Total Infectome Characterization of Respiratory Infections during the 2022–23 COVID-19 Outbreak in China Revealed Extensive Coinfections with Links to SARS-CoV-2 Status, Age, and Disease Severity

Between 7 December 2022 and 28 February 2023, China experienced a new wave of COVID-19 that swept across the entire country and resulted in an increasing amount of respiratory infections and hospitalizations. The purpose of this study is to reveal the intensity and composition of coinfecting microbial agents. In total, 196 inpatients were recruited from The Third People’s Hospital of Shenzhen, and 169 respiratory and 73 blood samples were collected for metagenomic next-generation sequencing. The total “Infectome” was characterized and compared across different groups defined by the SARS-CoV-2 detection status, age groups, and severity of disease. Our results revealed a total of 22 species of pathogenic microbes (4 viruses, 13 bacteria, and 5 fungi), and more were discovered in the respiratory tract than in blood. The diversity of the total infectome was highly distinguished between respiratory and blood samples, and it was generally higher in patients that were SARS-CoV-2-positive, older in age, and with more severe disease. At the individual pathogen level, HSV-1 seemed to be the major contributor to these differences observed in the overall comparisons. Collectively, this study reveals the highly complex respiratory infectome and high-intensity coinfection in patients admitted to the hospital during the period of the 2023 COVID-19 pandemic in China

GATA2−/− human ESCs undergo attenuated endothelial to hematopoietic transition and thereafter granulocyte commitment

Background: Hematopoiesis is a progressive process collectively controlled by an elaborate network of transcription factors (TFs). Among these TFs, GATA2 has been implicated to be critical for regulating multiple steps of hematopoiesis in mouse models. However, whether similar function of GATA2 is conserved in human hematopoiesis, especially during early embryonic development stage, is largely unknown. Results: To examine the role of GATA2 in human background, we generated homozygous GATA2 knockout human embryonic stem cells (GATA2−/− hESCs) and analyzed their blood differentiation potential. Our results demonstrated that GATA2−/− hESCs displayed attenuated generation of CD34+CD43+ hematopoietic progenitor cells (HPCs), due to the impairment of endothelial to hematopoietic transition (EHT). Interestingly, GATA2−/− hESCs retained the potential to generate erythroblasts and macrophages, but never granulocytes. We further identified that SPI1 downregulation was partially responsible for the defects of GATA2−/− hESCs in generation of CD34+CD43+ HPCs and granulocytes. Furthermore, we found that GATA2−/− hESCs restored the granulocyte potential in the presence of Notch signaling. Conclusion: Our findings revealed the essential roles of GATA2 in EHT and granulocyte development through regulating SPI1, and uncovered a role of Notch signaling in granulocyte generation during hematopoiesis modeled by human ESCs

Subepicardial endothelial cells invade the embryonic ventricle wall to form coronary arteries

Cardiolog