Use of Multiple Doses of Intravenous Infusion of Umbilical Cord-Mesenchymal Stem Cells for the Treatment of Adult Patients with Severe COVID-19-Related Acute Respiratory Distress Syndrome: Literature Review

Table 1

Comparison of the demographic characteristics, therapeutic doses of intravenous infusion (IVF) of predominantly umbilical cord (UC) or placenta-harvested mesenchymal stem cells (MSCs), and treatment outcomes among adult patients with COVID-19-induced acute-onset respiratory distress syndrome (ARDS) who received ventilatory support in different severe COVID-19 case series with detailed data regarding ratios of partial pressure in arterial blood oxygen to fraction of inspired oxygen from the ventilator.

References	Single vs. multiple doses of UC-MSCs (number)	Case number (male : female)	Percentage with comorbidities	Dose(s) of UC-MSC cells (case number(s), and administration days after the onset of ARDS)	Ventilator days	Survival rates (%)	Percentage of cases who had a significant improvement in ARDS within 7 days among COVID-19 survivors
Dilogo et al. [12]	Single	20 (15 : 5)	100 (DM, HTN, CKD, CAD, CHF, TB, PPU, obesity, AMI, et al.)	1.0 × 10^6 kg BW (20; an average of 6.5 days)	15.69 ± 10.37	(In hospital) 50 (10/20)	100 (10/10)
Iglesias et al. [13]	Single	5 (4 : 1)	100 (Obesity, DM, hypothyroidism, HTN, lung fibrosis	1.0 × 10^6 kg BW (5; D1–D3 after ARDS onset)	1–17	(In hospital) 60 (3/5)	75 (3/4^a)
Yip et al. [14]	Single	9 (7 : 2)	100 (DM, dyslipidemia, CKD, HTN, recipient of H/D for AKI, liver cirrhosis)	1.0 × 10^6 kg BW (3; 5–12); 5.0 × 10^6 kg BW (3; 5–7); 10 × 10^6 kg BW (3; all were 5); (an average of 6.4 days for overall nine patients)	6–15; 15–44; 0–8; (an average of 15.4 (±12.9) days)	(In hospital); 66.7 (2/3); 33.3 (1/3); 100 (3/3); (overall 66.7 (6/9))	83.3 (5/6)
Hashemian et al. [15]	Multiple (3 doses, given every other day)	11 (8 : 3)	54.5 (DM, HTN, CLL, CMP)	200 × 10^6 in each infusion (6 received UC-MSCs, while 5 received placental MSCs; at medians of D5, D7, and D9, respectively, after ARDS onset)	An average of 3, among 7 patients who had initial improvement	(D60) 54.5 (6/11)	100 (8/8^b)
Liang et al. [16]	Multiple (3 doses, 72 hr apart)	1 (0 : 1)	0	50 × 10^6 in each infusion (1; D8, D11, and D14, respectively, after onset of ARDS)	12	(D30) 100 (1/1)	100 (1/1)
Jean et al. (authors’ series)	Multiple (4–6 doses)	2 (1 : 1)	100 ((Case 1) Morbid obesity, and (case 2) DM, respectively)	5 × 10^6 kg BW in each infusion (2; for case 1, 4 doses: on D4, D10, D15, and D18; for case 2, 6 doses: on D5, D8, D13, D16, D20, and D23, respectively, after ARDS onset)	28 and 46, respectively	(In hospital) 100 (2/2)	100 (2/2)

UC-MSCs, umbilical cord of mesenchymal stem cells; M : F, male : female; ARDS, acute-onset respiratory distress syndrome; DM, diabetes mellitus; HTN, hypertension; CKD, chronic kidney disease; H/D, hemodialysis; AKI, acute kidney injury; BW, body weight; CAD, coronary artery disease; CHF, congestive heart failure; TB, Mycobacterium tuberculosis infection; PPU, perforated peptic ulcer; AMI, acute myocardial infarction; D, days; Afib, atrial fibrillation; CVA, cerebrovascular accident; CLL, chronic lymphocytic lymphoma; CMP, cardiomyopathy; NA, not applicable. ^aOne patient died on Day 15 after IV UC-MSCs infusion due to bacterial pneumonia and hepatic failure with active bleeding. ^bOne patient received the first dose of IVF-MSCs on Day 11 of admission of intensive care unit (ICU). A definite improvement in the pulmonary dysfunction was initially noticed, but this patient died due to sudden-onset cardiac arrest (unrelated to MSC infusion) 4 days after this IVF-MSCs dosing. The other patient, who received the first dose of IVF-MSCs on ICU admission Day 5, had a similar clinical scenario.