Alterations in the plasma proteome persist ten months after recovery from mild to moderate SARS-CoV-2 infection.

Background: Limited data are available describing the effects of SARS-CoV-2 breakthrough infections on the plasma proteome.

Methods: PCR-positive SARS-CoV-2 patients, enrolled in a natural history study, underwent analysis of the plasma proteome. A prospective cohort of 66 unvaccinated and 24 vaccinated persons with different degrees of infection severity were evaluated acutely (within 40 days of symptom onset), and at three and ten months.

Longitudinal analysis of the lung proteome reveals persistent repair months after mild to moderate COVID-19.

In order to assess homeostatic mechanisms in the lung after COVID-19, changes in the protein signature of bronchoalveolar lavage from 45 patients with mild to moderate disease at three phases (acute, recovery, and convalescent) are evaluated over a year. During the acute phase, inflamed and uninflamed phenotypes are characterized by the expression of tissue repair and host defense response molecules. With recovery, inflammatory and fibrogenic mediators decline and clinical symptoms abate.

Quantitative CT Metrics Associated with Variability in the Diffusion Capacity of the Lung of Post-COVID-19 Patients with Minimal Residual Lung Lesions.

(1) Background: A reduction in the diffusion capacity of the lung for carbon monoxide is a prevalent longer-term consequence of COVID-19 infection. In patients who have zero or minimal residual radiological abnormalities in the lungs, it has been debated whether the cause was mainly due to a reduced alveolar volume or involved diffuse interstitial or vascular abnormalities. (2) Methods: We performed a cross-sectional study of 45 patients with either zero or minimal residual lesions in the lungs (total volume < 7 cc) at two months to one year post COVID-19 infection.

Vaccination Ameliorates Cellular Inflammatory Responses in SARS-CoV-2 Breakthrough Infections.

Background: Data on cellular immune responses in persons with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection following vaccination are limited. The evaluation of these patients with SARS-CoV-2 breakthrough infections may provide insight into how vaccinations limit the escalation of deleterious host inflammatory responses.

Methods: We conducted a prospective study of peripheral blood cellular immune responses to SARS-CoV-2 infection in 21 vaccinated patients, all with mild disease, and 97 unvaccinated patients stratified based on disease severity.

Spleen tyrosine kinase inhibition restores myeloid homeostasis in COVID-19.

Spleen tyrosine kinase (SYK) is a previously unidentified therapeutic target that inhibits neutrophil and macrophage activation in coronavirus disease 2019 (COVID-19). Fostamatinib, a SYK inhibitor, was studied in a phase 2 placebo-controlled randomized clinical trial and was associated with improvements in many secondary end points related to efficacy. Here, we used a multiomic approach to evaluate cellular and soluble immune mediator responses of patients enrolled in this trial.

A cross-sectional study of quantitative CT measurements associated with the diffusion capacity of the lung in recovered COVID-19 patients with normalised chest CT.

Impairment of the diffusion capacity of the lung for carbon monoxide (DLco) is commonly reported in convalescent and recovered COVID-19 patients, although the cause is not fully understood especially in patients with no radiological sequelae. In a group of 47 patients at 7 - 51 weeks post infection with either none or minimal scarring or atelectasis on chest CT scans (total < 0.1% of lung volume), dispersions in DLco-adj % and total lung capacity (TLC) % of predicted were observed, with median(quartiles) of 87(78, 99)% and 84(78, 92)%, respectively.

Low-dose methylprednisolone treatment in critically ill patients with severe community-acquired pneumonia.

Purpose: Severe community-acquired pneumonia (CAP) requiring intensive care unit admission is associated with significant acute and long-term morbidity and mortality. We hypothesized that downregulation of systemic and pulmonary inflammation with prolonged low-dose methylprednisolone treatment would accelerate pneumonia resolution and improve clinical outcomes.

Methods: This double-blind, randomized, placebo-controlled clinical trial recruited adult patients within 72-96 h of hospital presentation.

Self-gated 3D stack-of-spirals UTE pulmonary imaging at 0.55T.

Purpose: To develop an isotropic high-resolution stack-of-spirals UTE sequence for pulmonary imaging at 0.55 Tesla by leveraging a combination of robust respiratory-binning, trajectory correction, and concomitant-field corrections.

Methods: A stack-of-spirals golden-angle UTE sequence was used to continuously acquire data for 15.

Fostamatinib Inhibits Neutrophils Extracellular Traps Induced by COVID-19 Patient Plasma: A Potential Therapeutic.

Neutrophil extracellular traps (NETs) contribute to immunothrombosis and have been associated with mortality in coronavirus disease 2019 (COVID-19). We stimulated donor neutrophils with plasma from patients with COVID-19 and demonstrated that R406 can abrogate the release of NETs. These data provide evidence for how fostamatinib may mitigate neutrophil-associated mechanisms contributing to COVID-19 immunopathogenesis.

Low Plasma Gelsolin Concentrations in Chronic Granulomatous Disease.

Plasma gelsolin (pGSN) is the secreted isoform of an intracellular actin remodeling protein found in high concentrations in human plasma. Clinical studies demonstrate reduced pGSN concentrations in several disease states, including severe trauma, burns, and sepsis. Markedly decreased pGSN concentrations in these conditions precede and predict adverse clinical outcomes.

Rapid Identification of New Delhi Metallo-β-Lactamase (NDM) Using Tryptic Peptides and LC-MS/MS.

There is significant interest in the development of mass spectrometry (MS) methods for antimicrobial resistance protein detection, given the ability of these methods to confirm protein expression. In this work, we studied the performance of a liquid chromatography, tandem MS multiple-reaction monitoring (LC-MS/MS MRM) method for the direct detection of the New Delhi metallo-β-lactamase (NDM) carbapenemase in clinical isolates. Using a genoproteomic approach, we selected three unique peptides (SLGNLGDADTEHYAASAR, AFGAAFPK, and ASMIVMSHSAPDSR) specific to NDM that were efficiently ionized and spectrally well-defined.

Health Disparities and Sepsis: a Systematic Review and Meta-Analysis on the Influence of Race on Sepsis-Related Mortality.

Rationale: Racial disparities in sepsis outcomes have been previously reported. However, recently, there have been inconsistencies in identifying which socioeconomic variables, such as race, account for these disparities. The objective of this study was to perform a systematic review in order to examine the impact of race on sepsis-attributable mortality.

Rapid detection of colistin resistance protein MCR-1 by LC-MS/MS.

Background: Colistin (polymyxin E) and polymixin B are important bactericidal antibiotics used in the treatment of serious infections caused by multi-drug resistant Gram-negative organisms. Transferrable plasmid-mediated colistin resistance, conferred by the product of the - gene, has emerged as a global healthcare threat. Consequently, the rapid detection of the MCR-1 protein in clinical bacterial isolates has become increasingly important.

Identification of the OXA-48 Carbapenemase Family by Use of Tryptic Peptides and Liquid Chromatography-Tandem Mass Spectrometry.

Phenotypic detection of the OXA-48-type class D β-lactamases in is challenging. We describe a rapid (less than 90 min) assay for the identification of OXA-48 family carbapenemases in subcultured bacterial isolates based on a genoproteomic approach. Following trypsin digestion to ascertain theoretical core peptides common to the OXA-48 family, liquid chromatography-tandem mass spectrometry (LC-MS/MS) data-dependent acquisition was used to identify candidate peptide markers.