Med
Volume 3, Issue 12, 9 December 2022, Pages 848-859.e4
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Clinical and Translational Report
Evidence for SARS-CoV-2 Delta and Omicron co-infections and recombination

https://doi.org/10.1016/j.medj.2022.10.002Get rights and content
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Highlights

  • Whole-genome sequencing of SARS-CoV-2 when Delta and Omicron variants co-circulated

  • 18 samples (<0.1%) were confirmed to be Delta-Omicron co-infections

  • Recombination of Delta and Omicron detected in one of the co-infection samples

  • Infections by clonal Delta-Omicron recombinants was rare, only 2 samples

Context and significance

Viruses can gain new properties by recombination. Recombination between SARS-CoV-2 Delta and Omicron variants can lead to a new set of mutations with unknown impact on transmissibility and severity of the virus. Here, the authors sequenced SARS-CoV-2-positive samples between November 2021 and February 2022, when Delta and Omicron were both present in the United States. After validation, they found 18 samples (<0.1%) infected by the two variants, with evidence that recombination occurred in at least one of these samples. They found only two samples where 100% of the virus was a Delta-Omicron recombinant. The methods and strategy used in this study could be used to track co-infections and new recombinations in the future.

Summary

Background

Between November 2021 and February 2022, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variants co-circulated in the United States, allowing for co-infections and possible recombination events.

Methods

We sequenced 29,719 positive samples during this period and analyzed the presence and fraction of reads supporting mutations specific to either the Delta or Omicron variant.

Findings

We identified 18 co-infections, one of which displayed evidence of a low Delta-Omicron recombinant viral population. We also identified two independent cases of infection by a Delta-Omicron recombinant virus, where 100% of the viral RNA came from one clonal recombinant. In the three cases, the 5′ end of the viral genome was from the Delta genome and the 3′ end from Omicron, including the majority of the spike protein gene, though the breakpoints were different.

Conclusions

Delta-Omicron recombinant viruses were rare, and there is currently no evidence that Delta-Omicron recombinant viruses are more transmissible between hosts compared with the circulating Omicron lineages.

Funding

This research was supported by the NIH RADx initiative and by the Centers for Disease Control Contract 75D30121C12730 (Helix).

Keywords

RNA virus
SARS-CoV-2
Delta
Omicron
BA.1
sequencing
alternative allele fraction
co-infection
recombination
breakpoint

CAT Scale

Translation to patients

Data and code availability

  • All samples with a qc_status of ‘pass’ were uploaded to GISAID. There are two ways to find them on GISAID. One way is to download all of the samples that have a collection date within the time period studied in this paper and filter for ‘Helix’ in the ‘Originating lab’ field. The other way is to search for all samples with ‘CDC-STM’ in the ‘Virus name’ field as only Helix uses this nomenclature for the name of the virus (and filter by collection date as above).

    • Identifiers for RECOMB1, GISAID: hCoV-19/USA/MA-CDC-STM-HZEBR92XC/2022, EPI_ISL_9088187

    • Identifiers for RECOMB2, GISAID: hCoV-19/USA/MA-CDC-STM-SP94WR2RW/2022, EPI_ISL_10114799

  • BAMs of co-infection samples and recombinant samples are available at SRA STUDY: PRJNA804575. Link: https://www.ncbi.nlm.nih.gov/Traces/study/?acc=PRJNA804575&o=acc_s%3Aa

  • SRA BioSample accessions:

  • The raw data used to generate all figures is available in the supplemental tables.

  • The code used to make the alternative allele fraction plots is deposited in Mendeley Data: https://data.mendeley.com/datasets/gvx4bwygdz/2, and is in Data S1.

  • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

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Twitter: @shishiluo

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Lead contact