RESUMEN
The COVID-19 pandemic caused by SARS-CoV-2 virus is an ongoing global health burden. Severe cases of COVID-19 and the rare cases of COVID-19 vaccine-induced-thrombotic-thrombocytopenia (VITT) are both associated with thrombosis and thrombocytopenia; however, the underlying mechanisms remain inadequately understood. Both infection and vaccination utilize the spike protein receptor-binding domain (RBD) of SARS-CoV-2. We found that intravenous injection of recombinant RBD caused significant platelet clearance in mice. Further investigation revealed the RBD could bind platelets, cause platelet activation, and potentiate platelet aggregation, which was exacerbated in the Delta and Kappa variants. The RBD-platelet interaction was partially dependent on the ß3 integrin as binding was significantly reduced in ß3-/- mice. Furthermore, RBD binding to human and mouse platelets was significantly reduced with related αIIbß3 antagonists and mutation of the RGD (arginine-glycine-aspartate) integrin binding motif to RGE (arginine-glycine-glutamate). We developed anti-RBD polyclonal and several monoclonal antibodies (mAbs) and identified 4F2 and 4H12 for their potent dual inhibition of RBD-induced platelet activation, aggregation, and clearance in vivo, and SARS-CoV-2 infection and replication in Vero E6 cells. Our data show that the RBD can bind platelets partially though αIIbß3 and induce platelet activation and clearance, which may contribute to thrombosis and thrombocytopenia observed in COVID-19 and VITT. Our newly developed mAbs 4F2 and 4H12 have potential not only for diagnosis of SARS-CoV-2 virus antigen but also importantly for therapy against COVID-19.
RESUMEN
Background: Post-traumatic stress disorder (PTSD) has various risk factors, complex pathogenesis, and diverse symptoms, and is often comorbid with other injuries and diseases, making forensic diagnosis difficult. Methods: To explore the current research status and trends of PTSD, we used the Web of Science Core Collection databases to screen PTSD-related literature published between 2010 and 2021 and CiteSpace to perform bibliometric analysis. Results: In recent years, PTSD-related research has grown steadily. The countries and institutions with the most research results were the United States and England, and King's College London and Boston University, respectively. Publications were identified from 2,821 different journals, including 13 forensic-related journals, but the journal distribution was relatively scattered and there was a lack of professional core journals. Keyword co-occurrence and clustering identified many hot topics; "rat model," "mental health," and "satisfaction" were the topics most likely to have a clear effect on future research. Analysis extracted nine turning points from the literature that suggested that neural network centers, the hypothalamic-pituitary-adrenal axis, and biomarkers were new research directions. It was found that COVID-19 can cause severe psychological stress and induce PTSD, but the relationship needs further study. The literature on stress response areas and biomarkers has gradually increased over time, but specific systemic neural brain circuits and biomarkers remain to be determined. Conclusion: There is a need to expand the collection of different types of biological tissue samples from patients with different backgrounds, screen PTSD biomarkers and molecular targets using multi-omics and molecular biology techniques, and establish PTSD-related molecular networks. This may promote a systematic understanding of the abnormal activation of neural circuits in patients with PTSD and help to establish a personalized, accurate, and objective forensic diagnostic standard.