Dynamic activity in cis-regulatory elements of leukocytes identifies transcription factor activation and stratifies COVID-19 severity in ICU patients.

Transcription factor programs mediating the immune response to coronavirus disease 2019 (COVID-19) are not fully understood. Capturing active transcription initiation from cis-regulatory elements such as enhancers and promoters by capped small RNA sequencing (csRNA-seq), in contrast to capturing steady-state transcripts by conventional RNA-seq, allows unbiased identification of the underlying transcription factor activity and regulatory pathways. Here, we profile transcription initiation in critically ill COVID-19 patients, identifying transcription factor motifs that correlate with clinical lung injury and disease severity. Unbiased clustering reveals distinct subsets of cis-regulatory elements that delineate the cell type, pathway-specific, and combinatorial transcription factor activity. We find evidence of critical roles of regulatory networks, showing that STAT/BCL6 and E2F/MYB regulatory programs from myeloid cell populations are activated in patients with poor disease outcomes and associated with COVID-19 susceptibility genetic variants. More broadly, we demonstrate how capturing acute, disease-mediated changes in transcription initiation can provide insight into the underlying molecular mechanisms and stratify patient disease severity.

Increased Peripheral Blood Neutrophil Activation Phenotypes and Neutrophil Extracellular Trap Formation in Critically Ill Coronavirus Disease 2019 (COVID-19) Patients: A Case Series and Review of the Literature.

BACKGROUND: Increased inflammation has been well defined in coronavirus disease 2019 (COVID-19), while definitive pathways driving severe forms of this disease remain uncertain. Neutrophils are known to contribute to immunopathology in infections, inflammatory diseases, and acute respiratory distress syndrome, a primary cause of morbidity and mortality in COVID-19. Changes in neutrophil function in COVID-19 may give insight into disease pathogenesis and identify therapeutic targets. METHODS: Blood was obtained serially from critically ill COVID-19 patients for 11 days. Neutrophil extracellular trap formation (NETosis), oxidative burst, phagocytosis, and cytokine levels were assessed. Lung tissue was obtained immediately postmortem for immunostaining. PubMed searches for neutrophils, lung, and COVID-19 yielded 10 peer-reviewed research articles in English. RESULTS: Elevations in neutrophil-associated cytokines interleukin 8 (IL-8) and interleukin 6, and general inflammatory cytokines IFN-inducible protien-19, granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin 1ß, interleukin 10, and tumor necrosis factor, were identified both at first measurement and across hospitalization (P < .0001). COVID-19 neutrophils had exaggerated oxidative burst (P < .0001), NETosis (P < .0001), and phagocytosis (P < .0001) relative to controls. Increased NETosis correlated with leukocytosis and neutrophilia, and neutrophils and NETs were identified within airways and alveoli in lung parenchyma of 40% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected lungs available for examination (2 of 5). While elevations in IL-8 and absolute neutrophil count correlated with disease severity, plasma IL-8 levels alone correlated with death. CONCLUSIONS: Literature to date demonstrates compelling evidence of increased neutrophils in the circulation and lungs of COVID-19 patients. Importantly, neutrophil quantity and activation correlates with severity of disease. Similarly, our data show that circulating neutrophils in COVID-19 exhibit an activated phenotype with enhanced NETosis and oxidative burst.

Data-Driven Insights on the Effects of COVID-19 on Public Interest in Medical Aesthetics: Part II (Active Analysis).

BACKGROUND: The COVID-19 pandemic significantly affected financial and psychosocial factors that influence plastic surgery demand. OBJECTIVES: The authors sought to actively assess public interest changes and the reasons underlying these shifts. METHODS: Using Amazons' Mechanical Turk, we crowdsourced public opinions regarding aesthetic interventions from April 30 to May 3, 2020. The survey assessed prior experience with and interest in 6 aesthetic interventions before and during the pandemic and reasons for changing interest. United States residents aged 18 years and over who passed the attention check were included. RESULTS: We included 704 of 838 total responses. One-half of respondents were female; the median age group was 25 to 34 years. During the pandemic, 21% of respondents had increased and 33% decreased interest in at least one intervention. Non-invasive procedures (7.3%), facial aesthetic surgery (6.6%), and medical-grade skincare (5.9%) elicited the greatest interest increase. Seeing themselves in the mirror more often (43.2%), desire to look better after the crisis (41.8%), and increased time on social media (40.4%) were the top reasons for increased interest. The most common reasons for decreased interest were changing spending priorities (58%), focusing on other health aspects (49.8%), and worrying about infection in medical facilities (46.3%). Almost one-half of respondents considered virtual consultations for interventions of increased interest. CONCLUSIONS: The COVID-19 pandemic significantly affected interest in medical aesthetics. Offering telemedicine and discussing detailed COVID-19 infection control policies with patients will be critical to address patient needs and concerns. These findings can be used to improve patient outreach, advertisement, and counseling as practices focus on reopening.

Data-Driven Insights on the Effects of COVID-19 on Aesthetics: Part I (Passive Analysis).

BACKGROUND: Since COVID-19 was declared to be a worldwide pandemic and US national emergency in March (week 11), it has significantly changed aesthetic plastic surgery. As plastic surgeons now move towards reopening practices, understanding public interest in medical aesthetics will be critical to maximize efforts and resource allocation in procedures and treatments that patients want. OBJECTIVES: In this study, the authors sought to passively query public interest in aesthetics utilizing Google Trends search data. METHODS: Google Trends was utilized to quantify relative search volumes over the past 4 years for a variety of categories: patient-related, surgery-related, injectables, breast procedures, face procedures, and body procedures. Data were deseasonalized and represented graphically. Z-scores of each time-point differing from the expected values were determined utilizing least squares regression. RESULTS: Of the 204 significantly anomalous search term data points in 2020, 172 (84.0%) occurred after week 11 (pandemic/national emergency declaration). Sixty percent of searches in all time-points after week 11 significantly differed, and 25/26 (96.0%) search terms experienced significant changes after week 11. There was decreased interest for 18 terms with variable recovery. Procedural nadirs for decreased search volume troughs occurred between weeks 11 and 14. Six patient-related chief complaints saw increased search interest after COVID-19, with peak interest between weeks 11 and 17. CONCLUSIONS: This is the first study, to the authors' knowledge, to assess real-time, national data about the impact of COVID-19 on public interest in aesthetics.