Browse
Submit Data
Databases
API
Help

Dataset Information

32 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dominance of Alpha and Iota variants in SARS-CoV-2 vaccine breakthrough infections in New York City.

ABSTRACT: The efficacy of COVID-19 mRNA vaccines is high, but breakthrough infections still occur. We compared the SARS-CoV-2 genomes of 76 breakthrough cases after full vaccination with BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna), or JNJ-78436735 (Janssen) to unvaccinated controls (February-April 2021) in metropolitan New York, including their phylogenetic relationship, distribution of variants, and full spike mutation profiles. The median age of patients in the study was 48 years; 7 required hospitalization and 1 died. Most breakthrough infections (57/76) occurred with B.1.1.7 (Alpha) or B.1.526 (Iota). Among the 7 hospitalized cases, 4 were infected with B.1.1.7, including 1 death. Both unmatched and matched statistical analyses considering age, sex, vaccine type, and study month as covariates supported the null hypothesis of equal variant distributions between vaccinated and unvaccinated in χ2 and McNemar tests (P > 0.1), highlighting a high vaccine efficacy against B.1.1.7 and B.1.526. There was no clear association among breakthroughs between type of vaccine received and variant. In the vaccinated group, spike mutations in the N-terminal domain and receptor-binding domain that have been associated with immune evasion were overrepresented. The evolving dynamic of SARS-CoV-2 variants requires broad genomic analyses of breakthrough infections to provide real-life information on immune escape mediated by circulating variants and their spike mutations.

SUBMITTER: Duerr R

PROVIDER: S-EPMC8439605 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Vaccine breakthrough infections with SARS-CoV-2 Alpha mirror mutations in Delta Plus, Iota, and Omicron.

Project description:Replication of SARS-CoV-2 in the human population is defined by distributions of mutants that are present at different frequencies within the infected host and can be detected by ultra-deep sequencing techniques. In this study, we examined the SARS-CoV-2 mutant spectra of amplicons from the spike-coding (S-coding) region of 5 nasopharyngeal isolates derived from patients with vaccine breakthrough. Interestingly, all patients became infected with the Alpha variant, but amino acid substitutions that correspond to the Delta Plus, Iota, and Omicron variants were present in the mutant spectra of the resident virus. Deep sequencing analysis of SARS-CoV-2 from patients with vaccine breakthrough revealed a rich reservoir of mutant types and may also identify tolerated substitutions that can be represented in epidemiologically dominant variants.

| S-EPMC9057617 | biostudies-literature

Vaccine Breakthrough Infections with SARS-CoV-2 Variants.

Project description:Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of clinical concern. In a cohort of 417 persons who had received the second dose of BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine at least 2 weeks previously, we identified 2 women with vaccine breakthrough infection. Despite evidence of vaccine efficacy in both women, symptoms of coronavirus disease 2019 developed, and they tested positive for SARS-CoV-2 by polymerase-chain-reaction testing. Viral sequencing revealed variants of likely clinical importance, including E484K in 1 woman and three mutations (T95I, del142-144, and D614G) in both. These observations indicate a potential risk of illness after successful vaccination and subsequent infection with variant virus, and they provide support for continued efforts to prevent and diagnose infection and to characterize variants in vaccinated persons. (Funded by the National Institutes of Health and others.).

| S-EPMC8117968 | biostudies-literature

Variants of concern responsible for SARS-CoV-2 vaccine breakthrough infections from India.

Project description:Emerging reports of SARS-CoV-2 breakthrough infections entail methodical genomic surveillance for determining the efficacy of vaccines. This study elaborates genomic analysis of isolates from breakthrough infections following vaccination with AZD1222/Covishield and BBV152/Covaxin. Variants of concern B.1.617.2 and B.1.1.7 responsible for cases surge in April-May 2021 in Delhi, were the predominant lineages among breakthrough infections.

| S-EPMC8662202 | biostudies-literature

Vaccine-breakthrough infections with SARS-CoV-2 Alpha mirror mutations in Delta Plus, Iota and Omicron

Project description:A SARS-CoV-2 ultra-deep sequencing study of the mutant spectrum of amplicons spike (S)-coding regions of five fully vaccinated cases with BNT162b2 (Pfizer-BioNTech) in March 2021 who mounted an effective antiviral response, and subsequently were infected with SARS-CoV-2 in April 2021, and developed COVID-19 clinical symptoms

| PRJEB49400 | ENA

Emerging vaccine-breakthrough SARS-CoV-2 variants.

Project description:The recent global surge in COVID-19 infections has been fueled by new SARS-CoV-2 variants, namely Alpha, Beta, Gamma, Delta, etc. The molecular mechanism underlying such surge is elusive due to 4,653 non-degenerate mutations on the spike protein, which is the target of most COVID-19 vaccines. The understanding of the molecular mechanism of transmission and evolution is a prerequisite to foresee the trend of emerging vaccine-breakthrough variants and the design of mutation-proof vaccines and monoclonal antibodies. We integrate the genotyping of 1,489,884 SARS-CoV-2 genomes isolates, 130 human antibodies, tens of thousands of mutational data points, topological data analysis, and deep learning to reveal SARS-CoV-2 evolution mechanism and forecast emerging vaccine-escape variants. We show that infectivity-strengthening and antibody-disruptive co-mutations on the S protein RBD can quantitatively explain the infectivity and virulence of all prevailing variants. We demonstrate that Lambda is as infectious as Delta but is more vaccine-resistant. We analyze emerging vaccine-breakthrough co-mutations in 20 countries, including the United Kingdom, the United States, Denmark, Brazil, and Germany, etc. We envision that natural selection through infectivity will continue to be the main mechanism for viral evolution among unvaccinated populations, while antibody disruptive co-mutations will fuel the future growth of vaccine-breakthrough variants among fully vaccinated populations. Finally, we have identified the co-mutations that have the great likelihood of becoming dominant: [A411S, L452R, T478K], [L452R, T478K, N501Y], [V401L, L452R, T478K], [K417N, L452R, T478K], [L452R, T478K, E484K, N501Y], and [P384L, K417N, E484K, N501Y]. We predict they, particularly the last four, will break through existing vaccines. We foresee an urgent need to develop new vaccines that target these co-mutations.

| S-EPMC8437313 | biostudies-literature

Emerging Vaccine-Breakthrough SARS-CoV-2 Variants.

Project description:The surge of COVID-19 infections has been fueled by new SARS-CoV-2 variants, namely Alpha, Beta, Gamma, Delta, and so forth. The molecular mechanism underlying such surge is elusive due to the existence of 28 554 unique mutations, including 4 653 non-degenerate mutations on the spike protein. Understanding the molecular mechanism of SARS-CoV-2 transmission and evolution is a prerequisite to foresee the trend of emerging vaccine-breakthrough variants and the design of mutation-proof vaccines and monoclonal antibodies. We integrate the genotyping of 1 489 884 SARS-CoV-2 genomes, a library of 130 human antibodies, tens of thousands of mutational data, topological data analysis, and deep learning to reveal SARS-CoV-2 evolution mechanism and forecast emerging vaccine-breakthrough variants. We show that prevailing variants can be quantitatively explained by infectivity-strengthening and vaccine-escape (co-)mutations on the spike protein RBD due to natural selection and/or vaccination-induced evolutionary pressure. We illustrate that infectivity strengthening mutations were the main mechanism for viral evolution, while vaccine-escape mutations become a dominating viral evolutionary mechanism among highly vaccinated populations. We demonstrate that Lambda is as infectious as Delta but is more vaccine-resistant. We analyze emerging vaccine-breakthrough comutations in highly vaccinated countries, including the United Kingdom, the United States, Denmark, and so forth. Finally, we identify sets of comutations that have a high likelihood of massive growth: [A411S, L452R, T478K], [L452R, T478K, N501Y], [V401L, L452R, T478K], [K417N, L452R, T478K], [L452R, T478K, E484K, N501Y], and [P384L, K417N, E484K, N501Y]. We predict they can escape existing vaccines. We foresee an urgent need to develop new virus combating strategies.

| S-EPMC8848511 | biostudies-literature

Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants.

Project description:Virus-like particle (VLP) and live virus assays were used to investigate neutralizing immunity against Delta and Omicron SARS-CoV-2 variants in 259 samples from 128 vaccinated individuals. Following Delta breakthrough infection, titers against WT rose 57-fold and 3.1-fold compared with uninfected boosted and unboosted individuals, respectively, versus only a 5.8-fold increase and 3.1-fold decrease for Omicron breakthrough infection. Among immunocompetent, unboosted patients, Delta breakthrough infections induced 10.8-fold higher titers against WT compared with Omicron (p = 0.037). Decreased antibody responses in Omicron breakthrough infections relative to Delta were potentially related to a higher proportion of asymptomatic or mild breakthrough infections (55.0% versus 28.6%, respectively), which exhibited 12.3-fold lower titers against WT compared with moderate to severe infections (p = 0.020). Following either Delta or Omicron breakthrough infection, limited variant-specific cross-neutralizing immunity was observed. These results suggest that Omicron breakthrough infections are less immunogenic than Delta, thus providing reduced protection against reinfection or infection from future variants.

| S-EPMC8930394 | biostudies-literature

Vaccine Breakthrough Infections by SARS-CoV-2 Variants after ChAdOx1 nCoV-19 Vaccination in Healthcare Workers.

Project description:This study elucidated the clinical, humoral immune response and genomic analysis of vaccine breakthrough (VBT) infections after ChAdOx1 nCoV-19/Covishield vaccine in healthcare workers (HCWs). Amongst 1858 HCWs, 1639 had received either two doses (1346) or a single dose (293) of ChAdOx1 nCoV-19 vaccine. SARS-CoV-2 IgG antibodies and neutralizing antibodies were measured in the vaccinated group and the development of SARS-CoV-2 infection was monitored.Forty-six RT-PCR positive samples from the 203 positive samples were subjected to whole genome sequencing (WGS). Of the 203 (10.92%) infected HCWs, 21.46% (47/219) were non-vaccinated, which was significantly more than 9.52% (156/1639) who were vaccinated and infection was higher in doctors and nurses. Unvaccinated HCWs had 1.57 times higher risk compared to partially vaccinated HCWs and 2.49 times higher risk than those who were fully vaccinated.The partially vaccinated were at higher risk than the fully vaccinated (RR 1.58). Antibody non-response was seen in 3.44% (4/116), low antibody levels in 15.51% (18/116) and medium levels were found in 81.03% (94/116). Fully vaccinated HCWs had a higher antibody response at day 42 than those who were partially vaccinated (8.96 + 4.00 vs. 7.17 + 3.82). Whole genome sequencing of 46 samples revealed that the Delta variant (B.1.617.2) was predominant (69.5%). HCWs who had received two doses of vaccine showed better protection from mild, moderate, or severe infection, with a higher humoral immune response than those who had received a single dose. The genomic analysis revealed the predominance of the Delta variant (B.1.617.2) in the VBT infections.

| S-EPMC8778656 | biostudies-literature

Clinical and genomic signatures of SARS-CoV-2 Delta breakthrough infections in New York

Project description:Background In 2021, Delta became the predominant SARS-CoV-2 variant worldwide. While vaccines have effectively prevented COVID-19 hospitalization and death, vaccine breakthrough infections increasingly occurred. The precise role of clinical and genomic determinants in Delta infections is not known, and whether they contributed to increased rates of breakthrough infections compared to unvaccinated controls. Methods We studied SARS-CoV-2 variant distribution, dynamics, and adaptive selection over time in relation to vaccine status, phylogenetic relatedness of viruses, full genome mutation profiles, and associated clinical and demographic parameters. Findings We show a steep and near-complete replacement of circulating variants with Delta between May and August 2021 in metropolitan New York. We observed an increase of the Delta sublineage AY.25 (14% in vaccinated, 7% in unvaccinated), its spike mutation S112L, and AY.44 (8% in vaccinated, 2% in unvaccinated) with its nsp12 mutation F192V in breakthroughs. Delta infections were associated with younger age and lower hospitalization rates than Alpha. Delta breakthrough infections increased significantly with time since vaccination, and, after adjusting for confounders, they rose at similar rates as in unvaccinated individuals. Interpretation We observed a modest adaptation of Delta genomes in breakthrough infections in New York, suggesting an improved genomic framework to support Delta's epidemic growth in times of waning vaccine protection despite limited impact on vaccine escape. Funding The study was supported by NYU institutional funds. The NYULH Genome Technology Center is partially supported by the Cancer Center Support Grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center.

| S-EPMC9323230 | biostudies-literature

Relative infectiousness of SARS-CoV-2 vaccine breakthrough infections, reinfections, and primary infections.

Project description:SARS-CoV-2 breakthrough infections in vaccinated individuals and in those who had a prior infection have been observed globally, but the transmission potential of these infections is unknown. The RT-qPCR cycle threshold (Ct) value is inversely correlated with viral load and culturable virus. Here, we investigate differences in RT-qPCR Ct values across Qatar's national cohorts of primary infections, reinfections, BNT162b2 (Pfizer-BioNTech) breakthrough infections, and mRNA-1273 (Moderna) breakthrough infections. Our matched-cohort analyses of the randomly diagnosed infections show higher mean Ct value in all cohorts of breakthrough infections compared to the cohort of primary infections in unvaccinated individuals. The Ct value is 1.3 (95% CI: 0.9-1.8) cycles higher for BNT162b2 breakthrough infections, 3.2 (95% CI: 1.9-4.5) cycles higher for mRNA-1273 breakthrough infections, and 4.0 (95% CI: 3.5-4.5) cycles higher for reinfections in unvaccinated individuals. Since Ct value correlates inversely with SARS-CoV-2 infectiousness, these differences imply that vaccine breakthrough infections and reinfections are less infectious than primary infections in unvaccinated individuals. Public health benefits of vaccination may have been underestimated, as COVID-19 vaccines not only protect against acquisition of infection, but also appear to protect against transmission of infection.

| S-EPMC8795418 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data