Previously, we demonstrated the therapeutic effects of human umbilical cord mesenchymal stromal cells (hUC-MSCs) in severe coronavirus disease 2019 (COVID-19) patients. In this 3-month follow-up study, we examined discharged patients who had received hUC-MSC therapy to assess the safety of this therapy and the health-related quality of life (HRQL) of these patients. The follow-up cohort consisted of 28 discharged severe COVID-19 patients who received either the standard treatment (the control group) or the standard treatment plus hUC-MSC therapy. We examined liver function, kidney function, pulmonary function, coagulation, tumor markers, and vision. We also conducted electrocardiography (ECG) analysis, let the patients answer the St. George's Respiratory Questionnaire (SGRQ), and performed computed tomography (CT) imaging for assessing the lung changes. No obvious adverse effects were observed in the hUC-MSC group after 3 months. Measurements of blood routine index, C-reactive protein and procalcitonin, liver and kidney function, coagulation, ECG, tumor markers, and vision were almost within the normal ranges in both the treatment and control groups. Forced expiratory volumes in 1 s (FEV1) (% of predicted) were 71.88% ± 8.46% and 59.45% ± 27.45% in the hUC-MSC and control groups (P < 0.01), respectively, and FEV1/forced vital capacity (FEV1/FVC) ratios were 79.95% ± 8.00% and 58.97% ± 19.16% in the hUC-MSC and control groups, respectively (P < 0.05). SGRQ scores were lower in the hUC-MSC group than in the control group (15.25 ± 3.69 vs. 31.9 ± 8.78, P < 0.05). The rate of wheezing in the hUC-MSC group was also significantly lower than that in the control group (37.5% vs. 75%, P < 0.05). There were no significant differences in CT scores between the two groups (0.60 ± 0.88 vs. 1.00 ± 1.31, P = 0.917). Overall, the intravenous transplantation of hUC-MSCs accelerated partial pulmonary function recovery and improved HRQL, indicating relative safety and preliminary efficacy of this treatment for patients with severe COVID-19.
Get full access to this article
View all access options for this article.
References
1.
HuangC, WangY, LiX, RenL, ZhaoJ, HuY, ZhangL, FanG, XuJ, et al. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 395:497–506.
2.
ZhuN, ZhangD, WangW, LiX, YangB, SongJ, ZhaoX, HuangB, ShiW, et al. (2020). A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med, 382:727–733.
3.
ZouL, RuanF, HuangM, LiangL, HuangH, HongZ, YuJ, KangM, SongY, et al. (2020). SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N Engl J Med, 382:1177–1179.
4.
WHO Coronavirus Disease (COVID-19) Dashboard Data last updated: June 16, 2021 CET. https://covid19.who.int.
5.
JeanSS, LeePI and HsuehPR. (2020). Treatment options for COVID-19: the reality and challenges. J Microbiol Immunol Infect, 53:436–443.
6.
RothanHA and ByrareddySN. (2020). The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun, 109:102433.
7.
HoffmannM, Kleine-WeberH, SchroederS, KrugerN, HerrlerT, ErichsenS, SchiergensTS, HerrlerG, WuNH, et al. (2020). SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell, 181:271–280.
8.
HuB, HuangS and YinL. (2021). The cytokine storm and COVID-19. J Med Virol, 93:250–256.
9.
GolchinA, SeyedjafariE and ArdeshirylajimiA. (2020). Mesenchymal stem cell therapy for COVID-19: present or future. Stem Cell Rev Rep, 16:427–433.
10.
ShuL, NiuC, LiR, HuangT, WangY, HuangM, JiN, ZhengY, ChenX, et al. (2020). Treatment of severe COVID-19 with human umbilical cord mesenchymal stem cells. Stem Cell Res Ther, 11:361.
11.
FengY, HuangJ, WuJ, XuY, ChenB, JiangL, XiangH, PengZ and WangX. (2020). Safety and feasibility of umbilical cord mesenchymal stem cells in patients with COVID-19 pneumonia: a pilot study. Cell Prolif, 53:e12947.
12.
New coronavirus pneumonia diagnosis and treatment program (5th ed.) (in Chinese). (2020). www.nhc.gov.cn/xcs/zhengcwj/202002/3b09b894ac9b4204a79db5b8912d4440.shtml Accessed May20, 2021.
13.
DominiciM, Le BlancK, MuellerI, Slaper-CortenbachI, MariniF, KrauseD, DeansR, KeatingA, ProckopD and HorwitzE. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8:315–317.
14.
WuM, ZhangR, ZouQ, ChenY, ZhouM, LiX, RanR and ChenQ. (2018). Comparison of the biological characteristics of mesenchymal stem cells derived from the human placenta and umbilical cord. Sci Rep, 8:5014.
15.
(1995). Standardization of Spirometry, 1994 Update. American Thoracic Society. Am J Respir Crit Care Med, 152:1107–1136.
16.
JonesPW, QuirkFH and BaveystockCM. (1991). The St George's Respiratory Questionnaire. Respir Med 85 Suppl, B:25–31, 33–37.
17.
JonesPW, QuirkFH, BaveystockCM and LittlejohnsP. (1992). A self-complete measure of health status for chronic airflow limitation. The St. George's Respiratory Questionnaire. Am Rev Respir Dis, 145:1321–1327.
18.
YorkeJ, JonesPW and SwigrisJJ. (2010). Development and validity testing of an IPF-specific version of the St George's Respiratory Questionnaire. Thorax, 65:921–926.
19.
OngKC, NgAW, LeeLS, KawG, KwekSK, LeowMK and EarnestA. (2005). 1-year pulmonary function and health status in survivors of severe acute respiratory syndrome. Chest, 128:1393–1400.
20.
LengZ, ZhuR, HouW, FengY, YangY, HanQ, ShanG, MengF, DuD, et al. (2020). Transplantation of ACE2(−) mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia. Aging Dis, 11:216–228.
21.
WeissA and DahlkeMH. (2019). Immunomodulation by mesenchymal stem cells (MSCs): mechanisms of action of living, apoptotic, and dead MSCs. Front Immunol, 10:1191.
22.
GlennJD and WhartenbyKA. (2014). Mesenchymal stem cells: emerging mechanisms of immunomodulation and therapy. World J Stem Cells, 6:526–539.
23.
Monguio-TortajadaM, Bayes-GenisA, RosellA and RouraS. (2020). Are mesenchymal stem cells and derived extracellular vesicles valuable to halt the COVID-19 inflammatory cascade? Current evidence and future perspectives. Thorax, 76:196–200.
XuX, JiangW, ChenL, XuZ, ZhangQ, ZhuM, YeP, LiH, YuL, et al. (2021). Evaluation of the safety and efficacy of using human menstrual blood-derived mesenchymal stromal cells in treating severe and critically ill COVID-19 patients: an exploratory clinical trial. Clin Transl Med, 11:e297.
26.
ShiL, HuangH, LuX, YanX, JiangX, XuR, WangS, ZhangC, YuanX, et al. (2021). Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients: a randomized, double-blind, placebo-controlled phase 2 trial. Signal Transduct Target Ther, 6:58.
27.
HashemianSR, AliannejadR, ZarrabiM, SoleimaniM, VosoughM, HosseiniSE, HossieniH, KeshelSH, NaderpourZ, et al. (2021). Mesenchymal stem cells derived from perinatal tissues for treatment of critically ill COVID-19-induced ARDS patients: a case series. Stem Cell Res Ther, 12:91.
28.
HuiDS, JoyntGM, WongKT, GomersallCD, LiTS, AntonioG, KoFW, ChanMC, ChanDP, et al. (2005). Impact of severe acute respiratory syndrome (SARS) on pulmonary function, functional capacity and quality of life in a cohort of survivors. Thorax, 60:401–409.
29.
HuiDS, WongKT, KoFW, TamLS, ChanDP, WooJ and SungJJ. (2005). The 1-year impact of severe acute respiratory syndrome on pulmonary function, exercise capacity, and quality of life in a cohort of survivors. Chest, 128:2247–2261.
30.
NgaiJC, KoFW, NgSS, ToKW, TongM and HuiDS. (2010). The long-term impact of severe acute respiratory syndrome on pulmonary function, exercise capacity and health status. Respirology, 15:543–550.
31.
ParkWB, JunKI, KimG, ChoiJP, RheeJY, CheonS, LeeCH, ParkJS, KimY, et al. (2018). Correlation between pneumonia severity and pulmonary complications in Middle East respiratory syndrome. J Korean Med Sci, 33:e169.
32.
ZhouF, YuT, DuR, FanG, LiuY, LiuZ, XiangJ, WangY, SongB, et al. (2020). Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet, 395:1054–1062.
33.
XuZ, ShiL, WangY, ZhangJ, HuangL, ZhangC, LiuS, ZhaoP, LiuH, et al. (2020). Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med, 8:420–422.
34.
MoodleyY, AtienzaD, ManuelpillaiU, SamuelCS, TchongueJ, IlancheranS, BoydR and TrounsonA. (2009). Human umbilical cord mesenchymal stem cells reduce fibrosis of bleomycin-induced lung injury. Am J Pathol, 175:303–313.
35.
SenguptaV, SenguptaS, LazoA, WoodsP, NolanA and BremerN. (2020). Exosomes derived from bone marrow mesenchymal stem cells as treatment for severe COVID-19. Stem Cells Dev, 29:747–754.
36.
OsmanIM, GoddenDJ, FriendJA, LeggeJS and DouglasJG. (1997). Quality of life and hospital re-admission in patients with chronic obstructive pulmonary disease. Thorax, 52:67–71.
37.
MesheOF, ClaydonLS, BungayH and AndrewS. (2017). The relationship between physical activity and health status in patients with chronic obstructive pulmonary disease following pulmonary rehabilitation. Disabil Rehabil, 39:746–756.
38.
HuangC, HuangL, WangY, LiX, RenL, GuX, KangL, GuoL, LiuM, et al. (2021). 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet, 397:220–232.
39.
FerrerM, VillasanteC, AlonsoJ, SobradilloV, GabrielR, VilagutG, MasaJF, ViejoJL, Jimenez-RuizCA and MiravitllesM. (2002). Interpretation of quality of life scores from the St George's Respiratory Questionnaire. Eur Respir J, 19:405–413.
40.
XieL, LiuY, XiaoY, TianQ, FanB, ZhaoH and ChenW. (2005). Follow-up study on pulmonary function and lung radiographic changes in rehabilitating severe acute respiratory syndrome patients after discharge. Chest, 127:2119–2124.
41.
AntonioGE, WongKT, HuiDS, WuA, LeeN, YuenEH, LeungCB, RainerTH, CameronP, et al. (2003). Thin-section CT in patients with severe acute respiratory syndrome following hospital discharge: preliminary experience. Radiology, 228:810–815.
42.
WongKT, AntonioGE, HuiDS, LeeN, YuenEH, WuA, LeungCB, RainerTH, CameronP, et al. (2003). Thin-section CT of severe acute respiratory syndrome: evaluation of 73 patients exposed to or with the disease. Radiology, 228:395–400.
