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.

Abstract

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.

• Authors: Thais G Moreira, Kimble T F Matos, Giovana S De Paula, Thais M M Santana, Raquel G Da Mata, Fernando C Pansera, Andre S Cortina, Marcelle G Spinola, Clare M Baecher-Allan, Gerson D Keppeke, Jules Jacob, Vaseem Palejwala, Karen Chen, Saef Izzy, Brian C Healey, Rafael M Rezende, Rogerio A Dedivitis, Kunwar Shailubhai, Howard L Weiner
• Journal: Frontiers in immunology (Front Immunol) 2021 Vol. 12 Pg. 709861 ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 34475873 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Moreira, Matos, De Paula, Santana, Da Mata, Pansera, Cortina, Spinola, Keppeke, Jacob, Palejwala, Chen, Izzy, Healey, Rezende, Dedivitis, Shailubhai and Weiner.

Chemical References

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

Topics

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