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1.
Gene ; 813: 146113, 2022 Mar 01.
Article in English | MEDLINE | ID: covidwho-1616498

ABSTRACT

Since late 2019, when SARS-CoV-2 was reported at Wuhan, several sequence analyses have been performed and SARS-CoV-2 genome sequences have been submitted in various databases. Moreover, the impact of these variants on infectivity and response to neutralizing antibodies has been assessed. In the present study, we retrieved a total number of 176 complete and high-quality S glycoprotein sequences of Iranian SARS-COV-2 in public database of the GISAID and GenBank from April 2020 up to May 2021. Then, we identified the number of variables, singleton and parsimony informative sites at both gene and protein levels and discussed the possible functional consequences of important mutations on the infectivity and response to neutralizing antibodies. Phylogenetic tree was constructed to represent the relationship between Iranian SARS-COV2 and variants of concern (VOC), variants of interest (VOI) and reference sequence. We found that the four current VOCs - Alpha, Beta, Gamma and Delta - are circulated in different regions in Iran. The Delta variant is notably more transmissible than other variants, and is expected to become a dominant variant. However, some of the Delta variants in Iran carry an additional mutation, namely E1202Q in the HR2 subdomain that might confer an advantage to viral/cell membrane fusion process. We also observed some more common mutations such as an N-terminal domain (NTD) deletion at position I210 and P863H in fusion peptide-heptad repeat 1 span region in Iranian SARS-COV-2. The reported mutations in the current project have practical significance in prediction of disease spread as well as design of vaccines and drugs.


Subject(s)
COVID-19/genetics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Antibodies, Neutralizing/immunology , Antibodies, Viral/genetics , COVID-19/epidemiology , COVID-19/metabolism , Databases, Genetic , Humans , Iran/epidemiology , Mutation/genetics , Phylogeny , Protein Binding , RNA, Viral , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Sequence Analysis, DNA/methods , Spike Glycoprotein, Coronavirus/metabolism
2.
PLoS One ; 16(12): e0261778, 2021.
Article in English | MEDLINE | ID: covidwho-1613357

ABSTRACT

Many CRISPR/Cas platforms have been established for the detection of SARS-CoV-2. But the detection platform of the variants of SARS-CoV-2 is scarce because its specificity is very challenging to achieve for those with only one or a few nucleotide(s) differences. Here, we report for the first time that chimeric crRNA could be critical in enhancing the specificity of CRISPR-Cas12a detecting of N501Y, which is shared by Alpha, Beta, Gamma, and Mu variants of SARS-CoV-2 without compromising its sensitivity. This strategy could also be applied to detect other SARS-CoV-2 variants that differ only one or a few nucleotide(s) differences.


Subject(s)
COVID-19/diagnosis , Nucleic Acid Amplification Techniques/methods , SARS-CoV-2/genetics , COVID-19/genetics , CRISPR-Cas Systems/genetics , DNA Primers/genetics , Diagnostic Tests, Routine/methods , Humans , Mutation/genetics , RNA, Guide/genetics , RNA, Guide/metabolism , Sensitivity and Specificity
3.
Cell Rep ; 38(2): 110205, 2022 01 11.
Article in English | MEDLINE | ID: covidwho-1588142

ABSTRACT

Spontaneous mutations introduce uncertainty into coronavirus disease 2019 (COVID-19) control procedures and vaccine development. Here, we perform a spatiotemporal analysis on intra-host single-nucleotide variants (iSNVs) in 402 clinical samples from 170 affected individuals, which reveals an increase in genetic diversity over time after symptom onset in individuals. Nonsynonymous mutations are overrepresented in the pool of iSNVs but underrepresented at the single-nucleotide polymorphism (SNP) level, suggesting a two-step fitness selection process: a large number of nonsynonymous substitutions are generated in the host (positive selection), and these substitutions tend to be unfixed as SNPs in the population (negative selection). Dynamic iSNV changes in subpopulations with different gender, age, illness severity, and viral shedding time displayed a varied fitness selection process among populations. Our study highlights that iSNVs provide a mutational pool shaping the rapid global evolution of the virus.


Subject(s)
COVID-19/virology , Host-Pathogen Interactions/genetics , SARS-CoV-2/genetics , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Genome, Viral/genetics , Humans , Infant , Infant, Newborn , Male , Middle Aged , Mutation/genetics , Phylogeny , Polymorphism, Single Nucleotide/genetics , Spike Glycoprotein, Coronavirus/genetics , Young Adult
4.
Front Immunol ; 12: 751778, 2021.
Article in English | MEDLINE | ID: covidwho-1581343

ABSTRACT

During the COVID-19 pandemic, SARS-CoV-2 variants have emerged and spread worldwide. The Delta (B.1.617.2) variant was first reported in India in October 2020 and was classified as a "variant of concern (VOC)" by the WHO on 11 May, 2021. Compared to the wild-type strain, several studies have shown that the Delta variant is more transmissible and has higher viral loads in infected samples. COVID-19 patients infected with the Delta variant have a higher risk of hospitalization, intensive care unit (ICU) admission, and mortality. The Delta variant is becoming the dominant strain in many countries around the world. This review summarizes and analyses the biological characteristics of key amino acid mutations, the epidemic characteristics, and the immune escape of the Delta variant. We hope to provide scientific reference for the monitoring and prevention measures of the SARS-CoV-2 Delta variant and the development strategy of a second-generation vaccine.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/epidemiology , Mutation/genetics , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/genetics , Animals , COVID-19/genetics , COVID-19/immunology , Epidemics , Hospitalization/statistics & numerical data , Humans , Immune Evasion , Mass Vaccination
5.
Immunity ; 54(12): 2681-2687, 2021 12 14.
Article in English | MEDLINE | ID: covidwho-1568762

ABSTRACT

Antigenic drift refers to the evolutionary accumulation of amino acid substitutions in viral proteins selected by host adaptive immune systems as the virus circulates in a population. Antigenic drift can substantially limit the duration of immunity conferred by infection and vaccination. Here, I explain the factors contributing to the rapid antigenic drift of the SARS-CoV-2 spike protein and receptor proteins of other viruses and discuss the implications for SARS-CoV-2 evolution and immunity.


Subject(s)
COVID-19/immunology , Mutation/genetics , SARS-CoV-2/physiology , Adaptive Immunity , Animals , Biological Evolution , Host-Pathogen Interactions , Humans , Spike Glycoprotein, Coronavirus/immunology , Vaccination
6.
J Med Virol ; 93(12): 6595-6604, 2021 12.
Article in English | MEDLINE | ID: covidwho-1544310

ABSTRACT

As a kind of human betacoronavirus, SARS-CoV-2 has endangered globally public health. As of January 2021, the virus had resulted in 2,209,195 deaths. By studying the evolution trend and characteristics of 265 SARS-CoV-2 strains in the United States from January to March, it is found that the strains can be divided into six clades, USA clade-1, USA clade-2, USA clade-3, USA clade-4, USA clade-5, and USA clade-6, in which US clade-1 may be the most ancestral clade, USA clade-2 is an interim clade of USA clade-1 and USA clade-3, the other three clades have similar codon usage pattern, while USA clade-6 is the newest and most adaptable clade. Mismatch analysis and protein alignment showed that the evolution of the clades arises from some special mutations in viral proteins, which may help the strain to invade, replicate, transcribe and so on. Compared with previous research and classifications, we suggest that clade O in GISAID should not be an independent clade and Wuhan-Hu-1 (EPI_ISL_402125) should not be an ancestral reference sequence. Our study decoded the evolutionary dynamic of SARS-CoV-2 in the early stage from the United States, which give some clues to infer the current evolution trend of SARS-CoV-2 and study the function of viral mutational protein.


Subject(s)
Evolution, Molecular , SARS-CoV-2/genetics , Bayes Theorem , COVID-19/virology , Humans , Mutation/genetics , Phylogeny , Principal Component Analysis , Sequence Alignment , United States/epidemiology
7.
J Med Virol ; 93(12): 6782-6787, 2021 12.
Article in English | MEDLINE | ID: covidwho-1544298

ABSTRACT

Sao Paulo State, currently experiences a second COVID-19 wave overwhelming the healthcare system. Due to the paucity of SARS-CoV-2 complete genome sequencing, we established a Network for Pandemic Alert of Emerging SARS-CoV-2 Variants to rapidly understand and monitor the spread of SARS-CoV-2 variants into the state. Through analysis of 210 SARS-CoV-2 complete genomes obtained from the largest regional health departments we identified cocirculation of multiple SARS-CoV-2 lineages such as B.1.1 (0.5%), B.1.1.28 (23.2%), B.1.1.7 (alpha variant, 6.2%), B.1.566 (1.4%), B.1.544 (0.5%), C.37 (0.5%) P.1 (gamma variant, 66.2%), and P.2 (zeta variant, 1.0%). Our analysis allowed also the detection, for the first time in Brazil, the South African B.1.351 (beta) variant of concern, B.1.351 (501Y.V2) (0.5%), characterized by the following mutations: ORF1ab: T265I, R724K, S1612L, K1655N, K3353R, SGF 3675_F3677del, P4715L, E5585D; spike: D80A, D215G, L242_L244del, A262D, K417N, E484K, N501Y, D614G, A701V, C1247F; ORF3a: Q57H, S171L, E: P71L; ORF7b: Y10F, N: T205I; ORF14: L52F. The most recent common ancestor of the identified strain was inferred to be mid-October to late December 2020. Our analysis demonstrated the P.1 lineage predominance and allowed the early detection of the South African strain for the first time in Brazil. We highlight the importance of SARS-CoV-2 active monitoring to ensure the rapid detection of potential variants for pandemic control and vaccination strategies. Highlights Identification of B.1.351 (beta) variant of concern in the Sao Paulo State. Dissemination of SARS-CoV-2 variants of concern and interest in the Sao Paulo State. Mutational Profile of the circulating variants of concern and interest.


Subject(s)
SARS-CoV-2/genetics , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Brazil , COVID-19/immunology , COVID-19/virology , Genomics/methods , Humans , Mutation/genetics , Mutation/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
10.
Sci Transl Med ; 13(617): eabh1803, 2021 10 27.
Article in English | MEDLINE | ID: covidwho-1494932

ABSTRACT

[Figure: see text].


Subject(s)
COVID-19 , SARS-CoV-2 , Austria , Genomics , Humans , Mutation/genetics
11.
Viruses ; 13(10)2021 10 18.
Article in English | MEDLINE | ID: covidwho-1471002

ABSTRACT

West Java Health Laboratory (WJHL) is one of the many institutions in Indonesia that have sequenced SARS-CoV-2 genome. Although having submitted a large number of sequences since September 2020, however, these submitted data lack advanced analyses. Therefore, in this study, we analyze the variant distribution, hotspot mutation, and its impact on protein structure and function of SARS-CoV-2 from the collected samples from WJHL. As many as one hundred sixty-three SARS-CoV-2 genome sequences submitted by West Java Health Laboratory (WJHL), with collection dates between September 2020 and June 2021, were retrieved from GISAID. Subsequently, the frequency and distribution of non-synonymous mutations across different cities and regencies from these samples were analyzed. The effect of the most prevalent mutations from dominant variants on the stability of their corresponding proteins was examined. The samples mostly consisted of people of working-age, and were distributed between female and male equally. All of the sample sequences showed varying levels of diversity, especially samples from West Bandung which carried the highest diversity. Dominant variants are the VOC B.1.617.2 (Delta) variant, B.1.466.2 variant, and B.1.470 variant. The genomic regions with the highest number of mutations are the spike, NSP3, nucleocapsid, NSP12, and ORF3a protein. Mutation analysis showed that mutations in structural protein might increase the stability of the protein. Oppositely, mutations in non-structural protein might lead to a decrease in protein stability. However, further research to study the impact of mutations on the function of SARS-CoV-2 proteins are required.


Subject(s)
Genome, Viral/genetics , SARS-CoV-2/genetics , Viral Proteins/genetics , Viral Proteins/metabolism , COVID-19/pathology , Coronavirus Nucleocapsid Proteins/genetics , Coronavirus Papain-Like Proteases/genetics , Coronavirus RNA-Dependent RNA Polymerase/genetics , Disease Hotspot , Female , Humans , Indonesia , Male , Molecular Docking Simulation , Mutation/genetics , Phosphoproteins/genetics , Protein Stability , Spike Glycoprotein, Coronavirus/genetics , Viroporin Proteins/genetics , Whole Genome Sequencing
12.
Viruses ; 13(10)2021 10 07.
Article in English | MEDLINE | ID: covidwho-1463836

ABSTRACT

Currently countries across the globe are preparing for the fourth wave of SARS-CoV-2 infections, which is mainly driven by the rapid spread of novel SARS-CoV-2 variants. Austria and, in particular, the capital city of Vienna, witnessed a disproportionally steep rise in SARS-CoV-2 infection rates during the last wave of infections. By the end of January 2021, the government of Vienna launched an innovative, state-wide SARS-CoV-2 screening program based on PCR analysis of self-collected mouthwash samples. More than 400,000 mouthwash samples were collected in Vienna during the third wave of infection from January to March 2021. All preanalytical and analytical steps were carried out in a highly standardized manner at a single certified testing center. SARS-CoV-2 specific PCR analysis revealed in these samples a positivity rate of 0.43%. The relative proportion of N501Y positive virus samples increased continually to 68% of weekly samples. Mutation K417N was detected only in three samples. With this study, we were able to map the temporal occurrence of SARS-CoV-2 variants in a highly unbiased manner. Positivity rates and variant prevalence rates in this study were lower than in other nationwide programs. The results presented in this study indicate that actual virus prevalence tends to be overestimated by surveillance programs such as results of cluster analysis or contact tracing programs.


Subject(s)
COVID-19 Testing/methods , COVID-19/epidemiology , SARS-CoV-2/genetics , Austria/epidemiology , Humans , Mass Screening , Mutation/genetics , Polymerase Chain Reaction , Prevalence , SARS-CoV-2/isolation & purification
13.
Front Immunol ; 12: 751584, 2021.
Article in English | MEDLINE | ID: covidwho-1463475

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel coronavirus disease (COVID-19). Though vaccines and neutralizing monoclonal antibodies (mAbs) have been developed to fight COVID-19 in the past year, one major concern is the emergence of SARS-CoV-2 variants of concern (VOCs). Indeed, SARS-CoV-2 VOCs such as B.1.1.7 (UK), B.1.351 (South Africa), P.1 (Brazil), and B.1.617.1 (India) now dominate the pandemic. Herein, we found that binding activity and neutralizing capacity of sera collected from convalescent patients in early 2020 for SARS-CoV-2 VOCs, but not non-VOC variants, were severely blunted. Furthermore, we observed evasion of SARS-CoV-2 VOCs from a VH3-30 mAb 32D4, which was proved to exhibit highly potential neutralization against wild-type (WT) SARS-CoV-2. Thus, these results indicated that SARS-CoV-2 VOCs might be able to spread in convalescent patients and even harbor resistance to medical countermeasures. New interventions against these SARS-CoV-2 VOCs are urgently needed.


Subject(s)
COVID-19/immunology , Mutation/genetics , SARS-CoV-2/physiology , Adult , Antibodies, Monoclonal/metabolism , Antibodies, Neutralizing/metabolism , Antibodies, Viral/metabolism , COVID-19/genetics , COVID-19/therapy , Female , Humans , Immune Evasion , Immunization, Passive , Male , Middle Aged , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism
14.
Front Immunol ; 12: 730766, 2021.
Article in English | MEDLINE | ID: covidwho-1463473

ABSTRACT

The SARS-CoV-2 pandemic has spread to all parts of the world and can cause life-threatening pneumonia and other severe disease manifestations known as COVID-19. This health crisis has resulted in a significant effort to stop the spread of this new coronavirus. However, while propagating itself in the human population, the virus accumulates mutations and generates new variants with increased fitness and the ability to escape the human immune response. Here we describe a color-based barcoded spike flow cytometric assay (BSFA) that is particularly useful to evaluate and directly compare the humoral immune response directed against either wild type (WT) or mutant spike (S) proteins or the receptor-binding domains (RBD) of SARS-CoV-2. This assay employs the human B lymphoma cell line Ramos, transfected for stable expression of WT or mutant S proteins or a chimeric RBD-CD8 fusion protein. We find that the alpha and beta mutants are more stably expressed than the WT S protein on the Ramos B cell surface and/or bind with higher affinity to the viral entry receptor ACE2. However, we find a reduce expression of the chimeric RBD-CD8 carrying the point mutation N501Y and E484K characteristic for the alpha and beta variant, respectively. The comparison of the humoral immune response of 12 vaccinated probands with 12 COVID-19 patients shows that after the boost, the S-specific IgG class immune response in the vaccinated group is similar to that of the patient group. However, in comparison to WT the specific IgG serum antibodies bind less well to the alpha variant and only poorly to the beta variant S protein. This is in line with the notion that the beta variant is an immune escape variant of SARS-CoV-2. The IgA class immune response was more variable than the IgG response and higher in the COVID-19 patients than in the vaccinated group. In summary, we think that our BSFA represents a useful tool to evaluate the humoral immunity against emerging variants of SARS-CoV-2 and to analyze new vaccination protocols against these variants.


Subject(s)
COVID-19/immunology , Cell Separation/methods , Flow Cytometry/methods , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Viral/metabolism , Antibody Formation , Female , Humans , Immunization, Secondary , Immunoglobulin A/metabolism , Immunoglobulin G/metabolism , Male , Middle Aged , Mutation/genetics , Spike Glycoprotein, Coronavirus/genetics , Vaccination
15.
Biochem Biophys Res Commun ; 574: 14-19, 2021 10 15.
Article in English | MEDLINE | ID: covidwho-1446453

ABSTRACT

Following the initial surges of the Alpha (B.1.1.7) and the Beta (B.1.351) variants, a more infectious Delta variant (B.1.617.2) is now surging, further deepening the health crises caused by the pandemic. The sharp rise in cases attributed to the Delta variant has made it especially disturbing and is a variant of concern. Fortunately, current vaccines offer protection against known variants of concern, including the Delta variant. However, the Delta variant has exhibited some ability to dodge the immune system as it is found that neutralizing antibodies from prior infections or vaccines are less receptive to binding with the Delta spike protein. Here, we investigated the structural changes caused by the mutations in the Delta variant's receptor-binding interface and explored the effects on binding with the ACE2 receptor as well as with neutralizing antibodies. We find that the receptor-binding ß-loop-ß motif adopts an altered but stable conformation causing separation in some of the antibody binding epitopes. Our study shows reduced binding of neutralizing antibodies and provides a possible mechanism for the immune evasion exhibited by the Delta variant.


Subject(s)
Angiotensin-Converting Enzyme 2/immunology , COVID-19/immunology , Immune Evasion/immunology , Mutation/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Amino Acids/genetics , Amino Acids/immunology , Amino Acids/metabolism , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Viral/immunology , Binding Sites/genetics , Binding Sites/immunology , COVID-19/metabolism , COVID-19/virology , Humans , Immune Evasion/genetics , Molecular Dynamics Simulation , Mutation/genetics , Neutralization Tests , Protein Binding , Protein Domains , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics
16.
PLoS One ; 16(9): e0258019, 2021.
Article in English | MEDLINE | ID: covidwho-1443854

ABSTRACT

As the COVID-19 pandemic continues to ravage across the globe and take millions of lives and like many parts of the world, the second wave of the pandemic hit Bangladesh, this study aimed at understanding its causative agent, SARS-CoV-2 at the genomic and proteomic level and provide precious insights about the pathogenesis, evolution, strengths and weaknesses of the virus. As of Mid-June 2021, over 1500 SARS-CoV-2 genomesequences have been deposited in the GISAID database from Bangladesh which were extracted and categorized into two waves. By analyzing these genome sequences, it was discovered that the wave-2 samples had a significantly greater average rate of mutation/sample (30.79%) than the wave-1 samples (12.32%). Wave-2 samples also had a higher frequency of deletion, and transversion events. During the first wave, the GR clade was the most predominant but it was replaced by the GH clade in the latter wave. The B.1.1.25 variant showed the highest frequency in wave-1 while in case of wave-2, the B.1.351.3 variant, was the most common one. A notable presence of the delta variant, which is currently at the center of concern, was also observed. Comparison of the Spike protein found in the reference and the 3 most common lineages found in Bangladesh namely, B.1.1.7, B.1.351, B.1.617 in terms of their ability to form stable complexes with ACE2 receptor revealed that B.1.617 had the potential to be more transmissible than others. Importantly, no indigenous variants have been detected so far which implies that the successful prevention of import of foreign variants can diminish the outbreak in the country.


Subject(s)
COVID-19/epidemiology , Genomics/methods , SARS-CoV-2/genetics , Bangladesh/epidemiology , Disease Outbreaks/prevention & control , Genetic Variation/genetics , Genome, Viral/genetics , Humans , Mutation/genetics , Pandemics , Phylogeny , Proteomics , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/genetics
17.
EBioMedicine ; 70: 103540, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1433159

ABSTRACT

BACKGROUND: The rise of new SARS-CoV-2 variants worldwide requires global molecular surveillance strategies to support public health control. Early detection and evaluation of their associated risk of spreading within the population are pivotal. METHODS: Between April 2020 and February 2021, the UK Lighthouse Labs Network at Alderley Park tested more than eight million nose and throat swab samples for the presence of SARS-CoV-2, via PCR. The assay targeted three genomic regions of the virus: N, Orf1ab and S. Whole-genome next-generation sequencing was used to confirm positive PCR results. Positive results were mapped using the postal district origin of samples to allow real-time tracking of the spread of a new variant through the UK. FINDINGS: In mid-November 2020, the assay identified an increasing number of S gene negative, N and Orf1ab positive samples. Whole-genome sequencing demonstrated that the loss of S gene detection was due to the appearance of a SARS-CoV-2 lineage (B.1.1.7) designated as Variant of concern (VOC) 202012/01. By the beginning of January 2021, the new SARS-CoV-2 VOC comprised 70% of daily positive samples tested at Alderley Park and ∼98% by the end of February 2021. INTERPRETATION: The timeline view identified the rapid spread of the new SARS-CoV-2 variant across England during the first three weeks of December. Coupling high-throughput diagnostics and molecular surveillance was pivotal to the early detection of the spread of this variant. The availability of real-time tracking of an emerging variant is an important new tool to inform decision-making authorities for risk mitigation. In a respiratory pandemic, a tool for the timely response to the emergence and spread of a novel variant is vital, even more so when a variant is associated with the enhanced transmission, as has occurred with VOC 202012/01. FUNDING: None.


Subject(s)
COVID-19/virology , SARS-CoV-2/genetics , England , High-Throughput Nucleotide Sequencing/methods , Humans , Mutation/genetics , Pandemics/prevention & control , Risk Assessment
18.
ACS Chem Neurosci ; 12(19): 3535-3549, 2021 10 06.
Article in English | MEDLINE | ID: covidwho-1415906

ABSTRACT

The prevalence of chemosensory dysfunction in patients with COVID-19 varies greatly between populations. It is unclear whether such differences are due to factors at the level of the human host, or at the level of the coronavirus, or both. At the host level, the entry proteins which allow virus binding and entry have variants with distinct properties, and the frequency of such variants differs between ethnicities. At the level of the virus, the D614G mutation enhances virus entry to the host cell. Since the two virus strains (D614 and G614) coexisted in the first six months of the pandemic in most populations, it has been difficult to distinguish between contributions of the virus and contributions of the host for anosmia. To answer this question, we conducted a systematic review and meta-analysis of studies in South Asian populations when either the D614 or the G614 virus was dominant. We show that populations infected predominantly with the G614 virus had a much higher prevalence of anosmia (pooled prevalence of 31.8%) compared with the same ethnic populations infected mostly with the D614 virus strain (pooled anosmia prevalence of 5.3%). We conclude that the D614G mutation is a major contributing factor that increases the prevalence of anosmia in COVID-19, and that this enhanced effect on olfaction constitutes a previously unrecognized phenotype of the D614G mutation. The new virus strains that have additional mutations on the background of the D614G mutation can be expected to cause a similarly increased prevalence of chemosensory dysfunctions.


Subject(s)
COVID-19 , Anosmia , Humans , Mutation/genetics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
19.
Cells ; 10(9)2021 09 12.
Article in English | MEDLINE | ID: covidwho-1408629

ABSTRACT

Extracellular vesicles (EVs) are cell-released, nanometer-scaled, membrane-bound materials and contain diverse contents including proteins, small peptides, and nucleic acids. Once released, EVs can alter the microenvironment and regulate a myriad of cellular physiology components, including cell-cell communication, proliferation, differentiation, and immune responses against viral infection. Among the cargoes in the vesicles, small non-coding micro-RNAs (miRNAs) have received attention in that they can regulate the expression of a variety of human genes as well as external viral genes via binding to the complementary mRNAs. In this study, we tested the potential of EVs as therapeutic agents for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. First, we found that the mesenchymal stem-cell-derived EVs (MSC-EVs) enabled the rescue of the cytopathic effect of SARS-CoV-2 virus and the suppression of proinflammatory responses in the infected cells by inhibiting the viral replication. We found that these anti-viral responses were mediated by 17 miRNAs matching the rarely mutated, conserved 3'-untranslated regions (UTR) of the viral genome. The top five miRNAs highly expressed in the MSC-EVs, miR-92a-3p, miR-26a-5p, miR-23a-3p, miR-103a-3p, and miR-181a-5p, were tested. They were bound to the complemented sequence which led to the recovery of the cytopathic effects. These findings suggest that the MSC-EVs are a potential candidate for multiple variants of anti-SARS-CoV-2.


Subject(s)
COVID-19/therapy , Extracellular Vesicles/metabolism , Mesenchymal Stem Cells/metabolism , MicroRNAs/therapeutic use , SARS-CoV-2/physiology , 3' Untranslated Regions/genetics , Animals , Antiviral Agents/pharmacology , Base Sequence , Cell Line , Conserved Sequence/genetics , Female , Genome, Viral , Humans , Models, Biological , Mutation/genetics , Placenta/metabolism , Pregnancy , RNA, Viral/genetics , SARS-CoV-2/genetics
20.
PLoS One ; 16(7): e0255438, 2021.
Article in English | MEDLINE | ID: covidwho-1388951

ABSTRACT

Although traditional models of epidemic spreading focus on the number of infected, susceptible and recovered individuals, a lot of attention has been devoted to integrate epidemic models with population genetics. Here we develop an individual-based model for epidemic spreading on networks in which viruses are explicitly represented by finite chains of nucleotides that can mutate inside the host. Under the hypothesis of neutral evolution we compute analytically the average pairwise genetic distance between all infecting viruses over time. We also derive a mean-field version of this equation that can be added directly to compartmental models such as SIR or SEIR to estimate the genetic evolution. We compare our results with the inferred genetic evolution of SARS-CoV-2 at the beginning of the epidemic in China and found good agreement with the analytical solution of our model. Finally, using genetic distance as a proxy for different strains, we use numerical simulations to show that the lower the connectivity between communities, e.g., cities, the higher the probability of reinfection.


Subject(s)
COVID-19/epidemiology , Epidemics/prevention & control , Mutation/genetics , SARS-CoV-2/genetics , China/epidemiology , Disease Susceptibility/epidemiology , Evolution, Molecular , Humans , Models, Statistical , Probability
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