Large-scale genomic surveillance reveals immunosuppression drives mutation dynamics in persistent SARS-CoV-2 infections

Mark P. Khurana; Alexandros Katsiferis; Neil Scheidwasser; Mathilde Marie Brünnich Sloth; Jacob Curran-Sebastian; Christian Morgenstern; Man-Hung Eric Tang; Jannik Fonager; Morten Rasmussen; Marc Stegger; Sune Lehmann; Charles Whittaker; Laust H. Mortensen; Pikka Jokelainen; Moritz U. G. Kraemer; Neil M. Ferguson; Mahan Ghafari; Tyra G. Krause; David A. Duchêne; Samir Bhatt

doi:10.1038/s41467-026-74445-7

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Large-scale genomic surveillance reveals immunosuppression drives mutation dynamics in persistent SARS-CoV-2 infections

Journal article

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Large-scale genomic surveillance reveals immunosuppression drives mutation dynamics in persistent SARS-CoV-2 infections

Mark P. Khurana, Alexandros Katsiferis, Neil Scheidwasser, Mathilde Marie Brünnich Sloth, Jacob Curran-Sebastian, Christian Morgenstern, Man-Hung Eric Tang, Jannik Fonager, Morten Rasmussen, Marc Stegger, …

Nature communications, Vol.17(1), 7730

2026

DOI: https://doi.org/10.1038/s41467-026-74445-7

PMID: 42321162

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Abstract

Persistent SARS-CoV-2 infections have been hypothesized to play a key role in the emergence of variants of concern. However, the factors determining which individuals are at risk and their viral molecular signatures during infection remain poorly understood. Using Denmark’s extensive COVID-19 surveillance, comprising over 700,000 genomes, we identify 303 persistent infections and, critically, link them to health and sociodemographic data. Our analysis confirms the hypothesis that immunocompromised individuals are at the highest risk of experiencing persistent infections. Other disease groups associated with mortality, such as diabetes, show no such associations. Among these persistent infections, the viral sequences exhibit signs of positive selection, with recurrent mutations linked to treatment resistance. Our findings suggest that immunosuppression plays a key role in the emergence of novelty in persistent infections. Using Denmark’s genomic surveillance linked to health registries, the authors identify immunosuppression as a key risk factor for persistent SARS-CoV-2 infections and show these infections accumulate mutations associated with treatment resistance.

Details

Title: Large-scale genomic surveillance reveals immunosuppression drives mutation dynamics in persistent SARS-CoV-2 infections
Authors/Creators: Mark P. Khurana - University of Copenhagen
Alexandros Katsiferis - University of Copenhagen
Neil Scheidwasser - Copenhagen, Denmark
Mathilde Marie Brünnich Sloth - University of Copenhagen
Jacob Curran-Sebastian - University of Copenhagen
Christian Morgenstern - Imperial College London
Man-Hung Eric Tang - Statens Serum Institut
Jannik Fonager - Statens Serum Institut
Morten Rasmussen - Statens Serum Institut
Marc Stegger - Statens Serum Institut
Sune Lehmann - Technical University of Denmark
Charles Whittaker - Imperial College London
Laust H. Mortensen - Statistics Denmark
Pikka Jokelainen - Statens Serum Institut
Moritz U. G. Kraemer - University of Oxford
Neil M. Ferguson - London, UK
Mahan Ghafari - University of Oxford
Tyra G. Krause - Statens Serum Institut
David A. Duchêne - University of Copenhagen
Samir Bhatt - Copenhagen, Denmark London, UK
Publication Details: Nature communications, Vol.17(1), 7730
Publisher: Nature Publishing Group
Identifiers: 991005909767807891
Murdoch Affiliation: Harry Butler Institute
Language: English
Resource Type: Journal article

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