Systematic comparison of published host gene expression signatures for bacterial/viral discrimination.

BACKGROUND: Measuring host gene expression is a promising diagnostic strategy to discriminate bacterial and viral infections. Multiple signatures of varying size, complexity, and target populations have been described. However, there is little information to indicate how the performance of various published signatures compare to one another. METHODS: This systematic comparison of host gene expression signatures evaluated the performance of 28 signatures, validating them in 4589 subjects from 51 publicly available datasets. Thirteen COVID-specific datasets with 1416 subjects were included in a separate analysis. Individual signature performance was evaluated using the area under the receiving operating characteristic curve (AUC) value. Overall signature performance was evaluated using median AUCs and accuracies. RESULTS: Signature performance varied widely, with median AUCs ranging from 0.55 to 0.96 for bacterial classification and 0.69-0.97 for viral classification. Signature size varied (1-398 genes), with smaller signatures generally performing more poorly (P < 0.04). Viral infection was easier to diagnose than bacterial infection (84% vs. 79% overall accuracy, respectively; P < .001). Host gene expression classifiers performed more poorly in some pediatric populations (3 months-1 year and 2-11 years) compared to the adult population for both bacterial infection (73% and 70% vs. 82%, respectively; P < .001) and viral infection (80% and 79% vs. 88%, respectively; P < .001). We did not observe classification differences based on illness severity as defined by ICU admission for bacterial or viral infections. The median AUC across all signatures for COVID-19 classification was 0.80 compared to 0.83 for viral classification in the same datasets. CONCLUSIONS: In this systematic comparison of 28 host gene expression signatures, we observed differences based on a signature's size and characteristics of the validation population, including age and infection type. However, populations used for signature discovery did not impact performance, underscoring the redundancy among many of these signatures. Furthermore, differential performance in specific populations may only be observable through this type of large-scale validation.

UMLF-COVID: an unsupervised meta-learning model specifically designed to identify X-ray images of COVID-19 patients.

BACKGROUND: With the rapid spread of COVID-19 worldwide, quick screening for possible COVID-19 patients has become the focus of international researchers. Recently, many deep learning-based Computed Tomography (CT) image/X-ray image fast screening models for potential COVID-19 patients have been proposed. However, the existing models still have two main problems. First, most of the existing supervised models are based on pre-trained model parameters. The pre-training model needs to be constructed on a dataset with features similar to those in COVID-19 X-ray images, which limits the construction and use of the model. Second, the number of categories based on the X-ray dataset of COVID-19 and other pneumonia patients is usually imbalanced. In addition, the quality is difficult to distinguish, leading to non-ideal results with the existing model in the multi-class classification COVID-19 recognition task. Moreover, no researchers have proposed a COVID-19 X-ray image learning model based on unsupervised meta-learning. METHODS: This paper first constructed an unsupervised meta-learning model for fast screening of COVID-19 patients (UMLF-COVID). This model does not require a pre-trained model, which solves the limitation problem of model construction, and the proposed unsupervised meta-learning framework solves the problem of sample imbalance and sample quality. RESULTS: The UMLF-COVID model is tested on two real datasets, each of which builds a three-category and four-category model. And the experimental results show that the accuracy of the UMLF-COVID model is 3-10% higher than that of the existing models. CONCLUSION: In summary, we believe that the UMLF-COVID model is a good complement to COVID-19 X-ray fast screening models.

Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics.

Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.

Have COVID-19-Related Economic Shocks Affected the Health Levels of Individuals in the United States and the United Kingdom?

This paper introduces a health index for measuring the health level of societies during the lockdown era, i. e., for the period from March 21, 2020 to April 7, 2020. For this purpose, individual-level survey data from the Global Behaviors and Perceptions in the COVID-19 Pandemic dataset are considered. We focus on cases in the United States and the United Kingdom, and the data come from 11,270 and 11,459 respondents, respectively. We then use unit root tests with structural breaks to examine whether COVID-19-related economic shocks significantly affect the health levels of the United States and the United Kingdom. The empirical results indicate that the health levels in the United States and the United Kingdom are not significantly affected by the COVID-19-related economic shocks. The evidence shows that government directives (such as lockdowns) did not significantly change the health levels of these societies.

Estrogen shields women from COVID-19 complications by reducing ER stress.

Estrogen hormone acts as a potential key player in providing immunity against certain viral infection. It is found to be associated in providing immunity against acute lungs inflammation and influenza virus by modulating cytokines storm and mediating adaptive immune alterations respectively. Women are less affected by SARS-CoV-2 infection because of the possible influence of estrogen hormone as compared to men. We hypothesized that SARS-CoV-2 causes stress in endoplasmic reticulum (ER) which in turn aggravates the infection, estrogen hormone might play key role in decreasing ER stress by activating estrogen mediated signaling pathways, results in unfolded protein response (UPR). Estrogen governs degradation of phosphotidylinositol 4,5-bisphosphate (PIP2) into diacylglycerol (DAG) and inositol triphosphate (IP3) with the help of phospholipase C. IP3 start in-fluxing Ca+2 ions that helps in UPR activation. To support our hypothesis, we analyzed the data of 162,392 COVID-19 patients to determine the relation of this disease with gender. We observed that 26% of women and 74% of men were affected by SARS-CoV-2. It indicated that women are less affected because of the possible influence of estrogen hormone in women.