Non-Viral Therapy in COVID-19: Where Are We Standing? Towards Cell Therapy Approaches for Long COVID Patients

Background: COVID-19, caused by the SARS-CoV-2 virus, has infected over 777 million individuals and led to approximately 7 million deaths worldwide. Despite significant efforts to develop effective therapies, treatment remains largely supportive, especially for severe complications like acute respiratory distress syndrome (ARDS). Numerous com-pounds from diverse pharmacological classes are currently undergoing preclinical and clinical evaluation, targeting both the virus and the host immune response. Methods: Despite the large number of articles published and after a preliminary attempt published, we discarded the option of a systematic review (PRISMA Method). Instead we have done a description of therapies with these results and tentative mechanism of action. Results: Preliminary studies and early-phase clinical trials have demonstrated the potential of Mesenchymal Stem Cells (MSCs) in mitigating severe lung damage in COVID-19 pa-tients. Previous research has shown MSCs to be effective in treating various pulmonary conditions, including acute lung injury, idiopathic pulmonary fibrosis, ARDS, asthma, chronic obstructive pulmonary disease, and lung cancer. Their ability to reduce inflam-mation and promote tissue repair supports their potential role in managing COVID-19-related complications. This review demonstrates the utility of MSCs on the acute phase of COVID-19 and postulates the etiopathogenic role of mitochondria in the Long-COVID. Even more, their combination with other therapies is also analyzed. Con-clusions: While the therapeutic application of MSCs in COVID-19 is still in early stages, emerging evidence suggests promising outcomes. As research advances, MSCs may be-come an integral part of treatment strategies for severe COVID-19, particularly in ad-dressing immune-related lung injury and promoting recovery. However, a full patho-genic mechanism which may explain or unify the complexity of signs and symptoms of Long COVID and Post-Acute Sequealae (PASC).