Significance
inflammation, infection, Foralumab) reduced lung inflammation, autoimmunity, coronavirus disease 2019
CORONAVIRUS DISEASE 2019, INFLAMMATORY RESPONSES, INFLAMMATION, DISEASE, SEVERE ACUTE RESPIRATORY SYNDROME, COVID-19 INFECTION, INFILTRATES, MULTIPLE SCLEROSIS (MS), INFECTION, MULTIPLE SCLEROSIS, CORONAVIRUS, AUTOIMMUNITY, DISEASES, COMPLICATIONS, INFLUENZA
Edited by Lawrence Steinman, Stanford University, Stanford, CA; received November 28, 2022; accepted January 30, 2023Activated T cells play an important role in the complications following COVID-19 infection. Anti-CD3 monoclonal antibody (mAb) binds to the T cell receptor and dampens inflammation by modulating T cell function. We show here that nasal administration of a fully human anti-CD3 Mab (Foralumab) modulates T cell inflammatory responses in COVID-19 by suppressing effector features in multiple T cell subsets, an effect also seen in subjects with multiple sclerosis. Immunomodulation by nasal anti-CD3 mAb represents a novel avenue for treatment of inflammatory human diseases.T cells are present in early stages of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and play a major role in disease outcome and long-lasting immunity. Nasal administration of a fully human anti-CD3 monoclonal antibody (Foralumab) reduced lung inflammation as well as serum IL-6 and C-reactive protein in moderate cases of COVID-19. Using serum proteomics and RNA-sequencing, we investigated the immune changes in patients treated with nasal Foralumab. In a randomized trial, mild to moderate COVID-19 outpatients received nasal Foralumab (100 μg/d) given for 10 consecutive days and were compared to patients that did not receive Foralumab. We found that naïve-like T cells were increased in Foralumab-treated subjects and NGK7The coronavirus disease 2019 (COVID-19) pandemic represents the greatest global public health crises since the pandemic influenza outbreak of 1918 (T cell responses are crucial for SARS-CoV-2 immunity. CD4We and others have shown the modulation of T cell function by the oral or nasal administration of anti-CD3 monoclonal antibody in animal models of autoimmunity and inflammation including multiple sclerosis (MS) (We previously conducted a pilot trial administering nasal Foralumab in subjects with mild to moderate COVID-19 and found a reduction in serum IL-6 and C-reactive protein and more rapid clearance of lung infiltrates in treated individuals (