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Insights into the Emergence of SARS-CoV-2 Variants: The Pivotal Role of Prolonged Infection in Immunocompromised Patients

Recent scientific findings, as published in The Journal of Infectious Diseases, are providing new insights into the emergence of SARS-CoV-2 variants. The study underscored that immunocompromised individuals, when infected with COVID-19, tend to harbor SARS-CoV-2 organisms showing higher genetic diversity. This increased diversity could potentially act as a catalyst for the development of new viral variants.

The processes involved in the genesis of SARS-CoV-2 variants are currently still not entirely understood. This mystery extends to two key probable mechanisms – one is the selective pressure exerted during treatment, and the other is the possibility that prolonged infection, beyond 30 days, especially among immunocompromised individuals, favors the manifestation of novel mutations.

In order to investigate this hypothesis, the researchers conducted a comprehensive retrospective case-control study at two university hospitals in France from 2020 to 2022. The study involved the collection and analysis of respiratory samples from immunocompromised patients (numbering 444) and healthcare workers (serving as controls numbering 234) who were infected with COVID-19. Whole-genome sequencing was employed to assess these samples and comparative analysis on genetic diversity was conducted between the two groups.

A number of patients provided multiple respiratory samples, and minor mutations were identified in samples showing frequencies between 5% and 19.99%. Patient demographics showed a median age of 63 for the immunocompromised group and 38 for the control group, with males comprising 55.9% and 29.5% of these groups, respectively.

In the immunocompromised group, 14 patients displayed prolonged COVID-19 infection. The reasons steering their immunocompromised status encompassed kidney transplants, autoimmune/inflammatory diseases, nonblood cancers, blood cancers, heart transplants, rituximab treatment, and HIV infection.

Majority of the samples collected were positive for variants including Omicron 21K, Omicron 21L, Delta 21J, Omicron 22B, and Alpha 20I. There were a few samples that were either unidentified or classified as recombinant variants.

Upon examination, mutations were seen scattered across the entire SARS-CoV-2 genome in all open reading frames (ORFs). Particularly, the spike gene exhibited the highest mutational density. Interestingly, the genetic diversity was greater among the Delta variant cluster than the Omicron variant cluster.

Significantly, minor mutations were more common in immunocompromised patients compared to the control group. The primary location for these mutations was found to be the ORF1ab and spike genes. Further scrutiny unveiled that some minor mutations identified in immunocompromised patients eventually emerged as signature mutations in future variants.

The study, however, is not without its limitations, as it lacks patient data or clinical data. Nevertheless, these findings underscore the urgent need for the healthcare professionals to recognize the potential for the emergence of new SARS-CoV-2 variants, particularly in immunocompromised patients with prolonged infection.


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