# A Comparative Analysis of Innate Immune Responses and the Structural Characterization of Spike from SARS-CoV-2 Gamma Variants and Subvariants

## TL;DR

This study compares the immune responses and spike protein structures of SARS-CoV-2 Gamma variants and the original strain.

## Contribution

The novelty lies in analyzing both innate immune responses and structural differences in the S protein of the P.1 variant compared to the original strain.

## Key findings

- No significant difference in cytokine production between P.1 and B.1 variants.
- B.1 showed higher cytopathogenicity but neither variant replicated in mononuclear cells.
- Structural variations in the S protein may explain differences in infectivity.

## Abstract

The SARS-CoV-2 P.1 variant, responsible for an outbreak in Manaus, Brazil, is distinguished by 12 amino acid differences in the S protein, potentially increasing its ACE-2 affinity and immune evasion capability. We investigated the innate immune response of this variant compared to the original B.1 strain, particularly concerning cytokine production. Blood samples from three severe COVID-19 patients were analyzed post-infection with both strains. Results showed no significant difference in cytokine production of mononuclear cells and neutrophils for either variant. While B.1 had higher cytopathogenicity, neither showed viral replication in mononuclear cells. Structural analyses of the S protein highlighted physicochemical variations, which might be linked to the differences in infectivity between the strains. Our studies point to the increased infectivity of P.1 could stem from altered immunogenicity and receptor-binding affinity.