Treatment of SARS-CoV-2-induced pneumonia with NAD⁺ and NMN in two mouse models

The global COVID-19 epidemic has spread rapidly around the world and caused the death of more than 5 million people. It is urgent to develop effective strategies to treat COVID-19 patients. Here, we revealed that SARS-CoV-2 infection resulted in the dysregulation of genes associated with NAD⁺ metabolism, immune response, and cell death in mice, similar to that in COVID-19 patients. We therefore investigated the effect of treatment with NAD⁺ and its intermediate (NMN) and found that the pneumonia phenotypes, including excessive inflammatory cell infiltration, hemolysis, and embolization in SARS-CoV-2-infected lungs were significantly rescued. Cell death was suppressed substantially by NAD⁺ and NMN supplementation. More strikingly, NMN supplementation can protect 30% of aged mice infected with the lethal mouse-adapted SARS-CoV-2 from death. Mechanically, we found that NAD⁺ or NMN supplementation partially rescued the disturbed gene expression and metabolism caused by SARS-CoV-2 infection. Thus, our in vivo mouse study supports trials for treating COVID-19 patients by targeting the NAD⁺ pathway.