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Review 2: "Infectivity and immune escape of the new SARS-CoV-2 variant of interest Lambda"

This preprint describes gain-of-function properties for mutations defining the Lambda variant and the effectiveness of the CoronaVac vaccine against this variant. Reviewers consider the data reliable and require minor revision to clarify methodology.

Published onAug 06, 2021
Review 2: "Infectivity and immune escape of the new SARS-CoV-2 variant of interest Lambda"
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Infectivity and immune escape of the new SARS-CoV-2 variant of interest Lambda
Description

ABSTRACTBackgroundThe newly described SARS-CoV-2 lineage C.37 was recently classified as a variant of interest by the WHO (Lambda variant) based on its high circulation rates in South American countries and the presence of critical mutations in the spike protein. The impact of such mutations in infectivity and immune escape from neutralizing antibodies are entirely unknown.MethodsWe performed a pseudotyped virus neutralization assay and determined the impact of the Lambda variant on infectivity and immune escape using plasma samples from healthcare workers (HCW) from two centers in Santiago, Chile who received the two-doses scheme of the inactivated virus vaccine CoronaVac.ResultsWe observed an increased infectivity mediated by the Lambda spike protein that was even higher than that of the D614G (lineage B) or the Alpha and Gamma variants. Compared to the Wild type (lineage A), neutralization was decreased by 3.05-fold for the Lambda variant while it was 2.33-fold for the Gamma variant and 2.03-fold for the Alpha variant.ConclusionsOur results indicate that mutations present in the spike protein of the Lambda variant of interest confer increased infectivity and immune escape from neutralizing antibodies elicited by CoronaVac. These data reinforce the idea that massive vaccination campaigns in countries with high SARS-CoV-2 circulation must be accompanied by strict genomic surveillance allowing the identification of new isolates carrying spike mutations and immunology studies aimed to determine the impact of these mutations in immune escape and vaccines breakthrough.

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:

Methods: In the population of interest, it is not clear if they were previously infected by SARS-CoV-2 prior to receiving the vaccine. This should be clarified in the text. Further, the number of plasma samples collected is not specified. In the figure in the results section, there appear to be 79 plasma samples. However, this should also be noted in the text.

Results: Calculating the correlation analysis between convalescent plasma and neutralization may be important to consider.

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