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1.
Curr Microbiol ; 79(2): 48, 2022 Jan 04.
Article in English | MEDLINE | ID: covidwho-1603303

ABSTRACT

This study aimed to characterize the whole genome of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) isolated from an oropharyngeal swab specimen of a Pashtun Pakistani patient using next-generation sequencing. Upon comparing the SARS-CoV2 genome to the reference genome, a total of 10 genetic variants were identified. Among the 10 genetic variants, 1 missense mutation (c.1139A > G, p.Lys292Glu) in the Open Reading Frame 1ab (ORF1ab) positioned at 112 in the non-structural protein 2 (NSP2) was found to be unique. Phylogenetic analysis (n = 84) revealed that the current SARS-CoV2 genome was closely clustered with 8 Pakistani strains belonging to Punjab, Federal Capital, Azad Jammu and Kashmir (AJK), and Khyber Pakhtunkhwa (KP). In addition, the current SARS-CoV2 genome was very similar to the genome of SARS-CoV2 reported from Guam, Taiwan, India, the USA, and France. Overall, this study reports a slight mismatch in the SARS-CoV2 genome, indicating the presence of a single unique missense mutation. However, phylogenetic analysis revealed that the current SARS-CoV2 genome was closely clustered with 8 other Pakistani strains.


Subject(s)
COVID-19 , RNA, Viral , Genome, Viral , Genomics , High-Throughput Nucleotide Sequencing , Humans , Pakistan , Phylogeny , SARS-CoV-2
2.
Ecohealth ; 18(4): 421-428, 2021 12.
Article in English | MEDLINE | ID: covidwho-1590480

ABSTRACT

We investigated the prevalence of coronaviruses in 44 bats from four families in northeastern Eswatini using high-throughput sequencing of fecal samples. We found evidence of coronaviruses in 18% of the bats. We recovered full or near-full-length genomes from two bat species: Chaerephon pumilus and Afronycteris nana, as well as additional coronavirus genome fragments from C. pumilus, Epomophorus wahlbergi, Mops condylurus, and Scotophilus dinganii. All bats from which we detected coronaviruses were captured leaving buildings or near human settlements, demonstrating the importance of continued surveillance of coronaviruses in bats to better understand the prevalence, diversity, and potential risks for spillover.


Subject(s)
Chiroptera , Coronavirus Infections , Coronavirus , Animals , Coronavirus/genetics , Eswatini , Genetic Variation , Genome, Viral , Humans , Phylogeny
3.
Sci Rep ; 11(1): 24145, 2021 12 17.
Article in English | MEDLINE | ID: covidwho-1585802

ABSTRACT

Recent studies suggest that coronaviruses circulate widely in Southeast Asian bat species and that the progenitors of the SARS-Cov-2 virus could have originated in rhinolophid bats in the region. Our objective was to assess the diversity and circulation patterns of coronavirus in several bat species in Southeast Asia. We undertook monthly live-capture sessions and sampling in Cambodia over 17 months to cover all phases of the annual reproduction cycle of bats and test specifically the association between their age and CoV infection status. We additionally examined current information on the reproductive phenology of Rhinolophus and other bat species presently known to occur in mainland southeast China, Vietnam, Laos and Cambodia. Results from our longitudinal monitoring (573 bats belonging to 8 species) showed an overall proportion of positive PCR tests for CoV of 4.2% (24/573) in cave-dwelling bats from Kampot and 4.75% (22/463) in flying-foxes from Kandal. Phylogenetic analysis showed that the PCR amplicon sequences of CoVs (n = 46) obtained clustered in Alphacoronavirus and Betacoronavirus. Interestingly, Hipposideros larvatus sensu lato harbored viruses from both genera. Our results suggest an association between positive detections of coronaviruses and juvenile and immature bats in Cambodia (OR = 3.24 [1.46-7.76], p = 0.005). Since the limited data presently available from literature review indicates that reproduction is largely synchronized among rhinolophid and hipposiderid bats in our study region, particularly in its more seasonal portions (above 16° N), this may lead to seasonal patterns in CoV circulation. Overall, our study suggests that surveillance of CoV in insectivorous bat species in Southeast Asia, including SARS-CoV-related coronaviruses in rhinolophid bats, could be targeted from June to October for species exhibiting high proportions of juveniles and immatures during these months. It also highlights the need to develop long-term longitudinal surveys of bats and improve our understanding of their ecology in the region, for both biodiversity conservation and public health reasons.


Subject(s)
Alphacoronavirus/genetics , Betacoronavirus/genetics , COVID-19/transmission , Chiroptera/growth & development , SARS-CoV-2/genetics , Alphacoronavirus/classification , Animals , Asia, Southeastern/epidemiology , Betacoronavirus/classification , COVID-19/epidemiology , COVID-19/virology , Cambodia/epidemiology , Chiroptera/classification , Chiroptera/virology , Epidemics/prevention & control , Evolution, Molecular , Genome, Viral/genetics , Geography , Humans , Longitudinal Studies , Male , Phylogeny , SARS-CoV-2/classification , SARS-CoV-2/physiology , Species Specificity
4.
BMC Res Notes ; 14(1): 466, 2021 Dec 23.
Article in English | MEDLINE | ID: covidwho-1582018

ABSTRACT

OBJECTIVES: SARS-CoV-2, severe respiratory syndrome coronavirus-2, is an RNA virus that emerged from China sweeping the globe in the form of a pandemic that became an international public health concern. This pilot study aimed to describe the genetic variation and molecular epidemiology of SARS-CoV-2 in Palestine in fall 2020. RESULTS: To achieve these aims, whole genome sequencing of SARS-CoV-2, phylogenetic analysis, haplotype networking and genetic diversity analysis were performed. These analyses revealed a unique spike mutation H245N that has never been reported before. The phylogenetic analysis depicted that three clusters existed in Palestinian SARS-CoV-2 genome sequences, in which cluster-I comprised the majority of clusters by 90%. Congruently, the haplotype network analysis depicted the same three clusters with a total of 39 haplotypes. The genetic diversity analysis showed that Cluster-I is highly diverse as confirmed by statistically significant mutation rate indices, Tajima's D and Fu-Li's-F tests (- 2.11 and 2.74, respectively), highest number of mutations (Eta = 120), highest number of haplotypes (h = 17), and highest average number of nucleotide differences between any two sequences (S = 118). The study confirmed the high genetic diversity among the Palestinian of SARS-CoV-2 which possessed high number of mutations including one which was reported for the first time.


Subject(s)
Genome, Viral , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics , Arabs , COVID-19/virology , Humans , Middle East , Mutation , Phylogeny , Pilot Projects , SARS-CoV-2/genetics , Whole Genome Sequencing
5.
PLoS One ; 16(12): e0260884, 2021.
Article in English | MEDLINE | ID: covidwho-1581769

ABSTRACT

OBJECTIVES: To exploit the features of digital PCR for implementing SARS-CoV-2 observational studies by reliably including the viral load factor expressed as copies/µL. METHODS: A small cohort of 51 Covid-19 positive samples was assessed by both RT-qPCR and digital PCR assays. A linear regression model was built using a training subset, and its accuracy was assessed in the remaining evaluation subset. The model was then used to convert the stored cycle threshold values of a large dataset of 6208 diagnostic samples into copies/µL of SARS-CoV-2. The calculated viral load was used for a single cohort retrospective study. Finally, the cohort was randomly divided into a training set (n = 3095) and an evaluation set (n = 3113) to establish a logistic regression model for predicting case-fatality and to assess its accuracy. RESULTS: The model for converting the Ct values into copies/µL was suitably accurate. The calculated viral load over time in the cohort of Covid-19 positive samples showed very low viral loads during the summer inter-epidemic waves in Italy. The calculated viral load along with gender and age allowed building a predictive model of case-fatality probability which showed high specificity (99.0%) and low sensitivity (21.7%) at the optimal threshold which varied by modifying the threshold (i.e. 75% sensitivity and 83.7% specificity). Alternative models including categorised cVL or raw cycle thresholds obtained by the same diagnostic method also gave the same performance. CONCLUSION: The modelling of the cycle threshold values using digital PCR had the potential of fostering studies addressing issues regarding Sars-CoV-2; furthermore, it may allow setting up predictive tools capable of early identifying those patients at high risk of case-fatality already at diagnosis, irrespective of the diagnostic RT-qPCR platform in use. Depending upon the epidemiological situation, public health authority policies/aims, the resources available and the thresholds used, adequate sensitivity could be achieved with acceptable low specificity.


Subject(s)
COVID-19/virology , Real-Time Polymerase Chain Reaction/methods , SARS-CoV-2/genetics , Viral Load/methods , Adolescent , Adult , Aged , COVID-19/mortality , COVID-19 Nucleic Acid Testing/methods , Child , Child, Preschool , Female , Genome, Viral , Humans , Logistic Models , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity , Young Adult
6.
Viruses ; 13(12)2021 12 16.
Article in English | MEDLINE | ID: covidwho-1580429

ABSTRACT

Several cases of naturally infected dogs with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported despite the apparently low susceptibility of this species. Here, we document the first reported case of infection caused by the Delta (B.1.617.2) variant of concern (VOC) in a dog in Spain that lived with several household members suffering from Coronavirus Infectious Disease 2019 (COVID-19). The animal displayed mild digestive and respiratory clinical signs and had a low viral load in the oropharyngeal swab collected at the first sampling. Whole-genome sequencing indicated infection with the Delta variant, coinciding with the predominant variant during the fifth pandemic wave in Spain. The dog seroconverted, as detected 21 days after the first sampling, and developed neutralizing antibodies that cross-neutralized different SARS-CoV-2 variants. This study further emphasizes the importance of studying the susceptibility of animal species to different VOCs and their potential role as reservoirs in the context of COVID-19.


Subject(s)
COVID-19/veterinary , Dog Diseases/virology , SARS-CoV-2/isolation & purification , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/diagnosis , COVID-19/transmission , COVID-19/virology , Dog Diseases/diagnosis , Dog Diseases/transmission , Dogs , Female , Genome, Viral/genetics , Pets/virology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Viral Zoonoses/diagnosis , Viral Zoonoses/transmission , Viral Zoonoses/virology
7.
PLoS One ; 16(3): e0243265, 2021.
Article in English | MEDLINE | ID: covidwho-1576038

ABSTRACT

Severe acute respiratory disease coronavirus 2 (SARS-CoV-2) which causes corona virus disease (COVID-19) was first identified in Wuhan, China in December 2019 and has since led to a global pandemic. Importations of SARS-CoV-2 to Israel in late February from multiple countries initiated a rapid outbreak across the country. In this study, SARS-CoV-2 whole genomes were sequenced from 59 imported samples with a recorded country of importation and 101 early circulating samples in February to mid-March 2020 and analyzed to infer clades and mutational patterns with additional sequences identified Israel available in public databases. Recorded importations in February to mid-March, mostly from Europe, led to multiple transmissions in all districts in Israel. Although all SARS-CoV-2 defined clades were imported, clade 20C became the dominating clade in the circulating samples. Identification of novel, frequently altered mutated positions correlating with clade-defining positions provide data for surveillance of this evolving pandemic and spread of specific clades of this virus. SARS-CoV-2 continues to spread and mutate in Israel and across the globe. With economy and travel resuming, surveillance of clades and accumulating mutations is crucial for understanding its evolution and spread patterns and may aid in decision making concerning public health issues.


Subject(s)
COVID-19/pathology , Genetic Variation , Genome, Viral/genetics , SARS-CoV-2/genetics , COVID-19/epidemiology , COVID-19/virology , High-Throughput Nucleotide Sequencing , Humans , Israel/epidemiology , Mutation , SARS-CoV-2/isolation & purification
8.
Int Microbiol ; 24(1): 123-124, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1573644

ABSTRACT

Until now, there is no current vaccine or treatment against SARS-CoV-2. There are previous successful RNAi studies performed on SARS-CoV. Therefore, similar line of investigation against SARS-CoV-2 could be successful.


Subject(s)
COVID-19/therapy , COVID-19/virology , RNA Interference , SARS-CoV-2/genetics , Animals , Gene Expression Regulation, Viral , Genome, Viral , Humans , SARS-CoV-2/physiology , Viral Proteins/genetics , Viral Proteins/metabolism
9.
BMC Med Genomics ; 14(Suppl 6): 289, 2021 12 14.
Article in English | MEDLINE | ID: covidwho-1571758

ABSTRACT

BACKGROUND: Virus screening and viral genome reconstruction are urgent and crucial for the rapid identification of viral pathogens, i.e., tracing the source and understanding the pathogenesis when a viral outbreak occurs. Next-generation sequencing (NGS) provides an efficient and unbiased way to identify viral pathogens in host-associated and environmental samples without prior knowledge. Despite the availability of software, data analysis still requires human operations. A mature pipeline is urgently needed when thousands of viral pathogen and viral genome reconstruction samples need to be rapidly identified. RESULTS: In this paper, we present a rapid and accurate workflow to screen metagenomics sequencing data for viral pathogens and other compositions, as well as enable a reference-based assembler to reconstruct viral genomes. Moreover, we tested our workflow on several metagenomics datasets, including a SARS-CoV-2 patient sample with NGS data, pangolins tissues with NGS data, Middle East Respiratory Syndrome (MERS)-infected cells with NGS data, etc. Our workflow demonstrated high accuracy and efficiency when identifying target viruses from large scale NGS metagenomics data. Our workflow was flexible when working with a broad range of NGS datasets from small (kb) to large (100 Gb). This took from a few minutes to a few hours to complete each task. At the same time, our workflow automatically generates reports that incorporate visualized feedback (e.g., metagenomics data quality statistics, host and viral sequence compositions, details about each of the identified viral pathogens and their coverages, and reassembled viral pathogen sequences based on their closest references). CONCLUSIONS: Overall, our system enabled the rapid screening and identification of viral pathogens from metagenomics data, providing an important piece to support viral pathogen research during a pandemic. The visualized report contains information from raw sequence quality to a reconstructed viral sequence, which allows non-professional people to screen their samples for viruses by themselves (Additional file 1).


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Computational Biology/methods , Genome, Viral , Genomics , Metagenomics , SARS-CoV-2/genetics , Algorithms , Animals , Automation , Coronavirus Infections/genetics , High-Throughput Nucleotide Sequencing , Humans , Mass Screening/methods , Pandemics , Pangolins , Reference Values , Software , Transcriptome , Workflow
10.
Viruses ; 13(12)2021 12 10.
Article in English | MEDLINE | ID: covidwho-1572657

ABSTRACT

The current COVID-19 pandemic demands massive testing by Real-time RT-PCR (Reverse Transcription Polymerase Chain Reaction), which is considered the gold standard diagnostic test for the detection of the SARS-CoV-2 virus. However, the virus continues to evolve with mutations that lead to phenotypic alterations as higher transmissibility, pathogenicity or vaccine evasion. Another big issue are mutations in the annealing sites of primers and probes of RT-PCR diagnostic kits leading to false-negative results. Therefore, here we identify mutations in the N (Nucleocapsid) gene that affects the use of the GeneFinder COVID-19 Plus RealAmp Kit. We sequenced SARS-CoV-2 genomes from 17 positive samples with no N gene detection but with RDRP (RNA-dependent RNA polymerase) and E (Envelope) genes detection, and observed a set of three different mutations affecting the N detection: a deletion of 18 nucleotides (Del28877-28894), a substitution of GGG to AAC (28881-28883) and a frameshift mutation caused by deletion (Del28877-28878). The last one cause a deletion of six AAs (amino acids) located in the central intrinsic disorder region at protein level. We also found this mutation in 99 of the 14,346 sequenced samples by the Sao Paulo state Network for Pandemic Alert of Emerging SARS-CoV-2 variants, demonstrating the circulation of the mutation in Sao Paulo, Brazil. Continuous monitoring and characterization of mutations affecting the annealing sites of primers and probes by genomic surveillance programs are necessary to maintain the effectiveness of the diagnosis of COVID-19.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19/diagnosis , Coronavirus Nucleocapsid Proteins/genetics , SARS-CoV-2/isolation & purification , Brazil/epidemiology , COVID-19/epidemiology , Coronavirus RNA-Dependent RNA Polymerase/genetics , DNA Primers , False Negative Reactions , Genome, Viral/genetics , Humans , Mutation , Phosphoproteins/genetics , RNA, Viral/genetics , SARS-CoV-2/genetics
11.
Curr Microbiol ; 79(1): 20, 2021 Dec 14.
Article in English | MEDLINE | ID: covidwho-1568357

ABSTRACT

The sudden rise in COVID-19 cases in 2020 and the incessant emergence of fast-spreading variants have created an alarming situation worldwide. Besides the continuous advancements in the design and development of vaccines to combat this deadly pandemic, new variants are frequently reported, possessing mutations that rapidly outcompeted an existing population of circulating variants. As concerns grow about the effects of mutations on the efficacy of vaccines, increased transmissibility, immune escape, and diagnostic failures are few other apprehensions liable for more deadly waves of COVID-19. Although the phenomenon of antigenic drift in new variants of SARS-CoV-2 is still not validated, it is conceived that the virus is acquiring new mutations as a fitness advantage for rapid transmission or to overcome immunological resistance of the host cell. Considerable evolution of SARS-CoV-2 has been observed since its first appearance in 2019, and despite the progress in sequencing efforts to characterize the mutations, their impacts in many variants have not been analyzed. The present article provides a substantial review of literature explaining the emerging variants of SARS-CoV-2 circulating globally, key mutations in viral genome, and the possible impacts of these new mutations on prevention and therapeutic strategies currently administered to combat this pandemic. Rising infections, mortalities, and hospitalizations can possibly be tackled through mass vaccination, social distancing, better management of available healthcare infrastructure, and by prioritizing genome sequencing for better serosurveillance studies and community tracking.


Subject(s)
COVID-19 , SARS-CoV-2 , Genome, Viral , Humans
13.
Int J Mol Sci ; 22(24)2021 Dec 07.
Article in English | MEDLINE | ID: covidwho-1554804

ABSTRACT

In the last few years, microRNA-mediated regulation has been shown to be important in viral infections. In fact, viral microRNAs can alter cell physiology and act on the immune system; moreover, cellular microRNAs can regulate the virus cycle, influencing positively or negatively viral replication. Accordingly, microRNAs can represent diagnostic and prognostic biomarkers of infectious processes and a promising approach for designing targeted therapies. In the past 18 months, the COVID-19 infection from SARS-CoV-2 has engaged many researchers in the search for diagnostic and prognostic markers and the development of therapies. Although some research suggests that the SARS-CoV-2 genome can produce microRNAs and that host microRNAs may be involved in the cellular response to the virus, to date, not enough evidence has been provided. In this paper, using a focused bioinformatic approach exploring the SARS-CoV-2 genome, we propose that SARS-CoV-2 is able to produce microRNAs sharing a strong sequence homology with the human ones and also that human microRNAs may target viral RNA regulating the virus life cycle inside human cells. Interestingly, all viral miRNA sequences and some human miRNA target sites are conserved in more recent SARS-CoV-2 variants of concern (VOCs). Even if experimental evidence will be needed, in silico analysis represents a valuable source of information useful to understand the sophisticated molecular mechanisms of disease and to sustain biomedical applications.


Subject(s)
MicroRNAs/genetics , SARS-CoV-2/genetics , Virus Replication/genetics , COVID-19/genetics , Computational Biology/methods , DNA Viruses/genetics , Gene Expression/genetics , Gene Expression Regulation, Viral/genetics , Genome, Viral/genetics , Host-Pathogen Interactions/genetics , RNA, Viral/genetics , Sequence Homology
14.
Life Sci Alliance ; 5(3)2022 03.
Article in English | MEDLINE | ID: covidwho-1552086

ABSTRACT

Murine neural stem cells (NSCs) were recently shown to release piRNA-containing exosomes/microvesicles (Ex/Mv) for exerting antiviral immunity, but it remains unknown if these Ex/Mv could target SARS-CoV-2 and whether the PIWI-piRNA system is important for these antiviral actions. Here, using in vitro infection models, we show that hypothalamic NSCs (htNSCs) Ex/Mv provided an innate immunity protection against SARS-CoV-2. Importantly, enhanced antiviral actions were achieved by using induced Ex/Mv that were derived from induced htNSCs through twice being exposed to several RNA fragments of SARS-CoV-2 genome, a process that was designed not to involve protein translation of these RNA fragments. The increased antiviral effects of these induced Ex/Mv were associated with increased expression of piRNA species some of which could predictably target SARS-CoV-2 genome. Knockout of piRNA-interacting protein PIWIL2 in htNSCs led to reductions in both innate and induced antiviral effects of Ex/Mv in targeting SARS-CoV-2. Taken together, this study demonstrates a case suggesting Ex/Mv from certain cell types have innate and adaptive immunity against SARS-CoV-2, and the PIWI-piRNA system is important for these antiviral actions.


Subject(s)
Argonaute Proteins/metabolism , COVID-19/immunology , COVID-19/metabolism , Cell-Derived Microparticles/metabolism , Exosomes , RNA, Small Interfering/metabolism , RNA/metabolism , SARS-CoV-2 , A549 Cells , Angiotensin-Converting Enzyme 2/metabolism , Animals , Genome, Viral , Humans , Hypothalamus/metabolism , Immune System , Immunity, Innate , In Vitro Techniques , Mice
15.
Euro Surveill ; 26(43)2021 10.
Article in English | MEDLINE | ID: covidwho-1547185

ABSTRACT

BackgroundIn the SARS-CoV-2 pandemic, viral genomes are available at unprecedented speed, but spatio-temporal bias in genome sequence sampling precludes phylogeographical inference without additional contextual data.AimWe applied genomic epidemiology to trace SARS-CoV-2 spread on an international, national and local level, to illustrate how transmission chains can be resolved to the level of a single event and single person using integrated sequence data and spatio-temporal metadata.MethodsWe investigated 289 COVID-19 cases at a university hospital in Munich, Germany, between 29 February and 27 May 2020. Using the ARTIC protocol, we obtained near full-length viral genomes from 174 SARS-CoV-2-positive respiratory samples. Phylogenetic analyses using the Auspice software were employed in combination with anamnestic reporting of travel history, interpersonal interactions and perceived high-risk exposures among patients and healthcare workers to characterise cluster outbreaks and establish likely scenarios and timelines of transmission.ResultsWe identified multiple independent introductions in the Munich Metropolitan Region during the first weeks of the first pandemic wave, mainly by travellers returning from popular skiing areas in the Alps. In these early weeks, the rate of presumable hospital-acquired infections among patients and in particular healthcare workers was high (9.6% and 54%, respectively) and we illustrated how transmission chains can be dissected at high resolution combining virus sequences and spatio-temporal networks of human interactions.ConclusionsEarly spread of SARS-CoV-2 in Europe was catalysed by superspreading events and regional hotspots during the winter holiday season. Genomic epidemiology can be employed to trace viral spread and inform effective containment strategies.


Subject(s)
COVID-19 , Cross Infection , Cross Infection/epidemiology , Genome, Viral , Genomics , Germany/epidemiology , Hospitals , Humans , Phylogeny , SARS-CoV-2
16.
J Med Virol ; 93(12): 6828-6832, 2021 12.
Article in English | MEDLINE | ID: covidwho-1544316

ABSTRACT

A cluster of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections was found in a cargo ship under repair in Zhoushan, China. Twelve of 20 crew members were identified as SARS-CoV-2 positive. We analyzed four sequences and identified them all in the Delta branch emerging from India with 7-8 amino acid mutation sites in the spike protein.


Subject(s)
COVID-19/virology , SARS-CoV-2/genetics , China , Genome, Viral/genetics , Humans , India , Phylogeny , Sequence Analysis/methods , Ships/methods , Spike Glycoprotein, Coronavirus/genetics
17.
J Med Virol ; 93(12): 6525-6534, 2021 12.
Article in English | MEDLINE | ID: covidwho-1544299

ABSTRACT

By analyzing newly collected SARS-CoV-2 genomes and comparing them with our previous study about SARS-CoV-2 single nucleotide variants (SNVs) before June 2020, we found that the SNV clustering had changed remarkably since June 2020. Apart from that the group of SNVs became dominant, which is represented by two nonsynonymous mutations A23403G (S:D614G) and C14408T (ORF1ab:P4715L), a few emerging groups of SNVs were recognized with sharply increased monthly incidence ratios of up to 70% in November 2020. Further investigation revealed sets of SNVs specific to patients' ages and/or gender, or strongly associated with mortality. Our logistic regression model explored features contributing to mortality status, including three critical SNVs, G25088T(S:V1176F), T27484C (ORF7a:L31L), and T25A (upstream of ORF1ab), ages above 40 years old, and the male gender. The protein structure analysis indicated that the emerging subgroups of nonsynonymous SNVs and the mortality-related ones were located on the protein surface area. The clashes in protein structure introduced by these mutations might in turn affect the viral pathogenesis through the alteration of protein conformation, leading to a difference in transmission and virulence. Particularly, we explored the fact that nonsynonymous SNVs tended to occur in intrinsic disordered regions of Spike and ORF1ab to significantly increase hydrophobicity, suggesting a potential role in the change of protein folding related to immune evasion.


Subject(s)
COVID-19/mortality , Genome, Viral/genetics , Polymorphism, Single Nucleotide/genetics , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Adult , Aged , Aged, 80 and over , COVID-19/pathology , Female , Humans , Male , Middle Aged , Mutation , Polyproteins/genetics , Spike Glycoprotein, Coronavirus/genetics , Viral Proteins/genetics , Virulence/genetics , Young Adult
18.
J Med Virol ; 94(1): 88-98, 2022 01.
Article in English | MEDLINE | ID: covidwho-1544348

ABSTRACT

The outbreak of the current coronavirus disease (COVID-19) occurred in late 2019 and quickly spread all over the world. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belongs to a genetically diverse group that mutates continuously leading to the emergence of multiple variants. Although a few antiviral agents and anti-inflammatory medicines are available, thousands of individuals have passed away due to emergence of new viral variants. Thus, proper surveillance of the SARS-CoV-2 genome is needed for the rapid identification of developing mutations over time, which are of the major concern if they occur specifically in the surface spike proteins of the virus (neutralizing analyte). This article reviews the potential mutations acquired by the SARS-CoV2 since the pandemic began and their significant impact on the neutralizing efficiency of vaccines and validity of the diagnostic assays.


Subject(s)
COVID-19/epidemiology , Genetic Drift , Genome, Viral/genetics , RNA, Viral/genetics , SARS-CoV-2/genetics , Antibodies, Neutralizing/immunology , Gene Frequency/genetics , Genetic Variation/genetics , Humans , Immunogenicity, Vaccine/immunology , Spike Glycoprotein, Coronavirus/genetics
19.
J Med Virol ; 93(12): 6479-6485, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1530178

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan, China in early December 2019 has rapidly widespread worldwide. Over the course of the pandemic, due to the advance of whole-genome sequencing technologies, an unprecedented number of genomes have been generated, providing both invaluable insights into the ongoing evolution and epidemiology of the virus and allowing the identification of hundreds of circulating genetic variants during the pandemic. In recent months variants of SARS-CoV-2 that have an increased number of mutations on the Spike protein have brought concern all over the world. These have been called "variants of concerns" (VOCs), and/or "variants of interests" (VOIs) as it has been suggested that their genome mutations might impact transmission, immune control, and virulence. Tracking the spread of emerging SARS-CoV-2 variants is crucial to inform public health efforts and control the ongoing pandemic. In this review, a concise characterization of the SARS-CoV-2 mutational patterns of the main VOCs and VOIs circulating and cocirculating worldwide has been presented to determine the magnitude of the SARS-CoV-2 threat to better understand the virus genetic diversity and its potential impact on vaccination strategy.


Subject(s)
COVID-19/epidemiology , COVID-19/transmission , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , COVID-19 Vaccines/immunology , China/epidemiology , Evolution, Molecular , Genome, Viral/genetics , Humans , Mutation , Mutation Rate , Phylogeny , Spike Glycoprotein, Coronavirus/immunology , Whole Genome Sequencing
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