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There is an unmet clinical need to end the COVID‐19 pandemic. In the past 2 years, the SARS‐CoV‐2 continued to evolve and poses a critical challenge to the efficacy of the vaccine and neutralizing antibody therapies. The fifth wave of the pandemic is driven by the Omicron variants, due to their ability to evade prior immunity and their resistance to therapeutic antibodies. The report by Zhang et al in the current issue of EMBO Molecular Medicine shows that the engineered decoy ACE2 can reduce lung injury and improve survival in K18‐hACE2 transgenic mice inoculated with a lethal dose of the SARS‐CoV‐2 and potentially targets the Omicron variant.