Research and clinical translation progress of SARS-CoV-2 detection approaches based on CRISPR technology

Since the Corona Virus Disease 2019 (COVID-19) caused by the infection of SARS-CoV-2 was first reported in 2019, COVID-19 has spread rapidly around the world, causing serious negative impacts on the daily life and work of people around the world. Recently, several studies on SARS-CoV-2 detection approaches based on Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology have been reported, showing that CRISPR technology can be used to detect SARS-CoV-2 rapidly, sensitively, specifically, visually and on-site. There are already detection kits based on CRISPR technology in clinical application at home and abroad, and good clinical feedback has been obtained. Therefore, the SARS-CoV-2 detection method based on CRISPR technology is expected to overcome the shortcomings of the existing RT-PCR approach in clinical practice, and replace RT-PCR as the gold standard for the next generation of SARS-CoV-2 nucleic acid detection. In this article, the research and progress of SARS-CoV-2 nucleic acid detection methods based on CRISPR technology are introduced, the principle and clinical application of CRISPR technology are reviewed, and the future development of the technology is prospected in order to promote its clinical transformation speed.

Emerging SARS-CoV-2 mutation hotspots associated with clinical outcomes (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding the influence of mutations in the SARS-CoV-2 gene on clinical outcomes and related factors is critical for treatment and prevention. Here, we analyzed 209,551 high-coverage complete virus sequences and 321 RNA-seq samples to mine the mutations associated with clinical outcome in the SARS-CoV-2 genome. Several important hotspot variants were found to be associated with severe clinical outcomes. Q57H variant in ORF3a protein were found to be associated with higher mortality rate, and was high proportion in severe cases (39.36%) and 501Y.V2 strains (100%) but poorly proportional to asymptomatic cases (10.04%). T265I could change nsp2 structure and mitochondrial permeability, and evidently higher in severe cases (20.12%) and 501Y.V2 strains (100%) but lower in asymptomatic cases (1.43%). Additionally, R203K and G204R could decrease the flexibility and immunogenic property of N protein with high frequency among severe cases, VUI 202012/01 and 484K.V2 strains. Interestingly, the SARS-CoV-2 genome was more susceptible to mutation because of the high frequency of nt14408 mutation (which located in RNA polymerase) and the high expression levels of ADAR and APOBEC in severe clinical outcomes. In conclusion, several important mutation hotspots in the SARS-CoV-2 genome associated with clinical outcomes was found in our study, and that might correlate with different SARS-CoV-2 mortality rates.