Are mesenchymal stem cells and derived extracellular vesicles valuable to halt the COVID-19 inflammatory cascade? Current evidence and future perspectives

Abstract

Clinical management of patients suffering from COVID-19 includes infection prevention, control measures and supportive care, including supplemental oxygen and mechanical ventilatory support.1 2 If not expertly and individually managed with consideration for vasocentric features,3 20% of COVID-19 patients who exhibit acute respiratory distress syndrome (ARDS; 14.8% of hospitalised patients4) may eventually progress to multiorgan failure and death, even when not of advanced age or predisposed by pre-existing comorbidities or chronic diseases.5 In these patients, infection by SARS-CoV-2 activates both the innate and adaptive immune responses, provoking the production of large amounts of pro-inflammatory cytokines and chemokines, resulting in a clinical presentation (ie, unremitting high fever, lymphadenopathy, hepatosplenomegaly, cytopenia, hyperferritinaemia, central nervous system abnormalities, hypoalbuminaemia and capillary leak) similar to other systemic, uncontrolled cytokine release syndromes (CRS)(figure 1).6 7 Thus, at present, management of the potential inflammatory complications of COVID-19 by using appropriate immunosuppressive and immunomodulatory drugs is being explored.8 Figure 1 COVID-19 pathophysiology, potential disease mechanisms and treatment options. ACS, acute coronary syndrome; ARDS, acute respiratory distress syndrome; CRP, C reactive protein; DAMPs, danger-associated molecular patterns; IL, interleukin; LDH, lactate dehydrogenase; MSC, mesenchymal stem cell; MSC-EV, MSC-derived extracellular vesicles; PAMPs, pathogen-associated molecular patterns; TNFα: tumour necrosis factor alpha. To date, a variety of novel and repurposed drugs with multiple pharmacological effects and therapeutic efficacies have been included in the potential armamentarium against COVID-19.9 10 For instance, among the antivirals preliminary tested, remdesivir has showing the best efficacy, with significant improvements in shortening the time to recovery and evidence of lower respiratory tract infection.11 It was issued an emergency use authorisation on 1 May 2020 for the treatment of COVID-19 patients hospitalised with severe disease by the Food and Drug Administration (FDA), and on 3 July 2020, it became the first treatment against …

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