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Project description:Airborne transmission of SARS-CoV-2 aerosol remains contentious. Importantly, whether cough or breath-generated bioaerosols can harbor viable and replicating virus remains largely unclarified. We perform size-fractionated aerosol sampling (Andersen cascade impactor) and evaluate viral culturability in human cell lines (infectiousness), viral genetics, and host immunity in ambulatory participants with COVID-19. Sixty-one percent (27/44) and 50% (22/44) of participants emitted variant-specific culture-positive aerosols <10μm and <5μm, respectively, for up to 9 days after symptom onset. Aerosol culturability is significantly associated with lower neutralizing antibody titers, and suppression of transcriptomic pathways related to innate immunity and the humoral response. A nasopharyngeal Ct <17 rules-in ~40% of aerosol culture-positives and identifies those who are probably highly infectious. A parsimonious three transcript blood-based biosignature is highly predictive of infectious aerosol generation (PPV> 95%). There is considerable heterogeneity in potential infectiousness i.e., only 29% of participants were probably highly infectious (produced culture-positive aerosols <5μm at ~6 days after symptom onset). These data, which comprehensively confirm variant-specific culturable SARS-CoV-2 in aerosol, inform the targeting of transmission-related interventions and public health containment strategies emphasizing improved ventilation.
2024-03-13 | GSE252508 | GEO
Project description:Since besides mucosal adaptive immunity, respiratory delivery of AdHu5Ag85A vaccine in experimental animals induced a trained phenotype in airway macrophages, we examined whether aerosol vaccination with AdHu5Ag85A could also alter the immune property of human alveolar macrophages (AM). To this end, we elected to examine the transcriptomics of BALF cells obtained from 5 participants before (wk0) and after (wk8) 1x106PFU AdHu5Ag85A aerosol vaccination. Before RNA isolation, the cells, upon revival from frozen stock, were enriched for AM and cultured with or without stimulation with M.tb lysates and transcriptionally profiled by RNAseq analysis. Principal component analysis (PCA) revealed that unstimulated (US) and stimulated (S) AM populations were separated away from each other. We then identified the differentially expressed genes (DEGs) by comparing wk0- and wk8-stimulated AM with respective unstimulated AM. By this pairwise analysis, we identified 194 and 426 genes uniquely upregulated and downregulated, respectively, in stimulated AM from aerosol vaccinated participants. The uniquely up-regulated genes in stimulated wk8 aerosol AM showed enrichment in a number of biological processes including response to anoxia (OXTR, CTGF), inflammatory response to antigenic stimuli (IL2RA, IL1B, IL20RB), tyrosine phosphorylation of STAT protein (IFNG, F2R, OSM), regulation of IL-10 production (CD83, IRF4, IL20RB, IDO1), response to IL-1 (RIPK2, SRC, IRAK2, IL1R1, XYLT1, RELA) and histone demethylation (KDM6B, KDM5B, KDM1A, KDM7A, JMJD6). In comparison, the uniquely down-regulated genes in wk8 aerosol AM did not appear significantly enriched for any biological processes. These data suggest that aerosol vaccination leads to persisting transcriptional changes in airway-resident alveolar macrophages poised for defense responses.
2022-02-23 | GSE190850 | GEO
Project description:Human BEAS-2B bronchial epithelial cells were exposed directly at the air-liquid interphase towards exhaust gas and particles of a ship engine. The goal was to compare the responses towards different fuel combustions. The engine run either on diesel fuel (DF) or on Heavy Fuel Oil (HFO). The lung cells were exposed 3 times to each combustion aerosol (DF or HFO). The duration of the exposure was 4h. The cells were seeded into transwell-inserts 24h before exposure. Within each exposure 3 transwell-inserts were exposed to the complete aerosol and 3 transwell-inserts were exposed to the filtered aerosol. Effects of the complete aerosol were referenced against the filtered aerosol to determine the effects of the aerosol particles.
2015-02-01 | E-GEOD-63962 | biostudies-arrayexpress
Project description:Multiple respiratory viruses including Influenza A virus (IAV) can be transmitted via expiratory aerosol particles, and many studies have established that environmental conditions can affect viral infectivity during airborne transmission. Low aerosol pH was recently identified as a major factor influencing the infectivity of aerosol-borne IAV and SARS-CoV-2, however, there is a fundamental lack of understanding as to the mechanisms leading to viral inactivation within the acidic aerosol micro-environment. Here, we identified that the early stages of the IAV infection cycle were impacted by transient exposure to acidic aerosol conditions (pH below 5.5), which was primarily attributed to loss of binding function of the viral protein haemagglutinin. Viral capsid integrity was also somewhat affected by transient acidic exposure. We then characterised the structural changes associated with loss of viral infectivity using whole-virus hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS), and observed discrete regions of unfolding in the external viral protein haemagglutinin and in the internal matrix protein 1. Viral nucleoprotein structure appeared to be unaffected by exposure to acidic aerosol conditions, and no changes to viral genome integrity or to lipids within the viral envelope were detected using our whole-virus methods. Collectively, these data indicate that viral inactivation observed under indoor aerosol conditions is mediated by specific protein conformational changes, particularly to haemagglutinin. This study additionally provides a proof-of-concept that HDX-MS is a highly effective method for characterisation of internal and external proteins of whole enveloped viruses such as IAV. Overall, improved understanding of the fate of respiratory viruses within exhaled aerosols will aid the development of novel strategies and therapeutics to control the severity of seasonal and/or pandemic influenza, and constitutes a global public health priority.
2023-08-10 | PXD037176 | Pride
Project description:Modified risk tobacco products (MRTPs) have the potential to reduce smoking-related health risks. The Carbon Heated Tobacco Product 1.2 (CHTP1.2) is a potential MRTP that uses a pressed carbon heat source to generate an aerosol by heating tobacco. This study reports the results from the systems toxicology arm of a 90-day rat inhalation study (OECD test guideline 413) to assess the effects of CHTP1.2 aerosol compared with cigarette smoke (CS). Rats were exposed to filtered air (sham), to CHTP1.2 aerosol (at 15, 23 and 50 µg nicotine / L), or to the 3R4F reference cigarette smoke (at 23 µg nicotine / L).
2018-03-19 | PXD008422 | Pride
Project description:Modified risk tobacco products (MRTPs) have the potential to reduce smoking-related health risks. The Carbon Heated Tobacco Product 1.2 (CHTP1.2) is a potential MRTP that uses a pressed carbon heat source to generate an aerosol by heating tobacco. This study reports the results from the systems toxicology arm of a 90-day rat inhalation study (OECD test guideline 413) to assess the effects of CHTP1.2 aerosol compared with cigarette smoke (CS). Rats were exposed to filtered air (sham), to CHTP1.2 aerosol (at 15, 23 and 50 µg nicotine / L), or to the 3R4F reference cigarette smoke (at 23 µg nicotine / L).
2018-03-19 | PXD008424 | Pride