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. 2021 Dec:4:100031.
doi: 10.1016/j.bbiosy.2021.100031. Epub 2021 Nov 24.

Proof-of-concept trial of an amniotic fluid-derived extracellular vesicle biologic for treating high risk patients with mild-to-moderate acute COVID-19 infection

Michael A Bellio  1 , Cassie Bennett  1 , Alissa Arango  1 , Aisha Khan  2 , Xiumin Xu  2 , Cesar Barrera  3 , Vincent Friedewald  3 , Maria Ines Mitrani  1
Affiliations

Proof-of-concept trial of an amniotic fluid-derived extracellular vesicle biologic for treating high risk patients with mild-to-moderate acute COVID-19 infection

Michael A Bellio et al. Biomater Biosyst. 2021 Dec.

Abstract

A pandemic brought on by COVID-19 has created a scalable health crisis. The search to help alleviate COVID-19-related complications through therapeutics has become a necessity. Zofin is an investigational, acellular biologic derived from full-term perinatal amniotic fluid that contains extracellular vesicles. Extracellular nanoparticles as such have been studied for their immunomodulatory benefits via cellular therapeutics and, if applied to COVID-19-related inflammation, could benefit patient outcome. Subjects (n = 8) experiencing mild-to-moderate COVID-19 symptoms were treated with the experimental intervention. Complete blood count, complete metabolic panel, inflammatory biomarkers, and absolute lymphocyte counts were recorded prior to and on days 4, 8, 14, 21, and 30 as markers of disease progression. Additionally, chest x-rays were taken of the patients prior to and on days 8 and 30. Patients experienced no serious adverse events. All COVID-19-associated symptoms resolved or became stable with no indication of disease worsening as found by patient and chest x-ray reports. Inflammatory biomarkers (CRP, IL-6, TNF- α ) and absolute lymphocyte counts improved throughout the study period. Findings from a proof-of-concept, expanded access trial for COVID-19 patients prove the acellular biologic is safe and potentially effective to prevent disease progression in a high-risk COVID-19 population with mild-to-moderate symptoms.

Keywords: Biologic; COVID-19; Expanded Access; Extracellular Vesicles; Therapeutic.

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Conflict of interest statement

Michael Bellio, Cassie Bennett, Alissa Arango, and Maria Ines Mitrani represent Organicell Regenerative Medicine employees. Maria Ines Mitrani is the chief science officer, serves on the Organicell Regenerative Medicine Board of Directors, has a patent pending, and holds equity in the company. Michael Bellio is the laboratory director of the company and holds equity in the company. Aisha Khan and Xiumin Xu disclose a relationship with AssureImmune Cord Blood Bank that includes equity. Aisha Khan and Xuimin Xu provides regulatory consulting for Organicell and hold equity in the company. Vincent Friedewald and Cesar Barrera have no commercial, proprietary, or financial interests.

Figures

Fig. 1.
Fig. 1
Observation of Patient Outcomes. (A) COVID-19 screening results at each testing time point detected by RT-qPCR. Reported cases of (B) cough, (C) fatigue, and (D) shortness of breath in all patients.  (E) Pulse oximetry measurements of each patient throughout the study period. Normal range: 95–100%O2. (F) Respiratory rate as recorded per patients in addition to the (G) percentage change in respiratory rate throughout the study. Normal range: 12–20 breaths/minute. * P-value <0.05.
Fig. 2.
Fig. 2
Representative chest x-ray (CXR) imaging and summary of pulmonary findings. A) Representative CXR images of patient 011 at baseline, day 8, and day 30. B) The observation of pulmonary findings as indicated from CXR reports at the three time points for all patients.
Fig. 3.
Fig. 3
Inflammatory Biomarker Testing. A) CRP levels in all patients throughout the study. Normal range: 0–5.0 mg/L. B) Percentage change of CRP concentration compared to baseline. C) d-Dimer level in all patients throughout the study. Normal range: 0.3–8.0 ugFEU. D) Percentage change of d-Dimer concentration compared to baseline. E) IL-6 levels in all patients throughout the study. Normal range: 0–13.0 pg/mL. F) Percentage change of IL-6 concentration compared to day 4. G) TNF-α levels in all patients throughout the study. Normal range: 0–2.2 pg/mL. H) Percentage change of TNF-α concentration compared to day 4. * P-value <0.05, ** P-value <0.01, *** P-value <0.001, **** P-value <0.0001.
Fig. 4.
Fig. 4
Absolute lymphocyte count (ALC) as determined by the white blood cell counts and lymphocyte percentages. Normal range: 1–4 x103/μL. The (A) calculated ALC and (B) percentage change of ALC as compared to baseline for all patients. * P-value <0.05.
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References

    1. Wu F., et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020;579(7798):265–269. 03/01 2020, doi: 10.1038/s41586-020-2008-3. - PMC - PubMed
    1. Callaway E. Delta coronavirus variant: scientists brace for impact. Nature. Jul 2021;595(7865):17–18. doi: 10.1038/d41586-021-01696-3. - DOI - PubMed
    1. Wan Y., Shang J., Graham R., Baric R.S., Li F. Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus. J Virol. Mar 17 2020;94(7) doi: 10.1128/JVI.00127-20. - DOI - PMC - PubMed
    1. M. Hoffmann et al., "SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor," Cell, vol. 181, no. 2, pp. 271–280 e8, Apr 16 2020, doi: 10.1016/j.cell.2020.02.052. - PMC - PubMed
    1. Sims A.C., Baric R.S., Yount B., Burkett S.E., Collins P.L., Pickles R.J. Severe acute respiratory syndrome coronavirus infection of human ciliated airway epithelia: role of ciliated cells in viral spread in the conducting airways of the lungs. J Virol. Dec 2005;79(24):15511–15524. doi: 10.1128/JVI.79.24.15511-15524.2005. - DOI - PMC - PubMed