Decisive reversal of lethal coronavirus disease 2019 in senescent hamster by synchronic antiviral and immunoregulatory intervention

The poor prognosis observed in elderly individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a serious clinical burden and the underlying mechanism is unclear, which necessities detailed investigation of disease characteristics and research for efficient countermeasures. To simulate lethal coronavirus disease 2019 (COVID-19) in senescent human patients, 80-week-old male hamsters are intranasally inoculated with different doses of SARS-CoV-2 Omicron BA.5 variant. Exposure to a low dose of the Omicron BA.5 variant results in early activation of the innate immune response, followed by rapid viral clearance and minimal lung damage. However, a high dose of BA.5 results in impaired interferon signaling, cytokine storm, uncontrolled viral replication, and severe lung injury. To decrease viral load and reverse the deterioration of COVID-19, a new bio-mimic decoy called CoVR-MV is used as a preventive or therapeutic agent. Administration of CoVR-MV as a preventive or therapeutic intervention in the early stages of infection can effectively suppress viral load, regulate the immune response, and rescue animals from death and critical illness. These findings underscore the risk associated with SARS-CoV-2 Omicron BA.5 exposure in senescent hamsters and highlight the importance of early intervention to prevent disease progression. This study reveals the dose-dependent disease outcomes of SARS-CoV-2 Omicron BA.5 exposure in senescent hamster. High-dose BA.5 exposure results in impaired IFN I signaling, cytokine storm, uncontrolled viral replication, severe lung injury, and death. Early intervention of bio-mimic decoy CoVR-MV rescues critical COVID-19 by viral load inhibition and simultaneous reserving the imbalanced innate immune response from inflammatory to antiviral. image