3.1 with an IC 50 of 6 nM and exhibited exquisite selectivity over calcium channels and a panel of >100 additional molecular targets. Using high-resolution structure determination by cryogenic electron microscopy together with mutagenesis and electrophysiology, we delineated the drug binding pocket for DHP-103 within the water-filled central cavity of the K Ca 3.1 channel pore, where bound drug directly impedes ion permeation. DHP-103 inhibited gain-of-function mutant K Ca 3.1 channels that cause hereditary xerocytosis, suggesting its potential use as a therapeutic for this hemolytic anemia. In a rat model of acute ischemic stroke, the second leading cause of death worldwide, DHP-103 administered 12 h postischemic insult in proof-of-concept studies reduced infarct volume, improved balance beam performance (measure of proprioception) and decreased numbers of activated microglia in infarcted areas. K Ca 3.1-selective 1,4-dihydropyridines hold promise for the many diseases for which K Ca 3.1 has been experimentally confirmed as a therapeutic target.

Ong, Seow Theng [Lee Kong Chian School of Medicine↗
NASA NTRS2002

Shear stress stimulates phosphorylation of eNOS at Ser(635) by a protein kinase A-dependent mechanism

Shear stress stimulates nitric oxide (NO) production by phosphorylating endothelial NO synthase (eNOS) at Ser(1179) in a phosphoinositide-3-kinase (PI3K)- and protein kinase A (PKA)-dependent manner. The eNOS has additional potential phosphorylation sites, including Ser(116), Thr(497), and Ser(635). Here, we studied these potential phosphorylation sites in response to shear, vascular endothelial growth factor (VEGF), and 8-bromocAMP (8-BRcAMP) in bovine aortic endothelial cells (BAEC). All three stimuli induced phosphorylation of eNOS at Ser(635), which was consistently slower than that at Ser(1179). Thr(497) was rapidly dephosphorylated by 8-BRcAMP but not by shear and VEGF. None of the stimuli phosphorylated Ser(116). Whereas shear-stimulated Ser(635) phosphorylation was not affected by phosphoinositide-3-kinase inhibitors wortmannin and LY-294002, it was blocked by either treating the cells with a PKA inhibitor H89 or infecting them with a recombinant adenovirus-expressing PKA inhibitor. These results suggest that shear stress stimulates eNOS by two different mechanisms: 1) PKA- and PI3K-dependent and 2) PKA-dependent but PI3K-independent pathways. Phosphorylation of Ser(635) may play an important role in chronic regulation of eNOS in response to mechanical and humoral stimuli.

Non-NASA Center↗
DOE OSTI2024

Submicron immunoglobulin particles exhibit FcγRII-dependent toxicity linked to autophagy in TNFα-stimulated endothelial cells

In intravenous immunoglobulins (IVIG), and some other immunoglobulin products, protein particles have been implicated in adverse events. Role and mechanisms of immunoglobulin particles in vascular adverse effects of blood components and manufactured biologics have not been elucidated. We have developed a model of spherical silica microparticles (SiMPs) of distinct sizes 200–2000 nm coated with different IVIG- or albumin (HSA)-coronas and investigated their effects on cultured human umbilical vein endothelial cells (HUVEC). IVIG products (1–20 mg/mL), bare SiMPs or SiMPs with IVIG-corona, did not display significant toxicity to unstimulated HUVEC. In contrast, in TNFα-stimulated HUVEC, IVIG-SiMPs induced decrease of HUVEC viability compared to HSA-SiMPs, while no toxicity of soluble IVIG was observed. 200 nm IVIG-SiMPs after 24 h treatment further increased ICAM1 (intercellular adhesion molecule 1) and tissue factor surface expression, apoptosis, mammalian target of rapamacin (mTOR)-dependent activation of autophagy, and release of extracellular vesicles, positive for mitophagy markers. Toxic effects of IVIG-SiMPs were most prominent for 200 nm SiMPs and decreased with larger SiMP size. Using blocking antibodies, toxicity of IVIG-SiMPs was found dependent on FcγRII receptor expression on HUVEC, which increased after TNFα-stimulation. Similar results were observed with different IVIG products and research grade IgG preparations. In conclusion, submicron particles with immunoglobulin corona induced size-dependent toxicity in TNFα-stimulated HUVEC via FcγRII receptors, associated with apoptosis and mTOR-dependent activation of autophagy. Testing of IVIG toxicity in endothelial cells prestimulated with proinflammatory cytokines is relevant to clinical conditions. Our results warrant further studies on endothelial toxicity of sub-visible immunoglobulin particles.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

A novel xylosylated fucoglucuronan in Penium reveals structural parallels to rhamnogalacturonan-I and its broad evolutionary footprint in lower plants

Green algae inhabit aquatic environments across the planet and play a crucial role in sustaining the global ecosystem. Ancestors of some Charophytes adapted to terrestrial conditions and eventually evolved into land plants. Extant green algae have inherited traits from their ancestors and evolved into their current morphological and chemical forms, as reflected by their cell walls with distinct shapes and compositions. To illuminate the evolution of plant cell walls and bridge the gap between green algae and land plants, we investigated the charophyte Penium margaritaceum, a close relative of terrestrial plants. We discovered a previously unknown polysaccharide in both its culture medium and cell wall. This polysaccharide, termed xylosylated fucoglucuronan (XFG), possesses a rhamnogalacturonan-I (RG-I)-like backbone composed of repeating [-3-α-Fucp-(1,4)-α-GlcpA-] disaccharides that are extensively xylosylated and acetylated. Surveying approximately 20 non-vascular plants revealed that XFG and RG-I (or related structures) first emerge in certain Chlorophyceae and subsequently co-occur throughout lineages along the evolutionary trajectory to bryophytes, thereby bridging aquatic green algae to early land plants. The striking structural parallels between XFG, RG-I, and ulvan suggest a shared evolutionary origin, offering new insight into how plant cell walls adapted during the transition from marine to freshwater environments and ultimately to land.

Algae↗
DOE OSTI2021

Maximum CO 2 diffusion inside leaves is limited by the scaling of cell size and genome size

Maintaining high rates of photosynthesis in leaves requires efficient movement of CO 2 from the atmosphere to the mesophyll cells inside the leaf where CO 2 is converted into sugar. CO 2 diffusion inside the leaf depends directly on the structure of the mesophyll cells and their surrounding airspace, which have been difficult to characterize because of their inherently three-dimensional organization. Yet faster CO 2 diffusion inside the leaf was probably critical in elevating rates of photosynthesis that occurred among angiosperm lineages. Here we characterize the three-dimensional surface area of the leaf mesophyll across vascular plants. We show that genome size determines the sizes and packing densities of cells in all leaf tissues and that smaller cells enable more mesophyll surface area to be packed into the leaf volume, facilitating higher CO 2 diffusion. Measurements and modelling revealed that the spongy mesophyll layer better facilitates gaseous phase diffusion while the palisade mesophyll layer better facilitates liquid-phase diffusion. Our results demonstrate that genome downsizing among the angiosperms was critical to restructuring the entire pathway of CO 2 diffusion into and through the leaf, maintaining high rates of CO 2 supply to the leaf mesophyll despite declining atmospheric CO 2 levels during the Cretaceous.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Development and validation of a 30-day mortality index based on pre-existing medical administrative data from 13,323 COVID-19 patients: The Veterans Health Administration COVID-19 (VACO) Index

Background Available COVID-19 mortality indices are limited to acute inpatient data. Using nationwide medical administrative data available prior to SARS-CoV-2 infection from the US Veterans Health Administration (VA), we developed the VA COVID-19 (VACO) 30-day mortality index and validated the index in two independent, prospective samples. Methods and findings We reviewed SARS-CoV-2 testing results within the VA between February 8 and August 18, 2020. The sample was split into a development cohort (test positive between March 2 and April 15, 2020), an early validation cohort (test positive between April 16 and May 18, 2020), and a late validation cohort (test positive between May 19 and July 19, 2020). Our logistic regression model in the development cohort considered demographics (age, sex, race/ethnicity), and pre-existing medical conditions and the Charlson Comorbidity Index (CCI) derived from ICD-10 diagnosis codes. Weights were fixed to create the VACO Index that was then validated by comparing area under receiver operating characteristic curves (AUC) in the early and late validation cohorts and among important validation cohort subgroups defined by sex, race/ethnicity, and geographic region. We also evaluated calibration curves and the range of predictions generated within age categories. 13,323 individuals tested positive for SARS-CoV-2 (median age: 63 years; 91% male; 42% non-Hispanic Black). We observed 480/3,681 (13%) deaths in development, 253/2,151 (12%) deaths in the early validation cohort, and 403/7,491 (5%) deaths in the late validation cohort. Age, multimorbidity described with CCI, and a history of myocardial infarction or peripheral vascular disease were independently associated with mortality–no other individual comorbid diagnosis provided additional information. The VACO Index discriminated mortality in development (AUC = 0.79, 95% CI: 0.77–0.81), and in early (AUC = 0.81 95% CI: 0.78–0.83) and late (AUC = 0.84, 95% CI: 0.78–0.86) validation. The VACO Index allows personalized estimates of 30-day mortality after COVID-19 infection. For example, among those aged 60–64 years, overall mortality was estimated at 9% (95% CI: 6–11%). The Index further discriminated risk in this age stratum from 4% (95% CI: 3–7%) to 21% (95% CI: 12–31%), depending on sex and comorbid disease. Conclusion Prior to infection, demographics and comorbid conditions can discriminate COVID-19 mortality risk overall and within age strata. The VACO Index reproducibly identified individuals at substantial risk of COVID-19 mortality who might consider continuing social distancing, despite relaxed state and local guidelines.

60 APPLIED LIFE SCIENCES↗