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


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GÜL F., GÖNEN Z. B., Jones O. Y., Taşlı N. P., ZARARSIZ G., ÜNAL E., ...More

Frontiers in Immunology, vol.13, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 13
  • Publication Date: 2022
  • Doi Number: 10.3389/fimmu.2022.963309
  • Journal Name: Frontiers in Immunology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CAB Abstracts, EMBASE, MEDLINE, Directory of Open Access Journals
  • Keywords: convalescent plasma, Coronavirus disease, COVID-19, exosomes, SARS-CoV-2, Severe acute respiratory syndrome-coronavirus-2
  • Kayseri University Affiliated: No

Abstract

Copyright © 2022 Gül, Gonen, Jones, Taşlı, Zararsız, Ünal, Özdarendeli, Şahin, Eken, Yılmaz, Karakukçu, Kırbaş, Gökdemir, Bozkurt, Özkul, Oktay, Uygut, Cinel and Çetin.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.