tetano
Editor, Senior Moderator
Front Immunol
. 2022 Nov 9;13:963309.
doi: 10.3389/fimmu.2022.963309. eCollection 2022.
A pilot study for treatment of severe COVID-19 pneumonia by aerosolized formulation of convalescent human immune plasma exosomes (ChipEXO™)
Fethi Gül[SUP] 1 [/SUP], Zeynep Burcin Gonen[SUP] 2 [/SUP], Olcay Y Jones[SUP] 3 [/SUP], Neslihan Pakize Taşlı[SUP] 4 [/SUP], Gökmen Zararsız[SUP] 5 [/SUP], Ekrem Ünal[SUP] 6 [/SUP], Aykut Özdarendeli[SUP] 7 [/SUP], Fikrettin Şahin[SUP] 4 [/SUP], Ahmet Eken[SUP] 8 [/SUP], Semih Yılmaz[SUP] 9 [/SUP], Musa Karakukçu[SUP] 6 [/SUP], Oğuz Kaan Kırbaş[SUP] 4 [/SUP], Nur Seda Gökdemir[SUP] 2 [/SUP], Batuhan Turhan Bozkurt[SUP] 4 [/SUP], Yusuf Özkul[SUP] 10 [/SUP], Burçin Doruk Oktay[SUP] 11 [/SUP], Muhammet Ali Uygut[SUP] 12 [/SUP], Ismail Cinel[SUP] 11 [/SUP], Mustafa Çetin[SUP] 10 [/SUP]
Affiliations
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 1-5x10[SUP]10[/SUP] 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[SUB]2[/SUB]) [6,7% (P < 0.05)] and partial pressure of oxygen to the fraction of inspired oxygen (PaO[SUB]2[/SUB]/FiO[SUB]2[/SUB]) [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.
Keywords: COVID-19; Coronavirus disease; SARS-CoV-2; Severe acute respiratory syndrome-coronavirus-2; convalescent plasma; exosomes.
. 2022 Nov 9;13:963309.
doi: 10.3389/fimmu.2022.963309. eCollection 2022.
A pilot study for treatment of severe COVID-19 pneumonia by aerosolized formulation of convalescent human immune plasma exosomes (ChipEXO™)
Fethi Gül[SUP] 1 [/SUP], Zeynep Burcin Gonen[SUP] 2 [/SUP], Olcay Y Jones[SUP] 3 [/SUP], Neslihan Pakize Taşlı[SUP] 4 [/SUP], Gökmen Zararsız[SUP] 5 [/SUP], Ekrem Ünal[SUP] 6 [/SUP], Aykut Özdarendeli[SUP] 7 [/SUP], Fikrettin Şahin[SUP] 4 [/SUP], Ahmet Eken[SUP] 8 [/SUP], Semih Yılmaz[SUP] 9 [/SUP], Musa Karakukçu[SUP] 6 [/SUP], Oğuz Kaan Kırbaş[SUP] 4 [/SUP], Nur Seda Gökdemir[SUP] 2 [/SUP], Batuhan Turhan Bozkurt[SUP] 4 [/SUP], Yusuf Özkul[SUP] 10 [/SUP], Burçin Doruk Oktay[SUP] 11 [/SUP], Muhammet Ali Uygut[SUP] 12 [/SUP], Ismail Cinel[SUP] 11 [/SUP], Mustafa Çetin[SUP] 10 [/SUP]
Affiliations
- PMID: 36439138
- PMCID: PMC9682905
- DOI: 10.3389/fimmu.2022.963309
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 1-5x10[SUP]10[/SUP] 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[SUB]2[/SUB]) [6,7% (P < 0.05)] and partial pressure of oxygen to the fraction of inspired oxygen (PaO[SUB]2[/SUB]/FiO[SUB]2[/SUB]) [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.
Keywords: COVID-19; Coronavirus disease; SARS-CoV-2; Severe acute respiratory syndrome-coronavirus-2; convalescent plasma; exosomes.