Revealing the roles of TLR7, a nucleic acid sensor for COVID-19 in pan-cancer.

Recent studies suggested that cancer was a risk factor for coronavirus disease 2019 (COVID-19). Toll-like receptor 7 (TLR7), a severe acute respiratory syndrome 2 (SARS-CoV-2) virus's nucleic acid sensor, was discovered to be aberrantly expressed in many types of cancers. However, its expression pattern across cancers and association with COVID-19 (or its causing virus SARS-CoV-2) has not been systematically studied. In this study, we proposed a computational framework to comprehensively study the roles of TLR7 in COVID-19 and pan-cancers at genetic, gene expression, protein, epigenetic, and single-cell levels. We applied the computational framework in a few databases, including The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE), Human Protein Atlas (HPA), lung gene expression data of mice infected with SARS-CoV-2, and the like. As a result, TLR7 expression was found to be higher in the lung of mice infected with SARS-CoV-2 than that in the control group. The analysis in the Opentargets database also confirmed the association between TLR7 and COVID-19. There are also a few exciting findings in cancers. First, the most common type of TLR7 was "Missense" at the genomic level. Second, TLR7 mRNA expression was significantly up-regulated in 6 cancer types and down-regulated in 6 cancer types compared to normal tissues, further validated in the HPA database at the protein level. The genes significantly co-expressed with TLR7 were mainly enriched in the toll-like receptor signaling pathway, endolysosome, and signaling pattern recognition receptor activity. In addition, the abnormal TLR7 expression was associated with mismatch repair (MMR), microsatellite instability (MSI), and tumor mutational burden (TMB) in various cancers. Mined by the ESTIMATE algorithm, the expression of TLR7 was also closely linked to various immune infiltration patterns in pan-cancer, and TLR7 was mainly enriched in macrophages, as revealed by single-cell RNA sequencing. Third, abnormal expression of TLR7 could predict the survival of Brain Lower Grade Glioma (LGG), Lung adenocarcinoma (LUAD), Skin Cutaneous Melanoma (SKCM), Stomach adenocarcinoma (STAD), and Testicular Germ Cell Tumors (TGCT) patients, respectively. Finally, TLR7 expressions were very sensitive to a few targeted drugs, such as Alectinib and Imiquimod. In conclusion, TLR7 might be essential in the pathogenesis of COVID-19 and cancers.

Time series analysis revealed prognostic value of continuous nasopharyngeal SARS-CoV-2 nucleic acid quantification for COVID-19: A retrospective study of >3000 COVID-19 patients from 2 centers.

BACKGROUND: Early stratification of disease progression remains one of the major challenges towards the post-coronavirus disease 2019 (COVID-19) era. The clinical relevance of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid load is debated due to the heterogeneity in patients' underlying health conditions. We determined the prognostic value of nasopharyngeal viral load dynamic conversion for COVID-19. METHODS: The cycling threshold (Ct) values of 28,937 nasopharyngeal SARS-CoV-2 RT-PCRs were retrospectively collected from 3,364 COVID-19 patients during hospitalization and coordinated to the onset of disease progression. The ROC curve was utilized to determine the predictive performance of the rate of Ct value alteration between two consecutive RT-PCR runs within 48 h (ΔCt%) for disease transformation across patients with different COVID-19 severity and immune backgrounds, and further validated with 1,860 SARS-CoV-2 RT-PCR results from an independent validation cohort of 262 patients. For the 67 patients with severe COVID-19, Kaplan-Meier analysis was performed to evaluate the difference in survival between patients stratified by the magnitude of Ct value alteration between the late and early stages of hospitalization. RESULTS: The kinetics of viral nucleic acid conversion diversified across COVID-19 patients with different clinical characteristics and disease severities. The ΔCt% is a clinical characteristic- and host immune status-independent indicator for COVID-19 progression prediction (AUC = 0.79, 95 % CI = 0.76 to 0.81), which outperformed the canonical blood test markers, including c-reactive protein (AUC = 0.57, 95 % CI = 0.53 to 0.61), serum amyloid A (AUC = 0.61, 95 % CI = 0.54 to 0.68), lactate dehydrogenase (AUC = 0.61, 95 % CI = 0.56 to 0.67), d-dimer (AUC = 0.56, 95 % CI = 0.46 to 0.66), and lymphocyte count (AUC = 0.62, 95 % CI = 0.58 to 0.66). Patients with persistent high SARS-CoV-2 viral load (an increase of mean Ct value < 50 %) during the first 3 days of hospitalization demonstrated a significantly unfavorable survival (HR = 0.16, 95 % CI = 0.04 to 0.65, P = 2.41 × 10-3). CONCLUSIONS: Viral nucleic acid dynamics of SARS-CoV-2 eliminates the inter-patient variance of basic health conditions and therefore, can serve as a prognostic marker for COVID-19.

The influence of removing home advantage on the Chinese Football Super League.

BACKGROUND: Due to the COVID-19 pandemic, the 2020 season Chinese Super League (CSL) was held in neutral venues, this study aims to analyse the impact of removing home advantage (HA) in CSL. METHOD: 240 games of the CSL 2019 season (home and away double round-robin system) and 160 games of the 2020 season (in neutral venues) were analysed. 27 technical and tactical performance indicators were involved as dependent variables. A multiple linear regression model was established to analyse the influence of removing HA on the performance indicators. RESULTS: After moving from home stadium to neutral venue in 2020 season, goal, shot, shot on target, shot from outside box, shot from inside box, shot on target from inside box, corner kick, key pass, cross, breakthrough, tackle decreased significantly (p < 0.05), while yellow card and foul increased steeply (p < 0.05). Comparing with playing away match, in neutral venue, free kicks and pass accuracy enhanced radically (p < 0.05), while tackle, clearance and block shot dropped noticeably (p < 0.05). CONCLUSION: When removing HA and playing in the neutral venue, teams' performance dropped significantly. This study confirmed the positive impact of HA on the teams' performance and may help elite football teams make proper playing strategies regarding different match locations.

Acute psychological effects of Coronavirus Disease 2019 outbreak among healthcare workers in China: a cross-sectional study.

To study the acute psychological effects of Coronavirus Disease 2019 (COVID-19) outbreak among healthcare workers (HCWs) in China, a cross-sectional survey was conducted among HCWs during the early period of COVID-19 outbreak. The acute psychological effects including symptoms of depression, anxiety, and post-traumatic stress disorder (PTSD) were assessed using the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder (GAD-7) questionnaire, and the Impact of Event Scale-Revised (IES-R). The prevalence of depression, anxiety, and PTSD was estimated at 15.0%, 27.1%, and 9.8%, respectively. Having an intermediate technical title, working at the frontline, receiving insufficient training for protection, and lacking confidence in protection measures were significantly associated with increased risk for depression and anxiety. Being a nurse, having an intermediate technical title, working at the frontline, and lacking confidence in protection measures were risk factors for PTSD. Meanwhile, not worrying about infection was a protective factor for developing depression, anxiety, and PTSD. Psychological interventions should be implemented among HCWs during the COVID-19 outbreak to reduce acute psychological effects and prevent long-term psychological comorbidities. Meanwhile, HCWs should be well trained and well protected before their frontline exposure.