Within-host evolution of SARS-CoV-2 in an immunosuppressed COVID-19 patient as a source of immune escape variants

Weigang, Sebastian; Fuchs, Jonas; Zimmer, Gert; Schnepf, Daniel; Kern, Lisa; Beer, Julius; Luxenburger, Hendrik; Ankerhold, Jakob; Falcone, Valeria; Kemming, Janine; Hofmann, Maike; Thimme, Robert; Neumann‐Haefelin, Christoph; Ulferts, Svenja; Grosse, Robert; Hornuß, Daniel; Tanriver, Yakup; Rieg, Siegbert; Wagner, Dirk; Huzly, Daniela; Schwemmle, Martin; Panning, Marcus; Kochs, Georg

doi:10.1038/s41467-021-26602-3

Cited by 148 publications

(134 citation statements)

References 35 publications

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“…However, lack of adherence to ART and development of drug resistance mutations leads to ongoing HIV replication, which, if left to persist for years, results in advanced HIV disease mediated immune suppression ( 28 ). We and others have recently shown that advanced HIV disease may lead to delayed clearance of SARS-CoV-2 and evolution of the SARS-CoV-2 virus ( 29 , 30 ), similar to what is observed in immune suppression caused by other factors ( 31 – 35 ).…”

supporting

confidence: 69%

SARS-CoV-2 evolved during advanced HIV disease immunosuppression has Beta-like escape of vaccine and Delta infection elicited immunity

Cele

Karim

Lustig

et al. 2021

Preprint

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SARS-CoV-2 continues to evolve variants of concern (VOC) which escape antibody neutralization and have enhanced transmission. One variant may escape immunity elicited by another, and the delta VOC has been reported to escape beta elicited immunity. Systematic mapping of the serological distance of current and emerging variants will likely guide the design of vaccines which can target all variants. Here we isolated and serologically characterized SARS-CoV-2 which evolved from an ancestral strain in a person with advanced HIV disease and delayed SARS-CoV-2 clearance. This virus showed evolving escape from self antibody neutralization immunity and decreased Pfizer BNT162b2 vaccine neutralization sensitivity. We mapped neutralization of evolved virus and ancestral, beta and delta variant viruses by antibodies elicited by each VOC in SARS-CoV-2 convalescent individuals. Beta virus showed moderate (7-fold) and delta slight escape from neutralizing immunity elicited by ancestral virus infection. In contrast, delta virus had stronger escape from beta elicited immunity (12-fold), and beta virus even stronger escape from delta immunity (34-fold). Evolved virus had 9-fold escape from ancestral immunity, 27-fold escape from delta immunity, but was effectively neutralized by beta immunity. We conclude that beta and delta are serologically distant, further than each is from ancestral, and that virus evolved in prolonged infection during advanced HIV disease is serologically close to beta and far from delta. These results suggest that SARS-CoV-2 is diverging into distinct serological phenotypes and that vaccines tailored to one variant may become vulnerable to infections with another.

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supporting

confidence: 69%

SARS-CoV-2 evolved during advanced HIV disease immunosuppression has Beta-like escape of vaccine and Delta infection elicited immunity

Cele

Karim

Lustig

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…Start of infection was taken to be the start of symptoms or the date of the first positive PCR test depending on what was available for each study. End of infection was the date of the final negative PCR test in the study (Avanzato et al 2020; Karim et al 2021; Stanevich et al 2021; Voloch et al 2020; Weigang et al 2021; Williamson et al 2021), death (Choi et al 2020) or when the individual was lost to follow up (Ramírez et al 2021).…”

Section: Methodsmentioning

confidence: 99%

The origins and molecular evolution of SARS-CoV-2 lineage B.1.1.7 in the UK

Hill

Plessis

Peacock

et al. 2022

Preprint

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The first SARS-CoV-2 variant of concern (VOC) to be designated was lineage B.1.1.7, later labelled by the World Health Organisation (WHO) as Alpha. Originating in early Autumn but discovered in December 2020, it spread rapidly and caused large waves of infections worldwide. The Alpha variant is notable for being defined by a long ancestral phylogenetic branch with an increased evolutionary rate, along which only two sequences have been sampled. Alpha genomes comprise a well-supported monophyletic clade within which the evolutionary rate is more typical of SARS-CoV-2. The Alpha epidemic continued to grow despite the continued restrictions on social mixing across the UK, and the imposition of new restrictions, in particular the English national lockdown in November 2020. While these interventions succeeded in reducing the absolute number of cases, the impact of these non-pharmaceutical interventions was predominantly to drive the decline of the SARS-CoV-2 lineages which preceded Alpha. We investigate the only two sampled sequences that fall on the branch ancestral to Alpha. We find that one is likely to be a true intermediate sequence, providing information about the order of mutational events that led to Alpha. We explore alternate hypotheses that can explain how Alpha acquired a large number of mutations yet remained largely unobserved in a region of high genomic surveillance: an under-sampled geographical location, a non-human animal population, or a chronically-infected individual. We conclude that the last hypothesis provides the best explanation of the observed behaviour and dynamics of the variant, although we find that the individual need not be immunocompromised, as persistently-infected immunocompetent hosts also display a higher within-host rate of evolution. Finally, we compare the ancestral branches and mutation profiles of other VOCs to each other, and identify that Delta appears to be an outlier both in terms of the genomic locations of its defining mutations, and its lack of rapid evolutionary rate on the ancestral branch. As new variants, such as Omicron, continue to evolve (potentially through similar mechanisms) it remains important to investigate the origins of other variants to identify ways to potentially disrupt their evolution and emergence.

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“…Because the Omicron variants are believed to have emerged in South Africa 1 , we speculate that some of these spike mutations may have been produced by long-term virus infections in immunocompromised patients. It was previously reported that evolution of SARS-CoV-2 in an immunosuppressed COVID-19 patient led to immune escape variants 45,46 . Deletions in NTD, for example, delY144, were detected in multiple immunosuppressed COVID-19 patients, which resulted in immune escape [45][46][47] .…”

Section: Co-infections Of Different Sars-cov-2 Variants In the Popula...mentioning

confidence: 96%

“…It was previously reported that evolution of SARS-CoV-2 in an immunosuppressed COVID-19 patient led to immune escape variants 45,46 . Deletions in NTD, for example, delY144, were detected in multiple immunosuppressed COVID-19 patients, which resulted in immune escape [45][46][47] .…”

Section: Co-infections Of Different Sars-cov-2 Variants In the Popula...mentioning

confidence: 96%

Tracking SARS-CoV-2 Omicron diverse spike gene mutations identifies multiple inter-variant recombination events

Lan

et al. 2022

Preprint

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The current pandemic of COVID-19 is fueled by more infectious emergent Omicron variants. Ongoing concerns of emergent variants include possible recombinants, as genome recombination is an important evolutionary mechanism for the emergence and re-emergence of human viral pathogens. Although recombination events among SARS-CoV-1 and MERS-CoV were well-documented, it has been difficult to detect the recombination signatures in SARS-CoV-2 variants due to their high degree of sequence similarity. In this study, we identified diverse recombination events between two Omicron major subvariants (BA.1 and BA.2) and other variants of concern (VOCs) and variants of interest (VOIs), suggesting that co-infection and subsequent genome recombination play important roles in the ongoing evolution of SARS-CoV-2. Through scanning high-quality completed Omicron spike gene sequences, eighteen core mutations of BA.1 variants (frequency >99%) were identified (eight in NTD, five near the S1/S2 cleavage site, and five in S2). BA.2 variants share three additional amino acid deletions with the Alpha variants. BA.1 subvariants share nine common amino acid mutations (three more than BA.2) in the spike protein with most VOCs, suggesting a possible recombination origin of Omicron from these VOCs. There are three more Alpha-related mutations (del69-70, del144) in BA.1 than BA.2, and therefore BA.1 may be phylogenetically closer to the Alpha variant. Revertant mutations are found in some dominant mutations (frequency >95%) in the BA.1 subvariant. Most notably, multiple additional amino acid mutations in the Delta spike protein were also identified in the recently emerged Omicron isolates, which implied possible recombination events occurred between the Omicron and Delta variants during the on-going pandemic. Monitoring the evolving SARS-CoV-2 genomes especially for recombination is critically important for recognition of abrupt changes to viral attributes including its epitopes which may call for vaccine modifications.

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Within-host evolution of SARS-CoV-2 in an immunosuppressed COVID-19 patient as a source of immune escape variants

Cited by 148 publications

References 35 publications

SARS-CoV-2 evolved during advanced HIV disease immunosuppression has Beta-like escape of vaccine and Delta infection elicited immunity

SARS-CoV-2 evolved during advanced HIV disease immunosuppression has Beta-like escape of vaccine and Delta infection elicited immunity

The origins and molecular evolution of SARS-CoV-2 lineage B.1.1.7 in the UK

Tracking SARS-CoV-2 Omicron diverse spike gene mutations identifies multiple inter-variant recombination events

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