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Review 1: "Transmission of SARS-CoV-2 Omicron VOC subvariants BA.1 and BA.2: Evidence from Danish Households"

This preprint compares infectivity rates of the BA.1 and BA.2 COVID-19 subvariants within the fully vaccinated, boosted, and unvaccinated populations. Reviewers deem this study as strong and reliable with minor limitations in methodology and the transmissibility context.

Published onMar 13, 2022
Review 1: "Transmission of SARS-CoV-2 Omicron VOC subvariants BA.1 and BA.2: Evidence from Danish Households"
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key-enterThis Pub is a Review of
Transmission of SARS-CoV-2 Omicron VOC subvariants BA.1 and BA.2: Evidence from Danish Households
Description

1AbstractThe Omicron SARS-CoV-2 variant of concern (VOC lineage B.1.1.529), which became dominant in many countries during early 2022, includes several subvariants with strikingly different genetic characteristics. Several countries, including Denmark, have observed the two Omicron subvariants: BA.1 and BA.2. In Denmark the latter has rapidly replaced the former as the dominant subvariant.Based on nationwide Danish data, we estimate the transmission dynamics of BA.1 and BA.2 following the spread of Omicron VOC within Danish households in late December 2021 and early January 2022.Among 8,541 primary household cases, of which 2,122 were BA.2, we identified a total of 5,702 secondary infections among 17,945 potential secondary cases during a 1-7 day follow-up period. The secondary attack rate (SAR) was estimated as 29% and 39% in households infected with Omicron BA.1 and BA.2, respectively.We found BA.2 to be associated with an increased susceptibility of infection for unvaccinated individuals (Odds Ratio (OR) 2.19; 95%-CI 1.58-3.04), fully vaccinated individuals (OR 2.45; 95%-CI 1.77-3.40) and booster-vaccinated individuals (OR 2.99; 95%-CI 2.11-4.24), compared to BA.1. We also found an increased transmissibility from unvaccinated primary cases in BA.2 households when compared to BA.1 households, with an OR of 2.62 (95%-CI 1.96-3.52). The pattern of increased transmissibility in BA.2 households was not observed for fully vaccinated and booster-vaccinated primary cases, where the OR of transmission was below 1 for BA.2 compared to BA.1.We conclude that Omicron BA.2 is inherently substantially more transmissible than BA.1, and that it also possesses immune-evasive properties that further reduce the protective effect of vaccination against infection, but do not increase its transmissibility from vaccinated individuals with breakthrough infections.

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 paper investigates determinants of the disease transmission for two SARS-CoV-2 subvariants, BA.1 and BA.2, by considering the infections in Danish households. Specifically, the differences in the two variants with respect to their transmissibility and susceptibility were considered by distinguishing individuals that were unvaccinated, fully vaccinated, or booster vaccinated. They find that both booster and fully vaccinated individuals have reduced susceptibility and transmissibility for both subvariants. However, there are additional reductions in both susceptibility and transmissibility for booster vaccinated compared to fully vaccinated individuals for both variants. All three categories (unvaccinated, fully vaccinated, and booster vaccinated) have a higher susceptibility for BA.2 than BA.1, where BA.2 has a particular advantage in the vaccinated population - providing an advantage for this variant spread in a highly vaccinated population. However, the effect of transmissibility differences for the two variants is mixed, i.e., they depend on the vaccination status (BA.2 seems to have higher transmissibility in unvaccinated individuals and the other way around for the vaccinated).

The topic of the study (transmission properties of two Omicron subvariants) is timely and important. The study design is reasonable, and the results appear plausible. However, to some extent, it is unclear how general the obtained results are, i.e., to what extent the conclusions can be applied to settings other than households. E.g., at some point, the study discusses differences in viral load – these may be quite different in, say, outdoor settings. The generality of the results should, thus, be discussed in the manuscript. Also, regarding the paper writing, the main study findings were not summarized clearly in the manuscript – i.e., a description along the lines of the first paragraph above. These are written in the manuscript but somewhat diffusive, and a reader may struggle to extract them. Thus, it may be helpful to have a separate summary/conclusion section, where the main results and practical implications would be summarized. As a minor writing comment, it would be more precise to refer to specific dates rather than weeks since the start of the year.

Regarding statistical methodology, the implementation with logistic regression seems reasonable. However, this does not systematically account for possible non-linearities or interactions among the predictors. The authors should consider using some machine learning methods (e.g., Random Forest, Gradient Boost) for the analysis – these have already been used to analyze Covid-19 transmissibility. Overall, the manuscript presents a relevant, timely, and interesting study, where some improvements in the presentation, and possibly methodology, could be made.

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