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

Fethi Gül, Department of Anesthesiology and Reanimation, Division of Critical Care Medicine, School of Medicine, Marmara University, Istanbul, Türkiye.
Zeynep Burcin Gonen, Betül-Ziya Eren Genome and Stem Cell Center (GENKOK), Kayseri, Türkiye.
Olcay Y. Jones, Division of Rheumatology, Department of Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, United States.
Neslihan Pakize Taşlı, Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, İstanbul, Türkiye.
Gökmen Zararsız, Department of Biostatistics, Faculty of Medicine, Erciyes University, Kayseri, Türkiye.
Ekrem Ünal, Department of Pediatrics, Division of Pediatric Hematology, Faculty of Medicine, Erciyes University, Kayseri, Türkiye.
Aykut Özdarendeli, Faculty of Medicine, Vaccine Research and Development Application and Research Center, Erciyes University, Kayseri, Türkiye.
Fikrettin Şahin, Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, İstanbul, Türkiye.
Ahmet Eken, Department of Biology, Faculty of Science, Erciyes University, Kayseri, Türkiye.
Semih Yılmaz, Institute of Health Sciences, Department of Medical Biochemistry, Erciyes University, Kayseri, Türkiye.
Musa Karakukçu, Department of Pediatrics, Division of Pediatric Hematology, Faculty of Medicine, Erciyes University, Kayseri, Türkiye.
Oğuz Kaan Kırbaş, Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, İstanbul, Türkiye.
Nur Seda Gökdemir, Betül-Ziya Eren Genome and Stem Cell Center (GENKOK), Kayseri, Türkiye.
Batuhan Turhan Bozkurt, Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, İstanbul, Türkiye.
Yusuf Özkul, Faculty of Medicine, Erciyes University, Kayseri, Türkiye.
Burçin Doruk Oktay, Department of Anesthesiology and Reanimation, Division of Critical Care Medicine, School of Medicine, Marmara University, İstanbul, Türkiye.
Muhammet Ali Uygut, Vaccine Research and Development Application and Research Center, Erciyes University, Kayseri, Türkiye.
Ismail Cinel, Department of Anesthesiology and Reanimation, Division of Critical Care Medicine, School of Medicine, Marmara University, İstanbul, Türkiye.
Mustafa Çetin, Faculty of Medicine, Erciyes University, Kayseri, Türkiye.

Document Type

Journal Article

Publication Date

1-1-2022

Journal

Frontiers in immunology

Volume

13

DOI

10.3389/fimmu.2022.963309

Keywords

COVID-19; Coronavirus disease; SARS-CoV-2; Severe acute respiratory syndrome-coronavirus-2; convalescent plasma; exosomes

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 jet nebulizer. Patients received 1-5x10 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 (SpO) [6,7% (P < 0.05)] and partial pressure of oxygen to the fraction of inspired oxygen (PaO/FiO) [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.

Department

Medicine

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