Sequential Appearance and Isolation of a SARS-CoV-2 Recombinant between Two Major SARS-CoV-2 Variants in a Chronically Infected Immunocompromised Patient.

in Viruses by Emilie Burel, Philippe Colson, Jean-Christophe Lagier, Anthony Levasseur, Marielle Bedotto, Philippe Lavrard-Meyer, Pierre-Edouard Fournier, Bernard La Scola, Didier Raoult

TLDR

  • The study investigates how a virus called SARS-CoV-2 can change its genetic makeup over time. The study found that a patient with a rare type of cancer called lymphoma had a virus that was a mix of two different types of SARS-CoV-2. The study also found that the virus changed over time, and eventually became a dominant strain that was isolated from the patient. The study highlights the importance of monitoring the genetic makeup of SARS-CoV-2 in patients with rare types of cancer, and calls for more research to understand how the virus changes over time.

Abstract

Genetic recombination is a major evolutionary mechanism among RNA viruses, and it is common in coronaviruses, including those infecting humans. A few SARS-CoV-2 recombinants have been reported to date whose genome harbored combinations of mutations from different mutants or variants, but only a single patient's sample was analyzed, and the virus was not isolated. Here, we report the gradual emergence of a hybrid genome of B.1.160 and Alpha variants in a lymphoma patient chronically infected for 14 months, and we isolated the recombinant virus. The hybrid genome was obtained by next-generation sequencing, and the recombination sites were confirmed by PCR. This consisted of a parental B.1.160 backbone interspersed with two fragments, including the spike gene, from an Alpha variant. An analysis of seven sequential samples from the patient decoded the recombination steps, including the initial infection with a B.1.160 variant, then a concurrent infection with this variant and an Alpha variant, the generation of hybrid genomes, and eventually the emergence of a predominant recombinant virus isolated at the end of the patient's follow-up. This case exemplifies the recombination process of SARS-CoV-2 in real life, and it calls for intensifying the genomic surveillance in patients coinfected with different SARS-CoV-2 variants, and more generally with several RNA viruses, as this may lead to the appearance of new viruses.

Overview

  • The study focuses on the emergence of a hybrid genome of B.1.160 and Alpha variants in a lymphoma patient chronically infected for 14 months. The study aims to investigate the recombination process of SARS-CoV-2 in real life and to call for intensifying genomic surveillance in patients coinfected with different SARS-CoV-2 variants and other RNA viruses. The methodology used for the experiment includes next-generation sequencing and PCR to analyze seven sequential samples from the patient and to confirm the recombination sites. The primary objective of the study is to understand the recombination process of SARS-CoV-2 and its potential impact on the evolution of the virus.

Comparative Analysis & Findings

  • The study compares the outcomes observed under different experimental conditions or interventions, specifically the emergence of a hybrid genome of B.1.160 and Alpha variants in a lymphoma patient chronically infected for 14 months. The study identifies the gradual emergence of the hybrid genome over time, starting with the initial infection with a B.1.160 variant, followed by a concurrent infection with this variant and an Alpha variant, the generation of hybrid genomes, and eventually the emergence of a predominant recombinant virus isolated at the end of the patient's follow-up. The study also highlights the importance of genomic surveillance in patients coinfected with different SARS-CoV-2 variants and other RNA viruses, as this may lead to the appearance of new viruses. The key findings of the study are that the recombination process of SARS-CoV-2 is common in real life and that it may have significant implications for the evolution of the virus.

Implications and Future Directions

  • The study's findings have significant implications for the field of research and clinical practice, as they provide insights into the recombination process of SARS-CoV-2 in real life and highlight the importance of genomic surveillance in patients coinfected with different SARS-CoV-2 variants and other RNA viruses. The study identifies limitations, such as the small sample size and the need for more research to understand the mechanisms underlying the recombination process. Future research directions could include studying the recombination process of SARS-CoV-2 in other patient populations, investigating the impact of recombination on vaccine efficacy, and exploring the potential of recombinant viruses as therapeutic agents. The study suggests that intensifying genomic surveillance in patients coinfected with different SARS-CoV-2 variants and other RNA viruses is crucial for monitoring the evolution of the virus and identifying new threats to public health.
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