Long-Term Intra-Host Evolution of SARS-CoV-2 in an Immunocompromised Patient: Recombination and Within-Host Mutations Driving Viral Adaptation
Bibliographic record
Abstract
An immuno-compromised patient with lymphoma experienced a prolonged SARS-CoV-2 infection lasting 14 months, initially infected with B.1.160, followed by B.1.1.7. This study focused on intra-host single nucleotide variants (iSNVs) and single nucleotide polymorphisms (SNPs), distinguishing their origin as either within-host mutations or parental. The whole genome analysis revealed accelerated evolution, with positive selection detected in key genes such as Spike, N, ORF9b, and nsp13, all involved in viral replication and immune evasion. Of the two evolutionary mechanisms involved, host-driven mutation has played a dominant role in this evolutionary story. C>T transitions emerged as the most widespread mutational signature, consistent with host-driven RNA editing mechanisms. Two host-internal mutations, A28271T in the translation initiation region of the N Kozak gene and C26858T in the M gene, were highly shared among the deposited SARS-CoV-2 sequences. Recombination with parental lineages played a major role particularly in Spike, ORF3a and M genes. In Spike, the B.1.1.7 sequence was selected, wild-type ORF3a and M were restored, suggesting a selective advantage in returning to an ancestral sequence. In addition, the temporary emergence of intra-host convergent mutations in Spike, notably L5F, D796H and T572I, underlines the strong selective pressures exerted on this gene. A 126-nucleotide deletion in ORF8 resulted in a truncated protein, reinforcing its uselessness for viral replication, as observed in circulating variants such as B.1.1.7. The present case highlights the complex interplay between viral recombination and mutations within the host in chronic infections and further underscores the remarkable evolutionary plasticity of SARS-CoV-2 and its potential to generate highly adapted viral strains.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".