Stem Cells as a Model of Study of SARS-CoV-2 and COVID-19: A Systematic Review of the Literature

Abstract

Background: The SARS-CoV-2 virus is the cause of the latest pandemic of the 21st century; it is responsible for the development of COVID-19. Within the multiple study models for both the biology and the treatment of SARS-CoV-2, the use of stem cells has been proposed because of their ability to increase the immune response and to repair tissue. Therefore, the objective of this review is to evaluate the role of stem cells against SARS-CoV-2 and COVID-19 in order to identify their potential as a study model and as a possible therapeutic source against tissue damage caused by this virus. Therefore, the following research question was established: What is the role of stem cells in the study of SARS-CoV-2 and the treatment of COVID-19?

Materials and methods: A search was carried out in the electronic databases of PUBMED, Scopus, and ScienceDirect. The following keywords were used: "SARS-CoV-2," "COVID-19," and "STEM CELL," plus independent search strategies with the Boolean operators "OR" and "AND." The identified reports were those whose main objective was the study of stem cells in relation to SARS-CoV-2 or COVID-19. For the development of this study, the following inclusion criteria were taken into account: studies whose main objective was the study of stem cells in relation to SARS-CoV-2 or COVID-19 and clinical case studies, case reports, clinical trials, pilot studies, in vitro, or in vivo studies. For assessment of the risk of bias for in vitro studies, the SciRAP tool was used. The data collected for each type of study, clinical or in vitro, were analyzed with descriptive statistics using the SPSS V.22 program.

Results: Of the total of studies included (n = 39), 22 corresponded to in vitro investigations and 17 to human studies (clinical cases (n = 9), case series (n = 2), pilot clinical trials (n = 5), clinical trials (n = 1)). In vitro studies that induced pluripotent stem cells were the most used (n = 12), and in clinical studies, the umbilical stem cells derived were the most reported (n = 11). The mean age of the study subjects was 58.3 years. After the application of stem cell therapy, the follow-up period was 8 days minimum and 90 days maximum. Discussion. The mechanism by which the virus enters the cell is through protein "S," located on the surface of the membrane, by recognizing the ACE2 receptor located on the target cell. The evidence that the expression of ACE2 and TMPRSS2 in stem cells indicates that stem cells from bone marrow and amniotic fluid have very little expression. This shows that stem cell has a low risk of infection with SARS-CoV-2.

Conclusion: The use of stem cells is a highly relevant therapeutic option. It has been shown in both in vitro studies and clinical trials that it counteracts the excessive secretion of cytokines. There are even more studies that focus on long-term follow-up; thus, the potential for major side effects can be analyzed more clearly. Finally, the ethical use of stem cells from fetal or infant origin needs to be regulated. The study was registered in PROSPERO (no. CRD42021229038). The limitations of the study were because of the methodology employed, the sample was not very large, and the follow-up period of the clinical studies was relatively short.