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2.
Elife ; 112022 11 08.
Article in English | MEDLINE | ID: covidwho-2110897

ABSTRACT

Public health emergencies like SARS, MERS, and COVID-19 have prioritized surveillance of zoonotic coronaviruses, resulting in extensive genomic characterization of coronavirus diversity in bats. Sequencing viral genomes directly from animal specimens remains a laboratory challenge, however, and most bat coronaviruses have been characterized solely by PCR amplification of small regions from the best-conserved gene. This has resulted in limited phylogenetic resolution and left viral genetic factors relevant to threat assessment undescribed. In this study, we evaluated whether a technique called hybridization probe capture can achieve more extensive genome recovery from surveillance specimens. Using a custom panel of 20,000 probes, we captured and sequenced coronavirus genomic material in 21 swab specimens collected from bats in the Democratic Republic of the Congo. For 15 of these specimens, probe capture recovered more genome sequence than had been previously generated with standard amplicon sequencing protocols, providing a median 6.1-fold improvement (ranging up to 69.1-fold). Probe capture data also identified five novel alpha- and betacoronaviruses in these specimens, and their full genomes were recovered with additional deep sequencing. Based on these experiences, we discuss how probe capture could be effectively operationalized alongside other sequencing technologies for high-throughput, genomics-based discovery and surveillance of bat coronaviruses.


Subject(s)
COVID-19 , Chiroptera , Animals , Phylogeny , Genetic Variation , Sequence Analysis, DNA , Genome, Viral/genetics , High-Throughput Nucleotide Sequencing , Genomics
3.
Sci Rep ; 12(1): 19416, 2022 Nov 12.
Article in English | MEDLINE | ID: covidwho-2119170

ABSTRACT

The current COVID-19 pandemic outbreak poses a serious threat to public health, demonstrating the critical need for the development of effective and reproducible detection tests. Since the RT-qPCR primers are highly specific and can only be designed based on the known sequence, mutation sensitivity is its limitation. Moreover, the mutations in the severe acute respiratory syndrome ß-coronavirus (SARS-CoV-2) genome led to new highly transmissible variants such as Delta and Omicron variants. In the case of mutation, RT-qPCR primers cannot recognize and attach to the target sequence. This research presents an accurate dual-platform DNA biosensor based on the colorimetric assay of gold nanoparticles and the surface-enhanced Raman scattering (SERS) technique. It simultaneously targets four different regions of the viral genome for detection of SARS-CoV-2 and its new variants prior to any sequencing. Hence, in the case of mutation in one of the target sequences, the other three probes could detect the SARS-CoV-2 genome. The method is based on visible biosensor color shift and a locally enhanced electromagnetic field and significantly amplified SERS signal due to the proximity of Sulfo-Cyanine 3 (Cy3) and AuNPs intensity peak at 1468 cm-1. The dual-platform DNA/GO/AuNP biosensor exhibits high sensitivity toward the viral genome with a LOD of 0.16 ng/µL. This is a safe point-of-care, naked-eye, equipment-free, and rapid (10 min) detection biosensor for diagnosing COVID-19 cases at home using a nasopharyngeal sample.


Subject(s)
Biosensing Techniques , COVID-19 , Metal Nanoparticles , Humans , SARS-CoV-2/genetics , Gold , Pandemics , COVID-19/diagnosis , Biosensing Techniques/methods , Genome, Viral/genetics , DNA , RNA, Viral/genetics
4.
Nat Commun ; 13(1): 7003, 2022 Nov 16.
Article in English | MEDLINE | ID: covidwho-2116500

ABSTRACT

Genomic sequencing is essential to track the evolution and spread of SARS-CoV-2, optimize molecular tests, treatments, vaccines, and guide public health responses. To investigate the global SARS-CoV-2 genomic surveillance, we used sequences shared via GISAID to estimate the impact of sequencing intensity and turnaround times on variant detection in 189 countries. In the first two years of the pandemic, 78% of high-income countries sequenced >0.5% of their COVID-19 cases, while 42% of low- and middle-income countries reached that mark. Around 25% of the genomes from high income countries were submitted within 21 days, a pattern observed in 5% of the genomes from low- and middle-income countries. We found that sequencing around 0.5% of the cases, with a turnaround time <21 days, could provide a benchmark for SARS-CoV-2 genomic surveillance. Socioeconomic inequalities undermine the global pandemic preparedness, and efforts must be made to support low- and middle-income countries improve their local sequencing capacity.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Genome, Viral/genetics , COVID-19/epidemiology , Pandemics , Genomics
5.
BMC Ecol Evol ; 22(1): 123, 2022 10 28.
Article in English | MEDLINE | ID: covidwho-2098309

ABSTRACT

The genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains many insertions/deletions (indels) from the genomes of other SARS-related coronaviruses. Some of the identified indels have recently reported to involve relatively long segments of 10-300 consecutive bases and with diverse RNA sequences around gaps between virus species, both of which are different characteristics from the classical shorter in-frame indels. These non-classical complex indels have been identified in non-structural protein 3 (Nsp3), the S1 domain of the spike (S), and open reading frame 8 (ORF8). To determine whether the occurrence of these non-classical indels in specific genomic regions is ubiquitous among broad species of SARS-related coronaviruses in different animal hosts, the present study compared SARS-related coronaviruses from humans (SARS-CoV and SARS-CoV-2), bats (RaTG13 and Rc-o319), and pangolins (GX-P4L), by performing multiple sequence alignment. As a result, indel hotspots with diverse RNA sequences of different lengths between the viruses were confirmed in the Nsp2 gene (approximately 2500-2600 base positions in the overall 29,900 bases), Nsp3 gene (approximately 3000-3300 and 3800-3900 base positions), N-terminal domain of the spike protein (21,500-22,500 base positions), and ORF8 gene (27,800-28,200 base positions). Abnormally high rate of point mutations and complex indels in these regions suggest that the occurrence of mutations in these hotspots may be selectively neutral or even benefit the survival of the viruses. The presence of such indel hotspots has not been reported in different human SARS-CoV-2 strains in the last 2 years, suggesting a lower rate of indels in human SARS-CoV-2. Future studies to elucidate the mechanisms enabling the frequent development of long and complex indels in specific genomic regions of SARS-related coronaviruses would offer deeper insights into the process of viral evolution.


Subject(s)
COVID-19 , Chiroptera , SARS Virus , Animals , Humans , Open Reading Frames/genetics , SARS-CoV-2/genetics , Genome, Viral/genetics , SARS Virus/genetics , Evolution, Molecular , Phylogeny , COVID-19/genetics , Chiroptera/genetics , Pangolins
7.
PLoS One ; 17(10): e0274889, 2022.
Article in English | MEDLINE | ID: covidwho-2054348

ABSTRACT

Fast surveillance strategies are needed to control the spread of new emerging SARS-CoV-2 variants and gain time for evaluation of their pathogenic potential. This was essential for the Omicron variant (B.1.1.529) that replaced the Delta variant (B.1.617.2) and is currently the dominant SARS-CoV-2 variant circulating worldwide. RT-qPCR strategies complement whole genome sequencing, especially in resource lean countries, but mutations in the targeting primer and probe sequences of new emerging variants can lead to a failure of the existing RT-qPCRs. Here, we introduced an RT-qPCR platform for detecting the Delta- and the Omicron variant simultaneously using a degenerate probe targeting the key ΔH69/V70 mutation in the spike protein. By inclusion of the L452R mutation into the RT-qPCR platform, we could detect not only the Delta and the Omicron variants, but also the Omicron sub-lineages BA.1, BA.2 and BA.4/BA.5. The RT-qPCR platform was validated in small- and large-scale. It can easily be incorporated for continued monitoring of Omicron sub-lineages, and offers a fast adaption strategy of existing RT-qPCRs to detect new emerging SARS-CoV-2 variants using degenerate probes.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/genetics , Genome, Viral/genetics , Humans , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
8.
Transbound Emerg Dis ; 69(5): e2443-e2455, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2053020

ABSTRACT

The porcine deltacoronavirus (PDCoV) is a newly discovered pig enteric coronavirus that can infect cells from various species. In Haiti, PDCoV infections in children with acute undifferentiated febrile fever were recently reported. Considering the great potential of inter-species transmission of PDCoV, we performed a comprehensive analysis of codon usage patterns and host adaptation profiles of 54 representative PDCoV strains with the spike (S) gene. Phylogenetic analysis of the PDCoV S gene indicates that the PDCoV strains can be divided into five genogroups. We found a certain codon usage bias existed in the S gene, in which the synonymous codons are often ended with U or A. Heat map analysis revealed that all the PDCoV strains shared a similar codon usage trend. The PDCoV S gene with a dN/dS ratio lower than 1 reveals a negative selection on the PDCoV S gene. Neutrality analysis showed that natural selection is the dominant force in shaping the codon usage bias of the PDCoV S gene. Unexpectedly, host adaptation analysis reveals a higher adaptation level of PDCoV to Homo sapiens and Gallus gallus than to Sus scrofa. Compared to the USA lineage, the PDCoV strains in the Early China lineage and Thailand lineage were less adapted to their hosts, which indicates that the evolutionary process plays an important role in the adaptation ability of PDCoV. These findings of this study add to our understanding of PDCoV's evolution, adaptability, and inter-species transmission.


Subject(s)
Coronavirus Infections , Swine Diseases , Animals , Codon/genetics , Codon Usage , Coronavirus Infections/epidemiology , Coronavirus Infections/veterinary , Deltacoronavirus , Genome, Viral/genetics , Phylogeny , Swine , Swine Diseases/epidemiology
10.
J Biotechnol ; 359: 130-141, 2022 Nov 20.
Article in English | MEDLINE | ID: covidwho-2049401

ABSTRACT

Pattern detection and string matching are fundamental problems in computer science and the accelerated expansion of bioinformatics and computational biology have made them a core topic for both disciplines. The requirement for computational tools for genomic analyses, such as sequence alignment, is very important, although, in most cases the resources and computational power required are enormous. The presented Multiple Genome Analytics Framework combines data structures and algorithms, specifically built for text mining and (repeated) pattern detection, that can help to efficiently address several computational biology and bioinformatics problems, concurrently, with minimal resources. A single execution of advanced algorithms, with space and time complexity O(nlogn), is enough to acquire knowledge on all repeated patterns that exist in multiple genome sequences and this information can be used as input by meta-algorithms for further meta-analyses. For the proof of concept and technology of the proposed Framework scalability, agility and efficiency, a publicly available dataset of more than 300,000 SARS-CoV-2 genome sequences from the National Center for Biotechnology Information has been used for the detection of all repeated patterns. These results have been used by newly introduced algorithms to provide answers to questions such as common patterns among all variants, sequence alignment, palindromes and tandem repeats detection, different organism genome comparisons, polymerase chain reaction primers detection, etc.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Genome, Viral/genetics , Sequence Alignment , Computational Biology
11.
JAMA Netw Open ; 5(9): e2230293, 2022 09 01.
Article in English | MEDLINE | ID: covidwho-2013243

ABSTRACT

Importance: With timely collection of SARS-CoV-2 viral genome sequences, it is important to apply efficient data analytics to detect emerging variants at the earliest time. Objective: To evaluate the application of a statistical learning strategy (SLS) to improve early detection of novel SARS-CoV-2 variants using viral sequence data from global surveillance. Design, Setting, and Participants: This case series applied an SLS to viral genomic sequence data collected from 63 686 individuals in Africa and 531 827 individuals in the United States with SARS-CoV-2. Data were collected from January 1, 2020, to December 28, 2021. Main Outcomes and Measures: The outcome was an indicator of Omicron variant derived from viral sequences. Centering on a temporally collected outcome, the SLS used the generalized additive model to estimate locally averaged Omicron caseload percentages (OCPs) over time to characterize Omicron expansion and to estimate when OCP exceeded 10%, 25%, 50%, and 75% of the caseload. Additionally, an unsupervised learning technique was applied to visualize Omicron expansions, and temporal and spatial distributions of Omicron cases were investigated. Results: In total, there were 2698 cases of Omicron in Africa and 12 141 in the United States. The SLS found that Omicron was detectable in South Africa as early as December 31, 2020. With 10% OCP as a threshold, it may have been possible to declare Omicron a variant of concern as early as November 4, 2021, in South Africa. In the United States, the application of SLS suggested that the first case was detectable on November 21, 2021. Conclusions and Relevance: The application of SLS demonstrates how the Omicron variant may have emerged and expanded in Africa and the United States. Earlier detection could help the global effort in disease prevention and control. To optimize early detection, efficient data analytics, such as SLS, could assist in the rapid identification of new variants as soon as they emerge, with or without lineages designated, using viral sequence data from global surveillance.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Genome, Viral/genetics , Humans , Mutation , SARS-CoV-2/genetics , South Africa , United States/epidemiology
12.
PLoS Genet ; 18(9): e1010200, 2022 09.
Article in English | MEDLINE | ID: covidwho-2009675

ABSTRACT

SARS-CoV-2 whole genome sequencing has played an important role in documenting the emergence of polymorphisms in the viral genome and its continuing evolution during the COVID-19 pandemic. Here we present data from over 360 patients to characterize the complex sequence diversity of individual infections identified during multiple variant surges (e.g., Alpha and Delta). Across our survey, we observed significantly increasing SARS-CoV-2 sequence diversity during the pandemic and frequent occurrence of multiple biallelic sequence polymorphisms in all infections. This sequence polymorphism shows that SARS-CoV-2 infections are heterogeneous mixtures. Convention for reporting microbial pathogens guides investigators to report a majority consensus sequence. In our study, we found that this approach would under-report sequence variation in all samples tested. As we find that this sequence heterogeneity is efficiently transmitted from donors to recipients, our findings illustrate that infection complexity must be monitored and reported more completely to understand SARS-CoV-2 infection and transmission dynamics. Many of the nucleotide changes that would not be reported in a majority consensus sequence have now been observed as lineage defining SNPs in Omicron BA.1 and/or BA.2 variants. This suggests that minority alleles in earlier SARS-CoV-2 infections may play an important role in the continuing evolution of new variants of concern.


Subject(s)
COVID-19 , COVID-19/genetics , Genome, Viral/genetics , Humans , Pandemics , SARS-CoV-2/genetics
13.
Nat Commun ; 13(1): 5240, 2022 09 06.
Article in English | MEDLINE | ID: covidwho-2008277

ABSTRACT

Novel variants continue to emerge in the SARS-CoV-2 pandemic. University testing programs may provide timely epidemiologic and genomic surveillance data to inform public health responses. We conducted testing from September 2021 to February 2022 in a university population under vaccination and indoor mask mandates. A total of 3,048 of 24,393 individuals tested positive for SARS-CoV-2 by RT-PCR; whole genome sequencing identified 209 Delta and 1,730 Omicron genomes of the 1,939 total sequenced. Compared to Delta, Omicron had a shorter median serial interval between genetically identical, symptomatic infections within households (2 versus 6 days, P = 0.021). Omicron also demonstrated a greater peak reproductive number (2.4 versus 1.8), and a 1.07 (95% confidence interval: 0.58, 1.57; P < 0.0001) higher mean cycle threshold value. Despite near universal vaccination and stringent mitigation measures, Omicron rapidly displaced the Delta variant to become the predominant viral strain and led to a surge in cases in a university population.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/prevention & control , Genome, Viral/genetics , Genomics , Humans , RNA, Viral/analysis , RNA, Viral/genetics , SARS-CoV-2/genetics , Universities
14.
Nature ; 610(7930): 154-160, 2022 10.
Article in English | MEDLINE | ID: covidwho-1991629

ABSTRACT

The SARS-CoV-2 Delta (Pango lineage B.1.617.2) variant of concern spread globally, causing resurgences of COVID-19 worldwide1,2. The emergence of the Delta variant in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions. Here we analyse 52,992 SARS-CoV-2 genomes from England together with 93,649 genomes from the rest of the world to reconstruct the emergence of Delta and quantify its introduction to and regional dissemination across England in the context of changing travel and social restrictions. Using analysis of human movement, contact tracing and virus genomic data, we find that the geographic focus of the expansion of Delta shifted from India to a more global pattern in early May 2021. In England, Delta lineages were introduced more than 1,000 times and spread nationally as non-pharmaceutical interventions were relaxed. We find that hotel quarantine for travellers reduced onward transmission from importations; however, the transmission chains that later dominated the Delta wave in England were seeded before travel restrictions were introduced. Increasing inter-regional travel within England drove the nationwide dissemination of Delta, with some cities receiving more than 2,000 observable lineage introductions from elsewhere. Subsequently, increased levels of local population mixing-and not the number of importations-were associated with the faster relative spread of Delta. The invasion dynamics of Delta depended on spatial heterogeneity in contact patterns, and our findings will inform optimal spatial interventions to reduce the transmission of current and future variants of concern, such as Omicron (Pango lineage B.1.1.529).


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/transmission , COVID-19/virology , Cities/epidemiology , Contact Tracing , England/epidemiology , Genome, Viral/genetics , Humans , Quarantine/legislation & jurisprudence , SARS-CoV-2/genetics , SARS-CoV-2/growth & development , SARS-CoV-2/isolation & purification , Travel/legislation & jurisprudence
15.
Nature ; 609(7929): 994-997, 2022 09.
Article in English | MEDLINE | ID: covidwho-1991628

ABSTRACT

Accurate and timely detection of recombinant lineages is crucial for interpreting genetic variation, reconstructing epidemic spread, identifying selection and variants of interest, and accurately performing phylogenetic analyses1-4. During the SARS-CoV-2 pandemic, genomic data generation has exceeded the capacities of existing analysis platforms, thereby crippling real-time analysis of viral evolution5. Here, we use a new phylogenomic method to search a nearly comprehensive SARS-CoV-2 phylogeny for recombinant lineages. In a 1.6 million sample tree from May 2021, we identify 589 recombination events, which indicate that around 2.7% of sequenced SARS-CoV-2 genomes have detectable recombinant ancestry. Recombination breakpoints are inferred to occur disproportionately in the 3' portion of the genome that contains the spike protein. Our results highlight the need for timely analyses of recombination for pinpointing the emergence of recombinant lineages with the potential to increase transmissibility or virulence of the virus. We anticipate that this approach will empower comprehensive real-time tracking of viral recombination during the SARS-CoV-2 pandemic and beyond.


Subject(s)
COVID-19 , Genome, Viral , Pandemics , Phylogeny , Recombination, Genetic , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/transmission , COVID-19/virology , Genome, Viral/genetics , Humans , Mutation , Recombination, Genetic/genetics , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Selection, Genetic/genetics , Spike Glycoprotein, Coronavirus/genetics , Virulence/genetics
17.
PLoS One ; 17(8): e0271074, 2022.
Article in English | MEDLINE | ID: covidwho-1968865

ABSTRACT

In spite of the availability of vaccine, the health burden associated with the COVID-19 pandemic continues to increase. An estimated 5 million people have died with SARS-CoV-2 infection. Analysis of evolution and genomic diversity can provide sufficient information to reduce the health burden of the pandemic. This study focused to conduct worldwide genomic surveillance. About 7.6 million genomic data were analyzed during 2019 to 2022. Multiple sequence alignment was conducted by using maximum likelihood method. Clade GK (52%) was the most predominant followed by GRY (12%), GRA (11%), GR (8%), GH (7%), G (6%), GV (3%), and O (1%), respectively. VOC Delta (66%) was the most prevalent variant followed by VOC Alpha (18%), VOC Omicron (13%), VOC Gamma (2%) and VOC Beta (1%), respectively. The frequency of point mutations including E484K, N501Y, N439K, and L452R at spike protein has increased 10%-92%. Evolutionary rate of the variants was 23.7 substitution per site per year. Substitution mutations E484K and N501Y had significant correlation with cases (r = .45, r = .23), fatalities (r = .15, r = .44) and growth rate R0 (r = .28, r = .54). This study will help to understand the genomic diversity, evolution and the impact of the variants on the outcome of the COVID-19 pandemic.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/genetics , Genome, Viral/genetics , Genomics , Humans , Mutation , Pandemics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
18.
Microb Genom ; 8(7)2022 07.
Article in English | MEDLINE | ID: covidwho-1961306

ABSTRACT

The COVID-19 pandemic continues to expand globally, with case numbers rising in many areas of the world, including the Eastern Mediterranean Region. Lebanon experienced its largest wave of COVID-19 infections from January to April 2021. Limited genomic surveillance was undertaken, with just 26 SARS-CoV-2 genomes available for this period, nine of which were from travellers from Lebanon detected by other countries. Additional genome sequencing is thus needed to allow surveillance of variants in circulation. In total, 905 SARS-CoV-2 genomes were sequenced using the ARTIC protocol. The genomes were derived from SARS-CoV-2-positive samples, selected retrospectively from the sentinel COVID-19 surveillance network, to capture diversity of location, sampling time, sex, nationality and age. Although 16 PANGO lineages were circulating in Lebanon in January 2021, by February there were just four, with the Alpha variant accounting for 97 % of samples. In the following 2 months, all samples contained the Alpha variant. However, this had changed dramatically by June and July 2021, when all samples belonged to the Delta variant. This study documents a ten-fold increase in the number of SARS-CoV-2 genomes available from Lebanon. The Alpha variant, first detected in the UK, rapidly swept through Lebanon, causing the country's largest wave to date, which peaked in January 2021. The Alpha variant was introduced to Lebanon multiple times despite travel restrictions, but the source of these introductions remains uncertain. The Delta variant was detected in Gambia in travellers from Lebanon in mid-May, suggesting community transmission in Lebanon several weeks before this variant was detected in the country. Prospective sequencing in June/July 2021 showed that the Delta variant had completely replaced the Alpha variant in under 6 weeks.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Genome, Viral/genetics , Humans , Lebanon/epidemiology , Pandemics , Phylogeny , Prospective Studies , Retrospective Studies , SARS-CoV-2/genetics
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