ABSTRACT
RNA aptamers provide useful biological probes and therapeutic agents. New methodologies to screen RNA aptamers will be valuable by complementing the traditional Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Meanwhile, repurposing clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated systems (Cas) has expanded their utility far beyond their native nuclease function. Here, CRISmers, a CRISPR/Cas-based novel screening system for RNA aptamers based on binding to a chosen protein of interest in a cellular context, is presented. Using CRISmers, aptamers are identified specifically targeting the receptor binding domain (RBD) of the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Two aptamer leads enable sensitive detection and potent neutralization of SARS-CoV-2 Delta and Omicron variants in vitro. Intranasal administration of one aptamer, further modified with 2'-fluoro pyrimidines (2'-F), 2'-O-methyl purines (2'-O), and conjugation with both cholesterol and polyethylene glycol of 40 kDa (PEG40K), achieves effective prophylactic and therapeutic antiviral activity against live Omicron BA.2 variants in vivo. The study concludes by demonstrating the robustness, consistency, and potential broad utility of CRISmers using two newly identified aptamers but switching CRISPR, selection marker, and host species.
ABSTRACT
BACKGROUND: Coronavirus Disease 2019 (COVID-19) has become a worldwide pandemic and affected more than 227 countries or territories, resulting in more than 25 million cases with over 0â¢85 million deaths, as of September 2, 2020. Taiwan has been successful in countering the COVID-19 outbreak, however, the potential risk for asymptomatic infections and the prevalence rates remain unknown. We aimed to estimate the seroprevalence of COVID-19 in Taiwan via serologically testing hospital patients with neither symptoms indicative of nor positive nucleic acid test for SARS-CoV-2 infection. METHODS: Residual specimens from laboratory blood tests for outpatient and emergency department patients visiting a medical centre in Taipei, Taiwan, within one week in May and another in July, 2020, were collected. We used Elecsys Anti-SARS-CoV-2 Assay to screen and further validated cases with high cutoff index by a confirmatory ELISA assay. We also analysed antibody responses against SARS-CoV-2 along disease progression in four nucleic acid test confirmed COVID-19 patients. FINDINGS: Blood samples from a total of 14,765 patients were tested. The unweighted seroprevalence of anti-SARS-CoV-2 antibodies was 0â¢07% [95% CI, 0â¢04%-0â¢13%]; after weighting with the population demographics of Taiwan, the estimated overall seroprevalence was 0â¢05% [95% CI, 0â¢02%-0â¢10%]. Furthermore, based on data of the four COVID-19 cases, the seroconversion dates for IgM were as early as 9 days and that for IgG 11 days after symptoms onset. INTERPRETATION: We screened the anti-SARS-CoV-2 antibodies in a small-scale population-based study and observed an approximately 0â¢05% seroprevalence of COVID-19, indicating that the current containment protocols emphasising mask wearing, hand washing, social distancing and mandatory quarantine for all incomers are effective in Taiwan. FUNDING: Taipei Veterans General Hospital, Taipei, Taiwan.
ABSTRACT
Corona virus disease 2019 (COVID-19) is an emerging pandemic of highly contagious caused by severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2). Understanding the infectivity of various clinical samples and its transmission routes have been the main focus of current researches since the causative pathogens was identified. In this comprehensive review, we discuss the viral shedding from different clinical samples and reveal that infectious virus may be mainly discharged through respiratory and digestive systems. Also, SARS-CoV-2 showed a potential tropism for eyes, kidney, testis, placenta and other extrapulmonary tissues and high viral loads correlated with severe conditions. A better understanding of viral shedding may help the studies on pathogenesis and transmission of SARS-CoV-2 and provide suggestions for the disease control.
ABSTRACT
Objective: To understand the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) specific IgM, IgC and IgA responses in corona Virus disease 2019(COVID-19) patients. Method: The SARS-CoV-2-specific IgM and IgG levels were determined by the enzyme-linked immunosorbent assay while IgA 1evels were detected by the chemiluminescence immune detection systems.
ABSTRACT
Objective: To analysis the related factors that influenced the elimination of virus in patients with coronavirus disease 2019 (COVID-19), and help with its prevention and control.
ABSTRACT
Background: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic, which has caused unprecedented damage to human health and life. The present study aimed to carry out and discover asymptomatic infected individuals in Shenzhen, China. The data will provide the control measures to stop COVID-19 prevalence. Methods: The study was a retrospective review of medical records from 462 confirmed patients with COVID-19 and 45 asymptomatic infected individuals in Shenzhen from January 19 to April 30, 2020; this is a retrospective, observational multicenter study. Results: A total of 462 confirmed cases were diagnosed in Shenzhen from January 19 to April 30, 2020. The cohort included 423 domestic cases (91.56%, 95% confidence interval [CI]: 88.67-93.76) and 39 (8.44%, 95% CI: 6.24-11.33) imported cases from other countries. Moreover, a total of 45 asymptomatic infections were found, encompassing 31 (68.89%, 95% CI: 54.34-80.47) local infections and 14 (31.11%, 95% CI: 19.53-45.66) individuals imported from other countries. The proportion of asymptomatic infected persons in Shenzhen is continuously increasing (Z = 13.19, p < 0.0001). The total number of local asymptomatic infections was more than that in other provinces (χ2 = 118.83, p < 0.0001). The proportion of asymptomatic infected individuals among cases imported from other countries was higher than the domestic cases (χ2 = 22.51, p < 0.0001, odds ratio = 4.90, 95% CI: 2.40-9.98). Conclusions: The proportion of asymptomatic infection is increasing. Hence, development and application of the diagnosis method with high sensitivity and specificity play a critical role in reducing COVID-19 global epidemics.