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1.
Cells ; 10(12)2021 12 08.
Article in English | MEDLINE | ID: covidwho-1598446

ABSTRACT

Organ-specific proteins (OSPs) possess great medical potential both in clinics and in biomedical research. Applications of them-such as alanine transaminase, aspartate transaminase, and troponins-in clinics have raised certain concerns of their organ specificity. The dynamics and diversity of protein expression in heterogeneous human populations are well known, yet their effects on OSPs are less addressed. Here, we used mice as a model and implemented a breadth study to examine the panorgan proteome for potential variations in organ specificity in different genetic backgrounds. Using reasonable resources, we generated panorgan proteomes of four in-bred mouse strains. The results revealed a large diversity that was more profound among OSPs than among proteomes overall. We defined a robustness score to quantify such variation and derived three sets of OSPs with different stringencies. In the meantime, we found that the enriched biological functions of OSPs are also organ-specific and are sensitive and useful to assess the quality of OSPs. We hope our breadth study can open doors to explore the molecular diversity and dynamics of organ specificity at the protein level.


Subject(s)
Organ Specificity/genetics , Proteins/genetics , Proteome/genetics , Proteomics , Animals , Genetic Variation/genetics , Humans , Mice
2.
Sci Rep ; 11(1): 24495, 2021 12 30.
Article in English | MEDLINE | ID: covidwho-1591495

ABSTRACT

The ability of SARS-CoV-2 to rapidly mutate represents a remarkable complicancy. Quantitative evaluations of the effects that these mutations have on the virus structure/function is of great relevance and the availability of a large number of SARS-CoV-2 sequences since the early phases of the pandemic represents a unique opportunity to follow the adaptation of the virus to humans. Here, we evaluated the SARS-CoV-2 amino acid mutations and their progression by analyzing publicly available viral genomes at three stages of the pandemic (2020 March 15th and October 7th, 2021 February 7th). Mutations were classified in conservative and non-conservative based on the probability to be accepted during the evolution according to the Point Accepted Mutation substitution matrices and on the similarity of the encoding codons. We found that the most frequent substitutions are T > I, L > F, and A > V and we observe accumulation of hydrophobic residues. These findings are consistent among the three stages analyzed. We also found that non-conservative mutations are less frequent than conservative ones. This finding may be ascribed to a progressive adaptation of the virus to the host. In conclusion, the present study provides indications of the early evolution of the virus and tools for the global and genome-specific evaluation of the possible impact of mutations on the structure/function of SARS-CoV-2 variants.


Subject(s)
COVID-19/virology , Genetic Variation , Genome, Viral , Pandemics , SARS-CoV-2/genetics , Humans , Mutation
3.
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 , Metagenomics , Animals , Chiroptera/virology , Coronavirus/genetics , Coronavirus Infections/veterinary , Eswatini , Genetic Variation , Genome, Viral , Phylogeny
4.
Biomed Res Int ; 2021: 2347872, 2021.
Article in English | MEDLINE | ID: covidwho-1582891

ABSTRACT

Introduction: Patients with acute respiratory distress syndrome caused by coronavirus disease 2019 (COVID-19) are at risk for superadded infections, especially infections caused by multidrug resistant (MDR) pathogens. Before the COVID-19 pandemic, the prevalence of MDR infections, including infections caused by MDR Klebsiella pneumoniae (K. pneumoniae), was very high in Iran. This study is aimed at assessing the genetic diversity, antimicrobial resistance pattern, and biofilm formation in K. pneumoniae isolates obtained from patients with COVID-19 and ventilator-associated pneumonia (VAP) hospitalized in an intensive care unit (ICU) in Iran. Methods: In this cross-sectional study, seventy K. pneumoniae isolates were obtained from seventy patients with COVID-19 hospitalized in the ICU of Shahid Beheshti hospital, Kashan, Iran, from May to September, 2020. K. pneumoniae was detected through the ureD gene. Antimicrobial susceptibility testing was done using the Kirby-Bauer disc diffusion method, and biofilm was detected using the microtiter plate assay method. Genetic diversity was also analyzed through polymerase chain reaction based on enterobacterial repetitive intergenic consensus (ERIC-PCR). The BioNumerics software (v. 8.0, Applied Maths, Belgium) was used for analyzing the data and drawing dendrogram and minimum spanning tree. Findings. K. pneumoniae isolates had varying levels of resistance to antibiotics meropenem (80.4%), cefepime-aztreonam-piperacillin/tazobactam (70%), tobramycin (61.4%), ciprofloxacin (57.7%), gentamicin (55.7%), and imipenem (50%). Around 77.14% of isolates were MDR, and 42.8% of them formed biofilm. Genetic diversity analysis revealed 28 genotypes (E1-E28) and 74.28% of isolates were grouped into ten clusters (i.e., clusters A-J). Clusters were further categorized into three major clusters, i.e., clusters E, H, and J. Antimicrobial resistance to meropenem, tobramycin, gentamicin, and ciprofloxacin in cluster J was significantly higher than cluster H, denoting significant relationship between ERIC clusters and antimicrobial resistance. However, there was no significant difference among major clusters E, H, and J respecting biofilm formation. Conclusion: K. pneumoniae isolates obtained from patients with COVID-19 have high antimicrobial resistance, and 44.2% of them have genetic similarity and can be clustered in three major clusters. There is a significant difference among clusters respecting antimicrobial resistance.


Subject(s)
Biofilms/growth & development , COVID-19/microbiology , Drug Resistance, Multiple, Bacterial/genetics , Genetic Variation/genetics , Klebsiella Infections/microbiology , Klebsiella pneumoniae/genetics , Pneumonia, Ventilator-Associated/microbiology , Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , COVID-19/virology , Cross-Sectional Studies , Humans , Intensive Care Units , Iran , Klebsiella Infections/drug therapy , Klebsiella pneumoniae/drug effects , Microbial Sensitivity Tests/methods , Pandemics/prevention & control , Pneumonia, Ventilator-Associated/virology
5.
PLoS One ; 16(12): e0260635, 2021.
Article in English | MEDLINE | ID: covidwho-1581779

ABSTRACT

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) showed susceptibility to diverse animal species. We conducted this study to understand the spatial epidemiology, genetic diversity, and statistically significant genetic similarity along with per-gene recombination events of SARS-CoV-2 and related viruses (SC2r-CoVs) in animals globally. We collected a number of different animal species infected with SARS-CoV-2 and its related viruses. Then, we retrieved genome sequences of SARS-CoV-2 and SC2r-CoVs from GISAID and NCBI GenBank for genomic and mutational analysis. Although the evolutionary origin of SARS-CoV-2 remains elusive, the diverse SC2r-CoV have been detected in multiple Rhinolophus bat species and in Malayan pangolin. To date, human-to-animal spillover events have been reported in cat, dog, tiger, lion, gorilla, leopard, ferret, puma, cougar, otter, and mink in 25 countries. Phylogeny and genetic recombination events of SC2r-CoVs showed higher similarity to the bat coronavirus RaTG13 and BANAL-103 for most of the genes and to some Malayan pangolin coronavirus (CoV) strains for the N protein from bats and pangolin showed close resemblance to SARS-CoV-2. The clustering of animal and human strains from the same geographical area has proved human-to-animal transmission of the virus. The Alpha, Delta and Mu-variant of SARS-CoV-2 was detected in dog, gorilla, lion, tiger, otter, and cat in the USA, India, Czech Republic, Belgium, and France with momentous genetic similarity with human SARS-CoV-2 sequences. The mink variant mutation (spike_Y453F) was detected in both humans and domestic cats. Moreover, the dog was affected mostly by clade O (66.7%), whereas cat and American mink were affected by clade GR (31.6 and 49.7%, respectively). The α-variant was detected as 2.6% in cat, 4.8% in dog, 14.3% in tiger, 66.7% in gorilla, and 77.3% in lion. The highest mutations observed in mink where the substitution of D614G in spike (95.2%) and P323L in NSP12 (95.2%) protein. In dog, cat, gorilla, lion, and tiger, Y505H and Y453F were the common mutations followed by Y145del, Y144del, and V70I in S protein. We recommend vaccine provision for pet and zoo animals to reduce the chance of transmission in animals. Besides, continuous epidemiological and genomic surveillance of coronaviruses in animal host is crucial to find out the immediate ancestor of SARS-CoV-2 and to prevent future CoVs threats to humans.


Subject(s)
SARS-CoV-2 , COVID-19 , Genetic Variation , Phylogeny
6.
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
7.
Viruses ; 13(12)2021 11 24.
Article in English | MEDLINE | ID: covidwho-1551630

ABSTRACT

During the four pandemic waves, a total of 560,504 cases and 10,178 deaths due to COVID-19 were reported in Croatia. The Alpha variant, dominant from March 2021 (>50% of positive samples), was rapidly replaced by Delta variants (>90%) by August 2021. Several seroprevalence studies were conducted in different populations (general population, children/adolescents, professional athletes, healthcare workers, veterinarians) and in immunocompromised patients (hemodialysis patients, liver/kidney transplant recipients). After the first pandemic wave, seroprevalence rates of neutralizing (NT) antibodies were reported to be 0.2-5.5%. Significantly higher seropositivity was detected during/after the second wave, 2.6-18.7%. Two studies conducted in pet animals (February-June 2020/July-December 2020) reported SARS-CoV-2 NT antibodies in 0.76% of cats and 0.31-14.69% of dogs, respectively. SARS-CoV-2 NT antibodies were not detected in wildlife. Environmental samples taken in the households of COVID-19 patients showed high-touch personal objects as most frequently contaminated (17.3%), followed by surfaces in patients' rooms (14.6%), kitchens (13.3%) and bathrooms (8.3%). SARS-CoV-2 RNA was also detected in 96.8% affluent water samples, while all effluent water samples tested negative. Detection of SARS-CoV-2 in humans, animals and the environment suggests that the 'One Health' approach is critical to controlling COVID-19 and future pandemics.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , One Health , Pandemics , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/transmission , COVID-19/veterinary , Cats , Croatia/epidemiology , Dogs , Genetic Variation , Health Personnel , Humans , Pets , Prevalence , RNA, Viral , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Seroepidemiologic Studies , Waste Water/virology
8.
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
10.
PLoS Pathog ; 17(9): e1009811, 2021 09.
Article in English | MEDLINE | ID: covidwho-1526706
11.
Cell Rep ; 37(3): 109838, 2021 10 19.
Article in English | MEDLINE | ID: covidwho-1517083

ABSTRACT

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads, variants with enhanced virulence and transmissibility have emerged. Although in vitro systems allow rapid characterization, they do not fully recapitulate the dynamic interaction of virions and neutralizing antibodies in the airway. Here, we demonstrate that the N501Y variant permits respiratory infection in unmodified mice. We utilize N501Y to survey in vivo pseudovirus infection dynamics and susceptibility to reinfection with the L452R (Los Angeles), K417N + E484K (South Africa), and L452R + K417N + E484Q (India) variants. Human coronavirus disease 2019 (COVID-19)+ or vaccinated antibody isotypes, titers, variant receptor binding domain (RBD) binding, and neutralization potential are studied, revealing numerous significant correlations. Immune escape of the K417N + E484K variant is observed because infection can be appreciated in the nasopharynx, but not lungs, of mice transferred with low-antibody-tier plasma. Conversely, near-complete protection is observed in animals receiving high-antibody-tier plasma, a phenomenon that can only be appreciated in vivo.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/therapy , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Animals , Antibodies, Neutralizing/immunology , Cell Line , Cricetinae , Genetic Variation , HEK293 Cells , Humans , Immune System , Immunization, Passive/methods , In Vitro Techniques , Mice , Mutation , Nasopharynx/virology , Protein Binding , Recombinant Proteins/metabolism , Spike Glycoprotein, Coronavirus/genetics
12.
BMC Nephrol ; 22(1): 381, 2021 11 13.
Article in English | MEDLINE | ID: covidwho-1515439

ABSTRACT

BACKGROUND: Kidney dysfunction occurs in severe COVID-19, and is a predictor of COVID-19 mortality. Whether kidney dysfunction causes severe COVID-19, and hence is a target of intervention, or whether it is a symptom, is unclear because conventional observational studies are open to confounding. To obtain unconfounded estimates, we used Mendelian randomization to examine the role of kidney function in severe COVID-19. METHODS: We used genome-wide significant, uncorrelated genetic variants to predict kidney function, in terms of estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR), and then assessed whether people with genetically instrumented higher eGFR or lower UACR, an indication of better kidney function, had a lower risk of severe COVID-19 (8779 cases, 1,001,875 controls), using the largest available cohorts with extensive genotyping. For comprehensiveness, we also examined their role in COVID-19 hospitalization (24,274 cases, 2,061,529 controls) and all COVID-19 (1,12,612 cases, 2,474,079 controls). RESULTS: Genetically instrumented higher eGFR was associated with lower risk of severe COVID-19 (odds ratio (OR) 0.90, 95% confidence interval (CI) 0.83, 0.98) but not related to COVID-19 hospitalization or infection. Genetically instrumented UACR was not related to COVID-19. CONCLUSIONS: Kidney function appears to be one of the key targets for severe COVID-19 treatment. Use of available medications to improve kidney function, such as antihypertensives, might be beneficial for COVID-19 treatment, with relevance to drug repositioning.


Subject(s)
COVID-19/complications , COVID-19/genetics , Glomerular Filtration Rate/genetics , Kidney/physiopathology , Patient Acuity , Albuminuria/urine , Case-Control Studies , Creatinine/urine , Genetic Variation , Genome-Wide Association Study , Hospitalization , Humans , Mendelian Randomization Analysis , Risk Factors , SARS-CoV-2 , /genetics
13.
Sci Rep ; 11(1): 22105, 2021 11 11.
Article in English | MEDLINE | ID: covidwho-1510611

ABSTRACT

The COVID-19 pandemic first emerged in Malaysia in Jan 2020. As of 12th Sept 2021, 1,979,698 COVID-19 cases that occurred over three major epidemic waves were confirmed. The virus contributing to the three epidemic waves has not been well-studied. We sequenced the genome of 22 SARS-CoV-2 strains detected in Malaysia during the second and the ongoing third wave of the COVID-19 epidemic. Detailed phylogenetic and genetic variation analyses of the SARS-CoV-2 isolate genomes were performed using these newly determined sequences and all other available sequences. Results from the analyses suggested multiple independent introductions of SARS-CoV-2 into Malaysia. A new B.1.524(G) lineage with S-D614G mutation was detected in Sabah, East Malaysia and Selangor, Peninsular Malaysia on 7th October 2020 and 14th October 2020, respectively. This new B.1.524(G) group was not the direct descendant of any of the previously detected lineages. The new B.1.524(G) carried a set of genetic variations, including A701V (position variant frequency = 0.0007) in Spike protein and a novel G114T mutation at the 5'UTR. The biological importance of the specific mutations remained unknown. The sequential appearance of the mutations, however, suggests that the spread of the new B.1.524(G) lineages likely begun in Sabah and then spread to Selangor. The findings presented here support the importance of SARS-CoV-2 full genome sequencing as a tool to establish an epidemiological link between cases or clusters of COVID-19 worldwide.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , SARS-CoV-2/genetics , Genetic Variation , Genome, Viral , Humans , Malaysia/epidemiology , Pandemics , Phylogeny
14.
Cell Rep ; 37(7): 110020, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1509641

ABSTRACT

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types.


Subject(s)
COVID-19/genetics , SARS-CoV-2/genetics , Chromosome Mapping/methods , Computational Biology/methods , Databases, Genetic , Gene Expression/genetics , Gene Expression Profiling/methods , Genetic Predisposition to Disease/genetics , Genetic Variation/genetics , Genome-Wide Association Study/methods , Humans , Organ Specificity/genetics , Polymorphism, Single Nucleotide/genetics , Quantitative Trait Loci/genetics , SARS-CoV-2/pathogenicity , Severity of Illness Index , Transcriptome/genetics
15.
J Med Virol ; 94(2): 521-530, 2022 02.
Article in English | MEDLINE | ID: covidwho-1508796

ABSTRACT

Measles is one of the most infectious diseases of humans. It is caused by the measles virus (MeV) and can lead to serious illness, lifelong complications, and even death. Whole-genome sequencing (WGS) is now available to study molecular epidemiology and identify MeV transmission pathways. In the present study, WGS of 23 MeV strains of genotype H1, collected in Mainland China between 2006 and 2018, were generated and compared to 31 WGSs from the public domain to analyze genomic characteristics, evolutionary rates and date of emergence of H1 genotype. The noncoding region between M and F protein genes (M/F NCR) was the most variable region throughout the genome. Although the nucleotide substitution rate of H1 WGS was around 0.75 × 10-3 substitution per site per year, the M/F NCR had an evolutionary rate three times higher, with 2.44 × 10-3 substitution per site per year. Phylogenetic analysis identified three distinct genetic groups. The Time of the Most Recent Common Ancestor (TMRCA) of H1 genotype was estimated at approximately 1988, while the first genetic group appeared around 1995 followed by two other genetic groups in 1999-2002. Bayesian skyline plot showed that the genetic diversity of the H1 genotype remained stable even though the number of MeV cases decreased 50 times between 2014 (52 628) and 2020 (993). The current coronavirus disease 2019 (COVID-19) pandemic might have some effect on the measles epidemic and further studies will be necessary to assess the genetic diversity of the H1 genotype in a post-COVID area.


Subject(s)
Evolution, Molecular , Genome, Viral/genetics , Measles virus/genetics , China/epidemiology , Genes, Viral/genetics , Genetic Variation , Genomics , Genotype , Humans , Measles/epidemiology , Measles/virology , Measles virus/classification , Phylogeny , RNA, Viral/genetics
16.
Virus Res ; 307: 198618, 2022 01 02.
Article in English | MEDLINE | ID: covidwho-1504602

ABSTRACT

The second wave of COVID-19 caused by severe acute respiratory syndrome virus (SARS-CoV-2) is rapidly spreading over the world. Mechanisms behind the flee from current antivirals are still unclear due to the continuous occurrence of SARS-CoV-2 genetic variants. Brazil is the world's second-most COVID-19 affected country. In the present study, we identified the genomic and proteomic variants of Brazilian SARS-CoV-2 isolates. We identified 16 different genotypic variants were found among the 27 isolates. The genotypes of three isolates such as Bra/1236/2021 (G15), Bra/MASP2C844R2/2020 (G11), and Bra/RJ-DCVN5/2020 (G9) have a unique mutant in NSP4 (S184N), 2'O-Mutase (R216N), membrane protein (A2V) and Envelope protein (V5A). A mutation in RdRp of SARS-CoV-2, particularly the change of Pro-to Leu-at 323 resulted in the stabilization of the structure in BRA/CD1739-P4/2020. NSP4, NSP5 protein mutants are more virulent in genotype 15 and 16. A fast protein folding rate changes the structural stability and leads to escape for current antivirals. Thus, our findings help researchers to develop the best potent antivirals based on the new mutant of Brazilian isolates.


Subject(s)
Coronavirus 3C Proteases/genetics , Protein Folding , SARS-CoV-2/genetics , Viral Nonstructural Proteins/genetics , Brazil , COVID-19/pathology , Coronavirus Nucleocapsid Proteins/genetics , Coronavirus RNA-Dependent RNA Polymerase/genetics , Genetic Variation/genetics , Genome, Viral/genetics , Humans , Phosphoproteins/genetics , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/genetics , Virulence/genetics
17.
Sci Rep ; 11(1): 21484, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1500516

ABSTRACT

Epidemiological efforts to model the spread of SARS-CoV-2, the virus that causes COVID-19, are crucial to understanding and containing current and future outbreaks and to inform public health responses. Mutations that occur in viral genomes can alter virulence during outbreaks by increasing infection rates and helping the virus evade the host immune system. To understand the changes in viral genomic diversity and molecular epidemiology in Oxford during the first wave of infections in the United Kingdom, we analyzed 563 clinical SARS-CoV-2 samples via whole-genome sequencing using Nanopore MinION sequencing. Large-scale surveillance efforts during viral epidemics are likely to be confounded by the number of independent introductions of the viral strains into a region. To avoid such issues and better understand the selection-based changes occurring in the SARS-CoV-2 genome, we utilized local isolates collected during the UK's first national lockdown whereby personal interactions, international and national travel were considerably restricted and controlled. We were able to track the short-term evolution of the virus, detect the emergence of several mutations of concern or interest, and capture the viral diversity of the region. Overall, these results demonstrate genomic pathogen surveillance efforts have considerable utility in controlling the local spread of the virus.


Subject(s)
COVID-19/epidemiology , Genetic Variation , SARS-CoV-2/genetics , COVID-19/prevention & control , COVID-19/virology , Genome, Viral , Humans , Phylogeny , Polymorphism, Single Nucleotide , Quarantine , SARS-CoV-2/classification , SARS-CoV-2/isolation & purification , Seasons , Spike Glycoprotein, Coronavirus/genetics , United Kingdom/epidemiology , Whole Genome Sequencing
18.
Eur Rev Med Pharmacol Sci ; 25(20): 6411-6424, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1503073

ABSTRACT

OBJECTIVE: The heterogeneity of clinical manifestations and mortality rates in Coronavirus disease 2019 (COVID-19) patients may be related to the existence of molecular subtypes in COVID-19. To improve current management, it is essential to find the hub genes and pathways associated with different COVID-19 subtypes. MATERIALS AND METHODS: The whole-genome sequencing information (GSE156063, GSE163151) of nasopharyngeal swabs from normal subjects and COVID-19 patients were downloaded from the Gene Expression Omnibus (GEO) database. The molecular subtypes of patients with COVID-19 were classified using the "consistent clustering" method, and the specific genes associated with each subtype were found. Differentially expressed genes (DEGs) were screened between normal subjects and COVID-19 patients; the Weighted gene co-expression network analysis (WGCNA) method was used to find the key module genes of COVID-19 patients. Subtype-specific, differentially expressed and module-related genes were collected and intersected. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out and protein-protein interaction (PPI) networks were generated. The pathways enriched in COVID-19 subtypes were analyzed by gene set variation analysis (GSVA). RESULTS: Patients with COVID-19 were divided into three subtypes, and there was no significant difference in gender and age distribution between subtypes. 82 differential gene pathways were screened between Subtypes I and II, 131 differential gene pathways were screened between Subtypes I and III, and 107 differential gene pathways were screened between Subtypes II and III. Finally, 44 differentially expressed key genes were screened, including 11 hub genes (RSAD2, IFIT1, MX1, OAS1, OAS2, BST2, IFI27, IFI35, IFI6, IFITM3, STAT2). CONCLUSIONS: There are significant differences in gene activation and pathway enrichment among different molecular subtypes of COVID-19, which may account for the heterogeneity in clinical presentation and the prognosis of patients.


Subject(s)
Biomarkers, Tumor/genetics , COVID-19/genetics , Oligonucleotide Array Sequence Analysis , COVID-19/diagnosis , Genetic Variation/genetics , Humans
19.
Sci Rep ; 11(1): 21108, 2021 10 26.
Article in English | MEDLINE | ID: covidwho-1493205

ABSTRACT

SARS-CoV-2, the virus causing the COVID-19 pandemic emerged in December 2019 in China and raised fears it could overwhelm healthcare systems worldwide. Mutations of the virus are monitored by the GISAID database from which we downloaded sequences from four West African countries Ghana, Gambia, Senegal and Nigeria from February 2020 to April 2020. We subjected the sequences to phylogenetic analysis employing the nextstrain pipeline. We found country-specific patterns of viral variants and supplemented that with data on novel variants from June 2021. Until April 2020, variants carrying the crucial Europe-associated D614G amino acid change were predominantly found in Senegal and Gambia, and combinations of late variants with and early variants without D614G in Ghana and Nigeria. In June 2021 all variants carried the D614G amino acid substitution. Senegal and Gambia exhibited again variants transmitted from Europe (alpha or delta), Ghana a combination of several variants and in Nigeria the original Eta variant. Detailed analysis of distinct samples revealed that some might have circulated latently and some reflect migration routes. The distinct patterns of variants within the West African countries point at their global transmission via air traffic predominantly from Europe and only limited transmission between the West African countries.


Subject(s)
COVID-19/transmission , COVID-19/virology , Computational Biology/methods , Mutation , SARS-CoV-2 , Africa, Western , Biodiversity , China , Europe , Gambia , Genetic Variation , Genome, Viral , Geography , Ghana , Humans , Nigeria , Phylogeny , Senegal , Time Factors
20.
Emerg Infect Dis ; 27(10): 2666-2668, 2021 10.
Article in English | MEDLINE | ID: covidwho-1486735

ABSTRACT

We sequenced 10% of imported severe acute respiratory syndrome coronavirus 2 infections detected in travelers to Hong Kong and revealed the genomic diversity of regions of origin, including lineages not previously reported from those countries. Our results suggest that international or regional travel hubs might be useful surveillance sites to monitor sequence diversity.


Subject(s)
COVID-19 , Communicable Diseases, Imported , Genetic Variation , Hong Kong/epidemiology , Humans , SARS-CoV-2
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