Search

PURIFY-OBS-1 is an observational study evaluating the safety and efficacy of Seraph 100 ® Microbind Affinity Blood Filter (Seraph 100) use for COVID-19 patients with respiratory failure admitted to the intensive care unit (ICU). The Seraph 100 is a hemoperfusion device containing heparin-coated beads that can bind to, and reduce levels of, some circulating pathogens and inflammatory molecules. This study evaluated whether treatment with the Seraph 100 affected circulating and mucosal antibody levels in critically ill COVID-19 subjects. SARS-CoV-2 anti-spike and anti-nucleocapsid IgG and IgA levels in serum were evaluated at enrollment and on days 1, 4, 7, and 28 after Seraph 100 application, while anti-spike and nucleocapsid IgG, IgA, and secretory IgA levels in tracheal aspirates were evaluated at enrollment and on days 1, 2, 3, 7, and 28. Serum samples were also collected from the pre- and post-filter lines at 1 and 4 h following Seraph 100 application to evaluate the direct impact of the filter on circulating antibody levels. Treatment with the Seraph 100 did not alter the levels of circulating or mucosal antibodies in critically ill COVID-19 subjects admitted to the ICU.

Introduction: We sought to determine pre-infection correlates of protection against SARS-CoV-2 post-vaccine inzfections (PVI) acquired during the first Omicron wave in the United States., Methods: Serum and saliva samples from 176 vaccinated adults were collected from October to December of 2021, immediately before the Omicron wave, and assessed for SARS-CoV-2 Spike-specific IgG and IgA binding antibodies (bAb). Sera were also assessed for bAb using commercial assays, and for neutralization activity against several SARS-CoV-2 variants. PVI duration and severity, as well as risk and precautionary behaviors, were assessed by questionnaires., Results: Serum anti-Spike IgG levels assessed by research assay, neutralization titers against Omicron subvariants, and low home risk scores correlated with protection against PVIs after multivariable regression analysis. Commercial assays did not perform as well as research assay, likely due to their lower dynamic range., Discussion: In the 32 participants that developed PVI, anti-Spike IgG bAbs correlated with lower disease severity and shorter duration of illness., Competing Interests: SP, TB, and DT report that the USU IDCRP, a U.S. Department of Defense DoD Institution, and the HJF were funded under a Cooperative Research and Development Agreement to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial sponsored by AstraZeneca. The HJF, in support of the USU IDCRP, was funded by the DoD Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense to augment the conduct of an unrelated phase III vaccine trial sponsored by AstraZeneca. Both trials were part of the USG COVID-19 response. Neither is related to the work presented here. Authors WM and SA were employed by the company Quest Diagnostics. Author JP was employed by company Leidos Biomedical Research, Inc. Authors LV, MF, AL and FM were employed by company Leidos. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Goguet, Olsen, Meyer, Ansari, Powers, Conner, Coggins, Wang, Wang, Illinik, Sanchez Edwards, Jackson-Thompson, Hollis-Perry, Wang, Alcorta, Wong, Saunders, Mohammed, Balogun, Kobi, Kosh, Bishop-Lilly, Cer, Arnold, Voegtly, Fitzpatrick, Luquette, Malagon, Ortega, Parmelee, Davies, Lindrose, Haines-Hull, Moser, Samuels, Rekedal, Graydon, Malloy, Tribble, Burgess, Campbell, Robinson, Broder, O’Connell, Weiss, Pollett, Laing and Mitre.)

Introduction: Natural killer (NK) cells can both amplify and regulate immune responses to vaccination. Studies in humans and animals have observed NK cell activation within days after mRNA vaccination. In this study, we sought to determine if baseline NK cell frequencies, phenotype, or function correlate with antibody responses or inflammatory side effects induced by the Pfizer-BioNTech COVID-19 vaccine (BNT162b2)., Methods: We analyzed serum and peripheral blood mononuclear cells (PBMCs) from 188 participants in the Prospective Assessment of SARS-CoV-2 Seroconversion study, an observational study evaluating immune responses in healthcare workers. Baseline serum samples and PBMCs were collected from all participants prior to any SARS-CoV-2 infection or vaccination. Spike-specific IgG antibodies were quantified at one and six months post-vaccination by microsphere-based multiplex immunoassay. NK cell frequencies and phenotypes were assessed on pre-vaccination PBMCs from all participants by multi-color flow cytometry, and on a subset of participants at time points after the 1 st and 2 nd doses of BNT162b2. Inflammatory side effects were assessed by structured symptom questionnaires, and baseline NK cell functionality was quantified by an in vitro killing assay on participants that reported high or low post-vaccination symptom scores., Results: Key observations include: 1) circulating NK cells exhibit evidence of activation in the week following vaccination, 2) individuals with high symptom scores after 1 st vaccination had higher pre-vaccination NK cytotoxicity indices, 3) high pre-vaccination NK cell numbers were associated with lower spike-specific IgG levels six months after two BNT162b2 doses, and 4) expression of the inhibitory marker NKG2A on immature NK cells was associated with higher antibody responses 1 and 6 months post-vaccination., Discussion: These results suggest that NK cell activation by BNT162b2 vaccination may contribute to vaccine-induced inflammatory symptoms and reduce durability of vaccine-induced antibody responses., Competing Interests: SP, TB, and DT report that the Uniformed Services University USU Infectious Disease Clinical Research Program IDCRP, a US Department of Defense institution, and the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. HJF were funded under a Cooperative Research and Development Agreement to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial sponsored by AstraZeneca. The HJF, in support of the USU IDCRP, was funded by the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense to augment the conduct of an unrelated phase III vaccine trial sponsored by AstraZeneca. Both trials were part of the US Government COVID-19 response. Neither is related to the work presented here. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Graydon, Conner, Dunham, Olsen, Goguet, Coggins, Rekedal, Samuels, Jackson-Thompson, Moser, Lindrose, Hollis-Perry, Wang, Maiolatesi, Alcorta, Reyes, Wong, Ramsey, Davies, Parmelee, Ortega, Sanchez, Moller, Inglefield, Tribble, Burgess, O’Connell, Malloy, Pollett, Broder, Laing, Anderson and Mitre.)

The September 11, 2001 attack on the World Trade Center (WTC) covered a large area of downtown New York City with dust and debris. This paper describes the testing of an analytical method designed to evaluate whether sampled dust contains dust that may have originated from the collapse of the WTC. Using dust samples collected from locations affected and not affected (referred to as 'background' locations) by the collapse, a scanning electron microscopy (SEM) analysis method was developed to screen for three materials that are believed to be present in large quantities in WTC dusts: slag wool, concrete, and gypsum. An inter-laboratory evaluation of the method was implemented by having eight laboratories analyze a number of 'blind' dust samples, consisting of confirmed background dust and confirmed background dust spiked with varying amounts of dust affected by the WTC collapse. The levels of gypsum and concrete in the spiked samples were indistinguishable from the levels in the background samples. Measurements of slag wool in dust demonstrated potential for distinguishing between spiked and background samples in spite of considerable within and between laboratory variability. Slag wool measurements appear to be sufficiently sensitive to distinguish dust spiked with 5% WTC-affected dust from 22 out of 25 background dust samples. Additional development work and inter-laboratory testing of the slag wool component will be necessary to improve the precision and accuracy of the method and reduce inter- and intra-laboratory variability from levels observed in the inter-laboratory evaluation.

The catastrophic destruction of the World Trade Center (WTC) on 11 September 2001 caused the release of high levels of airborne pollutants into the local environment. To assess the toxicity of fine particulate matter [particulate matter with a mass median aerodynamic diameter < 2.5 microm (PM2.5)], which may adversely affect the health of workers and residents in the area, we collected fallen dust samples on 12 and 13 September 2001 from sites within a half-mile of Ground Zero. Samples of WTC dust were sieved, aerosolized, and size-separated, and the PM2.5 fraction was isolated on filters. Here we report the chemical and physical properties of PM2.5 derived from these samples and compare them with PM2.5 fractions of three reference materials that range in toxicity from relatively inert to acutely toxic (Mt. St. Helens PM; Washington, DC, ambient air PM; and residual oil fly ash). X-ray diffraction of very coarse sieved WTC PM (< 53 microm) identified calcium sulfate (gypsum) and calcium carbonate (calcite) as major components. Scanning electron microscopy confirmed that calcium-sulfur and calcium-carbon particles were also present in the WTC PM2.5 fraction. Analysis of WTC PM2.5 using X-ray fluorescence, neutron activation analysis, and inductively coupled plasma spectrometry showed high levels of calcium (range, 22-33%) and sulfur (37-43% as sulfate) and much lower levels of transition metals and other elements. Aqueous extracts of WTC PM2.5 were basic (pH range, 8.9-10.0) and had no evidence of significant bacterial contamination. Levels of carbon were relatively low, suggesting that combustion-derived particles did not form a significant fraction of these samples recovered in the immediate aftermath of the destruction of the towers. Because gypsum and calcite are known to cause irritation of the mucus membranes of the eyes and respiratory tract, inhalation of high doses of WTC PM2.5 could potentially cause toxic respiratory effects.

The multivariate receptor model Unmix has been used to analyze a 3-yr PM2.5 ambient aerosol data set collected in Phoenix, AZ, beginning in 1995. The analysis generated source profiles and overall average percentage source contribution estimates (SCEs) for five source categories:gasoline engines (33 +/- 4%), diesel engines (16 +/- 2%), secondary SO4(2-) (19 +/- 2%), crustal/soil (22 +/- 2%), and vegetative burning (10 +/- 2%). The Unmix analysis was supplemented with scanning electron microscopy (SEM) of a limited number of filter samples for information on possible additional low-strength sources. Except for the diesel engine source category, the Unmix SCEs were generally consistent with an earlier multivariate receptor analysis of essentially the same data using the Positive Matrix Factorization (PMF) model. This article provides the first demonstration for an urban area of the capability of the Unmix receptor model.

A source apportionment study was conducted to identify sources within a large elemental phosphorus plant that contribute to exceedances of the National Ambient Air Quality Standards (NAAQS) for 24-hr PM10. Ambient data were collected at three monitoring sites from October 1996 through July 1999, and included the following: 24-hr PM10 mass, 24-hr PM2.5 and PM10-2.5 mass and chemistry, continuous PM10 and PM2.5 mass, continuous meteorological data, and wind-direction-resolved PM2.5 and PM10 mass and chemistry. Ambient-based receptor modeling and wind-directional analysis were employed to help identify major sources or source locations and source contributions. Fine-fraction phosphate was the dominant species observed during PM10 exceedances, though in general, resuspended coarse dusts from raw and processed materials at the plant were also needed to create an exceedance. Major sources that were identified included the calciners, the CO flares, process-related dust, and electric-arc furnace operations.