Viruses cause a wide spectrum of clinical disease, the majority being acute respiratory infections (ARI). In most cases, ARI symptoms are similar for different viruses although severity can be variable. The objective of this study was to understand the shared and unique elements of the host transcriptional response to different viral pathogens. We identified 162 subjects in the US and Sri Lanka with infections due to influenza, enterovirus/rhinovirus, human metapneumovirus, dengue virus, cytomegalovirus, Epstein Barr Virus, or adenovirus. Our dataset allowed us to identify common pathways at the molecular level as well as virus-specific differences in the host immune response. Conserved elements of the host response to these viral infections highlighted the importance of interferon pathway activation. However, the magnitude of the responses varied between pathogens. We also identified virus-specific responses to influenza, enterovirus/rhinovirus, and dengue infections. Influenza-specific differentially expressed genes (DEG) revealed up-regulation of pathways related to viral defense and down-regulation of pathways related to T cell and neutrophil responses. Functional analysis of entero/rhinovirus-specific DEGs revealed up-regulation of pathways for neutrophil activation, negative regulation of immune response, and p38MAPK cascade and down-regulation of virus defenses and complement activation. Functional analysis of dengue-specific up-regulated DEGs showed enrichment of pathways for DNA replication and cell division whereas down-regulated DEGs were mainly associated with erythrocyte and myeloid cell homeostasis, reactive oxygen and peroxide metabolic processes. In conclusion, our study will contribute to a better understanding of molecular mechanisms to viral infections in humans and the identification of biomarkers to distinguish different types of viral infections.
OBJECTIVES: Sepsis causes significant mortality. However, most patients who die of sepsis do not present with severe infection, hampering efforts to deliver early, aggressive therapy. It is also known that the host gene expression response to infection precedes clinical illness. This study seeks to develop transcriptomic models to predict progression to sepsis or shock within 72 hours of hospitalization and to validate previously identified transcriptomic signatures in the prediction of 28-day mortality. DESIGN:Retrospective differential gene expression analysis and predictive modeling using RNA sequencing data. PATIENTS:Two hundred seventy-seven patients enrolled at four large academic medical centers; all with clinically adjudicated infection were considered for inclusion in this study. MEASUREMENTS AND MAIN RESULTS:Sepsis progression was defined as an increase in Sepsis 3 category within 72 hours. Transcriptomic data were generated using RNAseq of whole blood. Least absolute shrinkage and selection operator modeling was used to identify predictive signatures for various measures of disease progression. Four previously identified gene signatures were tested for their ability to predict 28-day mortality. There were no significant differentially expressed genes in 136 subjects with worsened Sepsis 3 category compared with 141 nonprogressor controls. There were 1,178 differentially expressed genes identified when sepsis progression was defined as ICU admission or 28-day mortality. A model based on these genes predicted progression with an area under the curve of 0.71. Validation of previously identified gene signatures to predict sepsis mortality revealed area under the receiver operating characteristic values of 0.70-0.75 and no significant difference between signatures. CONCLUSIONS:Host gene expression was unable to predict sepsis progression when defined by an increase in Sepsis-3 category, suggesting this definition is not a useful framework for transcriptomic prediction methods. However, there was a differential response when progression was defined as ICU admission or death. Validation of previously described signatures predicted 28-day mortality with insufficient accuracy to offer meaningful clinical utility.
Background and aim It has been demonstrated that marginalized populations across the U.S. have suffered a disproportionate burden of the coronavirus disease 2019 (COVID-19) pandemic, illustrating the role that social determinants of health play in health outcomes. To better understand how these vulnerable and high-risk populations have experienced the pandemic, we conducted a qualitative study to better understand their experiences from diagnosis through recovery. Methods We conducted a qualitative study of patients in a North Carolina healthcare system’s registry who tested positive for COVID-19 from March 2020 through February 2021, identified from population-dense outbreaks of COVID-19 (hotspots). We conducted semi-structured phone interviews in English or Spanish, based on patient preference, with trained bilingual study personnel. Each interview was evaluated using a combination of deductive and inductive content analysis to determine prevalent themes related to COVID-19 knowledge, diagnosis, disease experience, and long-term impacts. Findings The 10 patients interviewed from our COVID-19 hotspot clusters were of equal distribution by sex, predominantly Black (70%), aged 22–70 years (IQR 45–62 years), and more frequently publicly insured (50% Medicaid/Medicare, vs 30% uninsured, vs 20% private insurance). Major themes identified included prior knowledge of COVID-19 and patient perceptions of their personal risk, the testing process in numerous settings, the process of quarantining at home after a positive diagnosis, the experience of receiving medical care during their illness, and difficulties with long-term recovery. Discussion Our findings suggest areas for targeted interventions to reduce COVID-19 transmission in these high-risk communities, as well as improve the patient experience throughout the COVID-19 illness course.
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