Discussion
SARS-CoV-2 infection, hyperactive T, COVID-19 infection
SARS-COV-2 INFECTION, INFLAMMATORY RESPONSES, DISEASE, COVID-19 INFECTION, PATHOGENESIS
T cells play an important role in subjects with COVID-19 infection as COVID-19 patients develop hyperactive T cell responses that contribute to disease pathogenesis (We found that In addition to treatment of COVID-19 subjects with nasal Foralumab, we have treated healthy volunteers (We chose a dose of 100 μg for 10 d in COVID-19 patients based on results in healthy volunteers and dose-response curves in animals given nasal anti-CD3. What is remarkable in our findings is that identical gene changes were observed in healthy subjects given 50 μg × 5 d, COVID-19 subjects given 100 μg × 10 d, as well as in MS subjects given 50 μg in an every-other-day regimen at 2-wk intervals. We believe this adds to the robustness of our findings and demonstrates that the dose used (50 to 100 μg) is in the appropriate range to induce immune effects of nasal Foralumab. In addition, identical gene expression changes were observed in animals treated with nasal anti-CD3 at a dose of 1 μg for 5 d. Formal clinical trials will be needed to establish an optimal dosing regimen.We propose a mechanism of action whereby nasal Foralumab in humans involves the induction of a quiescence program in T cells through the upregulation of We also found that the Rhoa/ROCK1 pathway, known to be negatively regulated by GTPases was downregulated in Foralumab-treated subjects. Several important immunomodulatory roles of the Rhoa/ROCK1 signaling pathway and its respective genes in T cell function have been shown including the role of Cofilin in T cell hyporesponsiveness (BDNF levels were increased in the overall COVID-19 cohort at baseline and several subjects in the subsequent non-treatment cohort had high baseline values. It has been shown that COVID-19 may be associated with increased BDNF perhaps related to an immune response to modulate the disease (In summary, we found that nasal Foralumab modulates T cell inflammatory responses that occurs in SARS-CoV-2 infection by suppressing effector features in multiple CD3Although our cohort it is limited by its size and is not powered to present a biomarker associated with clinical outcomes in COVID-19, the major finding in our study is the identification of a unique mechanism associated with nasal Foralumab in humans that will help advance use of Foralumab as an adjunct therapy for COVID-19 and guide long-term use of this therapy in autoimmune conditions.