Search

Introduction: Cancer causes a substantial burden to our society, both from a health and an economic perspective. To improve cancer patient outcomes and lower society expenses, early diagnosis and timely treatment are essential. The recent COVID-19 crisis has disrupted the care trajectory of cancer patients, which may affect their prognosis in a potentially negative way. The purpose of this paper is to present a flexible decision-analytic Markov model methodology allowing the evaluation of the impact of delayed cancer care caused by the COVID-19 pandemic in Belgium which can be used by researchers to respond to diverse research questions in a variety of disruptive events, contexts and settings., Methods: A decision-analytic Markov model was developed for 4 selected cancer types (i.e. breast, colorectal, lung, and head and neck), comparing the estimated costs and quality-adjusted life year losses between the pre-COVID-19 situation and the COVID-19 pandemic in Belgium. Input parameters were derived from published studies (transition probabilities, utilities and indirect costs) and administrative databases (epidemiological data and direct medical costs). One-way and probabilistic sensitivity analyses are proposed to consider uncertainty in the input parameters and to assess the robustness of the model's results. Scenario analyses are suggested to evaluate methodological and structural assumptions., Discussion: The results that such decision-analytic Markov model can provide are of interest to decision makers because they help them to effectively allocate resources to improve the health outcomes of cancer patients and to reduce the costs of care for both patients and healthcare systems. Our study provides insights into methodological aspects of conducting a health economic evaluation of cancer care and COVID-19 including insights on cancer type selection, the elaboration of a Markov model, data inputs and analysis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Khan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

GM-CSF promotes myelopoiesis and inflammation, and GM-CSF blockade is being evaluated as a treatment for COVID-19-associated hyperinflammation. Alveolar GM-CSF is, however, required for monocytes to differentiate into alveolar macrophages (AMs) that control alveolar homeostasis. By mapping cross-species AM development to clinical lung samples, we discovered that COVID-19 is marked by defective GM-CSF-dependent AM instruction and accumulation of pro-inflammatory macrophages. In a multi-center, open-label RCT in 81 non-ventilated COVID-19 patients with respiratory failure, we found that inhalation of rhu-GM-CSF did not improve mean oxygenation parameters compared with standard treatment. However, more patients on GM-CSF had a clinical response, and GM-CSF inhalation induced higher numbers of virus-specific CD8 effector lymphocytes and class-switched B cells, without exacerbating systemic hyperinflammation. This translational proof-of-concept study provides a rationale for further testing of inhaled GM-CSF as a non-invasive treatment to improve alveolar gas exchange and simultaneously boost antiviral immunity in COVID-19. This study is registered at ClinicalTrials.gov (NCT04326920) and EudraCT (2020-001254-22)., Competing Interests: Declaration of interests A.S. is a consultant for Gritstone bio, Flow Pharma, Arcturus, Immunoscape, CellCarta, Oxford Immunotec, and Avalia. L.J.I. has filed for patent protection for various aspects of T cell epitope and vaccine design work. D.F.R. is an employee of and has stock options in Partner Therapeutics., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Multiplexing of samples in single-cell RNA-seq studies allows a significant reduction of the experimental costs, straightforward identification of doublets, increased cell throughput, and reduction of sample-specific batch effects. Recently published multiplexing techniques using oligo-conjugated antibodies or -lipids allow barcoding sample-specific cells, a process called "hashing.", Results: Here, we compare the hashing performance of TotalSeq-A and -C antibodies, custom synthesized lipids and MULTI-seq lipid hashes in four cell lines, both for single-cell RNA-seq and single-nucleus RNA-seq. We also compare TotalSeq-B antibodies with CellPlex reagents (10x Genomics) on human PBMCs and TotalSeq-B with different lipids on primary mouse tissues. Hashing efficiency was evaluated using the intrinsic genetic variation of the cell lines and mouse strains. Antibody hashing was further evaluated on clinical samples using PBMCs from healthy and SARS-CoV-2 infected patients, where we demonstrate a more affordable approach for large single-cell sequencing clinical studies, while simultaneously reducing batch effects., Conclusions: Benchmarking of different hashing strategies and computational pipelines indicates that correct demultiplexing can be achieved with both lipid- and antibody-hashed human cells and nuclei, with MULTISeqDemux as the preferred demultiplexing function and antibody-based hashing as the most efficient protocol on cells. On nuclei datasets, lipid hashing delivers the best results. Lipid hashing also outperforms antibodies on cells isolated from mouse brain. However, antibodies demonstrate better results on tissues like spleen or lung., (© 2022. The Author(s).)

In rare instances, pediatric SARS-CoV-2 infection results in a novel immunodysregulation syndrome termed multisystem inflammatory syndrome in children (MIS-C). We compared MIS-C immunopathology with severe COVID-19 in adults. MIS-C does not result in pneumocyte damage but is associated with vascular endotheliitis and gastrointestinal epithelial injury. In MIS-C, the cytokine release syndrome is characterized by IFNγ and not type I interferon. Persistence of patrolling monocytes differentiates MIS-C from severe COVID-19, which is dominated by HLA-DRlo classical monocytes. IFNγ levels correlate with granzyme B production in CD16+ NK cells and TIM3 expression on CD38+/HLA-DR+ T cells. Single-cell TCR profiling reveals a skewed TCRβ repertoire enriched for TRBV11-2 and a superantigenic signature in TIM3+/CD38+/HLA-DR+ T cells. Using NicheNet, we confirm IFNγ as a central cytokine in the communication between TIM3+/CD38+/HLA-DR+ T cells, CD16+ NK cells, and patrolling monocytes. Normalization of IFNγ, loss of TIM3, quiescence of CD16+ NK cells, and contraction of patrolling monocytes upon clinical resolution highlight their potential role in MIS-C immunopathogenesis., Competing Interests: Disclosures: No disclosures were reported., (© 2021 Hoste et al.)