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The recently reported outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes 2019 coronavirus disease (COVID-19), has led to a pandemic. This novel virus and disease were unknown before the outbreak began in Wuhan, China, in December 2019. COVID-19 is now affecting almost all ...

The recently reported outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes 2019 coronavirus disease (COVID-19), has led to a pandemic. This novel virus and disease were unknown before the outbreak began in Wuhan, China, in December 2019. COVID-19 is now affecting almost all countries around the world. The COVID-19 disease is a real health threat that is currently becoming a major concern worldwide and an unprecedented burden to public health. From the economy to social interactions, COVID-19 has affected almost every aspect of our society. Outbreaks such as avian flu, swine flu, Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola in Africa, and bluetongue in Europe are recent reminders.

COVID-19 affects different people in different ways. Most infected people develop mild to moderate disease and recover without hospitalization, but a subset of patients progress to severe disease, with high mortality rate and limited treatment options. The clinical feature of COVID-19 varies from asymptomatic forms to conditions involving multiorgan and systemic manifestations in terms of septic shock and multiple organ dysfunction syndromes (MODS). The main pathologic features of critical COVID-19 were consistent with acute lung injure (ALI) and acute respiratory distress syndrome (ARDS). This pathology involves direct attacks by the virus on the cells and secondary attacks on the body after activation of the immune system. This means that both the virus and the immune response can cause damage to the body, and common complications or secondary infection can occur. At cellular level, the spike protein (S-protein) of SARS-CoV-2 interacts with cell receptors to infect target cells. SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) triggering endocytosis of virus particles. Consequently, ACE2 receptor would represent a potential therapeutic candidate to study SARS-CoV-2 infection mechanisms.

Treating COVID-19 patients is challenging as no specific treatment options or vaccines against SARS-CoV-2 are available. The current, supportive but not curative, treatments consist of the use of experimental medication. These include Remdesivir, hydroxychloroquine, abidol, lopinavir/ritonavir, plasma, antibody and other nonspecific vaccines. Currently, remdesivir appears to be the most promising drug for the treatment of pneumonia caused by COVID-19. Within this scenario, investigations are ongoing at a dizzying speed to achieve a vaccine, and the pioneering manufacturers of the vaccines ensure their rapid development (Moderna, CanSino-Biologics, Inovio, Sinovac, BioNTech-Pfizer, Univ. of Oxford-AstraZeneca, Novavax, Gamaleya Research Institute, CureVac, Clover Biopharmaceuticals, Johnson & Johnson, Sanofi-GlaxoSmithKline, Merck & Co.), even some are now being tested on people within clinical trials. Although important advances have been made, while waiting for the much-desired vaccines, no one knows how effective the new vaccines will be? Still, the development of feasible, safe and effective therapies is extremely urgent. Therefore, increasing experimental and clinical evidence have given credibility to the claim that advanced therapies research could change the future of COVID-19 and the forthcoming emergence of virulent viruses. Particularly, cell based-therapies will have an impact, not yet foreseen, on the present and future sequels of COVID-19.

On the one hand, recent studies focus on regenerative, immunomodulatory and anti-inflammatory properties of mesenchymal stromal cells (MSCs) to reduce the manifestation of cytokine storm and to restore ARDS and ALI, exhibiting an important option to be applied to critical COVID-19 patients; or on MSCs secretome to treat COVID-19 pneumonia. Other research includes the use of hematopoietic stem cells derived from umbilical cord blood, bone marrow, or mobilized peripheral blood, as well as immune chimeric antigen receptor T-cell (CAR-T cells). On the other hand, the understanding of the mechanism of infection and pathogenesis processes are still limited, in this regard the use of human pluripotent stem cells, both embryonic stem cells (hESC) and/or induced stem cells (hiPSC) to generate tissue-specific human organoids (lung, intestinal, liver, vascular, heart and kidney organoids) may provide a next generation cellular model for investigating viral infection and drug screening.

Altogether, the main propose of this Research Topic is to highlight recent advances, to cover the progress of preclinical and clinical research and to discuss the critical aspects to be considered for the application of stem cell to palliate the COVID-19. The topic is broad and covers all aspects related to COVID-19. Although the main focus is on stem cell-based application for COVID-19, research articles reporting on other aspects of SARS-CoV-2, such as its structure, function, mechanism of infection, interaction with the receptor of host cells (SARS-CoV-2-ACE2), the detection of new therapeutic target and the development of new detection tools are appreciated.

This Research Topic accepts original researches, reviews, methods, clinical trials, case reports, letters to the editor, brief research reports, commentaries and opinions.

Keywords: Covid-19, cell therapy, SARS-CoV-2, spike-protein

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