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Review 1: "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 1: "Infectivity and immune escape of the new SARS-CoV-2 variant of interest Lambda"
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key-enterThis Pub is a Review of
Infectivity and immune escape of the new SARS-CoV-2 variant of interest Lambda

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:

  • Strong. The main study claims are very well-justified by the data and analytic methods used. There is little room for doubt that the study produced has very similar results and conclusions as compared with the hypothetical ideal study. The study’s main claims should be considered conclusive and actionable without reservation.



The claims are strong given the data and the methods used. In this short manuscript, the authors test the escape of the Lambda SARS-CoV-2 variant from neutralization with plasma from healthcare workers vaccinated with two doses of the CoronaVac inactivated virus vaccine in Santiago, Chile. The authors make two claims: the mutations on the spike glycoprotein of the Lambda variant make it more infectious, and the spike mutations (and one deletion) mediate escape from CoronaVac-elicited neutralization.

These claims are based on a pseudo-neutralization assay (PNA) study design, where the authors made several observations. In the absence of vaccinated plasma, there is a greater luminescence signal per well of pseudovirus-infected cells, indicating more viruses entering each cell. In the presence of plasma, the Lambda variant is more poorly neutralized—about a 3-fold drop in neutralization capacity relative to their reference pseudovirus—with no spike mutations and more than the Gamma variant in their assay. A major strength of the work is that it is of immediate relevance—infections with Lambda are ramping up in South America and it is important to know why.

The higher infectivity data seems preliminary and should be verified using other systems (like live viruses). The fold-change for Gamma also seems to be low and may indicate low sensitivity in the assay due to technical factors. The Beta variant, which mediates strong neutralization escape, is most often used as a benchmark and would have provided a better comparison. Nevertheless, given the higher escape of the Lambda variant relative to Gamma in their system, the conclusion of the paper that this variant is effective at escaping vaccine-elicited neutralization is most likely correct.

As a side note, one of the mutations of Lambda, F490S, was previously observed in a patient with advanced HIV who had a prolonged SARS-CoV-2 infection—showing possible convergent evolution.

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