Cysteine supplementation reverses immune dysfunction in cancer patients with severe COVID-19

Severe COVID-19 in cancer patients is characterized by immune dysfunction including weakened adaptive immune responses. Researchers using proteomic and metabolomic analysis identified dysfunctional cysteine metabolism as uniquely associated with severe COVID-19 in cancer patients. In a clinical trial (NCT04374461), cancer patients with steroid-refractory COVID-19 received N-acetylcysteine, which improved clinical outcomes compared to untreated patients. N-acetylcysteine treatment reduced inflammatory markers, decreased suppressive monocytes, and increased CD8+ T cell abundance and activation. The mechanism involves reduced prostaglandin E2, which suppresses T cells, and decreased activity of inhibitory transcription factors. Similar results were confirmed in mouse models of severe respiratory viral infection.