Nasal Administration of Anti-CD3 Monoclonal Antibody (Foralumab) Reduces Lung Inflammation and Blood Inflammatory Biomarkers in Mild to Moderate COVID-19 Patients: A Pilot Study

Front Immunol. 2021 Aug 12:12:709861. doi: 10.3389/fimmu.2021.709861. eCollection 2021.


Background: Immune hyperactivity is an important contributing factor to the morbidity and mortality of COVID-19 infection. Nasal administration of anti-CD3 monoclonal antibody downregulates hyperactive immune responses in animal models of autoimmunity through its immunomodulatory properties. We performed a randomized pilot study of fully-human nasal anti-CD3 (Foralumab) in patients with mild to moderate COVID-19 to determine if its immunomodulatory properties had ameliorating effects on disease.

Methods: Thirty-nine outpatients with mild to moderate COVID-19 were recruited at Santa Casa de Misericordia de Santos in Sao Paulo State, Brazil. Patients were randomized to three cohorts: 1) Control, no Foralumab (n=16); 2) Nasal Foralumab (100ug/day) given for 10 consecutive days with 6 mg dexamethasone given on days 1-3 (n=11); and 3) Nasal Foralumab alone (100ug/day) given for 10 consecutive days (n=12). Patients continued standard of care medication.

Results: We observed reduction of serum IL-6 and C-reactive protein in Foralumab alone vs. untreated or Foralumab/Dexa treated patients. More rapid clearance of lung infiltrates as measured by chest CT was observed in Foralumab and Foralumab/Dexa treated subjects vs. those that did not receive Foralumab. Foralumab treatment was well-tolerated with no severe adverse events.

Conclusions: This pilot study suggests that nasal Foralumab is well tolerated and may be of benefit in treatment of immune hyperactivity and lung involvement in COVID-19 disease and that further studies are warranted.

Keywords: COVID-19; SARS-CoV-2; anti-CD3; foralumab; immune responses.

MeSH terms

  • Administration, Intranasal
  • Adolescent
  • Adult
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use*
  • Biomarkers
  • C-Reactive Protein / analysis
  • COVID-19 / immunology*
  • COVID-19 / physiopathology
  • COVID-19 / prevention & control*
  • COVID-19 / therapy
  • Cohort Studies
  • Female
  • Humans
  • Immunity / drug effects
  • Interleukin-6 / blood
  • Lung / drug effects
  • Lung / immunology
  • Lung / pathology
  • Male
  • Middle Aged
  • Outpatients / statistics & numerical data
  • Pilot Projects
  • Pneumonia / prevention & control
  • Pneumonia / therapy*
  • Young Adult


  • Antibodies, Monoclonal
  • Biomarkers
  • Interleukin-6
  • C-Reactive Protein
  • foralumab