Positives

• Patients with persistent SARS-CoV-2 viral shedding cleared the virus at 80% on leflunomide compared with 16.7% on standard care, suggesting potential benefit for viral-persistence Long COVID phenotypes Oxford Academic.
  
  
• Hospitalized patients given leflunomide weaned off oxygen earlier and shortened their hospital stay by roughly one day compared with controls PMC.
  
  

Negatives

• Roughly one in five patients on leflunomide develops diarrhea, with severe colitis and weight loss documented in case reports PubMed.
  
  
• A multicenter trial found leflunomide added to standard care did not improve 28- or 90-day Long COVID symptom prevalence in hospitalized patients PMC.
  
  

Hurdles & Side Effects

• Patients face hepatotoxicity risk and may wait 6 to 12 weeks before noticing benefit, requiring liver-enzyme monitoring throughout therapy Hopkins Arthritis.
  
  
• The drug's extremely long half-life means patients who develop side effects need a cholestyramine washout protocol to clear it from the body NCBI.