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.
Subject(s)
Antibodies, Monoclonal/therapeutic use , COVID-19/immunology , COVID-19/prevention & control , Pneumonia/therapy , Administration, Intranasal , Adolescent , Adult , Antibodies, Monoclonal/administration & dosage , Biomarkers , C-Reactive Protein/analysis , COVID-19/physiopathology , 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 , Young AdultABSTRACT
[This corrects the article DOI: 10.3389/fimmu.2021.709861.].