Recombination is a common evolutionary tool for RNA viruses, and coronaviruses are no exception. We review here the evidence for recombination in SARS-CoV-2 and reconcile nomenclature for recombinants, discuss their origin and fitness, and speculate how recombinants could make a difference in the future of the COVID-19 pandemics.

/pdf/recombination-in-coronaviruses-with-a-focus-on-sars-cov-2-1kn1h3n8.pdf

Recombination in Coronaviruses, with a Focus on SARS-CoV-2

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9581791

Evidence for SARS-CoV-2 Delta and Omicron co-infections and recombination

Multiple SARS‐CoV‐2 variants have successively, or concomitantly spread worldwide since the summer of 2020. A few co‐infections with different variants were reported and genetic recombinations, common among coronaviruses, were reported or suspected based on co‐detection of signature mutations of different variants in a given genome. Here we report three infections in southern France with a Delta 21J_AY.4‐Omicron 21K/BA.1 “Deltamicron” recombinant. The hybrid genome harbors signature mutations of the two lineages, supported by a mean sequencing depth of 1163–1421 reads and a mean nucleotide diversity of 0.1%–0.6%. It is composed of the near full‐length spike gene (from codons 156–179) of an Omicron 21K/BA.1 variant in a Delta 21J/AY.4 lineage backbone. Importantly, we cultured an isolate of this recombinant and sequenced its genome. It was observed by scanning electron microscopy. As it is misidentified with current variant screening quantitative polymerase chain reaction (qPCR), we designed and implemented for routine diagnosis a specific duplex qPCR. Finally, structural analysis of the recombinant spike suggested its hybrid content could optimize viral binding to the host cell membrane. These findings prompt further studies of the virological, epidemiological, and clinical features of this recombinant.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jmv.27789

Culture and identification of a “Deltamicron” SARS‐CoV‐2 in a three cases cluster in southern France

Abstract From December 2021-February 2022, an intense and unprecedented co-circulation of SARS-CoV-2 variants with high genetic diversity raised the question of possible co-infections between variants and how to detect them. Using 11 mixes of Delta:Omicron isolates at different ratios, we evaluated the performance of 4 different sets of primers used for whole-genome sequencing and developed an unbiased bioinformatics method for the detection of co-infections involving genetically distinct SARS-CoV-2 lineages. Applied on 21,387 samples collected between December 6, 2021 to February 27, 2022 from random genomic surveillance in France, we detected 53 co-infections between different lineages. The prevalence of Delta and Omicron (BA.1) co-infections and Omicron lineages BA.1 and BA.2 co-infections were estimated at 0.18% and 0.26%, respectively. Among 6,242 hospitalized patients, the intensive care unit (ICU) admission rates were 1.64%, 4.81% and 15.38% in Omicron, Delta and Delta/Omicron patients, respectively. No BA.1/BA.2 co-infections were reported among ICU admitted patients. Among the 53 co-infected patients, a total of 21 patients (39.6%) were not vaccinated. Although SARS-CoV-2 co-infections were rare in this study, their proper detection is crucial to evaluate their clinical impact and the risk of the emergence of potential recombinants. 

/pdf/detection-and-prevalence-of-sars-cov-2-co-infections-during-3cxrr1rl.pdf

Detection and prevalence of SARS-CoV-2 co-infections during the Omicron variant circulation in France

http://www.clinicalmicrobiologyandinfection.com/article/S1198743X22003457/pdf

Evidence of co-infections during Delta and Omicron SARS-CoV-2 variants co-circulation through prospective screening and sequencing

Co-infections with different variants of SARS-CoV-2 are a key precursor to recombination events that are likely to drive SARS-CoV-2 evolution. Rapid identification of such co-infections is required to determine their frequency in the community, particularly in populations at-risk of severe COVID-19, which have already been identified as incubators for punctuated evolutionary events. However, limited data and tools are currently available to detect and characterise the SARS-CoV-2 co-infections associated with recognised variants of concern. Here we describe co-infection with the SARS-CoV-2 variants of concern Omicron and Delta in two epidemiologically unrelated adult patients with chronic kidney disease requiring maintenance haemodialysis. Both variants were co-circulating in the community at the time of detection. Genomic surveillance based on amplicon- and probe-based sequencing using short- and long-read technologies identified and quantified subpopulations of Delta and Omicron viruses in respiratory samples. These findings highlight the importance of integrated genomic surveillance in vulnerable populations and provide diagnostic pathways to recognise SARS-CoV-2 co-infection using genomic data. 

/pdf/co-infection-with-sars-cov-2-omicron-and-delta-variants-h6s5ajle.pdf

Co-infection with SARS-CoV-2 Omicron and Delta variants revealed by genomic surveillance

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Co-infection with SARS-CoV-2 Omicron and Delta variants revealed by genomic surveillance