SARS-CoV-2 recombinant isolated from patients with chronic COVID-19

The epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was weakened and weakened, depending on the level of herd immunity and the biological characteristics of the virus. For example, the emergence of new variants of the virus with higher infectious or antigenic properties has changed the course of the pandemic.Journal’s new research paper virus We have reported the isolation of recombinant strains in patients infected with the virus for more than 1 year.

study: Continuous appearance and isolation of SARS-CoV-2 recombinants between two major SARS-CoV-2 mutants in chronically infected immunocompromised patients.. Image credit: NIAID

Preface

Genetic recombination refers to the combination of corresponding parts of a genomic molecule to form a new sequence. It generally occurs with the currently circulating SARS-CoV-2 containing ribonucleic acid (RNA) virus. coronavirus.. In fact, it is suspected of causing a pandemic virus.

It is speculated that this phenomenon also occurs in human patients with this infection, as indicated by the presence of characteristic mutations in different strains of the virus in the same patient. However, so far, none of these have been separated.

In the current paper, it is published in the journal virusScientists have found evidence of the slow emergence of recombinant SARS-CoV-2 strains in patients with chronic immunodeficiency. The patient was a 56-year-old man with lymphoma.

The first positive test developed pneumonia in August 2020 and required admission to the intensive care unit (ICU). This was successfully processed, but the virus was not cleared. During the last 14 months of his life, he repeated positive tests for the virus before he died of complications following the first diagnosed lymphoma and progressive multifocal leukoencephalitis in May 2021.

The first detection of the hybrid genomic SARS-CoV-2 mutant was made 14 months after infection. The two recombinant strains were identified as B.1.160, and alpha mutants. The former two regions were replaced by the latter, and the spike gene showed all eight characteristic mutations in the Alpha variant, but none of the S477N mutations characteristic of B.1.160.

There was little evidence to suggest that the presence of these Alpha mutations was due to coinfection or contamination by both mutants. Instead, “These findings indicate that this mosaic genome is the result of recombination between B.1.160 and the parent genome of the alpha mutant... “

The viral RNA test positive timeline suggests that the first infection occurred at B.1.160 and was widely circulated from August 2020 to January 2021 when the Alpha variant replaced it. rice field. The following sequence was obtained after only 8 months, indicating that the mosaic genome had already been formed between the two strains.

This recombinant is formed in several steps, and the recombination occurs at three sites in the two parent genomes. Detection of multiple chimeric copies indicated the presence of several breakpoints between the ancestral strains.

Schematic representation of the structure of the SARS-CoV-2 genome obtained from nasopharyngeal samples and culture supernatants with reference to the parent genomes of B.1.160 and Alpha mutants, as well as the recombination events over time. (A) Genome map and annotation. (B) Genome structure and mutation. The blue rectangle indicates the sequence of B.1.160 variants. Yellow indicates an array of alpha variants. Green indicates simultaneous detection of sequences from the B.1.160 and Alpha variants. Gray indicates a sequence of uncertain origin. Signature mutations from B.1.160 and Alpha variants are shown on a blue and yellow background, respectively. Signature mutations that do not exist are shown in red font. Δ21,765: -6 nucleotides; Δ21,991: -3 nucleotides. Nsp, nonstructural protein; ORF, open reading frame.

What is the impact?

The results of this study highlighted the presence of recombination in immunocompromised lymphoma patients who developed a long-term course of SARS-CoV-2 infection despite receiving multiple treatments. As a result, a hybrid virus strain formed by B.1.160 and the alpha variant was developed. Replacing the characteristic B.1.160 mutation with some characteristic alpha mutations between 8 and 14 months was not considered a coincidence and was the result of recombination at three sites.

Further analysis of genomic samples from successive respiratory samples and viral cultures showed the gradual development of several hybrid viruses in this patient, one of which established itself and was in the host to the end. Continued to duplicate.

This early sampling study over a year provides much insight into how RNA viruses recombine to form new strains, especially the production of recombinant SARS-CoV-2 strains isolated in culture. Will be revealed. Previous studies have shown that there will be 16 alpha-non-alpha recombinants in the UK in 2021. Others have suggested that recombinants make up 5% of the viruses circulating in the United Kingdom and the United States.

Despite the fact that more recombinants are detected each month, researchers are investigating different pathways in different cell types or among different types of RNA viruses. This helps to understand how the human pathogenic RNA virus emerges.

The importance of such discoveries is “It leads to enhanced genomic surveillance in patients, especially long-term viral carriers of immunodeficiency.Such infectious episodes could probably lead to the emergence of new viruses... “