Researchers from the University of São Paulo (USP) in Brazil, in collaboration with colleagues from Germany and the United States, conducted a systematic review and meta-analysis, which revealed a promising aspect of cell therapy in treating COVID-19. According to their findings, published in the journal Frontiers in Immunology, cell therapy can potentially reduce the risk of death from the disease by 60%.
This comprehensive review encompassed 195 clinical trials conducted in 30 countries between January 2020 and December 2021, along with 26 trials with outcomes published by July 2022. Cell therapy, a technique that involves introducing healthy cells into a patient’s body to restore or modify specific cell functions, has gained traction in recent years, primarily in cancer treatment. It utilizes stem cells and their derivatives, either from the patient (autologous) or a donor (allogenic), which are cultured or modified in the laboratory before administration.
The predominant cell types used in these COVID-19-related trials were multipotent mesenchymal stem cells from connective tissue (used in 72% of the studies), natural killer cells from lymphoblasts (used in 9%), and mononuclear cells from blood (used in 6%).
Otávio Cabral-Marques, a professor at USP’s Medical School and the study’s coordinator, emphasized the significant advancements in cell therapy. This treatment approach was explored in clinical trials during the pandemic, with a focus on stem cell therapy and organoids derived from stem cells. Stem cells, particularly the mesenchymal variety, possess immune regulatory capabilities and tissue repair functions. Trials have shown that advanced cell therapy can mitigate the inflammatory response in COVID-19 patients, reduce lung damage, enhance lung function, and combat fibrosis.
However, Cabral-Marques stressed that while cell therapy shows promise, vaccination remains the most effective means of preventing COVID-19. He emphasized that while advanced cell therapy could become an important adjunct treatment, vaccination remains the best protection against the disease.
Data standardization
The clinical trials exploring advanced cell therapy for COVID-19, as examined by the authors of the review, took place in 30 different countries, with notable participation from the United States, China, Iran, and Spain. However, these trials displayed significant heterogeneity, varying widely in terms of participant numbers, designs, and methodologies. To facilitate meaningful meta-analysis, the researchers established a dedicated COVID-19 trials database at CellTrials.org. They refined this database with quality improvements, such as including trials from all national registries, eliminating false positives based on keywords, and preventing duplicate counting of the same trials.
The authors also noted differences in trial phases. Strict regulations in many countries, particularly in Europe, limit the number of human cell therapy products with established safety profiles that can undergo testing. Consequently, 56% of the trials did not progress beyond phase 2, which typically assesses safety, efficacy, and dose-response in a few hundred participants with the disease. Another limitation was the absence of a control group in 31% of the analyzed trials.
Igor Salerno Filgueiras, a co-author of the article and a Ph.D. candidate, highlighted the complexity of arriving at a substantial reduction in the risk of death, necessitating the consideration of various study findings and characteristics, along with corrections and estimations.
Dennyson Leandro M. Fonseca, another co-author, emphasized the importance of techniques for standardizing data, eliminating biases, and producing impartial results. These methods enable analysts to draw conclusions that might not be apparent in individual studies but gain significance when supported by other data.
The article also underscored the significant heterogeneity in fabrication and clinical delivery methods in studies involving mesenchymal stem cells. While these results highlight the potential of these cells in adjuvant COVID-19 therapies and associated complications, they also emphasize the need for improved control of key parameters related to the production of cell therapy products to ensure comparability between studies, as noted by Cabral-Marques.
Source: FAPESP