IntroductionNorovirus is a key pathogen of acute gastroenteritis and poses a significant burden on both the economy and public health. This study focuses on continuous monitoring of norovirus in Shenzhen, China, from 2016 to 2022, aiming to analyze the epidemic characteristics and genetic diversity of norovirus in the context of global sequence data.MethodsThe study was based on data collected from local sentinel hospitals. It involved analyzing the demographic, spatial, and temporal distribution of norovirus infections. Phylogenetic analysis was conducted, and genotype dynamics were compared across geographic levels. Mutations affecting protein stability were evaluated, and recombination analysis was performed to identify critical breakpoints and fragments for norovirus.ResultsThe study found that norovirus primarily infected infants under 3 years old, with epidemics occurring in winter and concentrated in developed districts. Phylogenetic analysis revealed both similarities and differences in the evolutionary patterns of various genotypes at different geographical levels. Mutations in the VP1 protein, based on the protein structure of GII.4_Sydney[P31], provided insights into the evolutionary trends of key genotypes. Additionally, recombination analysis identified important breakpoints and fragments for norovirus.DiscussionThe findings offer valuable insights to evolution and transmission of norovirus. These results can serve as a reference for future research, and they may aid in vaccine development efforts aimed at controlling norovirus outbreaks.

BACKGROUND:Rotavirus A group (RVA) is a leading cause of viral diarrhea, posing a substantial economic and public health burden. Compared to other enteric viruses, RVA possesses diverse genetic mechanisms, making it more challenging to control and prevent. Moreover, surveillance and evolutionary studies on RVA remain limited in Southern China. METHODS:We collected diarrheal stool samples from sentinel hospitals in Shenzhen and Zhuhai between 2020 and 2023. RVA-positive samples were identified via RT-PCR, followed by RNA extraction, sequencing, and genome assembly, yielding 57 RVA strains, comprising 604 sequences. Genotype trends were analyzed statistically. For phylogenetic analysis, global sequences were curated by CD-HIT, aligned with contributed sequences by MAFFT, and analyzed using IQ-TREE. Recombination and reassortment events were detected via RDP4. RESULTS:We analyzed the temporal distribution and genetic diversity of 57 newly sequenced strains from Shenzhen and Zhuhai in the context of global sequences. Our findings reveal that the prevalent genotypes of RVA in China have undergone changes over time with the decreasing of G9P[8] and the rising of G8P[8]. Phylogenetic analysis focusing on the VP7 and VP4 genes revealed distinct evolutionary patterns among different genotypes across temporal and geographical dimensions. Additionally, we discovered one reassortment event in the VP7 gene and two recombination events in the NSP1 and NSP5/6 gene. CONCLUSIONS:we observed significant variability and complexity in the evolutionary characteristics of RVA in Shenzhen and Zhuhai. These insights enhance our understanding of global evolution and transmission of RVA and provide guidance for future research and vaccine development.

BACKGROUND:Coinfections involving multiple diarrheal viruses have gained increasing recognition as a significant cause of acute gastroenteritis in recent years. Understanding the genetic diversity and evolutionary relationships of these viruses is crucial for effective outbreak identification and tracking. OBJECTIVE:To report two cases of HAdV and SaV coinfections and elucidate the genetic diversity and evolutionary patterns of these viruses through whole-genome sequencing (WGS) and phylogenetic analysis. METHODS:A total of 873 diarrheal stool samples were collected from sentinel hospitals in Shenzhen, China, in 2021. The collected stool samples were identified using RT-PCR and positive samples were subjected to WGS on the NovaSeq platform. phylogenetic trees were constructed using MEGA to analyze genetic relationships. RESULTS:The sequencing results showed that both samples were human adenovirus type 41, which clustered in two distinct evolutionary clades. Additionally, we also retrieved the complete genome of sapovirus (GI.1 genotype) from the same sample. Phylogenetic analysis revealed that they were similar to previously reported strains, belonging to the clade predominating in China. CONCLUSIONS:This study reveals the genetic diversity of epidemic strains involved in coinfections of human adenovirus and sapovirus. The findings establish a groundwork for the identification and traces of acute gastroenteritis outbreaks.

OBJECTIVE:This study aims to systematically investigate the molecular epidemiology and genomic characteristics of Enterobacter cloacae complex (ECC) strains globally harbouring blaKPC and mcr, as well as the co-existence of drug resistance genes. The goal is to provide insights and recommendations for monitoring clinical drug-resistant strains and super-resistant plasmids. METHODS:This study analysed 281 ECC isolates harbouring both blaKPC and mcr, obtained from NCBI GenBank database (2003-2024) with whole-genome sequencing data. We constructed a phylogenetic tree of ECC strains for phylogenetic analysis. Resistance genes were identified using the ABRicate and CARD databases, and their distribution was examined. Plasmid replicon types for blaKPC and mcr were analysed with PlasmidFinder, including upstream and downstream genetic environments of these genes. RESULTS:The predominant genotype combinations harbouring both blaKPC and mcr are blaKPC-3 and mcr-9.1, followed by blaKPC-4 and mcr-9.1, with the dominant strain being E. hormaechei ssp. xiangfangensis. The IncHI2(2A) plasmid co-harbouring blaKPC and mcr-9 was mainly detected in genomes from the United States. Phylogenetic analysis indicated that the blaKPC-mcr-9-IncHI2(2A) plasmids in ECC strains have a high genetic similarity to mcr-9-IncHI2(2A), suggesting that the latter may have acquired the additional highly transferable blaKPC. CONCLUSIONS:ECC strains have become an important reservoir cluster for blaKPC and mcr-9, and the IncHI2(2A) plasmid is a potential vector for the horizontal co-transmission of carbapenem and colistin resistance genes. Effective monitoring should be implemented to assess the prevalence of co-harbouring blaKPC and mcr-9 in individual ECC isolates and even in single plasmid.

Diarrhea is one of the major public health issues worldwide. Although the infections of individual enteric virus have been extensively studied, elucidation of the coinfection involving multiple viruses is still limited. In this study, we identified the coinfection of human adenovirus (HAdV) and human astrovirus (HAstV) in a child with acute gastroenteritis, analyzed their genotypes and molecular evolution characteristics. The sample was collected and identified using RT-PCR and subjected to whole-genome sequencing on the NovaSeq (Illumina) platform. Obtained sequences were assembled into the complete genome of HAdV and the ORF1 of HAstV. We conducted phylogenetic analysis using IQ-TREE software and conducted recombination analysis with the Recombination Detection Program. The sequenced HAdV was confirmed to be genotype 41, and was genetically close to some European strains. Phylogenetic analysis revealed that the HAstV was genetically close to both HAstV-2 and HAstV-4 and was different from the genotype prevalent in Shenzhen before. The recombination analysis confirmed that the sequenced HAstV strain is a recombinant of HAstV-2 and HAstV-4. Our analysis has shown that the strains in this coinfection are both uncommon variants in this geographical region, instead of dominant subtypes that have prevailed for years. This study presents a coinfection of HAdV and HAstV and conducts an evolutionary analysis on involved viruses, which reveals the genetic diversity of epidemic strains in Southern China and offers valuable insights into vaccine and medical research.

目的 了解广东省深圳市疱疹性咽峡炎(HA)病原组成与病原体的分子特征,为HA的预防与控制提供科学依据.方法 2017-2018年收集了 157例HA患者的314份临床样本,其中粪便样本和咽拭子各157份.使用荧光定量逆转录-聚合酶链反应(RT-PCR)和基于半巢式RT-PCR扩增的测序方法对肠道病毒(EV)进行检测与分型.使用生物信息学软件对病毒VP1基因进行序列分析.结果 在126例(80.30％,126/157)EV阳性的患者中,共检出10种EV,检出率最高的是柯萨奇病毒A 组 10 型(CVA10)(19.70％,31/157),其次是 CVA4(17.80％,28/157)、CVA6(15.30％,24/157)和 CVA2(10.80％,17/157),其他病原体包括 CVA5(4.50％,7/157)、CVA 16(3.20％,5/157)、EV-A71(1.30％,2/157)、CVA8(0.60％,1/157)、CVB5(0.60％,1/157)和埃可病毒11(E11)(0.60％,1/157),1例为CVA4与CVA10的混合感染(0.60％,1/157).2017年检出率最高的两种病原体是CVA2和CVA6,而2018年却是CVA10和CVA4.粪便样本与咽拭子的病原检出率之间的差异没有统计学意义(x2=0.019,P=0.892).基于VP1序列的分子系统发育分析表明,本研究CVA10毒株均为C2基因型.CVA4除了 1株为C5基因型外,其余均为C2基因型.1株CVA6毒株位于先前未描述的进化分支,其他CVA6毒株均为D3a基因亚型.CVA2毒株均为D2基因型.结论 粪便样本与咽拭子都适用于HA的病原体核酸检测.CVA10、CVA4、CVA6和CVA2是2017-2018年深圳市HA的优势病原体,大部分毒株是我国主流基因型,个别毒株处于不常见的基因型或进化分支.

The coronavirus disease 2019 (COVID-19) caused by coronavirus SARS-CoV-2 infection has become a global pandemic due to the high viral transmissibility and pathogenesis, bringing enormous burden to our society. Most patients infected by SARS-CoV-2 are asymptomatic or have mild symptoms. Although only a small proportion of patients progressed to severe COVID-19 with symptoms including acute respiratory distress syndrome (ARDS), disseminated coagulopathy, and cardiovascular disorders, severe COVID-19 is accompanied by high mortality rates with near 7 million deaths. Nowadays, effective therapeutic patterns for severe COVID-19 are still lacking. It has been extensively reported that host metabolism plays essential roles in various physiological processes during virus infection. Many viruses manipulate host metabolism to avoid immunity, facilitate their own replication, or to initiate pathological response. Targeting the interaction between SARS-CoV-2 and host metabolism holds promise for developing therapeutic strategies. In this review, we summarize and discuss recent studies dedicated to uncovering the role of host metabolism during the life cycle of SARS-CoV-2 in aspects of entry, replication, assembly, and pathogenesis with an emphasis on glucose metabolism and lipid metabolism. Microbiota and long COVID-19 are also discussed. Ultimately, we recapitulate metabolism-modulating drugs repurposed for COVID-19 including statins, ASM inhibitors, NSAIDs, Montelukast, omega-3 fatty acids, 2-DG, and metformin.

目的 探讨2021年深圳地区疱疹性咽峡炎的流行病学和病原学特征,为疱疹性咽峡炎的防控提供科学参考.方法 收集2021年深圳地区哨点医院210例疱疹性咽峡炎病例的基本信息及其咽拭子、肛拭子和粪便样本408份.采用荧光定量PCR进行肠道病毒检测,采用半巢式PCR结合测序分析进行肠道病毒分型.结果 210例疱疹性咽峡炎患者年龄集中在5岁以下,平均年龄(2.7±1.7)岁,疾病流行高峰在春季,患者的主要临床表现为发热和口腔疱疹.咽拭子和肛拭子样本的阳性率一致且一致性较高(Kappa=0.785,P=1.000).粪便样本的检出阳性率高于咽拭子,差异有统计学意义(x2=12.000,P＜0.001).总肠道病毒阳性率为84.8％,共检测出7种肠道病毒,包括柯萨奇病毒 A2 型(CV-A2)、CV-A4、CV-A5、CV-A6、CV-A10、CV-A16和CV-B3,其中CV-A4(38.8％)和CV-A10(35.4％)占比较高.不同月份的病原分布不同,差异有统计学意义(x2=115.344,P＜0.001).感染CV-A16患者出现发热症状的比例低于其他病原体,差异有统计学意义(x2=11.005,P＜0.05).感染CV-A2患者发热体温高于其他病原体,差异有统计学意义(F=2.658,P＜0.05).结论 2021年深圳地区疱疹性咽峡炎发病人群以5岁以下为主,春季为流行高峰,感染肠道病毒主要为CV-A4和CV-A10,需加强柯萨奇病毒的监测.

Dear Editor, The Omicron(B.1.1.529)variant of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)was first identified in November 2021,in South Africa and Botswana.The first Omicron sub-lineage that emerged was BA.1,which was supplanted by BA.2 in many countries.One of the most notable features of the Omicron variant is its ability to evade neutralizing antibodies(nAbs)targeting the original virus lineages,owing to new mutations dotted among the spike protein,especiallyin the receptor-binding domain(RBD)and N-terminal domain.1,2 There-fore,the immune response arising from Omicron in individuals who have already been inoculated with vaccines is a cause of concern.However,to date,little is known about how the Omicron/BA.2 variant interacts with vaccine-induced immunity to affect the infection.In this study,we collected sera from individuals in the acute or convalescent phase after BA.2-breakthrough infection and then detected levels of antibodies and their neutralizing ability,followed by cross-assessments among different variants.

Objective:To understand the molecular epidemiological features of norovirus outbreaks in Shenzhen of China from January 2019 to December 2021.Methods:The norovirus outbreaks information and specimen from January 2019 to December 2021 were collected. Norovirus was detected by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Positive samples were amplified by RT-PCR and sequenced. The sequences were then analyzed. Genome amplification and sequence analysis were performed on three strains of GII.2 [P16].Results:From January 2019 to December 2021, a total of 246 outbreaks caused by norovirus were reported, mainly in kindergartens (132, 53.66%) and primary schools (52, 21.14%). The number of cases in an outbreak ranged from 3 to 130, with a median value of 8. The epidemic peak of norovirus outbreak was from November to the next March. The viruses in 211 outbreaks were successfully genotyped. Seven genotypes of GI group and eleven genotypes of GII group were detected. Norovirus GII.2[P16] was responsible for 78 (36.97%) outbreaks. According to the genome analysis of GII.2[P16], the strains from the outbreaks in 2020 still belonged to GII.2[2016](2016-2017) subcluster. Amino acid mutations were observed in the non-structural protein P22 (L777S) and 3C protease (A1047V and P1074T).Conclusions:GII.2[P16] was the predominant genotype that caused the outbreak of norovirus in Shenzhen from January 2019 to December 2021, mainly in kindergartens and schools. Continuous surveillance and genome analysis can help to find the mutations of epidemic strains and the emergence of novel variants.

Human astrovirus (HAstV) is a single-stranded, positive-sense RNA virus and is the leading cause of viral gastroenteritis. However, despite its prevalence, astroviruses still remain one of the least studied enteroviruses. In this study, we sequenced 11 classical astrovirus strains from clinical samples collected in Shenzhen, China from 2016 to 2019, analyzed their genetic characteristics, and deposited them into GenBank. We conducted phylogenetic analysis using IQ-TREE software, with references to astrovirus sequences worldwide. The phylogeographic analysis was performed using the Bayesian Evolutionary Analysis Sampling Trees program, through Bayesian Markov Chain Monte Carlo sampling. We also conducted recombination analysis with the Recombination Detection Program. The newly sequenced strains were categorized as HAstV genotype 1, which is the predominant genotype in Shenzhen. Phylogeographic reconstruction indicated that HAstV-1 may have migrated from the United States to China, followed by frequent transmission between China and Japan. The recombination analysis revealed recombination events within and across genotypes, and identified a recombination-prone region that produced relatively uniform recombination breakpoints and fragment lengths. The genetic analysis of HAstV strains in Shenzhen addresses the current lack of astrovirus data in the region of Shenzhen and provides key insights to the evolution and transmission of astroviruses worldwide. These findings highlight the importance of improving surveillance of astroviruses.

Since the end of 2019, a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has deprived numerous lives worldwide, called COVID-19. Up to date, omicron is the latest variant of concern, and BA.5 is replacing the BA.2 variant to become the main subtype rampaging worldwide. These subtypes harbor an L452R mutation, which increases their transmissibility among vaccinated people. Current methods for identifying SARS-CoV-2 variants are mainly based on polymerase chain reaction (PCR) followed by gene sequencing, making time-consuming processes and expensive instrumentation indispensable. In this study, we developed a rapid and ultrasensitive electrochemical biosensor to achieve the goals of high sensitivity, the ability of distinguishing the variants, and the direct detection of RNAs from viruses simultaneously. We used electrodes made of MXene-AuNP (gold nanoparticle) composites for improved sensitivity and the CRISPR/Cas13a system for high specificity in detecting the single-base L452R mutation in RNAs and clinical samples. Our biosensor will be an excellent supplement to the RT-qPCR method enabling the early diagnosis and quick distinguishment of SARS-CoV-2 Omicron BA.5 and BA.2 variants and more potential variants that might arise in the future.

Introduction:Since 2019, numerous variants of concern for severe acute respiratory syndrome virus 2 (SARS-CoV-2) have emerged, leading to significant outbreaks. The development of novel, highly accurate, and rapid detection techniques for these new SARS-CoV-2 variants remains a primary focus in the ongoing efforts to control and prevent the coronavirus disease 2019 (COVID-19) pandemic.Methods:Reverse transcription-recombinase polymerase amplification combined with the clustered regularly interspaced short palindromic repeats-associated protein 12a (CRISPR/Cas12a) system was used to validate the detection of the Omicron BA.2, BA.4, and BA.5 variants of SARS-CoV-2.Results:Our results demonstrate that the CRISPR/Cas12a assay is capable of effectively detecting the SARS-CoV-2 BA.2, BA.4, and BA.5 variants with a limit of detection of 10, 1, and 10 copies/μL, respectively. Importantly, our assay successfully differentiated the three SARS-CoV-2 Omicron strains from one another. Additionally, we evaluated 46 SARS-CoV-2 positive clinical samples consisting of BA.2 (n=20), BA.4 (n=6), and BA.5 (n=20) variants, and the sensitivity of our assay ranged from 90% to 100%, while the specificity was 100%.Discussion:This research presents a swift and reliable CRISPR-based method that may be employed to track the emergence of novel SARS-CoV-2 variants.

Relay of information from the extracellular environment into the cell often results from a peptide growth factor binding to its cognate cell surface receptor; this event is an integral mechanism by which many cellular functions occur, including cell growth, motility, and survival. In recent years, however, this requirement for ligand binding has been shown to be surpassed by several distinct mechanisms, including cell surface receptor cross-talk (e.g., between epidermal growth factor receptor [EGFR] and G-coupled receptors), receptor-extracellular matrix interactions (e.g., EGFR: integrin complexes), and finally by structural mutations within the receptor itself. While all of these pathways result in so-called ligand-independent signaling by the EGF receptor, to date, only structural mutations in the receptor have been shown to result in qualitative changes in downstream targets of the receptor, which specifically result in oncogenic signaling, transformation, and tumorigenicity. In this review, we describe aspects of the known signaling properties of the retroviral oncogene v-ErbB as a model of ligand-independent oncogenic signaling, and compare these properties to results emerging from ongoing studies on structurally related EGF receptor mutants originally identified in human tumors. A better understanding of the signaling pathways used by these uniquely oncogenic receptor tyrosine kinase mutants may ultimately reveal new targets for the development of novel therapeutics selective for the inhibition of tumor cell growth.

Respiratory viruses have long been a major cause of a global pandemic, emphasizing the urgent need for high-sensitivity diagnostic tools. Typical PCR technology can only determine the type of virus in the sample, which is unable to detect different variants of the same virus without costly and time-consuming gene sequencing. Here, we introduce a simple, fully enclosed, and highly integrated microfluidic system based on CRISPR/Cas12a and isothermal amplification techniques (LOC-CRISPR) that can specifically identify multiple common respiratory viruses and their variants. The LOC-CRISPR chip integrates viral nucleic acid extraction, recombinant polymerase amplification, and CRISPR/Cas12a cleavage reaction-based detection, contamination-free detection. In addition, the LOC-CRISPR chip was designed for multiplexed detection (two-sample input and ten-result outputs), which can not only detect the presence of SARS-CoV-2, H1N1, H3N2, IVB and HRSV but also differentiate the BA.1, BA.2, and BA.5 variants of SARS-COV-2. For clinical validation, the LOC-CRISPR chip was used to analyze 50 nasopharyngeal swab samples (44 positive and 6 negative) and achieved excellent sensitivity (97.8%) and specificity (100%). This innovative LOC-CRISPR system has the ability to quickly, sensitively, and accurately detect multiple target nucleic acid sequences with single-base mutations, which will further improve the rapid identification and traceability of respiratory viruses infectious diseases.

The Coronavirus disease 19 (COVID-19) pandemic has accumulated over 550 million confirmed cases and more than 6.34 million deaths worldwide. Although vaccinations has largely protected the population through the last two years, the effect of vaccination has been increasingly challenged by the emerging SARS-CoV-2 variants. Although several therapeutics including both monoclonal antibodies and small molecule drugs have been used clinically, high cost, viral escape mutations, and potential side effects have reduced their efficacy. There is an urgent need to develop a low cost treatment with wide-spectrum effect against the novel variants of SARS-CoV-2. Here we report a product of equine polyclonal antibodies that showed potential broad spectrum neutralization effect against the major variants of SARS-CoV-2. The equine polyclonal antibodies were generated by horse immunization with the receptor binding domain (RBD) of SARS-CoV-2 spike protein and purified from equine serum. A high binding affinity between the generated equine antibodies and the RBD was observed. Although designed against the RBD of the early wild type strain sequenced in 2020, the equine antibodies also showed a highly efficient neutralization capacity against the major variants of SARS-CoV-2, including the recent BA.2 Omicron variant (IC50 =1.867μg/ml) in viral neutralization assay in Vero E6 cells using live virus cultured. The broad-spectrum neutralization capacity of the equine antibodies was further confirmed using pseudovirus neutralization assay covering the major SARS-CoV-2 variants including wild type, alpha, beta, delta, and omicron, showing effective neutralization against all the tested strains. Ex vivo reconstructed human respiratory organoids representing nasal, bronchial, and lung epitheliums were employed to test the treatment efficacy of the equine antibodies. Antibody treatment protected the human nasal, bronchial, and lung epithelial organoids against infection of the novel SARS-CoV-2 variants challenging public health, the Delta and Omicron BA.2 isolates, by reducing >95% of the viral load. The equine antibodies were further tested for potential side effects in a mouse model by inhalation and no significant pathological feature was observed. Equine antibodies, as a mature medical product, have been widely applied in the treatment of infectious diseases for more than a century, which limits the potential side effects and are capable of large scale production at a low cost. A cost-effective, wide-spectrum equine antibody therapy effective against the major SARS-CoV-2 variants can contribute as an affordable therapy to cover a large portion of the world population, and thus potentially reduce the transmission and mutation of SARS-CoV-2.

2020年8月,广东省深圳市发生一起上呼吸道感染聚集性疫情,经对咽拭子样本进行病毒RNA的提取、逆转录和荧光定量PCR检测,确认为人类冠状病毒(Human coronavirus,HCoV)NL63感染所致,然后利用二代测序技术对阳性标本进行病毒全基因组测序,最终获取7条HCoV-NL63序列全长.在对毒株的棘突蛋白(Spike glycoprotein,S)基因及其S1 domain进行PCR扩增和序列测定分析中发现,S基因的160个碱基变异导致41个氨基酸突变和1个氨基酸缺失,其中39个位于S1 domain中,含1个位于受体结合结构域的突变(E572A).在N端结构域内,三个氨基酸变异(N24S、S100P和N178S)造成三处潜在N-糖基化位点缺失,而四个氨基酸变异(N24S、E94N、G96S和L131S)却造成另三处潜在N-糖基化位点增加,使得潜在N-糖基化位点的总数保持不变.同时,结合GenBank数据库下载的45条多国的HCoV-NL63流行代表株序列,构建基于S基因中S1 domain的基因亲缘性关系树.进化分析发现,HCoV-NL63代表株主要被划分为A和B两大基因型,本次疫情中检测出的7株毒株和2株中国广东省流行的HCoV-NL63毒株进化距离最近,同属一个新的单独进化树分支,暂被划分为新基因亚型B3.本研究通过对毒株中S基因序列的比对、功能区域特征的分析以及基因型鉴定,从分子流行病学上初步阐明了深圳本次聚集性疫情中HCoV-NL63的基因特征及基因型/基因亚型,丰富和完善了我国流行的HCoV-NL63基因数据库,为今后对HCoV-NL63的分子检测、疫苗研发及致病机制研究提供了科学依据.

We identified an individual who was coinfected with two SARS-CoV-2 variants of concern, the Beta and Delta variants. The ratio of the relative abundance between the two variants was maintained at 1:9 (Beta:Delta) in 14 days. Furthermore, possible evidence of recombinations in the Orf1ab and Spike genes was found.

We read with interest the report in this Journal by Elgner and colleagues which emphasizes the critical role of person-to-person transmission in the epidemiology of Norovirus infection.1 Imported cases can rapidly spread allowing novel clones to disseminate rapidly. In the following, we will describe the genetic diversity and persistent transmission of norovirus in Shenzhen, China.

The outbreak of the CO VID-19 pandemic was partially due to the challenge of identifying asymptomatic and presymptomatic carriers of the virus,and thus highlights a strong motivation for diagnostics with high sensitivity that can be rapidly deployed.On the other hand,several concerning SARS-CoV-2 variants,including Omicron,are required to be identified as soon as the samples are identified as'positive'.Unfortunately,a traditional PCR test does not allow their specific identification.Herein,for the first time,we have developed MOPCS(Methodologies of Photonic CRISPR Sensing),which combines an optical sensing technology-surface plasmon resonance(SPR)with the'gene scissors'clustered regularly interspaced short palindromic repeat(CRISPR)technique to achieve both high sensitivity and specificity when it comes to measurement of viral variants.MOPCS is a low-cost,CRISPR/Cas12a-system-empowered SPR gene-detecting platform that can analyze viral RNA,without the need for amplification,within 38 min from sample input to results output,and achieve a limit of detection of 15 fM.MOPCS achieves a highly sensitive analysis of SARS-CoV-2,and mutations appear in variants B.1.617.2(Delta),B.1.1.529(Omicron)and BA.1(a subtype of Omicron).This platform was also used to analyze some recently collected patient samples from a local outbreak in China,identified by the Centers for Disease Control and Prevention.This innovative CRISPR-empowered SPR platform will further contribute to the fast,sensitive and accurate detection of target nucleic acid sequences with single-base mutations.