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Review 2: "Evidence for SARS-CoV-2 Delta and Omicron Co-infections and Recombination"

Though it’s bibliographic citations and discussion section could be refined, reviewers agree that this paper provides strong evidence of co-infection, utilizes robust and appropriate methods, and addresses any caveats in their data.

Published onMar 30, 2022
Review 2: "Evidence for SARS-CoV-2 Delta and Omicron Co-infections and Recombination"
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key-enterThis Pub is a Review of
Evidence for SARS-CoV-2 Delta and Omicron co-infections and recombination

Between November 2021 and February 2022, SARS-CoV-2 Delta and Omicron variants co-circulated in the United States, allowing for co-infections and possible recombination events. 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. 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. Delta-Omicron recombinant viruses were rare, and there is currently no evidence that Delta-Omicron recombinant viruses are more transmissible between hosts compared to the circulating Omicron lineages.

RR:C19 Evidence Scale rating by reviewer:

  • Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.



The authors present evidence for co-infection of single patients by both the Delta and Omicron variants of SARS-CoV-2. They also state that they have found 2 examples of recombinant viral genomes between Delta and Omicron. I find the evidence for co-infection to be strong. I find the evidence for recombinant genomes to be reliable but am less convinced that the data are unambiguous for these genomes than for the co-infections. The authors do a good job of explaining caveats in their data, mostly having to do with library preparation and the fundamental nature of short read sequencing and challenges in assigning reads to genomic sequences. For such analyses I would prefer to see long-read single molecule sequencing, which is presumably the referenced “another sequencing technology”. The fact that there are relatively few reads obtained for the recombinant genomes could be emphasized more, but is somewhat reassuring to the general public that these genomes do not seem to compete well with other genotypes. The citations for a number of references are incomplete in that they are lacking publications (deKlerk et al., Laceke et al., Lai et al., Samson et al, and Sanderson et al.).


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