Efficient Targeted Delivery of Bifunctional Circular Aptamer ASO Chimera to Suppress the SARS-CoV-2 Proliferation and Inflammation (preprint)

Inhibition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and excessive inflammation is the current task in the prevention and treatment of COVID-19. Here, we designed a dual-function circular aptamerASO chimera (circSApt-NASO) to suppress SARS-CoV-2 replication and inflammation. The chemically unmodified circSApt-NASO exhibited high serum stability by artificial cyclization, significantly enhancing the utility of oligonucleotides. It presents great efficiency in knocking down, demonstrating the superiority of the circular ASO as a novel tool for sequence-specific silencing of gene expression. Furthermore, we propose and demonstrate that the SApt binding to spike protein enables the chimera to be efficiently delivered into the susceptible host cells expressing ACE2 along with the infection of SARS-CoV-2. At high concentrations of SARS-CoV-2, the efficiency of targeted delivery of circSApt-NASO can even be compared to transfection. Among them, the anti-spike aptamer (SApt) that blocks the Spike-TLR4 interaction potently inhibits spike-induced inflammation. The NASO targeting to silence N genes not only display robust anti-N-induced inflammatory activity, but also achieve efficient inhibition of SARS-CoV-2 replication. Therefore, benefiting from the high stability of the cyclization, anti-spike aptamer-dependent and viral infection-mediate targeted delivery, the circSApt-NASO displays robust potential against authentic SARS-CoV-2 and Omicron (B.1.1.529), providing a promising specific anti-inflammatory and anti-proliferative reagent for therapeutic COVID-19 based on the oligonucleotide therapeutics strategy.

The COVID-19 Pandemic and Its Impact on Tourism: The Effect of Tourism Knowledge on Risk Perception, Attitude, and Intention

This study used structural equation modeling and examined how tourists’ risk perceptions and intentions are determined by their knowledge of tourism risk and infectious diseases. Data were collected through an online survey with Chinese people who had traveled within the past six months. The analysis revealed that tourists’ knowledge caused a reduction in risk perception and risks associated with tourism activities negatively impacted tourists’ attitudes. Therefore, this study confirmed the relationship between tourists’ knowledge and their risk perception, and its results can be used to reduce tourists’ anxieties and promote safe tourism during the pandemic. [ FROM AUTHOR] Copyright of Journal of Quality Assurance in Hospitality & Tourism is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Abnormal Upregulation of Cardiovascular Disease Biomarker PLA2G7 Induced by Proinflammatory Macrophages in COVID-19 patients (preprint)

BACKGROUNDCoronavirus disease 2019 (COVID-19) triggers distinct patterns of pneumonia progression with multiorgan disease, calling for cell- and/or tissue-type specific host injury markers. METHODSAn integrated hypothesis-free single biomarker analysis framework was performed on nasal swabs (n = 484) from patients with COVID-19 in GSE152075. The origin of candidate biomarker was assessed in single-cell RNA data (GSE145926). The candidate biomarker was validated in a cross-sectional cohort (n = 564) at both nucleotide and protein levels. RESULTSPhospholipase A2 group VII (PLA2G7) was identified as a candidate biomarker in COVID-19. PLA2G7 was predominantly expressed by proinflammatory macrophages in lungs emerging with progression of COVID-19. In the validation stage, PLA2G7 was found in patients with COVID-19 and pneumonia, especially in severe pneumonia, rather than patients suffered mild H1N1 influenza infection. Up to 100% positive rates of PLA2G7 were positively correlated with not only viral loads in patients with COVID-19 but also severity of pneumonia in non-COVID-19 patients. Although Ct values of PLA2G7 in severe pneumonia was significantly lower than that in moderate pneumonia (P = 7.2e-11), no differences were observed in moderate pneumonia with COVID-19 between severe pneumonia without COVID-19 (P = 0.81). Serum protein levels of PLA2G7, also known as lipoprotein-associated phospholipase A2 (Lp-PLA2), were further found to be elevated and beyond the upper limit of normal in patients with COVID-19, especially among the re-positive patients. CONCLUSIONSWe firstly identified and validated PLA2G7, a biomarker for cardiovascular diseases (CVDs), was abnormally enhanced in COVID-19 patients at both nucleotide and protein aspects. These findings provided indications into the prevalence of cardiovascular involvements seen in COVID-19 patients. PLA2G7 could be a hallmark of COVID-19 for monitoring disease progress and therapeutic response. FUNDINGThis study was supported by grants from China Mega-Projects for Infectious Disease (2018ZX10711001), National Natural Science Foundation of China (82041023).

Coronavirus disease 2019 in pregnancy.

OBJECTIVES: This study aimed to compare clinical courses and outcomes between pregnant and reproductive-aged non-pregnant women with COVID-19, and to assess the vertical transmission potential of COVID-19 in pregnancy. METHODS: Medical records of pregnant and reproductive-aged non-pregnant women hospitalized with COVID-19 from January 15 to March 15, 2020 were retrospectively reviewed. The severity of disease, virus clearance time, and length of hospital stay were measured as the primary objective, while the vertical transmission potential of COVID-19 was also assessed. RESULTS: Eighty-two patients (28 pregnant women, 54 reproductive-aged non-pregnant women) with laboratory-confirmed COVID-19 were enrolled in this study. Univariate regression indicated no association between pregnancy and severity of disease (OR 0.73, 95% CI 0.08-5.15; p=0.76), virus clearance time (HR 1.16, 95% CI 0.65-2.01; p=0.62), and length of hospital stay (HR 1.10, 95% CI 0.66-1.84; p=0.71). Of the pregnant women, 22 delivered 23 live births, either by cesarean section (17, 60.7%) or vaginal delivery (5, 17.9%), and no neonate was infected with SARS-CoV-2. CONCLUSIONS: Pregnant women have comparable clinical courses and outcomes with reproductive-aged non-pregnant women when infected with SARS-CoV-2. No evidence supported vertical transmission of COVID-19 in the late stage of pregnancy, including vaginal delivery.

The Value of High-flow Nasal Cannula Oxygen Therapy in Treating Patients With Severe Novel Coronavirus Pneumonia (preprint)

Objective This study aimed to investigate the value of high-flow nasal cannula (HNFC) oxygen therapy in treating patients with severe novel coronavirus pneumonia (COVID-19).Methods The clinical data of 22 patients with severe COVID-19 were collected. The heart rate (HR), respiratory rate (RR) and oxygenation index (PO2/FiO2) at 0, 6, 24 and 72 hours after treatment were compared between the HFNC oxygen therapy group and the conventional oxygen therapy (COT) group. In addition, the white blood cell (WBC) count, lymphocyte (L) count, C-reactive protein (CRP) and procalcitonin (PCT) were compared before and at 72 hours after oxygen therapy treatment.Results Of the included patients, 12 were assigned to the HFNC oxygen therapy group and 10 were assigned to the COT group. The differences in HR, RR, PaO2/FiO2, WBC, L, CRP and PCT at 0 hours between the two groups were not statistically significant. At 6 hours after treatment with the two oxygen therapies, HR, RR and PaO2/FiO2 were better in the HFNC oxygen therapy group than in the COT group (p < 0.05), while at 24 and 72 hours after treatment with the two oxygen therapies, PaO2/FiO2 was better in the HFNC oxygen therapy group than in the COT group (p < 0.05), but the differences in HR and RR were not statistically significant. At 72 hours after treatment, L and CRP had significantly improved in the HFNC oxygen therapy group compared with the COT group, but the differences in WBC and PCT were not statistically significant. The length of stay in the intensive care unit (ICU) and the total length of hospitalization were shorter in the HFNC oxygen therapy group than in the COT group, and the differences between the two groups were statistically significant.Conclusion Compared with COT, early application of HFNC oxygen therapy in patients with severe COVID-19 can significantly improve oxygenation and RR, and HFNC oxygen therapy can improve the infection indexes of patients and reduce the length of stay in the ICU of patients. Therefore, it has high clinical application value.

Eosinopenia Phenotype in Patients with Coronavirus Disease 2019: A Multi-center Retrospective Study from Anhui, China (preprint)

Background: Coronavirus disease 19 (COVID-19) has become a global unprecedented pandemic infecting more than one millon people, which is declared by WHO as a international public health emergency. Eosinopenia may predict a poor prognosis of COVID-19. However, to date, there is no detailed analysis of the clinical characteristics of COVID-19 patients with eosinopenia. Research question: The aim of this study was to describe clinical characteristics of COVID-19 patients with eosinopenia. Study Design and Methods: This was a multi-center retrospective study conducted in three tertiary hospitals. A total of 59 patients with COVID-19 were reviewed from January 23, 2020 to March 10, 2020. We described clincial characteristics of patients with COIVD-19 and eosinopenia phenotype. Results: The median age of patients with COVID-19 was 39 years old, and 32 (54,2%) were male. Patients with severe type had higher proportions of dyspnea (50%) and gastrointestinal symptoms (50%) compared with mild or moderate patients. Laboratory findings indicated that lower counts of lymphocyte and eosnophils were observed in patients with severe type. Cough, sputum, and fatigue were more common symptoms in eosinopenia patients compared with non-eosinopenia patients. High proportion of comorbidities was observed in eosinopenia patients. Laboratory findings indicated that lymphocyte counts (median: 101 cells/l ) in eosinopenia patients were significantly less than those of non-eosinopenia patients (median: 167 cells/l, p<0.001). The use of corticosteroids therapy in COVID-19 patients with eosinopenia were notably higher than those in patients with non-eosinopenia (50% vs 13.8%, respectively, p=0.005). Compared with parameters in non-eosinopenia patients, eosinopenia patients were more inclined to have less lymphocyte counts (OR value 6.566, 95%CI[1.101-39.173], p=0.039). Interpretation Eosinopenia are very common in COVID-19 patient, particularly in severe patients. Common symptoms included fever, cough, sputum, and fatigue are frequent in eosinopenia patients. Eosinopenia may represent a novel phenotype in COVID-19, which needs further investigation.

HRCT Features of COVID-19 Patients Admitted out of Wuhan: Comparison against Common Pneumonia (preprint)

Background: Chest CT is working as a first-line imaging modality for diagnosing Corona Virus Disease 2019 (COVID-19). Whether the CT findings could differentiate between the COVID-19 admitted out of Wuhan and common pneumonia has not been investigated. This study aimed to compare the chest CT features of patients with COVID-19 admitted out of Wuhan, as against the patients with common pneumonia. Methods: This retrospective study enrolled 37 individuals with COVID-19 from six medical centers out of Wuhan from January 17 th to February 26 th . Another group of 41 patients with acute pneumonia collected from the same timeframe in 2019 were enrolled as the control group. All the patients had high-resolution chest CT (HRCT) scans. Clinical variables were recorded including exposure history, clinical symptoms and laboratory findings. For each HRCT, pulmonary lesions including ground-glass opacification (GGO), consolidation, and evidence of fibrosis were recorded. The Student’s t test or Wilcoxon’s test was used for comparison between COVID-19 and common pneumonia. Spearman correlation was used to evaluate correlations between the pneumonia findings on CT and clinical variables.  Results: A total of 37 patients (M/F:19/18; 43.73±16.71 years) in COVID-19 group and 41(M/F:13/28; 49.77±15.00 years) in common pneumonia group were evaluated. Patients with COVID-19 demonstrated a typical pattern of bilateral, multi-lobal GGO, sometimes with consolidation and fibrosis, but a mild degree of pneumonia findings than the control group ( P = 0.0024). 23/37 (62.16%) patients with COVID-19 had a preferable subpleural distribution, while the patients with common pneumonia had higher frequency of peribronchovascular pattern (16/41, 39.02%, P =0.0046). The duration between the illness onset and CT were significantly correlated with the severity scores in both groups. Conclusion: Patients with COVID-19 admitted out of Wuhan demonstrated a milder pulmonary change and a preferable subpleural pattern on HRCT when comparing with the patients with common pneumonia.