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

Publication date: Jun 19, 2026

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.

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Concepts Keywords
Denmark Cov
Diabetes Emergence
Genomes Genomic
Immunosuppression Immunosuppression
Individuals
Infections
Key
Large
Persistent
Reveals
Risk
Sars
Scale
Surveillance
Viral

Semantics

Type Source Name
disease MESH SARS-CoV-2 infections
disease MESH infection
disease MESH persistent infections
drug DRUGBANK Etodolac
disease MESH David
pathway REACTOME Reproduction
disease MESH included
disease MESH Infectious Diseases
drug DRUGBANK Aspartame
drug DRUGBANK Methionine
disease MESH ICD
drug DRUGBANK Coenzyme M
drug DRUGBANK Amino acids
drug DRUGBANK Ritonavir
disease MESH AIC
drug DRUGBANK Indoleacetic acid
pathway KEGG Viral replication
disease MESH reinfections
disease MESH frailty
drug DRUGBANK Trimebutine
drug DRUGBANK Esomeprazole
drug DRUGBANK L-Phenylalanine
disease MESH AIDS
disease MESH COH
disease MESH Recurrence
disease MESH Viremia
drug DRUGBANK Azelaic acid
disease MESH Tam
drug DRUGBANK Carboxyamidotriazole
drug DRUGBANK (S)-Des-Me-Ampa
drug DRUGBANK Ranitidine
drug DRUGBANK Guanosine
disease MESH Park
disease MESH Chronic Diseases
disease MESH severe acute respiratory syndrome
disease MESH Ito
disease MESH Amelia
disease MESH I’ah
drug DRUGBANK Troleandomycin
disease MESH Breakthrough Infection
disease MESH Lam
disease MESH uan
disease MESH HIV Infection
pathway REACTOME HIV Infection
disease MESH hos
disease MESH Mota
disease MESH fac
pathway REACTOME Apoptosis
disease MESH Syndrome
disease MESH pneumonia
disease MESH mul
disease MESH Dis
drug DRUGBANK Amber
disease MESH Eco
disease MESH Autoimmune Diabetes

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