A late-stage multi-dimensional intervention rescues lethal viral pneumonia in an aged hamster model

Pulmonary transcriptomic profiling reveals that diffuse cell death, inadequate antiviral responses, myeloid-driven excessive inflammation and immune-thrombosis dictate the pulmonary microenvironment are typical molecular pathology characteristics of the SARS-CoV-2-infected aged hamsters rather than the adult controls.

To reverse the progression of lethal severe pneumonia in the aged hamsters, we initiate a multidimensional combination therapy of dexamethasone, heparin and the broad-spectrum viral decoy CoVR-MV at three days after infection. Although single- and dual-drug therapies were insufficient to achieve functional cure, the three-drug combined therapy resulted in a potent reduction of high mortality, body weight loss, viral load, lung pathology and cytokine storms through the synergism of immunoregulatory, anticoagulant and antiviral effects, effectively intercepting the multifaceted pathogenic network.