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Quantifying the potential for dominant spread of SARS-CoV-2 variant B.1.351 in the United States.

ABSTRACT: Recent evidence suggests that the SARS-CoV-2 variant B.1.351 exhibits partial immune evasion to antibodies generated by natural infection or vaccination. We used a dynamic transmission model to evaluate whether this variant could become dominant in the United States given mounting vaccination coverage and other circulating variants. We show that B.1.351 is unlikely to become dominant even when all fully vaccinated individuals return to their pre-pandemic behavior. However, an improved selection advantage of B.1.351 arising from a combination of increased transmission and immune escape could drive this variant to dominance as early as July 2021 and fuel a resurgence of cases and hospitalizations. Our study underscores the urgency for continued rollout of the current generation of vaccines despite the emergence of immune escape variants.

SUBMITTER: Sah P

PROVIDER: S-EPMC8132270 | biostudies-literature |

REPOSITORIES: biostudies-literature

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The great escape? SARS-CoV-2 variants evading neutralizing responses.

Project description:In the latest issues of Cell Host & Microbe and Cell, three articles describe new mutations in the SARS-CoV-2 Spike receptor binding domain that escape neutralizing responses. These highlight the importance of surveillance of SARS-CoV-2 evolution to anticipate and manage new variants that could impact reinfection, vaccine efficacy, and immunotherapies.

| S-EPMC7945862 | biostudies-literature

Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity.

Project description:SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines and antibody therapeutics. Here, we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is a highly variable region of S and provide epidemiological, clinical, and molecular characterization of a prevalent, sentinel RBM mutation, N439K. We demonstrate N439K S protein has enhanced binding affinity to the hACE2 receptor, and N439K viruses have similar in vitro replication fitness and cause infections with similar clinical outcomes as compared to wild type. We show the N439K mutation confers resistance against several neutralizing monoclonal antibodies, including one authorized for emergency use by the US Food and Drug Administration (FDA), and reduces the activity of some polyclonal sera from persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics.

| S-EPMC7843029 | biostudies-literature

SARS-CoV-2 Genomes From Oklahoma, United States.

Project description:Genomic sequencing has played a major role in understanding the pathogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the current pandemic, it is essential that SARS-CoV-2 viruses are sequenced regularly to determine mutations and genomic modifications in different geographical locations. In this study, we sequenced SARS-CoV-2 from five clinical samples obtained in Oklahoma, United States during different time points of pandemic presence in the state. One sample from the initial days of the pandemic in the state and four during the peak in Oklahoma were sequenced. Previously reported mutations including D614G in S gene, P4715L in ORF1ab, S194L, R203K, and G204R in N gene were identified in the genomes sequenced in this study. Possible novel mutations were also detected in the S gene (G1167V), ORF1ab (A6269S and P3371S), ORF7b (T28I), and ORF8 (G96R). Phylogenetic analysis of the genomes showed similarity to other SARS-CoV-2 viruses reported from across the globe. Structural characterization indicates that the mutations in S gene possibly influences conformational flexibility and motion of the spike protein, and the mutations in N gene are associated with disordered linker region within the nucleocapsid protein.

| S-EPMC7886813 | biostudies-literature

Characterizing SARS-CoV-2 mutations in the United States.

Project description:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been mutating since it was first sequenced in early January 2020. The genetic variants have developed into a few distinct clusters with different properties. Since the United States (US) has the highest number of viral infected patients globally, it is essential to understand the US SARS-CoV-2. Using genotyping, sequence-alignment, time-evolution, k-means clustering, protein-folding stability, algebraic topology, and network theory, we reveal that the US SARS-CoV-2 has four substrains and five top US SARS-CoV-2 mutations were first detected in China (2 cases), Singapore (2 cases), and the United Kingdom (1 case). The next three top US SARS-CoV-2 mutations were first detected in the US. These eight top mutations belong to two disconnected groups. The first group consisting of 5 concurrent mutations is prevailing, while the other group with three concurrent mutations gradually fades out. We identify that one of the top mutations, 27964C>T-(S24L) on ORF8, has an unusually strong gender dependence. Based on the analysis of all mutations on the spike protein, we further uncover that three of four US SASR-CoV-2 substrains become more infectious. Our study calls for effective viral control and containing strategies in the US.

| S-EPMC7430589 | biostudies-literature

SARS-CoV-2 Delta-Omicron Recombinant Viruses, United States.

Project description:To detect new and changing SARS-CoV-2 variants, we investigated candidate Delta-Omicron recombinant genomes from Centers for Disease Control and Prevention national genomic surveillance. Laboratory and bioinformatic investigations identified and validated 9 genetically related SARS-CoV-2 viruses with a hybrid Delta-Omicron spike protein.

| S-EPMC9239886 | biostudies-literature

Surveillance of SARS-CoV-2 in Zimbabwe shows dominance of variants of concern.

Project description: Not available

| S-EPMC7946415 | biostudies-literature

SARS-CoV-2 cumulative incidence, United States, August-December 2020.

Project description:BackgroundReported COVID-19 cases underestimate SARS-CoV-2 infections. We conducted a national probability survey of US households to estimate the cumulative incidence adjusted for antibody waning.MethodsFrom August-December 2020, a multistage random sample of US addresses were mailed a survey and materials to self-collect nasal swabs and dried blood spots. One adult household member completed the survey and mail specimens for viral detection with PCR and total (IgA, IgM, IgG) nucleocapsid antibody by a commercial, EUA-approved antigen capture assay. We estimated cumulative incidence of SARS-CoV-2 adjusted for waning antibodies and calculated reported fraction and infection fatality ratio (IFR). Differences in seropositivity among demographic, geographic and clinical subgroups were explored with weighted prevalence ratios (PR).ResultsAmong 39,500 sampled households, 4,654 respondents provided responded. Cumulative incidence adjusted for waning was 11.9% (95% credible interval (CrI): 10.5-13.5%) as of October 30, 2020. We estimated 30,332,842 (CrI: 26,703,753- 34,335,338) total infections in the U.S. adult population by October 30, 2020. Reported fraction was 17% and IFR was 0.85% among adults. Non-Hispanic Black (PR: 2.2) and Hispanic (PR: 3.1) persons were more likely than White non-Hispanic to be seropositive, as were those living in metropolitan areas (PR: 2.5).ConclusionsOne in 8 US adults had been infected with SARS-CoV-2 by late October 2020; but few had been accounted for in public health reporting. The scope of the COVID-19 pandemic is likely substantially underestimated by reported cases. Disparities in COVID-19 by race observed among reported cases cannot be attributed to differential diagnosis or reporting of infections in some population subgroups.

| S-EPMC8406864 | biostudies-literature

Estimating unobserved SARS-CoV-2 infections in the United States.

Project description:By March 2020, COVID-19 led to thousands of deaths and disrupted economic activity worldwide. As a result of narrow case definitions and limited capacity for testing, the number of unobserved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during its initial invasion of the United States remains unknown. We developed an approach for estimating the number of unobserved infections based on data that are commonly available shortly after the emergence of a new infectious disease. The logic of our approach is, in essence, that there are bounds on the amount of exponential growth of new infections that can occur during the first few weeks after imported cases start appearing. Applying that logic to data on imported cases and local deaths in the United States through 12 March, we estimated that 108,689 (95% posterior predictive interval [95% PPI]: 1,023 to 14,182,310) infections occurred in the United States by this date. By comparing the model's predictions of symptomatic infections with local cases reported over time, we obtained daily estimates of the proportion of symptomatic infections detected by surveillance. This revealed that detection of symptomatic infections decreased throughout February as exponential growth of infections outpaced increases in testing. Between 24 February and 12 March, we estimated an increase in detection of symptomatic infections, which was strongly correlated (median: 0.98; 95% PPI: 0.66 to 0.98) with increases in testing. These results suggest that testing was a major limiting factor in assessing the extent of SARS-CoV-2 transmission during its initial invasion of the United States.

| S-EPMC7486725 | biostudies-literature

SARS-CoV-2 Evades Immune Detection in Alveolar Macrophages

Project description:Respiratory infections, like the current COVID-19 pandemic, target epithelial cells in the respiratory tract. Alveolar macrophages (AMs) are tissue-resident macrophages located within the lung. They play a key role in the early phases of an immune response to respiratory viruses. AMs are likely the first immune cells to encounter SARS-CoV-2 during an infection and their reaction to the virus will have a profound impact on the outcome of the infection. Interferons (IFNs) are antiviral cytokines and among the first cytokines produced upon viral infection. In this study, AMs from non-infectious donors are challenged with SARS-CoV-2. We demonstrate that challenged AMs are incapable of sensing SARS-CoV-2 and of producing an IFN response in contrast to other respiratory viruses, like influenza A virus and Sendai virus, which trigger a robust IFN response. The absence of IFN production in AMs upon challenge with SARS-CoV2 could explain the initial asymptotic phase observed during COVID-19 and argues against AMs being the sources of proinflammatory cytokines later during infection.

| S-SCDT-EMBOR-2020-51252V1 | biostudies-other

Analysis of SARS-CoV-2 mutations in the United States suggests presence of four substrains and novel variants.

Project description:SARS-CoV-2 has been mutating since it was first sequenced in early January 2020. Here, we analyze 45,494 complete SARS-CoV-2 geneome sequences in the world to understand their mutations. Among them, 12,754 sequences are from the United States. Our analysis suggests the presence of four substrains and eleven top mutations in the United States. These eleven top mutations belong to 3 disconnected groups. The first and second groups consisting of 5 and 8 concurrent mutations are prevailing, while the other group with three concurrent mutations gradually fades out. Moreover, we reveal that female immune systems are more active than those of males in responding to SARS-CoV-2 infections. One of the top mutations, 27964C > T-(S24L) on ORF8, has an unusually strong gender dependence. Based on the analysis of all mutations on the spike protein, we uncover that two of four SASR-CoV-2 substrains in the United States become potentially more infectious.

| S-EPMC7884689 | biostudies-literature

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