Table 2.

Characteristics of studies using stem cell EV-based therapeutics as an anti-COVID19 intervention

Study (Year - country)	Patients’ characteristics	Model (Induction)	Source of EVs	EV effects	EV treatment outcome summary	Reference
Zhu et al. (2022- USA)	Severe (n = 7)	SARS-CoV-2	Human adipose MSC	↑ Lymphocyte counts ↓CRP, IL-6, LDH Normal ALT and creatinine	haMSC‑EV inhalation is feasible and well-tolerated in COVID‑19 patients, with no evidence of prespecified adverse events, immediate clinical instability, or dose‑relevant toxicity.	[34]
Mitrani et al. (2021-USA)	Severe (n = 3)	SARS-CoV-2	Human amniotic fluid	↑ Oxygen saturation ↓ TNF-α, IL-6, D-Dimer, and CRP. Improved SOFA score, PaO2/FiO2, Glasgow score, and creatinine levels	Human amniotic fluid-derived nanoparticles as a safe and potentially efficacious treatment for respiratory failure induced by COVID-19 infection	[35]
Mitrani et al. (2021-USA)	Long hauler (n = 1)	SARS-CoV-2	Human amniotic fluid	↑ Oxygen saturation and monocyte ↓TNF-α, IL-6, D-Dimer, platelets, and CRP	Zofin acts as a potentially safe and therapeutically efficient treatment option for the growing number of COVID-19 long-hauler patients	[36]
Bellio et al. (2021-USA)	Mild to moderate acute (n = 8)	SARS-CoV-2	Human amniotic fluid	↑ALC ↓CRP, IL-6, TNF-α, cough, shortness of breath No abnormalities in CBC, CMP, and d-dimer	Zofin is a feasible, safe, and potentially efficacious therapy for patients with mild-to-moderate COVID-19 who are at increased risk for progression, including the need for hospitalization, ventilation, and death	[37]
Sengupta et al. (2020- USA)	Severe (n = 27)	SARS-CoV-2	Human bone marrow MSCs	↑ Absolute lymphocyte count, PaO2/FiO2 ratio, and survival rate ↓ CRP, ferritin, and D-dimer, absolute neutrophil count. Improved SOFA score, Glasgow score, and creatinine levels	ExoFlo is a promising therapeutic safe candidate for severe COVID-19 due to its capacity to restore oxygenation, downregulate cytokine storm, and reconstitute immunity	[38]
FKazerooni et al. (2022- Iran)	Severe (n = 30)	SARS-CoV-2	Human MenSCs	↑ Oxygen levels, survival rate, lymphocytes count ↓CRP, LDH l, D-Dimer, and ferritin	MenSC-derived secretome is a safe and feasible therapeutic strategy severe COVID19 patients	[39]
Chu et al. (2022- China)	COVID-19 pneumonia (n = 7)	SARS-CoV-2	Human umbilical cord MSCs	↓CRP and NK cells ↑IFN-γ, IL-17 A and TH19. No allergic reactions or adverse events. No change in oxygen saturation level, total white blood cell count, lymphocyte count, fever, or shortness of breath	Nebulization of MSC-derived EVs at early stages of COVID-19 is a simple, safe, and effective treatment for patients	[40]

MSC Mesenchymal stem cells, ADCS Adipose-derived stem cell, MenSC Menstrual stromal cells, sEVs Extracellular vesicles, TNF-α Tumor necrosis factor-alpha, IL-6 Interleukin 6, CRP C-reactive protein, PaO2/FiO2 partial pressure of arterial oxygen to fraction of inspired oxygen ratio, CBC complete blood count, CMP complete metabolic panel, ALC absolute lymphocyte count, LDH lactate dehydrogenase, IFN-γ Interferon gamma, TH19 T helper 19