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Review 3: "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 16, 2021
Review 3: "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

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.


General comments: 

This report describes the appearance of a new SARS-CoV2 variant (CAL.20C) in Southern California that the authors claim contributed to the surge of COVID-19 that occurred in the region in fall 2020. The analysis is not very thorough and the conclusions do not support their main claim.  

Specific comments:

1. This is a very small-sample study based on genome sequence analysis of only 181 viral samples.  There is no description of the sources of these samples.  The estimation of proportion of a single variant among such a collection can be greatly biased by local outbreaks in large congregate settings (e.g., college campus, long-term care facility, hospital, meat processing warehouse, etc), where an investigation happened to have been conducted and samples collected. 

2. The authors claim that this variant has mutations in the Spike protein similar to those variants of concern reported from the UK and South Africa.  This is not correct.  The Spike protein mutation of concern in the UK's variant (B.1.1.7) is N501Y and those of SA's variant (B.1.351)  are N501Y and E484K, which are also found in another variant of concern from Brazil (P.1).  Cal.20C has neither but has a mutation in the receptor binding domain (L452R). The significance of this mutation with respect to viral neutralization by anti-Spike protein antibodies has not been determined.

3. The legend in Fig 2 has no detail. It is unclear what the viral variant data are based on.  Are the CAL.20C data based on the sequences obtained from the GISAID database or are they from the analysis done by the authors? If they are based on the GISAID database, then the authors' observation shows nothing new.

In summary, this report is devoid of detail, misinterprets the significance of the mutations found in Cal,20C, and does not provide any convincing evidence that explains the reason for the surge of the epidemic in LA in fall 2020.

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