The UCSF COMET Consortium, Michael Matthay, David J. E rl e , P re scot t G. Woodruff, Charles Langelier, Kirsten K an ge la ri s, C ar ol yn M.
Recent advances in dry electrodes technology have facilitated the recording of EEG in situations not previously possible, thanks to the relatively swift electrode preparation and avoidance of applying gel to subject's hair. However, to become a true alternative, these systems should be compared to state-of-the-art wet EEG systems commonly used in clinical or research applications. In our study, we conducted a systematic comparison of electrodes application speed, subject comfort, and most critically electrophysiological signal quality between the conventional and wired Biosemi EEG system using wet active electrodes and the compact and wireless F1 EEG system consisting of dry passive electrodes. All subjects (n = 27) participated in two recording sessions on separate days, one with the wet EEG system and one with the dry EEG system, in which the session order was counterbalanced across subjects. In each session, we recorded their EEG during separate rest periods with eyes open and closed followed by two versions of a serial visual presentation target detection task. Each task component allows for a neural measure reflecting different characteristics of the data, including spectral power in canonical low frequency bands, event-related potential components (specifically, the P3b), and single trial classification based on machine learning. The performance across the two systems was similar in most measures, including the P3b amplitude and topography, as well as low frequency (theta, alpha, and beta) spectral power at rest. Both EEG systems performed well above chance in the classification analysis, with a marginal advantage of the wet system over the dry. Critically, all aforementioned electrophysiological metrics showed significant positive correlations (r = 0.54-0.89) between the two EEG systems. This multitude of measures provides a comprehensive comparison that captures different aspects of EEG data, including temporal precision, frequency domain as well as multivariate patterns of activity. Taken together, our results indicate that the dry EEG system used in this experiment can effectively record electrophysiological measures commonly used across the research and clinical contexts with comparable quality to the conventional wet EEG system.
The immunological features that distinguish COVID-19-associated acute respiratory distress syndrome (ARDS) from other causes of ARDS are incompletely understood. Here, we report the results of comparative lower respiratory tract transcriptional profiling of tracheal aspirate from 52 critically ill patients with ARDS from COVID-19 or from other etiologies, as well as controls without ARDS. In contrast to a “cytokine storm,” we observe reduced proinflammatory gene expression in COVID-19 ARDS when compared to ARDS due to other causes. COVID-19 ARDS is characterized by a dysregulated host response with increased PTEN signaling and elevated expression of genes with non-canonical roles in inflammation and immunity. In silico analysis of gene expression identifies several candidate drugs that may modulate gene expression in COVID-19 ARDS, including dexamethasone and granulocyte colony stimulating factor. Compared to ARDS due to other types of viral pneumonia, COVID-19 is characterized by impaired interferon-stimulated gene (ISG) expression. The relationship between SARS-CoV-2 viral load and expression of ISGs is decoupled in patients with COVID-19 ARDS when compared to patients with mild COVID-19. In summary, assessment of host gene expression in the lower airways of patients reveals distinct immunological features of COVID-19 ARDS.
SARS coronavirus-2 (SARS-CoV-2) is causing a global pandemic with large variation in COVID-19 disease spectrum. SARS-CoV-2 infection requires host receptor ACE2 on lung epithelium, but epithelial underpinnings of variation are largely unknown. We capitalized on comprehensive organoid assays to report remarkable variation in SARS-CoV-2 infection rates of lung organoids from different subjects. Tropism is highest for TUBA- and MUC5AC-positive organoid cells, but levels of TUBA-, MUC5A-, or ACE2- positive cells do not predict infection rate. We identify surface molecule Tetraspanin 8 (TSPAN8) as novel mediator of SARS-CoV-2 infection, which is not downregulated by this specific virus. TSPAN8 levels, prior to infection, strongly correlate with infection rate and TSPAN8-blocking antibodies diminish SARS-CoV-2 infection. We propose TSPAN8 as novel functional biomarker and potential therapeutic target for COVID-19.
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