Since the outbreak of the COVID-19 pandemic, according to the official statistics from the WHO website, there have been over 694 million confirmed cases worldwide until August 2023, with approximately 6.9 million deaths. In addition to the high incidence and mortality rates in the initial weeks following infection, up to 70% of COVID-19 patients may experience long-term complications, significantly impacting human health and placing a substantial burden on hospital resources.

A study evaluated 2,320 adult participants who were discharged between March 7, 2020, and April 18, 2021 from several National Health Service (NHS) hospitals in the United Kingdom, and found that only 25.5% of COVID-19 patients had fully recovered five months after discharge. And the improvement in patients' conditions was minimal even when study period was extended to one year. 71% of patients continued to experience one or more post-COVID-19 sequelae, with common symptoms including fatigue, difficulty breathing, muscle pain, and insomnia, etc. According to multiple studies, post-COVID-19 sequelae may involve 203 different symptoms and affect 10 organ systems in the body, including the neurological, reproductive, cardiovascular, and pulmonary systems. The World Health Organization (WHO) published an official definition of long COVID in October 2021. They define it as a condition that "occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis." Despite some guidelines for the management of long COVID, there is still a lack of specific treatment methods. Currently, the most important strategy is vaccination. Vaccination can help alleviate symptoms during the acute infection period, and studies have found that individuals who are vaccinated against COVID-19 have approximately a 50% lower risk of developing long COVID compared to those who are unvaccinated. Also, there are other therapies that are in the clinical research stage, and one of which is stem cell therapy. Mesenchymal stem cells (MSCs) are a type of cell with self-renewal and multi-directional differentiation abilities. They are the primitive "seed cells" that form various tissues and organs in the human body. Under specific conditions, MSCs can differentiate into various cells in the human body, including osteoblasts, adipocytes, chondrocytes, and other cells of the stromal lineage, and repair tissue damage through the secretion of corresponding factors. Meanwhile, MSCs also act as "inflammation terminators" by regulating immune reactions through paracrine functions and interactions with immune cells. This ultimately leads to the downregulation of local inflammatory responses and alleviation of excessive immune reactions.

The research team led by Wang Fusheng published a study in the journal "eBioMedicine" (impact factor: 8.143) in 2022, which explored the use of umbilical cord mesenchymal stem cells (UC-MSCs) for the treatment of severe COVID-19 patients and followed up patients for one year. The study confirmed that UC-MSCs therapy, as an adjuvant therapy, has long-term benefits for lung injury in severe COVID-19 patients. This was a randomized, double-blind, controlled trial, with 100 patients randomly assigned in a 2:1 ratio (65 in the UC-MSCs group and 35 in the control group). The results showed that UC-MSCs helped in the resolution of lung consolidative lesions, with 17.9% of patients in the UC-MSCs group having normal CT images after one year of follow-up. In contrast, the control placebo group had not recovered from lung injury. There were no significant differences in the incidence of adverse events between the two groups. And in Japan, the Japanese Respiratory Syndrome Society has been conducting research on the long-term effects of COVID-19 since August 1, 2020. According to foreign media reports, the Kyushu Regenerative Medicine Special Committee in Japan has approved a program for the use of autologous adipose-derived mesenchymal stem cells in the treatment of post-COVID-19 syndrome. This patented technology developed by the Korean Stem Cell Research Institute has undergone a 120-day review and three rounds of screening by a committee of 16 experts from various fields, and has passed the review of the current regenerative medical plan for post-COVID-19 syndrome. The director of the Stem Cell Research Institute, who developed this therapy, stated, "This approval has received strong support from the Regenerative Medicine Special Committee. The investigators believe that mesenchymal stem cells, through their anti-inflammatory and tissue regeneration effects, will have good results in treating post-COVID-19 syndrome." This study aims to evaluate the effectiveness and safety of mesenchymal cell therapy for long COVID-19 patients. It is a prospective exploratory study, randomized, double-blind, placebo-controlled trial, planning to include a total of 76 patients who have been infected with COVID-19. By assessing the improvement of CTCAE 5.0 symptom scores in the treatment group and control group at 28 days, 12 weeks, and 24 weeks after treatment completion, the effectiveness and safety of mesenchymal stem cells in patients with long- term COVID-19 will be evaluated. This study is divided into two stages. Stage one: 10 patients will be enrolled, all receiving mesenchymal stem cell treatment, primarily assessing their safety. Stage two: 66 patients will be enrolled, randomly assigned in a 1:1 ratio to the treatment group and control group, evaluating the effectiveness and safety of mesenchymal stem cell therapy for long-term COVID-19.