No abstract

Patients infected with SARS-CoV-2 variants lacking open reading frame 8 (ORF8) have been associated with milder infection and disease outcome, but the molecular mechanism behind how this viral accessory protein mediates disease pathogenesis is not yet known. In our study, we revealed that secreted ORF8 protein mimics host IL-17 to activate IL-17 receptors A and C (IL-17RA/C) and induces a significantly stronger inflammatory response than host IL-17A, providing molecular insights into the role of ORF8 in COVID-19 pathogenesis and serving as a potential therapeutic target.

While pregnancy increases the risk for severe COVID19, the clinical and immunological implications of COVID19 on maternal-fetal health remain unknown. Here, we present the clinical and immunological landscapes of 93 COVID19 mothers and 45 of their SARS-CoV-2-exposed infants through comprehensive serum proteomics profiling for >1400 cytokines of their peripheral and cord blood specimens. Prenatal SARS-CoV-2 infection triggers NF-κB-dependent proinflammatory immune activation. Pregnant women with severe COVID19 show increased inflammation and unique IFNλ antiviral signaling, with elevated levels of IFNL1 and IFNLR1. Furthermore, SARS-CoV-2 infection re-shapes maternal immunity at delivery altering the expression of pregnancy complication-associated cytokines, inducing MMP7, MDK, ESM1, and reducing BGN and CD209. Finally, COVID19-exposed infants exhibit induction of T cell-associated cytokines (IL33, NFATC3 and CCL21), while some undergo IL-1β/IL-18/CASP1 axis-driven neonatal respiratory distress despite birth at term. Our findings demonstrate COVID19-induced immune rewiring in both mothers and neonates, warranting long-term clinical follow-up to mitigate potential health risks.

Genome sequencing has shown strong capabilities in the initial stages of the COVID-19 pandemic such as pathogen identification and virus preliminary tracing. While the rapid acquisition of SARS-CoV-2 genome from clinical specimens is limited by their low nucleic acid load and the complexity of the nucleic acid background. To address this issue, we modified and evaluated an approach by utilizing SARS-CoV-2-specific amplicon amplification and Oxford Nanopore PromethION platform. This workflow started with the throat swab of the COVID-19 patient, combined reverse transcript PCR, and multi-amplification in one-step to shorten the experiment time, then can quickly and steadily obtain high-quality SARS-CoV-2 genome within 24 h. A comprehensive evaluation of the method was conducted in 42 samples: the sequencing quality of the method was correlated well with the viral load of the samples; high-quality SARS-CoV-2 genome could be obtained stably in the samples with Ct value up to 39.14; data yielding for different Ct values were assessed and the recommended sequencing time was 8 h for samples with Ct value of less than 20; variation analysis indicated that the method can detect the existing and emerging genomic mutations as well; Illumina sequencing verified that ultra-deep sequencing can greatly improve the single read error rate of Nanopore sequencing, making it as low as 0.4/10,000 bp. In summary, high-quality SARS-CoV-2 genome can be acquired by utilizing the amplicon amplification and it is an effective method in accelerating the acquisition of genetic resources and tracking the genome diversity of SARS-CoV-2. Supplementary Information The online version contains supplementary material available at 10.1007/s12250-021-00378-8.

No abstract

BackgroundThe number of cesarean scar pregnancy (CSP) has significantly increased in the recent decade. Although uterine artery embolization (UAE) has been adopted to minimize the blood loss during uterine curettage removing of CSP, massive bleeding and uterine rupture can still be frequently encountered. The aim of this study was to compare the efficacy and safety of a novel combined laparoscopy and hysteroscopy technique with the traditional curettage in removing the conceptus and repairing the incision defect following the UAE management of CSP.MethodsThe CSP patients (n = 58) diagnosed between March 1, 2005 and March 1, 2010 were enrolled in three medical centers in Shanghai, China. All of these patients have undergone intra-arterial methotrexate, UAE and one of the following treatments: combined laparoscopy and hysteroscopy (study group, n = 25) and uterine curettage (control group, n = 33). Their medical records and 2-year outcomes were reviewed. The CSP removal rate, amount of blood loss during the treatment, incision repair rate (note: the post-curettage healing process of the incision defect was seen as a form of natural incision repairing, i.e., the self-repair mode), hospital stay, β-hCG regression time and postoperative sequelae were compared between two groups.ResultsThe CSP removal rate in the study group (100%) was significantly higher than that (79%) in the control group (p = 0.024). The average blood loss was 78.0 mL in the study group, which was much less than the 258.5 mL (p = 0.004) in the control group. A satisfactory incision repair rate (96%) was achieved in the study group, while it was 25% (p < 0.001) in the control group. Moreover, the study group had significantly shorter hospital stays (p = 0.043) and β-hCG regression times (p = 0.033), lower rates of postoperative abdominal pain (p = 0.035) and menstruation abnormalities (p = 0.043).ConclusionsCombined laparoscopy and hysteroscopy is much safer and more effective than uterine curettage as a supplementary measure to remove the conceptus and repair the cesarean incision following the UAE management of CSP.

No abstract

No abstract