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In this preprint study, Suryawanshi et al., have made significant advances in assessing various immunity responses to COVID-19 strains. They review three COVID-19 variant infections in mice and track the inflammatory and innate immunity response to the strains. The mice sera were then crossed with the other COVID-19 variants to assess their neutralization efficacies. The Delta strain had the broadest neutralization against the other strains, including Omicron. When transitioned to human sera of vaccinated or previously infected individuals, the overarching result was that sera from vaccinated individuals who had an Omicron breakthrough infection had the highest level of protection from all other variants despite the Omicron infection producing negligible immunity in non-vaccinated exposed sera. This led the authors to conclude that Omicron infection in vaccinated individuals boosted immune response to infection against other variants. 

I would firstly like to commend the authors for their astutely relevant work on this study. I found this preprint important not only for furthering multivalent vaccine development for broad COVID-19 protection but also because there’s currently controversy with acquiring an Omicron infection as reason for vaccine hesitancy amongst the general public. Furthermore, this preprint may have contradicting evidence to a claim made in a recent publication that states the Delta variant does not elicit cross-variant neutralization for Omicron.

One minor concern would be that the authors do not seem confident the strain the convalescent sera were exposed to was in fact Delta. It therefore makes me question whether or not the inability to confirm the antibodies that the convalescent sera contain would have an effect on the results. 

I highly look forward to reading subsequent versions of this paper.