A pilot study for treatment of severe COVID-19 pneumonia by aerosolized formulation of convalescent human immune plasma exosomes (ChipEXO™)

Abstract

This is a single-center prospective, open-label, single arm interventional study to test the safety and efficacy of recently described ChipEXO™ for severe COVID-19 pneumonia. The ChipEXO™ is a natural product derived from convalescent human immune plasma of patients recovered from moderate COVID-19 infection. In September 2021, 13 patients with pending respiratory failure were treated with ChipEXO™ adapted for aerosolized formulation delivered via jet nebulizer. Patients received 1-5x1010 nano vesicle/5 mL in distilled water twice daily for five days as an add-on to ongoing conventional COVID-19 treatment. The primary endpoint was patient safety and survival over a 28-day follow-up. The secondary endpoint was longitudinal assessment of clinical parameters following ChipEXO™ to evaluate treatment response and gain insights into the pharmacodynamics. ChipEXO™ was tolerated well without any allergic reaction or acute toxicity. The survival rate was 84.6% and 11 out of 13 recovered without any sequel to lungs or other organs. ChipEXO™ treatment was effective immediately as shown in arterial blood gas analyses before and two hours after exosome inhalation. During the 5 days of treatment, there was a sustainable and gradual improvement on oxygenation parameters: i.e. respiratory rate (RR) [20.8% (P < 0.05)], oxygen saturation (SpO2) [6,7% (P < 0.05)] and partial pressure of oxygen to the fraction of inspired oxygen (PaO2/FiO2) [127.9% (P < 0.05)] that correlated with steep decrease in the disease activity scores and inflammatory markers, i.e. the sequential organ failure assessment (SOFA) score (75%, p < 0.05), C-reactive protein (46% p < 0.05), ferritin (58% p = 0.53), D-dimer (28% p=0.46). In conclusion, aerosolized ChipEXO™ showed promising safety and efficacy for life-threatening COVID-19 pneumonia. Further studies on larger patient populations are required to confirm our findings and understand the pathophysiology of improvement toward a new therapeutic agent for the treatment of severe COVID-19 pneumonia.

Respiratory delivery of passive immunotherapies for SARS-CoV-2 prophylaxis and therapy

“…Passive immunotherapies are not the only protein biologics considered for COVID-19. Other biologics considered for respiratory delivery include ACE2 decoys 58 and exosomes from convalescent human immune cells, 59 but passive immunotherapies remain the most tested and reliable antiviral.…”

Extracellular vesicles: a rising star for therapeutics and drug delivery

“…Oxygenation parameters and inflammatory markers were improved. Thus, ChipEXO ™ showed good safety and efficacy [229].…”

Extracellular vesicles as human therapeutics: A scoping review of the literature

“…Finally, a single‐centre prospective, single arm interventional study has tested the safety and efficacy of ChipEXO, a product derived from convalescent plasma of COVID‐19 patients, in patients with severe COVID‐19 pneumonia at risk of respiratory failure via jet nebulization, as an add‐on to ongoing conventional COVID‐19 treatment. During the 5 days of treatment, all oxygenation parameters improved and inflammatory markers decreased, with 11 out of 13 treated subjects recovering without any sequelae to lungs or other organs (study n.16, Table 1 ) (Gul et al., 2022 ).…”