Health
The study investigates recombinant SARS-CoV-2 mutants in immunocompromised individuals
In a recent study posted on medRxiv* Preprint server, researchers have identified recombination of two severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mutants.
Background
Genetic recombination of ribonucleic acid (RNA) virus is an important evolutionary mechanism. coronavirus.. There is speculation that genetic recombination may be involved in the origin of SARS-CoV-2. In addition, coinfection with a separate SARS-CoV-2 mutant in the same patient has been documented, and few reports speculate on the possibility of genetic recombination. However, these conclusions were drawn based on the identification of coexisting signature mutations of SARS-CoV-2 mutants in the isolated viral genome. They did not report the isolation of distinct variants in culture.
In the United Kingdom (UK), 16 interstrain recombinants between non-alpha virus and alpha virus were reported in 2021 based on analysis of over 270,000 genomic sequences. In addition, it has been reported that nearly 5% of SARS-CoV-2 epidemics in the United Kingdom and the United States may be recombinants.
the study
In this study, researchers reported that recombination of two SARS-CoV-2 mutants in patients led to the production of hybrid SARS-CoV-2 mutants. Subjects were immunocompromised patients with chronic SARS-CoV-2 infection for 14 months before death. Since January 2020, the author’s laboratory has processed over 1 million respiratory samples of SARS-CoV-2 by real-time reverse transcription-polymerase chain reaction (RT-qPCR), utilizing continuous samples from multiple patients. It was possible. This allowed us to detect reinfections and chronic infections in individuals with severe immunosuppression.
Researchers have sequenced the viral genome from a patient’s respiratory specimen. Viral RNA was extracted from the nasopharyngeal swab using the EZ1 virus minikit and was subject to next-generation sequencing (NGS) using the Illumina COVIDSeq protocol or ARTIC multiplex PCR sequencing using nanopore technology. .. In addition, PCR amplification overlapped with the putative site of recombination and was performed on sequences sequenced by nanopore technology. Finally, respiratory samples were used to perform virus culture analysis on Vero E6 cells to sequence the isolated virus.
Survey results
The patient was first diagnosed with COVID-19 in 2020 and was previously diagnosed with Hodgkin lymphoma and follicular lymphoma. He developed severe pneumonia associated with COVID-19. SARS-CoV-2 was persistent. That is, no viral clearance was observed despite the subject’s clinical improvement. The patient was negative 5 months after infection, but positive 7 months.
The research team identified a viral genome that is a hybrid of two SARS-CoV-2 variants (B.1.160 and Alpha (B.1.1.7)). The recombinant genome contains a matrix of the B.1.160 genome, with some regions replaced by regions of the Alpha variant. One is at the 5’end of the genome containing C913U (synonymous mutation) and the other is 17,109 –18,877 and 25,710–27,972 sites. The recombinant contained all mutations in the alpha variant in the spike (S) gene, but lacked the characteristic S477N mutation in the B.1.160 variant. Co-infection or contamination of the two mutants was ruled out because of the low nucleotide diversity at 35 sites containing the characteristic mutations of B.1.160 or alpha mutants.
A sample of the patient when first diagnosed in the summer of 2020 was examined, and researchers determined that the infection was due to the B.1.160 mutant because it was prevalent at the time. Although the B.1.160 variant was not retroactively isolated, they found that the genomic sequence was typical of the variant without significant nucleotide diversity. It was unclear whether this (sample) contained B.1.160 or the Alpha variant, as his sample was not available for NGS when he was still PCR positive 4 months after infection. The hybrid virus was first observed in his sample 8 months after infection.
Conclusion
Current studies report that immunocompromised individuals with chronic COVID-19 infection had hybrid variants resulting from recombination between B.1.160 and the alpha variant at three sites. In particular, the pre-detection sample of the hybrid genome was not available for sequencing. Therefore, (severe) infections with alpha variants could not be dated for that period (0-8 months).
Nevertheless, it is unlikely that random mutations may have led to the appearance of alpha mutant sequences in the recombinant genome. These observations shed light on the mechanism of SARS-CoV-2 virus recombinant and suggest intensive genomic monitoring in patients co-infected with SARS-CoV-2 and co-infected with other RNA viruses. doing.
*Important Notices
medRxiv publishes unpeer-reviewed preliminary scientific reports and should not be considered definitive, guide clinical / health-related behaviors, or be treated as established information.
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