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Eur J Immunol ; 51(7): 1641-1651, 2021 07.
Article in English | MEDLINE | ID: covidwho-1473829


Emerging life-threatening viruses have posed great challenges to public health. It is now increasingly clear that epigenetics plays a role in shaping host-virus interactions and there is a great need for a more thorough understanding of these intricate interactions through the epigenetic lens, which may represent potential therapeutic opportunities in the clinic. In this review, we highlight the current understanding of the roles of key epigenetic regulators - chromatin remodeling and histone modification - in modulating chromatin openness during host defense against virus. We also discuss how the RNA modification m6A (N6-methyladenosine) affects fundamental aspects of host-virus interactions. We conclude with future directions for uncovering more detailed functions that epigenetic regulation exerts on both host cells and viruses during infection.

Antiviral Agents/immunology , Epigenesis, Genetic/genetics , Epigenesis, Genetic/immunology , Immunity, Innate/genetics , Immunity, Innate/immunology , Animals , Chromatin/genetics , Chromatin/immunology , Histones/genetics , Histones/immunology , Host Microbial Interactions/genetics , Host Microbial Interactions/immunology , Humans , RNA Processing, Post-Transcriptional/genetics , RNA Processing, Post-Transcriptional/immunology
Medicine (Baltimore) ; 100(12): e25083, 2021 Mar 26.
Article in English | MEDLINE | ID: covidwho-1150005


ABSTRACT: The purpose of this study was to investigate the predictive value of combined clinical and imaging features, compared with the clinical or radiological risk factors only. Moreover, the expected results aimed to improve the identification of severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) patients who may have critical outcomes.This retrospective study included laboratory-confirmed SARS-COV-2 cases between January 18, 2020, and February 16, 2020. The patients were divided into 2 groups with noncritical illness and critical illness regarding severity status within the hospitalization. Univariable and multivariable logistic regression models were used to explore the risk factors associated with clinical and radiological outcomes in patients with SARS-COV-2. The ROC curves were performed to compare the prediction performance of different factors.A total of 180 adult patients in this study included 20 critical patients and 160 noncritical patients. In univariate logistic regression analysis, 15 risk factors were significantly associated with critical outcomes. Of importance, C-reactive protein (1.051, 95% confidence interval 1.024-1.078), D-dimer (1.911, 95% CI, 1.050-3.478), and CT score (1.29, 95% CI, 1.053-1.529) on admission were independent risk factors in multivariate analysis. The combined model achieved a better performance in disease severity prediction (P = .05).CRP, D-dimer, and CT score on admission were independent risk factors for critical illness in adults with SARS-COV-2. The combined clinical and radiological model achieved better predictive performance than clinical or radiological factors alone.

COVID-19/epidemiology , COVID-19/physiopathology , Diagnostic Techniques and Procedures/statistics & numerical data , Adult , Aged , C-Reactive Protein/analysis , Female , Fibrin Fibrinogen Degradation Products/analysis , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , ROC Curve , Retrospective Studies , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Tomography, X-Ray Computed
Cell Host Microbe ; 29(2): 222-235.e4, 2021 02 10.
Article in English | MEDLINE | ID: covidwho-987276


The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an unprecedented public health crisis. Evidence suggests that SARS-CoV-2 infection causes dysregulation of the immune system. However, the unique signature of early immune responses remains elusive. We characterized the transcriptome of rhesus macaques and mice infected with SARS-CoV-2. Alarmin S100A8 was robustly induced in SARS-CoV-2-infected animal models as well as in COVID-19 patients. Paquinimod, a specific inhibitor of S100A8/A9, could rescue the pneumonia with substantial reduction of viral loads in SARS-CoV-2-infected mice. Remarkably, Paquinimod treatment resulted in almost 100% survival in a lethal model of mouse coronavirus infection using the mouse hepatitis virus (MHV). A group of neutrophils that contributes to the uncontrolled pathological damage and onset of COVID-19 was dramatically induced by coronavirus infection. Paquinimod treatment could reduce these neutrophils and regain anti-viral responses, unveiling key roles of S100A8/A9 and aberrant neutrophils in the pathogenesis of COVID-19, highlighting new opportunities for therapeutic intervention.

Alarmins/pharmacology , Antiviral Agents/pharmacology , COVID-19/drug therapy , Neutrophils/drug effects , SARS-CoV-2/drug effects , Animals , COVID-19/metabolism , COVID-19/virology , Disease Models, Animal , Female , Humans , Macaca mulatta , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Neutrophils/metabolism , Transcriptome , Viral Load