Self-Assembled TLR7/8 Agonist-Mannose Conjugate as An Effective Vaccine Adjuvant for SARS-CoV-2 RBD Trimer.

Small synthetic TLR7/8-agonists can be used as vaccine adjuvants to enhance cell and humoral-mediated immune responses to specific antigens. Despite their potency, after local injection they can be dispersed to undesired body parts causing high reactogenicity, limiting their clinical applications. Here we describe a vaccination strategy that employs the covalent conjugate of a mannose and TLR7/8 agonist as a vaccine adjuvant to take advantage of mannose binding C-type lectins on dendritic cells to enhance the vaccine's immunogenicity. The mannose-TLR7/8 agonist conjugate can self-assemble into nanoparticles with the hydrophilic mannose on the outside and hydrophobic TLR7/8 agonist inside. Although its ability to stimulate HEK-BlueTM hTLR7/8 cells dropped, it can efficiently stimulate mouse bone marrow-derived dendritic cells as indicated by the up-regulation of CD80 and CD86, and higher cytokine expression levels of TNF-α, IL6, and IL-12p70 than the native TLR7/8 agonist. In vivo, vaccination using the SARS-CoV-2 RBD trimer as the antigen and the conjugate as the adjuvant induced a significantly higher amount of IgG2a. These results suggest that the mannose-TLR7/8-agonist conjugate can be used as an effective vaccine adjuvant.

Establishment of a quantitative RT-PCR detection of SARS-CoV-2 virus.

BACKGROUND: The outbreak of novel coronavirus disease 2019 (COVID-19) has become a public health emergency of international concern. Quantitative testing of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus is demanded in evaluating the efficacy of antiviral drugs and vaccines and RT-PCR can be widely deployed in the clinical assay of viral loads. Here, we developed a quantitative RT-PCR method for SARS-CoV-2 virus detection in this study. METHODS: RT-PCR kits targeting E (envelope) gene, N (nucleocapsid) gene and RdRP (RNA-dependent RNA polymerase) gene of SARS-CoV-2 from Roche Diagnostics were evaluated and E gene kit was employed for quantitative detection of COVID-19 virus using Cobas Z480. Viral load was calculated according to the standard curve established by series dilution of an E-gene RNA standard provided by Tib-Molbiol (a division of Roche Diagnostics). Assay performance was evaluated. RESULTS: The performance of the assay is acceptable with limit of detection (LOD) below 10E1 copies/µL and lower limit of quantification (LLOQ) as 10E2 copies/µL. CONCLUSION: A quantitative detection of the COVID-19 virus based on RT-PCR was established.

Fibrinolysis Therapy Combined with Deferred PCI versus Primary Angioplasty for STEMI Patients During the COVID-19 Pandemic: Preliminary Results from a Single Center.

INTRODUCTION: The efficacy of fibrinolysis therapy with deferred percutaneous coronary angioplasty (FPCI) versus primary angioplasty (PPCI) during the coronavirus disease 2019 (COVID-19) pandemic is unclear when medical quarantine is needed. PATIENTS AND METHODS: Acute ST segment elevation myocardial infarction (STEMI) patients underwent PPCI after finishing the screening protocol from January 23, 2020 to June 10, 2020 while FPCI was applied when COVID-19-confirmed cases reoccurred in Beijing near our hospital from June 11, 2020 to July 20, 2020. The door-to-balloon time (DTB) or door-to-needle time (DTN) as well as in-hospital adverse clinical outcomes were compared between the two groups. A propensity score-matched (PSM) analysis was performed to diminish the potential influence of confounding factors on the clinical outcomes. RESULTS: A total of 126 STEMI patients underwent PPCI after finishing the screening protocol and 17 patients received FPCI before PSM. Patients who received FPCI were younger than patients who underwent PPCI (50.8±14.0 versus 64.1±14.2 years, p=0.001), and chronic kidney disease (CKD) was less common in FPCI patients than in patients who underwent PPCI (0% versus 24.6%, p=0.024). The DTN was significantly shorter than DTB (25.8±4.2 versus 61.1±10.7, p=0.000) before PSM. The DTN was significantly shorter than DTB (26.9±4.2 versus 64.9±23.6, p=0.000); however, the incidence rate of in-hospital ischemia and bleeding adverse clinical outcomes were comparable between the two groups after PSM. CONCLUSION: Fibrinolysis therapy combined with deferred PCI can reduce the ischemia time and has a similar in-hospital adverse clinical outcome rate compared with patients who underwent primary PCI during the COVID-19 pandemic.

The Impact of the COVID-19 Pandemic and the Importance of Telemedicine in Managing Acute ST Segment Elevation Myocardial Infarction Patients: Preliminary Experience and Literature Review.

The coronavirus disease 2019 (COVID-19), which is caused by a novel coronavirus (SARS-COV-2), has compromised health care systems and normal management of patients with cardiovascular diseases [1-3]. Patients with non-communicable diseases, including acute myocardial infarction (AMI) are vulnerable to this stress [4, 5]. Acute ST segment elevation myocardial infarction (STEMI), the most critical type of AMI, is associated with high mortality even with modern medicine [6-8]. Timely reperfusion therapy is critical for STEMI patients because a short ischemia time is associated with better clinical outcomes and lower acute and long -term mortality [9-12]. The COVID-19 pandemic placed the management of STEMI patients in a difficult situation due to the need to balance timely reperfusion therapy and maintaining strict infection control practices [13, 14]. Telemedicine, which is used to deliver health care services using information or communication technology, provides an opportunity to carry out the evaluation, diagnosis, and even monitor the patients after discharge when social distancing is needed [15]. In this article, we reported our preliminary experience with the usefulness of telemedicine in managing STEMI patients during the COVID-19 pandemic. We also provided a review of this topic.

Comparison of Clinical Outcomes in Patients with ST Elevation Myocardial Infarction with Percutaneous Coronary Intervention and the Use of a Telemedicine App Before and After the COVID-19 Pandemic at a Center in Beijing, China, from August 2019 to March 2020.

BACKGROUND The efficacy of telemedicine in reducing delay times and short-term adverse clinical outcomes in patients with ST segment elevation myocardial infarction (STEMI) during the coronavirus disease 2019 (COVID-19) pandemic is unclear. This study compared outcomes in patients with STEMI who had percutaneous coronary intervention (PCI) and the use of a telemedicine app from August 2019 to March 2020 at a single center in Beijing, China. MATERIAL AND METHODS A total of 243 patients with STEMI who underwent PCI were consecutively enrolled and divided into 2 groups according to the date, before or after the pandemic. The 2 groups were further divided into patients who used the app for consulting and those who did not. RESULTS The time from symptom onset to calling an ambulance (SCT), door to balloon time (DTB), and total ischemia time (TIT) were significantly prolonged in patients after the pandemic. Patients who used the app had shorter SCT, DTB, and TIT before and after the pandemic compared to those who did not. Adverse clinical outcomes were significantly higher after compared with before the pandemic, despite the incidence rate of stroke, any revascularization, and stent thrombosis. However, there was no significant difference in short-term adverse clinical outcomes between patients who used the app and those who did not before and after the pandemic. CONCLUSIONS Telemedicine reduced the delay time of STEMI patients during the COVID-19 pandemic. The difference in short-term adverse clinical outcomes was not statistically significant between patients who used the app and those who did not.