Interaction between hepatitis B virus and SARS-CoV-2 infections

Coronavirus disease 2019(COVID-19)has become a global pandemic and garnered international attention.The causative pathogen of COVID-19 is severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),a novel,highly contagious coronavirus.Numerous studies have reported that liver injury is quite common in patients with COVID-19.Hepatitis B has a worldwide distribution as well as in China.At present,hepatitis B virus(HBV)remains a leading cause of cirrhosis,liver failure,and hepatocellular carcinoma.Because both viruses challenge liver physiology,it raises questions as to how coinfection with HBV and SARS-CoV-2 affect disease progression and mortality.Is there an increased risk of COVID-19 in patients with HBV infection?In this review,we summarize the current reports of SARS-CoV-2 and HBV coinfection and elaborate the interaction of the two diseases.The emphasis was placed on evaluating the impact of HBV infection on disease severity and clinical outcomes in patients with COVID-19 and discussing the potential mechanism behind this effect.

Cytokine storm promoting T cell exhaustion in severe COVID-19 revealed by single cell sequencing data analysis

Background:Evidence has suggested that cytokine storms may be associated with T cell exhaustion(TEX)in COVID-19.However,the interaction mechanism between cytokine storms and TEX remains unclear.Methods:With the aim of dissecting the molecular relationship of cytokine storms and TEX through single-cell RNA sequencing data analysis,we identified 14 cell types from bronchoalveolar lavage fluid of COVID-19 patients and healthy people.We observed a novel subset of severely exhausted CD8 T cells(Exh T_CD8)that co-expressed multiple inhibitory receptors,and two macrophage subclasses that were the main source of cytokine storms in bronchoalveolar.Results:Correlation analysis between cytokine storm level and TEX level suggested that cytokine storms likely promoted TEX in severe COVID-19.Cell–cell communication analysis indicated that cytokines(e.g.CXCL10,CXCL11,CXCL2,CCL2,and CCL3)released by macrophages acted as ligands and significantly interacted with inhibitory receptors(e.g.CXCR3,DPP4,CCR1,CCR2,and CCR5)expressed by Exh T_CD8.These interactions formed the cytokine–receptor axes,which were also verified to be significantly correlated with cytokine storms and TEX in lung squamous cell carcinoma.Conclusions:Cytokine storms may promote TEX through cytokine-receptor axes and be associated with poor prognosis in COVID19.Blocking cytokine-receptor axes may reverse TEX.Our finding provides novel insights into TEX in COVID-19 and new clues for cytokine-targeted immunotherapy development.

Emerging resistance vs. losing response to immune check point inhibitors in renal cell carcinoma: two differing phenomena

The introduction of immune checkpoint inhibitor (ICI) has revolutionized the treatment of metastatic renal cell carcinoma (mRCC) and has dramatically improved the outcomes of patients. The use of monotherapy or combinations of ICIs targeting PD-1/PD-L1 and CTLA-4, as well as the addition of ICIs with tyrosine kinase inhibitors, has significantly enhanced the overall survival of mRCC patients. Despite these promising results, there remains a subset of patients who either do not respond to treatment (primary resistance) or develop resistance to therapy over time (acquired resistance). Understanding the mechanisms underlying the development of resistance to ICI treatment is crucial in the management of mRCC, as they can be used to identify new targets for innovative therapeutic strategies. Currently, there is an unmet need to develop new predictive and prognostic biomarkers that can aid in the development of personalized treatment options for mRCC patients. In this review, we summarize several mechanisms of ICI resistance in RCC, including alterations in tumor microenvironment, upregulation of alternative immune checkpoint pathways, and genetic and epigenetic changes. Additionally, we highlight potential strategies that can be used to overcome resistance, such as combination therapy, targeted therapy, and immune modulation.