SARS-CoV-2 variants of concern (VOCs) display enhanced transmissibility and resistance to antibody neutralization. Comparing the early 2020 isolate EU-1 to the VOCs Alpha, Beta and Gamma in mice transgenic for human ACE2 reveals that VOCs induce a broadened scope of symptoms, expand systemic infection to the gastrointestinal tract, elicit depletion of natural killer cells and trigger variant-specific cytokine production patterns. Gamma infections result in accelerated disease progression associated with increased immune activation and inflammation. All four SARS-CoV-2 variants induce pDC depletion in lungs, paralleled by reduced interferon responses. Remarkably, VOCs also use the murine ACE2 receptor for infection to replicate in lungs of wildtype animals, which induce cellular and innate immune responses that apparently curtailed spread and overt disease. VOCs thus display distinct intrinsic pathogenic properties with broadened tissue and host range. Enhanced pathogenicity of VOCs and their potential for reverse zoonotic transmission poses challenges to clinical and pandemic management.

Fuente: Cell Reports
Available online 28 January 2022, 110387