Accelerated SARS-CoV-2 intrahost evolution leading to distinct genotypes during chronic infection DOI Creative Commons
Chrispin Chaguza, Anne M. Hahn, Mary E. Petrone

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: July 2, 2022

The chronic infection hypothesis for novel SARS-CoV-2 variant emergence is increasingly gaining credence following the appearance of Omicron. Here we investigate intrahost evolution and genetic diversity lineage B.1.517 during a lasting 471 days (and still ongoing) with consistently recovered infectious virus high viral loads. During infection, found an accelerated evolutionary rate translating to 35 nucleotide substitutions per year, approximately two-fold higher than global rate. This led persistence at least three genetically distinct genotypes suggesting establishment spatially structured populations continually reseeding different into nasopharynx. Finally, using unique molecular indexes accurate sequencing, tracked temporal dynamics identify advantageous mutations highlight hallmark changes infection. Our findings demonstrate that untreated infections accelerate evolution, ultimately providing opportunity divergent potentially highly transmissible variants as seen Delta

Language: Английский

SARS-CoV-2 variant biology: immune escape, transmission and fitness DOI Creative Commons
Alessandro M. Carabelli, Thomas P. Peacock, Lucy Thorne

et al.

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 18, 2023

In late 2020, after circulating for almost a year in the human population, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibited major step change its adaptation to humans. These highly mutated forms of SARS-CoV-2 had enhanced rates transmission relative previous variants and were termed 'variants concern' (VOCs). Designated Alpha, Beta, Gamma, Delta Omicron, VOCs emerged independently from one another, turn each rapidly became dominant, regionally or globally, outcompeting variants. The success VOC previously dominant variant was enabled by altered intrinsic functional properties virus and, various degrees, changes antigenicity conferring ability evade primed immune response. increased fitness associated with is result complex interplay biology context changing immunity due both vaccination prior infection. this Review, we summarize literature on transmissibility variants, role mutations at furin spike cleavage site non-spike proteins, potential importance recombination success, evolution T cells, innate population immunity. shows complicated relationship among antigenicity, virulence, which has unpredictable implications future trajectory disease burden COVID-19.

Language: Английский

Citations

1011
The evolution of SARS-CoV-2 DOI Open Access
Peter V. Markov, Mahan Ghafari, Martin Beer

et al.

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: 21(6), P. 361 - 379

Published: April 5, 2023

Language: Английский

Citations

791
A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes DOI Creative Commons
Theo Sanderson, Ryan Hisner, I’ah Donovan-Banfield

et al.

Nature, Journal Year: 2023, Volume and Issue: 623(7987), P. 594 - 600

Published: Sept. 25, 2023

Molnupiravir, an antiviral medication widely used against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), acts by inducing mutations in the virus genome during replication. Most random are likely to be deleterious and many will lethal; thus, molnupiravir-induced elevated mutation rates reduce viral load1,2. However, if some patients treated with molnupiravir do not fully clear SARS-CoV-2 infections, there could potential for onward transmission of molnupiravir-mutated viruses. Here we show that sequencing databases contain extensive evidence mutagenesis. Using a systematic approach, find specific class long phylogenetic branches, distinguished high proportion G-to-A C-to-T mutations, found almost exclusively sequences from 2022, after introduction treatment, countries age groups widespread use drug. We identify mutational spectrum, preferred nucleotide contexts, viruses known have been its signature matches seen these cases molnupiravir-derived lineages. Finally, analyse treatment records confirm direct association between branches molnupiravir.

Language: Английский

Citations

122
Convergent Evolution in SARS-CoV-2 Spike Creates a Variant Soup from Which New COVID-19 Waves Emerge DOI Open Access
Daniele Focosi, Rodrigo Quiroga, Scott A. McConnell

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2264 - 2264

Published: Jan. 23, 2023

The first 2 years of the COVID-19 pandemic were mainly characterized by recurrent mutations SARS-CoV-2 Spike protein at residues K417, L452, E484, N501 and P681 emerging independently across different variants concern (Alpha, Beta, Gamma, Delta). Such homoplasy is a marker convergent evolution. Since Spring 2022 third year pandemic, with advent Omicron its sublineages, evolution has led to observation lineages acquiring an additional group amino acid residues, namely R346, K444, N450, N460, F486, F490, Q493, S494. Mutations these have become increasingly prevalent during Summer Autumn 2022, combinations showing increased fitness. most likely reason for this convergence selective pressure exerted previous infection- or vaccine-elicited immunity. accelerated caused failure all anti-Spike monoclonal antibodies, including bebtelovimab cilgavimab. While we are learning how fast coronaviruses can mutate recombine, should reconsider opportunities economically sustainable escape-proof combination therapies, refocus antibody-mediated therapeutic efforts on polyclonal preparations that less allow viral immune escape.

Language: Английский

Citations

121
Molecular mechanisms of SARS-CoV-2 resistance to nirmatrelvir DOI
Yinkai Duan, Hao Zhou, Xiang Liu

et al.

Nature, Journal Year: 2023, Volume and Issue: 622(7982), P. 376 - 382

Published: Sept. 11, 2023

Language: Английский

Citations

104
SARS-CoV-2 evolution in the Omicron era DOI
Cornelius Roemer, Daniel J. Sheward, Ryan Hisner

et al.

Nature Microbiology, Journal Year: 2023, Volume and Issue: 8(11), P. 1952 - 1959

Published: Oct. 16, 2023

Language: Английский

Citations

81
Accelerated SARS-CoV-2 intrahost evolution leading to distinct genotypes during chronic infection DOI Creative Commons
Chrispin Chaguza, Anne M. Hahn, Mary E. Petrone

et al.

Cell Reports Medicine, Journal Year: 2023, Volume and Issue: 4(2), P. 100943 - 100943

Published: Jan. 27, 2023

The chronic infection hypothesis for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant emergence is increasingly gaining credence following the appearance of Omicron. Here, we investigate intrahost evolution and genetic diversity lineage B.1.517 during a SARS-CoV-2 lasting 471 days (and still ongoing) with consistently recovered infectious virus high viral genome copies. During infection, find an accelerated evolutionary rate translating to 35 nucleotide substitutions per year, approximately 2-fold higher than global rate. This results in persistence at least three genetically distinct genotypes, suggesting establishment spatially structured populations continually reseeding different genotypes into nasopharynx. Finally, track temporal dynamics identify advantageous mutations highlight hallmark changes infection. Our findings demonstrate that untreated infections accelerate evolution, providing opportunity divergent variants.

Language: Английский

Citations

75
Prevalence of persistent SARS-CoV-2 in a large community surveillance study DOI Creative Commons
Mahan Ghafari, Matthew Hall, Tanya Golubchik

et al.

Nature, Journal Year: 2024, Volume and Issue: 626(8001), P. 1094 - 1101

Published: Feb. 21, 2024

Persistent SARS-CoV-2 infections may act as viral reservoirs that could seed future outbreaks

Language: Английский

Citations

74
Persistent SARS-CoV-2 infection: significance and implications DOI Creative Commons
Heather Machkovech, Anne M. Hahn, Jacqueline Garonzik‐Wang

et al.

The Lancet Infectious Diseases, Journal Year: 2024, Volume and Issue: 24(7), P. e453 - e462

Published: Feb. 7, 2024

SARS-CoV-2 causes persistent infections in a subset of individuals, which is major clinical and public health problem that should be prioritised for further investigation several reasons. First, infection often goes unrecognised, therefore might affect substantial number people, particularly immunocompromised individuals. Second, the formation tissue reservoirs (including non-respiratory tissues) underlie pathophysiology require new strategies diagnosis treatment. Finally, replication, setting suboptimal immune responses, possible source new, divergent virus variants escape pre-existing immunity on individual population levels. Defining optimal diagnostic treatment patients with replication monitoring viral evolution are urgent medical priorities.

Language: Английский

Citations

66
SARS-CoV-2 viral clearance and evolution varies by type and severity of immunodeficiency DOI Open Access
Yijia Li, Manish C. Choudhary, James Regan

et al.

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(731)

Published: Jan. 24, 2024

Despite vaccination and antiviral therapies, immunocompromised individuals are at risk for prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but the immune defects that predispose an individual to persistent disease 2019 (COVID-19) remain incompletely understood. In this study, we performed detailed viro-immunologic analyses of a prospective cohort participants with COVID-19. The median times nasal viral RNA culture clearance in immunosuppression due hematologic malignancy or transplant (S-HT) were 72 40 days, respectively, both which significantly longer than rates autoimmunity B cell deficiency (S-A), nonsevere immunodeficiency, nonimmunocompromised groups ( P < 0.01). Participants who severely had greater SARS-CoV-2 evolution higher developing resistance against therapeutic monoclonal antibodies. Both S-HT S-A diminished SARS-CoV-2–specific humoral responses, whereas only group reduced T cell–mediated responses. This highlights varied COVID-19 across distinct immunosuppressive conditions suggests suppression responses results highest contributing infection.

Language: Английский

Citations

58