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PubMed2026

SARS-CoV-2 intra-host variation shows evidence of transmission and convergent evolution in a university surveillance cohort.

Monitoring and understanding the transmission and evolution of SARS-CoV-2 remains a significant public health priority. Within-host genetic variation provides insight into viral evolution during infection and may help infer transmission events. In this study, we analysed intra-host variation in SARS-CoV-2 genome sequences from Boston University's testing mandate. Focusing on intra-host single nucleotide variants (iSNVs), we inferred transmission events and assessed the selective forces shaping within-host viral evolution. To minimize false-positive iSNVs resulting from systematic biases, we implemented stringent data filtering and developed a heuristic to exclude contamination-derived artefacts arising from batched sequencing. We find that intra-host variation is limited and infrequently transmitted during acute infections, suggesting that shared iSNVs serve as highly specific but insensitive markers of transmission. We also observed incomplete purifying selection shaping within-host diversity, with the loci most affected changing among variants of concern. Finally, we identified a highly recurrent iSNV (G11083T) which may represent a site of positive selection. Our results highlight that within-host variation provides insight into within-host pathogen evolution, in spite of its limited use in genomic epidemiology.

SARS-CoV-2↗

PubMed2025

Characterisation of a persistent SARS-CoV-2 infection lasting more than 750 days in a person living with HIV: a genomic analysis.

BACKGROUND: People who are immunocompromised can develop persistent SARS-CoV-2 infections. Several viral mutations accumulated during the course of such persistent infections have also been observed in prominent variants of concern (VOCs). Here, we characterise persistent infection and viral evolution of SARS-CoV-2 lasting more than 750 days in a person with advanced HIV-1 infection. METHODS: Between March, 2021, and July, 2022, eight clinical specimens were collected from a person living with HIV, neither receiving antiretroviral therapy nor virally suppressed, and presumed to have been initially infected with SARS-CoV-2 in mid-May, 2020. Viral RNA was extracted from each swab and an amplicon-based sequencing approach was used for genomic analysis of SARS-CoV-2. Variable sites were characterised at the consensus and subconsensus levels, and phylogenetic tools were applied to analyse viral evolution. Publicly available SARS-CoV-2 sequences from GenBank were leveraged to contextualise our sequenced samples and identify any potential evidence of transmission. FINDINGS: Genomes formed a monophyletic cluster in the B.1 lineage. 68 consensus and 67 subconsensus single nucleotide variants were observed over the course of infection. The intrahost clock rate remained similar to that of the interhost rate in contemporaneous community sequences (6·74 × 10-4 [95% credible interval 5·05 × 10-4 to 8·54 × 10-4] substitutions per site per year vs 6·11 × 10-4 [5·54 × 10-5 to 6·66 × 10-4]). Mutations grouped into two distinct subpopulations present throughout infection. 10 non-synonymous mutations in the spike protein gene were at positions in common with those defining the omicron lineage (BA.1 or BA.2), of which nine were present before November, 2021. Nine of 18 substitutions present throughout infection were rare in online databases, suggesting a lack of long transmission chains descending from this individual. INTERPRETATION: Convergent SARS-CoV-2 evolution, both in and outside the spike protein, observed in this study suggests parallels with the evolutionary process leading to emergence of the omicron VOC. The inferred absence of onward infections might indicate a loss of transmissibility during adaptation to a single host. Our results underscore the importance of appropriate treatment to cure persistent SARS-CoV-2 infections and monitoring them to understand how mutations contribute to viral adaptation. FUNDING: National Institute of General Medical Sciences of the National Institutes of Health, Centers for Disease Control and Prevention, the National Institute of Allergy and Infectious Diseases, MassCPR, and Morris Singer Foundation.

Humans↗