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Review 2: "Emergence of a novel SARS-CoV-2 strain in Southern California, USA"

This preprint, for which additional peer reviews are pending, identifies a CAL20C variant, which has spread throughout southern California. Additional epidemiological research is needed to determine if this variant could be responsible for increased transmissibility state-wide.

Published onFeb 11, 2021
Review 2: "Emergence of a novel SARS-CoV-2 strain in Southern California, USA"
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key-enterThis Pub is a Review of
Emergence of a novel SARS-CoV-2 strain in Southern California, USA
Description

AbstractSince October 2020, novel strains of SARS-CoV-2 including B.1.1.7, have been identified to be of global significance from an infection and surveillance perspective. While this strain (B.1.1.7) may play an important role in increased COVID rates in the UK, there are still no reported strains to account for the spike of cases in Los Angeles (LA) and California as a whole, which currently has some of the highest absolute and per-capita COVID transmission rates in the country. From the early days of the pandemic when LA only had a single viral genome uploaded onto GISAID we have been at the forefront of generating and analyzing the SARS-CoV-2 sequencing data from the LA region. We report a novel strain emerging in Southern California. Most current cases in the catchment population in LA fall into two distinct subclades: 1) 20G (24% of total) is the predominant subclade currently in the United States 2) a relatively novel strain in clade 20C, CAL.20C strain (∼36% of total) is defined by five concurrent mutations. After an analysis of all of the publicly available data and a comparison to our recent sequences, we see a dramatic growth in the relative percentage of the CAL.20C strain beginning in November of 2020. The predominance of this strain coincides with the increased positivity rate seen in this region. Unlike 20G, this novel strain CAL.20C is defined by multiple mutations in the S protein, a characteristic it shares with both the UK and South African strains, both of which are of significant clinical and scientific interest

RR:C19 Evidence Scale rating by reviewer:

  • Misleading. Serious flaws and errors in the methods and data render the study conclusions misinformative. The results and conclusions of the ideal study are at least as likely to conclude the opposite of its results and conclusions than agree. Decision-makers should not consider this evidence in any decision.

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Review:

This very short paper (doi: https://doi.org/10.1101/2021.01.18.21249786) relates to the B.1.429 / CAL.20C lineage. It provides some background information and speculates that the spike in cases in California may have been caused by the higher transmissibility of the lineage.

The background is very sketchy and would have benefitted from being expanded on. In short, the first genome from that lineage was identified in Mexico on the 6th of July 2020 (GISAID accession number EPI_ISL_942929). At the time of writing this review, there have been 1298 sequences made available, with 873 from California. I’m aware of no evidence, including in the preprint that the surges in cases in California might have been caused by the higher transmissibility of this lineage.

The B.1429 is characterized by a combination of mutations (as all other lineages). Though, none of them looks overly concerning. The S protein L452R mutation marginally contributes to immune escape, though it lacks any of the more problematic mutations such as E484K, or indels in the S1 domain. It also lacks the N501Y mutation which is a feature of three variants of concern.

In the absence of any functional evidence, I believe this lineage should not be considered as a ‘variant of concern’ and its local rise in frequency seems best explained by epidemiological stochasticity.

There are many lineages at reasonably high frequency in many places in the world. Some deserve our attention as they could be more transmissible, and others don’t. Given the evidence provided in this preprint, I suspect that B 1.429 may be a fairly anonymous SARS-CoV-2 lineage.

Figure 1 is not a phylogenetic tree contrarily to its caption; I also didn’t find it informative. Figure 2 is lifted as-is from NextStrain (https://nextstrain.org), without any acknowledgment to the original source. The submission lacks the acknowledgment table to contributors of genomes to the GISAID database.

To summarize, while I appreciate it is important to keep an eye on the B 1.429 lineage, the preprint does not provide any new meaningful evidence and would need significantly more work to be considered for publication.

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