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

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.

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

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.

Effect of Coronavirus Disease-2019 Infection on Left Atrial Functions

Objective: Left atrial (LA) dysfunction is a crucial risk factor for cardiovascular events, and various pathologies may affect LA function. Coronavirus disease-2019 (COVID-19) is an ongoing global pandemic causing morbidity and mortality. In the present study, we aimed to evaluate LA functions in patients who recovered from COVID-19. Methods: Sixty consecutive patients recovered from COVID-19 and 60 healthy individuals as a control group were included in the study. Blood samples and echocardiography measurements were obtained from each subject. The two groups were compared in terms of demographic and echocardiographic characteristics. Results: In the COVÍD-19 group, LA maximum volume (LAVmax) (P = 0.040), LA pre-A volume (LAVpre-A) (P = 0.014), and LA active emptying fraction (P = 0.027) were higher, while LA passive emptying fraction (P = 0.035) was lower. In addition, left ventricular ejection fraction (P = 0.006) and isovolumetric relaxation time (P = 0.008) were decreased in this group. Although LA volume index was higher in the COVID-19 group, it does not reach statistical significance. Conclusion: LA functions may be impaired in patients recovered from COVID-19 infection.

Effect of Coronavirus Disease-2019 Infection on Left Atrial Functions.

Objective: Left atrial (LA) dysfunction is a crucial risk factor for cardiovascular events, and various pathologies may affect LA function. Coronavirus disease-2019 (COVID-19) is an ongoing global pandemic causing morbidity and mortality. In the present study, we aimed to evaluate LA functions in patients who recovered from COVID-19. Methods: Sixty consecutive patients recovered from COVID-19 and 60 healthy individuals as a control group were included in the study. Blood samples and echocardiography measurements were obtained from each subject. The two groups were compared in terms of demographic and echocardiographic characteristics. Results: In the COVID-19 group, LA maximum volume (LAVmax) (P = 0.040), LA pre-A volume (LAVpre-A) (P = 0.014), and LA active emptying fraction (P = 0.027) were higher, while LA passive emptying fraction (P = 0.035) was lower. In addition, left ventricular ejection fraction (P = 0.006) and isovolumetric relaxation time (P = 0.008) were decreased in this group. Although LA volume index was higher in the COVID-19 group, it does not reach statistical significance. Conclusion: LA functions may be impaired in patients recovered from COVID-19 infection.

Preclinical Studies on Convalescent Human Immune Plasma-Derived Exosome: Omics and Antiviral Properties to SARS-CoV-2.

The scale of the COVID-19 pandemic forced urgent measures for the development of new therapeutics. One of these strategies is the use of convalescent plasma (CP) as a conventional source for passive immunity. Recently, there has been interest in CP-derived exosomes. In this report, we present a structural, biochemical, and biological characterization of our proprietary product, convalescent human immune plasma-derived exosome (ChipEXO), following the guidelines set forth by the Turkish Ministry of Health and the Turkish Red Crescent, the Good Manufacturing Practice, the International Society for Extracellular Vesicles, and the Gene Ontology Consortium. The data support the safety and efficacy of this product against SARS-CoV-2 infections in preclinical models.

COVID 19 disease independently predicted endothelial dysfunction measured by flow-mediated dilatation.

The systemic effects of COVID-19 disease are still largely uncertain and needs to be scrutinized with further trials. Endothelial dysfunction (ED) is responsible for the majority of adverse cardiovascular events. Flow-mediated dilation (FMD) is easily obtainable method to assess ED accurately. It is aimed to evaluate ED by measuring FMD following COVID-19 disease. Patients diagnosed with COVID-19 disease were recruited to the hospital two month after the discharge. Sex and age-matched healthy subjects were determined as the control group. Blood samples and FMD measurements were obtained from each participant. All subjects were divided into two groups according to the presence of ED determined by FMD measurements. These two groups were compared in terms of demographic features and the presence of recovered COVID-19 disease. A total of 92 subjects consisting of 59 without ED and 33 with ED were included in the study. ED (+) group was older (p = 0.015) and more likely to have hypertension (p = 0.044) and COVID-19 rate was higher in ED (+) group (p = 0.009). While neutrophil count (p = 0.047) and CRP (p = 0.036) were higher, eGFR (p = 0.044) was lower in ED (+) group. In the backward multivariable regression analysis, COVID-19 disease [OR = 3.611, 95% CI 1.069-12.198, p = 0.039] and BMI [OR = 1.122, 95% CI 1.023-1.231, p = 0.015] were independent predictors of ED. COVID-19 disease may cause ED which is the major underlying factor of cardiovascular diseases. Furthermore, COVID-19 disease may deteriorate the existing cardiovascular disease course. Detecting ED in the early phase or preventing by new treatment modalities may improve short and long-term outcome.