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.
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Review:
The Omicron variant of SARS-CoV-2 has quickly spread globally and became the predominant stain in most countries and regions. An Omicron BA.1-specific PCR assay targeted on the S-gene was developed and added into the CDC N1 test. The modified test was used for detection of SARS-CoV-2 in Sweden and the resulting data from the first quarter of 2022 was analyzed and discussed. Clearly BA.1 of Omicron variant had been outcompeted by BA.2 variant, based on WGS data on BA.1-negative, and CDC N1-positive samples. A molecular target other than the S-gene may tolerate future variation better, as the S-gene is the most variable one in the viral genome, yet the “dropout” of SBA.1 signal led to the identification of the BA.2 variant through WGS technology. An average of 1.9 Ct lower in BA.2 than BA.1 strains indicated a higher viral concentrations of BA.2 from clinical samples, and was proposed to be one of the reasons that BA.2 had outcompeted BA.1 in Sweden. The high correlation between tests with and without using RNA extraction was used to illustrate minor differences between assays. However, Ct differences between the N-gene and the BA.1-specific S-gene (SBA.1) for BA.1 positive samples should provide more meaningful insight into whether the 1.9 Ct difference between BA.1 and BA.2 is significant. Additionally, given the fact that the Ct range of both BA.1 and BA.2 variants in clinical samples were about 15 Cts in this study (~Ct 18-33 in Fig. 1d and 1e) and from many other reports, the significance of the 1.9 Ct deference between BA.1 and BA.2 in transmission rate may need further analysis, including studies on their ability to skip or suppress our immune systems. Tables may provide useful information, if they were included in the submission. It is likely the X-axes in Fig. 1c should be changed to Log concentration, and not Log dilutions. This is a rather comprehensive study on the prevalence of BA.1 and BA.2 variants using relatively large data sets, and should provide very useful information for evolving of Omicron variants of SARS-CoV-2 in Sweden.
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