Advances in the application of CRISPR-Cas system for SARS-CoV-2 diagnostic test

The outbreak of coronavirus disease 2019（COVID-19）, caused by severe acute respiratory syndrome coronavirus（SARS-CoV-2） at the end of 2019, results in a global rapid pandemic.The emerging infectious disease is life threaten and profoundly undermines the normal operation all over the world.Rapid and accurate detection of SARS-CoV-2 is an essential component of efforts to combat SARS-CoV-2 spread.Although many technologies for SARS-CoV-2 detection have been commercialized and have played a role in the control of COVID-19 epidemic to some extent yet, each of them is still with certain limitations.Recently, increasing number of teams attempt to detect SARS-CoV-2 by CRISPR-Cas（clustered regularly interspaced short palindromic repeats-Cas） system.With excellent specificity and sensitivity, it has been believed to be a potential technology in COVID-19 diagnosis and therapy.The review provides an overview of CRISPR-Cas system for SARS-CoV-2 detection and COVID-19 therapy, along with its clinical translation potential.Hope it has some referential significance for the control of SARS-CoV-2 spread and COVID-19 epidemic.

Polyketone metabolites isolated from Rhodiola tibetica endohytic fungus Alternaria sp. HJT-Y7 and their SARS-CoV-2 virus inhibitory activitives.

Six new polyketone metabolites, compounds (1-6) and seven known polyketone compounds (7-13) were isolated from Rhodiola tibetica endophytic fungus Alternaria sp. The structural elucidation of five new polyketone metabolites were elucidated on the basis of spectroscopic including 2D NMR and HRMS and spectrometric analysis. Inhibition rate evaluation revealed that compounds 1(EC50 = 0.02 mM), 3(EC50 = 0.3 mM), 6(EC50 = 0.07 mM), 8(EC50 = 0.1 mM) and 9(EC50 = 0.04 mM) had inhibitory effect on the SARS-CoV-2 virus.

Interferon-α-2b aerosol inhalation is associated with improved clinical outcomes in patients with coronavirus disease-2019.

AIMS: Type 1 interferon (IFN) is used to treat patients with coronavirus disease-2019 (COVID-19) but robust supporting evidence is lacking. We investigated the association between IFN-α-2b and the clinical outcomes of patients with COVID-19. METHODS: A total of 1401 patients were enrolled, with 852 (60.8%) patients receiving 5 000 000 U of IFN-α-2b via aerosol inhalation twice daily. The primary outcome was a composite measure consisting of mechanical ventilation, intensive care unit (ICU) admission and death. A subgroup analysis was performed to investigate the impact of the IFN-α-2b initiation schedule on symptom onset. RESULTS: The risk probability for crude endpoints was lower in the IFN-α-2b group (3.8%) than in the non-IFN-α-2b group (9.3%, P < .001). After adjusting the confounding factors, IFN-α-2b therapy achieved a reduction of 64% in occurrence of endpoint events (hazard ratio, 0.36; 95% confidence interval [CI], 0.21-0.62). In the subgroup analysis, compared with patients who received IFN-α-2b treatment 0-2 days after symptom onset, the hazard ratio for endpoints was 2.2 (95% CI, 0.43-11.13) in patients who received the therapy 3-5 days after symptom onset, 5.89 (95% CI, 0.99-35.05) in patients who received the therapy 6-8 days after symptom onset, and remained at a high level thereafter. CONCLUSIONS: IFN-α-2b aerosol inhalation therapy may be associated with improved clinical outcomes in patients with COVID-19, and delayed IFN-α-2b intervention was associated with increased probabilities of risk events. Further randomized clinical trials are needed to validate the preliminary findings of this study.

Supplementary research on K150del variant of activated protein C.

Activated protein C (APC) is an anticoagulant with potent cytoprotective and anti-inflammatory effects. K150del, a natural variant of APC, is associated with reduced anticoagulant activity. We performed a comprehensive study to analyze the functional alterations of the K150del mutant. Transcriptome analysis of HEK 293T cells treated with wild and mutant APC revealed differentially expressed genes enriched in inflammatory, apoptotic, and virus defense-related signaling pathways. Both wild and mutant APC displayed concentration-dependent cytoprotective effects. Low concentrations of K150del mutant resulted in decreased anti-inflammatory and anti-apoptotic activities, whereas its higher concentrations restored these effects. Expression of virus defense-related genes improved in mouse lung tissues after repeated administration of the APC variant. These results suggest that the APC K150del mutant could help clinicians to accurately predict disease risks and serve as a potential auxiliary therapeutic in viral infections, including 2019 coronavirus disease (COVID-19).

Modern Senicide in the Face of a Pandemic: An Examination of Public Discourse and Sentiment About Older Adults and COVID-19 Using Machine Learning.

OBJECTIVES: This study examined public discourse and sentiment regarding older adults and COVID-19 on social media and assessed the extent of ageism in public discourse. METHODS: Twitter data (N = 82,893) related to both older adults and COVID-19 and dated from January 23 to May 20, 2020, were analyzed. We used a combination of data science methods (including supervised machine learning, topic modeling, and sentiment analysis), qualitative thematic analysis, and conventional statistics. RESULTS: The most common category in the coded tweets was "personal opinions" (66.2%), followed by "informative" (24.7%), "jokes/ridicule" (4.8%), and "personal experiences" (4.3%). The daily average of ageist content was 18%, with the highest of 52.8% on March 11, 2020. Specifically, more than 1 in 10 (11.5%) tweets implied that the life of older adults is less valuable or downplayed the pandemic because it mostly harms older adults. A small proportion (4.6%) explicitly supported the idea of just isolating older adults. Almost three-quarters (72.9%) within "jokes/ridicule" targeted older adults, half of which were "death jokes." Also, 14 themes were extracted, such as perceptions of lockdown and risk. A bivariate Granger causality test suggested that informative tweets regarding at-risk populations increased the prevalence of tweets that downplayed the pandemic. DISCUSSION: Ageist content in the context of COVID-19 was prevalent on Twitter. Information about COVID-19 on Twitter influenced public perceptions of risk and acceptable ways of controlling the pandemic. Public education on the risk of severe illness is needed to correct misperceptions.