SARS-CoV-2 evolution during treatment of chronic infection

@article{Kemp2021SARSCoV2ED,
  title={SARS-CoV-2 evolution during treatment of chronic infection},
  author={Steven A Kemp and Dami A Collier and Rawlings P Datir and Isabella A.T.M. Ferreira and Salma Gayed and Aminu S. Jahun and Myra Hosmillo and Chloe Rees-Spear and Petra Mlcochova and Ines Ushiro Lumb and David J. Roberts and Anita Chandra and Nigel J. Temperton and Katherine Sharrocks and Elizabeth Blane and Yorgo Modis and Kendra E. Leigh and John A. G. Briggs and Marit J. van Gils and Kenneth G. C. Smith and John R. Bradley and Christen Smith and Rainer Doffinger and Lourdes Ceron-Gutierrez and Gabriela Barcenas-Morales and David D. Pollock and Richard A. Goldstein and Anna Smielewska and Jordan P. Skittrall and Theodore Gouliouris and Ian G. Goodfellow and Effrossyni Gkrania-Klotsas and Christopher J. R. Illingworth and Laura E. McCoy and Ravindra K. Gupta},
  journal={Nature},
  year={2021},
  volume={592},
  pages={277 - 282}
}
Summary SARS-CoV-2 Spike protein is critical for virus infection via engagement of ACE21, and is a major antibody target. Here we report chronic SARS-CoV-2 with reduced sensitivity to neutralising antibodies in an immune suppressed individual treated with convalescent plasma, generating whole genome ultradeep sequences over 23 time points spanning 101 days. Little change was observed in the overall viral population structure following two courses of remdesivir over the first 57 days. However… 
Chronic SARS-CoV-2 infection and viral evolution in a hypogammaglobulinaemic individual.
TLDR
The data confirms the significance of this deletion in immunocompromised patients but illustrates it can arise independently of passive antibody transfer, suggesting the deletion may be an enabling mutation that compensates for distant changes in the spike protein that arise under selective pressure.
SARS-CoV-2 shedding dynamics and transmission in immunosuppressed patients
TLDR
Intrahost variants emerging during infection showed diversity between individual hosts, and N501Y, P681R, and E484K, key substitutions within spike protein, emerged in vivo during infection and became the dominant population.
The effect of spike mutations on SARS-CoV-2 neutralization
SARS-CoV-2 variants, spike mutations and immune escape
TLDR
The literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, is summarized, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discussed in the context of observed mutation frequencies in global sequence datasets.
Immune Evasion of SARS-CoV-2 Emerging Variants: What Have We Learnt So Far?
TLDR
The VOCs characteristics, their mutational patterns, and the role mutations play in immune evasion are summarized in this review.
Year-long COVID-19 infection reveals within-host evolution of SARS-CoV-2 in a patient with B cell depletion
TLDR
The unique viral mutations found in this study highlight the importance of analyzing viral evolution in protracted SARS-CoV-2 infection, especially in immunosuppressed hosts, and the implication of these mutations in the emergence of viral variants.
Intra-host evolution provides for continuous emergence of SARS-CoV-2 variants
TLDR
It is estimated that in 2% of COVID cases, viral variants with multiple mutations can become the dominant strains in as little as one month of persistent in patient virus replication, suggesting the continued local emergence of VOC independent of travel patterns.
Within-host evolution of SARS-CoV-2 in an immunosuppressed COVID-19 patient as a source of immune escape variants
TLDR
It is demonstrated that a late viral isolate exhibiting genome mutations similar to those found in variants of concern first identified in UK, South Africa, and Brazil, can escape neutralization by COVID-19 antisera and suggest that immunocompromised patients could be a source for the emergence of potentially harmful SARS-CoV-2 variants.
...
...

References

SHOWING 1-10 OF 71 REFERENCES
Convergent Antibody Responses to SARS-CoV-2 in Convalescent Individuals
TLDR
Most convalescent plasma samples obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity, and rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.
Measuring SARS-CoV-2 neutralizing antibody activity using pseudotyped and chimeric viruses
TLDR
A collection of approaches based on SARS-CoV-2 spike-pseudotyped, single-cycle, replication-defective human immunodeficiency virus type-1 (HIV-1) and vesicular stomatitis virus (VSV), as well as a replication-competent VSV/SARS- CoV- 2 chimeric virus are described.
Remdesivir induced viral RNA and subgenomic RNA suppression, and evolution of viral variants in SARS-CoV-2 infected patients.
While changes in SARS-CoV-2 viral load over time have been documented, detailed information on the impact of remdesivir and how it might alter intra-host viral evolution is limited. Sequential viral
Distinct conformational states of SARS-CoV-2 spike protein
TLDR
Two cryo–electron microscopy structures derived from a preparation of the full-length S protein, representing its prefusion and postfusion conformations, are reported, advancing the understanding of SARS-CoV-2 entry and may guide the development of vaccines and therapeutics.
Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability
TLDR
It is shown that the patients had strong immune responses against the viral spike protein, a complex that binds to receptors on the host cell, and monoclonal antibodies isolated here are promising candidates for COVID-19 treatment and prevention.
Recurrent emergence and transmission of a SARS-CoV-2 spike deletion H69/V70
TLDR
Recurrent emergence and significant onward transmission of a six-nucleotide out of frame deletion in the S gene, which results in loss of two amino acids: H69 and V70 is reported, which likely acts as a permissive mutation that allows acquisition of otherwise deleterious immune escape mutations.
Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans.
TLDR
The present study has important implications when considering widespread serological testing and antibody protection against reinfection with SARS-CoV-2, and may suggest that vaccine boosters are required to provide long-lasting protection.
Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity
TLDR
A systematic characterization of the humoral response to severe acute respiratory system coronavirus 2 (SARS-CoV-2) epitopes has yet to be performed, important for understanding the immunogenicity of the viral proteome and the basis for cross-reactivity with the common-cold coronaviruses.
...
...